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Intra-amniotic LPS modulates expression of antimicrobial peptides in the fetal sheep lung.
Damage-associated molecular patterns (DAMPs) and antimicrobial peptides (AMPs) are components of pulmonary innate immunity and tissue repair. We hypothesized that DAMPs and AMPs would increase in response to fetal pulmonary inflammation caused by chorioamnionitis in a time-dependent manner. Fetal sheep were exposed to intra-amniotic saline or lipopolysaccharide (LPS) (10 mg) between 5 h and 15 d prior to preterm delivery at 125 ± 2 d. Lung tissue mRNAs for proinflammatory cytokines; AMPs: myeloid AMP-29 (MAP29), dodecapeptide, sheep β-defensin-1 (SBD1), and sheep β-defensin-2 (SBD2); and DAMPs: interleukin (IL)-1α, lactoferrin, heat-shock protein-70 (HSP70), high-mobility group box protein-B1 (HMGB1), and receptor for advanced glycation endproducts (RAGE) were measured by reverse-transcriptase quantitative polymerase chain reaction. Immunohistochemistry of DAMPs and in situ hybridization of AMPs was performed. IL-1α, IL-1β, IL-6, IL-8, IL-10, MCP-1, and tumor necrosis factor (TNF)-α mRNA increased after LPS exposure. MAP29, dodecapeptide, SBD1, and SBD2 mRNA were suppressed at 24 h. MAP29 and dodecapeptide mRNA then increased at 8 d. Lactoferrin increased at 24 h. There were no changes for HMGB1, HSP70, or RAGE. MAP29 and dodecapeptide localized to alveolar cells, increased 8 d after exposure to LPS. AMPs are initially suppressed in the fetal lung by LPS-induced chorioamnionitis. The late induction of MAP29 and dodecapeptide may be related to lung repair.
25,105,257
[ -0.2490768, -0.4776784, -0.2594079, 0.1399785, 0.4275296, -0.2603321, -0.3494435, -0.01630299, 0.2357273, -0.0210985, -0.04263203, -0.0744418, 0.1920902, -0.1200396, 0.003180772, 0.03584113, -0.2414056, -0.1324263, -0.1295599, -0.2006536, 0.2570539, 0.2162111, -0.03854025...
Hereditary interstitial lung diseases manifesting in early childhood in Japan.
Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants. Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of granulocyte macrophage colony-stimulating factor-stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively. ILD were diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis, hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with interstitial pneumonitis (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 bronchoalveolar lavage or tracheal aspirates contained enough SP-B protein. The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.
25,105,258
[ 0.1728792, -0.5109862, 0.1656784, -0.2913582, 0.02951778, 0.003383416, 0.08568985, 0.02743514, 0.008801131, 0.0930264, 0.2215196, 0.2377707, -0.5827726, 0.1642175, 0.02221169, -0.213958, -0.1078441, -0.2160961, -0.1686825, 0.08283499, -0.1903993, 0.07931821, -0.3132889, ...
The heat-transfer method: a versatile low-cost, label-free, fast, and user-friendly readout platform for biosensor applications.
In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.
25,105,260
[ -0.2982621, -0.1278745, -0.4154349, -0.2233595, 0.0639726, -0.1084085, 0.01939134, 0.5398622, 0.3307662, 0.2389929, 0.02902563, -0.2631212, -0.1383798, -0.1018204, -0.9126505, 0.130503, -0.4498528, 0.1545794, -0.03004614, 0.240888, 0.6957064, 0.2398275, -0.2597502, 0.30...
Effect of multidisciplinary disease management for hospitalized heart failure under a national health insurance programme.
Multidisciplinary disease management programmes (MDPs) for heart failure have been shown to be effective in Western countries. However, it is not known whether they improve outcomes in a high population density country with a national health insurance programme. In total, 349 patients hospitalized because of heart failure were randomized into control and MDP groups. All-cause death and re-hospitalization related to heart failure were analyzed. The median follow-up period was approximately 2 years. Mean patient age was 60 years; 31% were women; and 50% of patients had coronary artery disease. MDP was associated with fewer all-cause deaths [hazard ratio (HR) = 0.49, 95% confidence interval (CI) = 0.27-0.91, P = 0.02] and heart failure-related re-hospitalizations (HR = 0.44, 95% CI = 0.25-0.77, P = 0.004). MDP was still associated with better outcomes for all-cause death (HR = 0.53, 95% CI = 0.29-0.98, P = 0.04) and heart failure-related re-hospitalization (HR = 0.46, 95% CI = 0.26-0.81, P = 0.007), after adjusting for age, diuretics, diabetes mellitus, chronic kidney disease, hypertension, sodium, and albumin. However, MDPs' effect on all-cause mortality and heart failure-related re-hospitalization was significantly attenuated after adjusting for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or β-blockers. A stratified analysis showed that MDP combined with guideline-based medication had synergistic effects. MDP is effective in lowering all-cause mortality and re-hospitalization rates related to heart failure under a national health insurance programme. MDP synergistically improves the effectiveness of guidelines-based medications for heart failure.
25,105,284
[ -0.1732587, -0.02683263, -0.02683334, 0.04970139, 0.1824621, -0.3051234, 0.1391514, 0.04267584, 0.1375285, -0.2001638, -0.1961869, 0.1879543, -0.1124271, 0.08790397, -0.1839136, 0.0359205, -0.02765838, 0.08498307, -0.1931547, -0.008150213, -0.2284897, 0.02887005, -0.28153...
Lapatinib antagonizes multidrug resistance-associated protein 1-mediated multidrug resistance by inhibiting its transport function.
Lapatinib, a tyrosine kinase inhibitor, is used in the treatment of advanced or metastatic breast cancer overexpressing human epidermal receptor 2 (HER2). Lapatinib can modulate the function of ATP-binding cassette (ABC) transporters (ABCB1 and ABCG2), which are the major mechanism responsible for multidrug resistance (MDR) in cancer. In this study, we investigated the effect of lapatinib on multidrug resistance-associated protein 1 (MRP1 [ABCC1]), MRP2 (ABCC2), MRP4 (ABCC4) and lung relative resistance protein (LRP) drug efflux pumps. We demonstrated that lapatinib could enhance the efficacy of conventional chemotherapeutic agents in MRP1-overexpressing cells in vitro and in vivo, but no effect in MRP2-, MPR4- and LRP-overexpressing cells. Furthermore, lapatinib significantly increased the accumulation of rhodamine 123 (Rho123) and doxorubicin (DOX) in MRP1-overexpressing cells. However, lapatinib did not alter the protein or mRNA expression levels of MRP1. Further studies showed that the level of phosphorylation of AKT and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were not altered at the indicated concentrations of lapatinib. In conclusion, lapatinib enhanced the efficacy of conventional chemotherapeutic agents in MRP1-overexpressing cells by inhibiting MRP1 transport function without altering the level of AKT or ERK1/2 phosphorylation. These findings will encourage the clinical research of lapatinib combined with conventional chemotherapeutic drugs in MRP1-overexpressing cancer patients.
25,105,301
[ -0.1137145, -0.2615901, -0.0767173, -0.337264, -0.08884361, -0.180774, -0.2199254, 0.1734574, -0.1152387, 0.330643, 0.3615242, 0.4167876, -0.137775, 0.150636, -0.2963654, -0.2609222, -0.5344608, 0.1762729, 0.05210181, -0.2905258, 0.2044767, 0.1712789, -0.08653083, 0.112...
Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States.
Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study. Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design. A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45-1.16]) and 26% (HR = 0.74; 95% CI [0.48-1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57-0.93]; and HR = 0.75; 95% CI [0.57-0.98], respectively). LIMITATIONS include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period. In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.
25,105,304
[ 0.06312454, 0.1221107, -0.05874641, -0.4390136, 0.1597379, -0.2762454, 0.217185, -0.01352156, 0.1164979, -0.02137572, 0.08108767, 0.508932, 0.01994851, 0.1646226, -0.3054757, -0.2435178, -0.07857522, 0.2001391, -0.004353198, 0.2358772, -0.03179353, 0.2072724, -0.4100657, ...
Cell death and DAMPs in acute pancreatitis.
Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP.
25,105,302
[ -0.001664075, -0.153407, 0.1494648, -0.136927, 0.04193274, 0.1164944, 0.06102495, 0.3162208, 0.08842873, 0.1616771, 0.1089901, 0.03549403, -0.116194, 0.1095591, -0.0847239, -0.1470777, -0.5938756, -0.04889553, 0.01118408, -0.04031771, 0.0167677, 0.1316341, -0.4386668, -...
Treatment preference, adherence and outcomes in patients with cancer: literature review and development of a theoretical model.
A patient's preference may guide their behavior and influence their willingness to take medication or undergo treatment affecting outcomes, such as health-related quality of life, or survival. The importance of understanding patient preferences within oncology is unclear and few adherence studies exist compared with other therapeutic areas. This study was designed to review the literature regarding patient preferences, adherence and their link to outcomes specifically in the oncology setting and to propose a theoretical model. An in-depth review was conducted, using Embase, MEDLINE and Cochrane Library databases to search for published data examining patient preference, adherence and oncology-specific outcomes, from 1982-2012. Articles were reviewed independently by two authors and rated for relevance and quality. Information from high-quality articles and discussion with oncology and patient preference experts were used to identify associations between important individual concepts as a basis for a theoretical model. In total, 1362 abstracts were identified. After removal of duplicates and initial review, 1269 were excluded and 93 reviewed in detail. Of these publications, 18 were deemed 'high-quality' and used to develop the final model. Variables associated with patient preference, adherence and outcome were identified. External variables included communication, treatment and mode of administration; patient beliefs and values were identified as cognitive variables; and adherence was attributed as a behavioral variable. Relationships between patient preference, adherence and clinical outcomes were established. Adverse events had a strong relationship with adherence; patient beliefs and values were identified as having a moderating effect on adherence. Adherence behavior had a direct relationship to outcomes. Improving our understanding of patient preference may improve clinical outcomes in oncology patients. Although the proposed theoretical model is limited, it provides a basis to develop testable hypotheses for the relationships between patient preference, adherence and outcomes specific to oncology.
25,105,306
[ -0.2092796, 0.05487997, -0.3258166, -0.3440981, 0.146447, -0.2160039, 0.06361762, 0.2228702, 0.1034158, 0.1451311, 0.1593468, 0.1215948, -0.1754438, -0.2411877, -0.1826811, -0.1754951, -0.3952546, 0.2689852, -0.07684009, 0.09271254, 0.08774444, 0.2437354, -0.092246, -0....
Intravitreal ranibizumab injections with and without pneumatic displacement for treating submacular hemorrhage secondary to neovascular age-related macular degeneration.
To evaluate the efficacy of intravitreal ranibizumab with and without pneumatic displacement for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration. We retrospectively reviewed the medical records of 93 treatment-naive patients (93 eyes) with submacular hemorrhage secondary to neovascular age-related macular degeneration. All patients were treated with an initial series of 3 monthly intravitreal ranibizumab injections, followed by as-needed injections. For the patients treated with pneumatic displacement, expansive gas was injected at the time of the first ranibizumab injection. Mean submacular hemorrhage area was 8.2 ± 5.8 disk areas, and mean symptom duration was 8.2 ± 5.2 days at baseline. Twelve months into treatment, the mean logarithm of the minimum angle of resolution of best-corrected visual acuity of all subjects significantly improved from 1.19 ± 0.55 (20/309) at baseline to 0.96 ± 0.39 (20/182, P = 0.007) at 12 months. The mean central foveal thickness also significantly improved from 473 ± 223 μm at baseline to 279 ± 134 μm (P < 0.001) at 12 months. However, no significant difference in best-corrected visual acuity and mean central foveal thickness between ranibizumab monotherapy (58 eyes) and combination therapy groups (35 eyes) was observed at 12 months. Intravitreal ranibizumab injections with and without pneumatic displacement are viable treatment options for submacular hemorrhage secondary to neovascular age-related macular degeneration.
25,105,310
[ -0.3732549, 0.1293909, -0.1357264, -0.2186075, 0.06414771, -0.1950733, 0.01828611, 0.2270746, 0.06764021, -0.2037034, -0.04854205, -0.1601353, -0.3864062, -0.2412367, 0.3421663, -0.2704058, -0.2177701, 0.2938235, 0.1242273, -0.1711283, 0.08310404, 0.3331614, -0.1282456, ...
Expansion of the CRISPR-Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs.
The repurposed CRISPR-Cas9 system has recently emerged as a revolutionary genome-editing tool. Here we report a modification in the expression of the guide RNA (gRNA) required for targeting that greatly expands the targetable genome. gRNA expression through the commonly used U6 promoter requires a guanosine nucleotide to initiate transcription, thus constraining genomic-targeting sites to GN19NGG. We demonstrate the ability to modify endogenous genes using H1 promoter-expressed gRNAs, which can be used to target both AN19NGG and GN19NGG genomic sites. AN19NGG sites occur ~15% more frequently than GN19NGG sites in the human genome and the increase in targeting space is also enriched at human genes and disease loci. Together, our results enhance the versatility of the CRISPR technology by more than doubling the number of targetable sites within the human genome and other eukaryotic species.
25,105,359
[ -0.04748925, -0.09622498, -0.2807695, -0.1280137, 0.1064747, -0.006434937, -0.007984001, 0.0622817, 0.1056063, -0.06180608, -0.1147855, -0.168087, 0.1545164, -0.0523322, -0.4222461, 0.1878123, -0.2811489, -0.09775708, -0.2584287, -0.2221946, 0.3383001, 0.2181344, -0.24940...
What is the risk of diagnostic endoscopic retrograde cholangiopancreatography before cholecystectomy?
Many surgeons prefer to perform endoscopic retrograde cholangiopancreatography (ERCP) before cholecystectomy, specifically in patients at significant risk of having biliary pathology. However, a preoperative diagnostic ERCP, without the use of an endoscopic ultrasound or magnetic retrograde cholangiopancreatoscopy, remains controversial. This is the result of the risk of either performing an unnecessary procedure and/or the development of post-ERCP pancreatitis (PEP). We performed a retrospective review of all surgeon-performed ERCPs at our institution between July 2011 and May 2013. This was done to examine patients who had pericholecystectomy ERCP. We had 550 ERCPs performed at our institution during this time period, 169 of which were pericholecystectomy procedures. We divided the 169 patients who had a diagnostic procedure (Diagnostic group) from those who had known biliary pathology before intervention (Therapeutic group). As a result, 34 patients (20.1%) were placed in the Diagnostic group and 135 patients (79.9%) in the Therapeutic group. Of the 34 Diagnostic patients, four (11.8%) developed PEP. Fifteen (44.1%) had unnecessary procedures, two of which had PEP (2.9%). Of the 135 ERCPs in the Therapeutic group, 18 patients (13.4%) developed PEP. Five of the 11 who had unnecessary procedures developed PEP. Based on the low incidence of complications, diagnostic ERCP has an acceptable rate of pancreatitis and/or unnecessary procedures when performed in highly selected patients and before cholecystectomy when compared with patients undergoing therapeutic ERCP. However, more aggressive use of diagnostic imaging before ERCP should be adopted given the number of unnecessary procedures performed.
25,105,391
[ 0.08774065, -0.09426495, -0.2920833, -0.166922, -0.3091048, -0.1425347, 0.02021056, -0.05154528, 0.03303645, 0.221204, 0.09561349, 0.1367799, -0.0892616, -0.1552168, -0.2961298, -0.2582914, -0.3253059, 0.2753721, 0.2684462, -0.362938, 0.06548464, 0.1487433, -0.02108438, ...
Reassessment of the role of enteral tube feedings for patients with esophageal cancer.
Nutrition is important for patients with esophageal cancer because dysphagia can be exacerbated by chemoradiotherapy. Some centers suggest routine enteral tube placement (TF) to facilitate nutrition. This investigation was to evaluate the use of TF access for patients undergoing multimodality therapy for esophageal carcinoma. This retrospective study analyzed 113 patients who underwent esophagectomy and 97 patients who underwent definition chemoradiotherapy for esophageal cancer between 2001 and 2013. Throughout this time period, a strategy for selective tube placement was used. Nutrition was assessed through absolute lymphocyte counts, protein, and albumin levels. A total of 28 (30%) patients during preoperative chemoradiotherapy and 31 (32%) of those undergoing definitive chemoradiation received TFs. There were 16 Dobhoff tubes, 28 gastrostomy tubes, and 15 jejunostomies. Tubes were maintained an average of 3.9 months with 20 (34%) of these patients reporting tube-related complications. At the time of surgery, there was no statistical difference in any of the nutritional assessments between those patients who received TF and those who did not. Both groups experienced similar total postoperative complication rates (64% vs 65%) and similar median length of hospital stay (12 to 13 days). Chemoradiotherapy resulted in decreased nutritional parameters; however, there was no difference in the degree of reduction between those who underwent TF and those who did not. The data show that routine placement of enteral access is not necessary for esophageal carcinoma. In fact, the risks of placing enteral access may outweigh the benefits. Administration of TF should be restricted to select patients during chemoradiotherapy or before esophagectomy.
25,105,392
[ 0.03419556, -0.04318491, -0.4516689, -0.4151312, 0.3250051, -0.3043279, 0.2853689, 0.16462, -0.06191543, 0.496834, 0.04525753, -0.4128492, -0.007427636, -0.2020973, -0.03615212, -0.1261369, 0.00823492, 0.07211822, -0.1375743, -0.1549818, -0.1973172, 0.2504402, 0.08574992,...
Program directors' perspective of transplant training during general surgery residency.
In 2011, the Accreditation Council for Graduate Medical Education (ACGME) began to mandate "a formal transplant experience" rather than a formal rotation to allow programs more flexibility. What constitutes a "transplant experience" or how to optimize such education remains unclear. The objectives of this study were to identify changes in residents' transplant exposure and determine the opinions of program directors (PDs) in response to the new requirements. A 15-item questionnaire was sent to all general surgery PDs. Demographics, resident experiences, and PDs' opinions regarding transplant rotations were collected. The response rate was 50 per cent from university and community programs at transplant and nontransplant centers. Although 55 per cent of PDs felt transplant should not be a required rotation, 92 per cent of programs reported having a formal rotation. Transplant rotations should be four months or less, according to 97 per cent of PDs. Most PDs (93%) think there should not be a minimum number of required transplant operations. Whether residencies were based at transplant centers or size of residencies did not affect PDs' responses. Transplant requirements were similar between residency programs regardless of PD opinions. Survey participants provided diverse feedback regarding this controversial topic. The new ACGME requirements have made little impact on program requirements. Most programs still mandate a formal transplant rotation. Diverse opinions exist regarding whether such a rotation should be required, highlighting the controversial nature of this issue. To facilitate education in an era of limited work hours, the ACGME changed requirements of general surgery programs to mandate "a formal transplant experience" rather than a transplant rotation. A survey of program directors revealed that although only 45 per cent of support mandatory transplant rotations, 93 per cent of programs still require transplant rotations despite the more lax ACGME requirements. This finding suggests a lack of suitable alternative to provide exposure to the concepts fundamental to transplant surgery, which are valuable in general surgery education.
25,105,401
[ -0.3281229, -0.3211675, -0.1090263, 0.002694721, 0.2235007, -0.0385357, 0.634572, 0.1467776, 0.1013187, 0.3101898, 0.07921854, -0.2400756, -0.03781611, 0.02321664, -0.2694313, -0.002199898, -0.2991123, 0.01519386, -0.2805482, -0.1312852, -0.001451848, 0.026728, 0.09442205...
Hinokitiol induces DNA damage and autophagy followed by cell cycle arrest and senescence in gefitinib-resistant lung adenocarcinoma cells.
Despite good initial responses, drug resistance and disease recurrence remain major issues for lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations taking EGFR-tyrosine kinase inhibitors (TKI). To discover new strategies to overcome this issue, we investigated 40 essential oils from plants indigenous to Taiwan as alternative treatments for a wide range of illnesses. Here, we found that hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, exhibited potent anticancer effects. In this study, we demonstrated that hinokitiol inhibited the proliferation and colony formation ability of lung adenocarcinoma cells as well as the EGFR-TKI-resistant lines PC9-IR and H1975. Transcriptomic analysis and pathway prediction algorithms indicated that the main implicated pathways included DNA damage, autophagy, and cell cycle. Further investigations confirmed that in lung cancer cells, hinokitiol inhibited cell proliferation by inducing the p53-independent DNA damage response, autophagy (not apoptosis), S-phase cell cycle arrest, and senescence. Furthermore, hinokitiol inhibited the growth of xenograft tumors in association with DNA damage and autophagy but exhibited fewer effects on lung stromal fibroblasts. In summary, we demonstrated novel mechanisms by which hinokitiol, an essential oil extract, acted as a promising anticancer agent to overcome EGFR-TKI resistance in lung cancer cells via inducing DNA damage, autophagy, cell cycle arrest, and senescence in vitro and in vivo.
25,105,411
[ -0.0026367, -0.06093445, -0.1380579, -0.4256795, 0.488512, 0.316943, -0.1772202, 0.2396857, 0.4449082, 0.1328373, -0.03116805, 0.1090387, -0.3320118, -0.2500286, -0.1217079, 0.01801708, -0.1329456, 0.5108692, -0.1178633, 0.7683267, -0.02406358, 0.2686154, -0.3202164, 0....
MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1.
miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.
25,105,419
[ -0.1593174, 0.08713292, -0.03167227, -0.1317271, 0.0329099, 0.1453136, -0.1890418, 0.1300122, 0.141696, 0.00670142, 0.2273807, 0.08044323, -0.2054792, -0.2228527, -0.01949241, 0.1307003, -0.01348942, -0.1137124, -0.2686662, -0.1352076, -0.1031321, 0.1683741, -0.2244771, ...
[From psychopathophysiology towards a biomarker-based classification and stratified treatment of schizophrenic disorders].
This article gives an overview of the role of functional neuroimaging for 1. a better understanding of the phenotypic symptoms and their underlying pathophysiology, 2. research into the genetic and environmental factors involved in the pathogenesis, and 3. current and future developments towards a biomarker-based classification and tailored therapy of schizophrenic disorders. In particular, neuroimaging of endophenotypic brain dysfunctions and imaging genetics are promising research approaches as endophenotypes may guide the development of functional neuroimaging biomarkers for clinically relevant pathophysiological processes. These biomarkers may permit a more precise differential diagnosis of pathophysiological and pathogenetic subtypes of the heterogeneous diagnostic category of schizophrenic disorders. Furthermore, they may allow us to predict individual treatment responses to specific therapies and to personalise treatment selection.
25,105,430
[ -0.06612039, 0.2576354, 0.1257526, -0.2417363, 0.1956188, -0.3369365, -0.1639348, -0.190157, 0.04609028, 0.2183648, 0.04927574, -0.06544592, 0.02119284, -0.07527066, -0.271595, -0.1009004, -0.05161846, 0.2743409, 0.1616413, 0.2272205, 0.0592698, 0.3492429, -0.2989306, -...
Unique effects of the chain lengths and anions of tetra-alkylammonium salts on quenching pyrene excimer.
Pyrene (Py) excimer, through its unique fluorescence quenching, exhibits high sensitivity and high selectivity in detecting specific electron-deficient molecules, providing a potential platform for sensing technology, optical switch, and probing hydrophobicity of molecular environment. In solution state, its quenching mechanism has been well-studied. However, there remain many unknown properties regarding the quenching mechanism of the solid-state Py excimer. In this paper, the effects of a series of tetra-alkylammonium salts (with a variety of chain lengths and anions) on Py excimer quenching are investigated to identify the controlling parameters of the fluorescence quenching in the binary system. Several experimental approaches including steady-state fluorescence spectroscopy, UV absorption, (13)C-nuclear magnetic resonance (NMR) spectra, X-ray diffraction, scanning electron microscopy, and time-dependent fluorescence decay are employed to seek for the fundamental understanding of the quenching mechanism. The result indicates a unique quenching effect of tetrabutylammonium cation on the pyrene excimer, and which is not observed in the other cations with different chain lengths (the same associated hexafluorophosphate anions). Meanwhile, hexafluorophosphate anion (in the presence of tetrabutylammonium) is able to effectively retain Py excimer fluorescence when the system is prepared by evaporating solvent at high temperature. It is also confirmed that dynamic quenching is involved in the process. Hydrophobic environment around Py molecules shows strong correlation with the formation of Py excimer. The knowledge obtained in this study provides the insights to how the interaction between salt and Py molecule affects the excimer fluorescence.
25,105,459
[ -0.008923648, 0.1512201, 0.06382381, 0.1579253, -0.09210162, -0.152813, -0.1744643, 0.06995933, 0.1629135, 0.2659965, -0.1304166, -0.2098297, 0.1020048, 0.04585645, -0.2840602, -0.3902397, -0.6531736, 0.1431334, -0.09350059, 0.01928404, 0.04587206, 0.1893539, -0.03354814,...
Supertough polylactide materials prepared through in situ reactive blending with PEG-based diacrylate monomer.
Supertough biocompatible and biodegradable polylactide materials were fabricated by applying a novel and facile method involving reactive blending of polylactide (PLA) and poly(ethylene glycol) diacylate (PEGDA) monomer with no addition of exogenous radical initiators. Torque analysis and FT-IR spectra confirm that cross-linking reaction of acylate groups occurs in the melt blending process according to the free radical polymerization mechanism. The results from differential scanning calorimetry, phase contrast optical microscopy and transmission electron microscopy indicate that the in situ polymerization of PEGDA leads to a phase separated morphology with cross-linked PEGDA (CPEGDA) as the dispersed particle phase domains and PLA matrix as the continuous phase, which leads to increasing viscosity and elasticity with increasing CPEGDA content and a rheological percolation CPEGDA content of 15 wt %. Mechanical properties of the PLA materials are improved significantly, for example, exhibiting improvements by a factor of 20 in tensile toughness and a factor of 26 in notched Izod impact strength at the optimum CPEGDA content. The improvement of toughness in PLA/CPEGDA blends is ascribed to the jointly contributions of crazing and shear yielding during deformation. The toughening strategy in fabricating supertoughened PLA materials in this work is accomplished using biocompatible PEG-based polymer as the toughening modifier with no toxic radical initiators involved in the processing, which has a potential for biomedical applications.
25,105,468
[ -0.08865684, 0.1538659, 0.007215763, -0.03136701, 0.08621438, -0.1221701, -0.4413067, 0.1439286, 0.231831, 0.3040501, -0.2209943, -0.4350613, -0.06206977, -0.2620614, -0.283072, 0.1730077, -0.3878248, 0.001779101, -0.1173143, 0.2433338, 0.1712639, 0.01503363, 0.04912453, ...
Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa.
HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650-1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.
25,105,489
[ -0.157727, 0.08082855, -0.2534205, -0.06560311, 0.06241839, -0.2786866, -0.3145562, -0.04564823, -0.03763158, -0.1232512, 0.004252417, -0.1753742, -0.08875024, 0.1521123, -0.0977126, -0.35647, 0.0997357, 0.311035, 0.3801504, -0.2299043, 0.1885047, 0.2841903, -0.1370653, ...
Response of Saccharomyces cerevisiae to the stimulation of lipopolysaccharide.
Lipopolysaccharide, known as endotoxin, can stimulate potent host immune responses through the complex of Toll-like-receptor 4 and myeloid differentiation protein 2; but its influence on Saccharomyces cerevisiae, a model organism for studying eukaryotes, is not clear. In this study, we found that lipopolysaccharide-treated S. cerevisiae cells could be stained by methylene blue, but did not die. Transcriptional profiling of the lipopolysaccharide-treated S. cerevisiae cells showed that 5745 genes were modulated: 2491 genes up-regulated and 3254 genes down-regulated. Significantly regulated genes (460 up-regulated genes and 135 down-regulated genes) in lipopolysaccharide-treated S. cerevisiae cells were analyzed on Gene Ontology, and used to establish physical protein-protein interaction network and protein phosphorylation network. Based on these analyses, most of the regulated genes in lipopolysaccharide-treated S. cerevisiae cells were related to cell wall, membrane, peroxisome and mitochondrion. Further experiments demonstrated that lipopolysaccharide stimulation caused the exposure of phosphatidylserine and the increase of mitochondrial membrane potential in S. cerevisiae cells, but levels of intracellular reactive oxygen species and metacaspase activation were not increased. This study demonstrated that lipopolysaccharide stimulation causes significant changes in S. cerevisiae cells, and the results would contribute to understand the response of eukaryotic cells to lipopolysaccharide stimulation.
25,105,496
[ 0.2128548, -0.2996961, 0.3226363, 0.2035982, 0.2243161, 0.1894316, -0.04524164, 0.2336416, 0.1034441, -0.07400495, -0.1036048, 0.07210313, -0.2490604, 0.4012232, -0.3202041, 0.6046083, -0.2859415, 0.04940217, -0.02209949, -0.00341377, 0.494052, 0.2563794, 0.2502623, 0.0...
Systemic CD8+ T cell-mediated tumoricidal effects by intratumoral treatment of oncolytic herpes simplex virus with the agonistic monoclonal antibody for murine glucocorticoid-induced tumor necrosis factor receptor.
Oncolytic virotherapy combined with immunomodulators is a novel noninvasive strategy for cancer treatment. In this study, we examined the tumoricidal effects of oncolytic HF10, a naturally occurring mutant of herpes simplex virus type-1, combined with an agonistic DTA-1 monoclonal antibody specific for the glucocorticoid-induced tumor necrosis factor receptor. Two murine tumor models were used to evaluate the therapeutic efficacies of HF10 virotherapy combined with DTA-1. The kinetics and immunological mechanisms of DTA-1 in HF10 infection were examined using flow cytometry and immunohistochemistry. Intratumoral administration of HF10 in combination with DTA-1 at a low dose resulted in a more vigorous attenuation of growth of the untreated contralateral as well as the treated tumors than treatment with either HF10 or DTA-1 alone. An accumulation of CD8(+) T cells, including tumor- and herpes simplex virus type-1-specific populations, and a decrease in the number of CD4(+) Foxp3(+) T regulatory cells were seen in both HF10- and DTA-1-treated tumors. Studies using Fc-digested DTA-1 and Fcγ receptor knockout mice demonstrated the direct participation of DTA-1 in regulatory T cell depletion by antibody-dependent cellular cytotoxicity primarily via macrophages. These results indicated the potential therapeutic efficacy of a glucocorticoid-induced tumor necrosis factor receptor-specific monoclonal antibody in oncolytic virotherapy at local tumor sites.
25,105,508
[ 0.0899476, -0.1398028, -0.04881953, -0.05251493, 0.02081134, -0.1528726, 0.1428051, -0.03809046, -0.1578939, -0.1867694, -0.1011228, -0.2246192, 0.005742984, -0.03950683, -0.6595123, -0.2796305, 0.03192504, -0.03537259, 0.1496045, 0.1324414, -0.3228399, 0.1524681, -0.1481...
Enantioselective carbocycle formation through intramolecular Pd-catalyzed allyl-aryl cross-coupling.
Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found to be quite general, affording 5, 6, and 7-membered carbocyclic products as single regioisomers and with moderate enantioselectivities. Examination of differential coupling partners points to rapid allyl-equilibration as a key stereodefining feature.
25,105,510
[ -0.1562773, -0.0298636, -0.1154116, -0.03463928, 0.152937, 0.002821265, -0.4710883, -0.004757643, 0.1437396, 0.04703344, -0.03332209, -0.2007653, 0.006531964, 0.1899851, -0.1576359, -0.28468, -0.5682971, 0.2957656, -0.008768895, 0.09457102, 0.09190073, 0.02230547, -0.1353...
What is the risk of infecting a cerebrospinal fluid-diverting shunt with percutaneous tapping?
Most CSF-diverting shunt systems have an access port that can be percutaneously tapped. Tapping the shunt can yield valuable information as to its function and whether an infection is present. The fear of causing a shunt infection by tapping may limit the physician's willingness to do so. The authors of this study investigate the risk of infecting a shunt secondary to percutaneous tapping. Following institutional review board approval, CSF specimens obtained from tapping an indwelling CSF-diverting shunt during the 2011 and 2012 calendar years were identified and matched with clinical information. A culture-positive CSF sample was defined as an infection. If results were equivocal, such as a broth-only-positive culture, a repeat CSF specimen was examined. The CSF was obtained by tapping the shunt access port with a 25-gauge butterfly needle after prepping the unshaven skin with chlorhexidine. During the study period, 266 children underwent 542 shunt taps. With 541 taps, no clinical evidence of a subsequent shunt infection was found. One child's CSF went from sterile to infected 11 days later; however, this patient had redness along the shunt tract at the time of the initial sterile tap. The risk of infection from tapping a shunt is remote if the procedure is done correctly.
25,105,511
[ -0.1268402, 0.001507279, -0.676531, -0.1626796, 0.1774256, -0.3377992, -0.3798591, -0.4156549, -0.1653822, -0.02609068, 0.383459, 0.1443356, 0.09835244, 0.3650155, -0.1078134, -0.1800517, -0.02391717, -0.02232074, -0.1659648, -0.3637242, -0.1407189, -0.1090034, 0.1448199,...
Elastic nature of the lacrimal canalicular wall.
To examine the elastic nature of the lacrimal canalicular wall. Fifteen postmortem specimens of 11 Japanese individuals (8 right, 7 left; age range, 45-89 years at death) fixed in 10% buffered formalin were axially sliced parallel to the lower eyelid margin to include all 3 portions of the lacrimal canaliculi (intrasac, extrasac-extramuscular, and intramuscular portions). All specimens were stained with Elastica van Gieson. Microscopic photographs were taken and converted to white (elastic fibers) and black (the other tissues) images to measure the elastic fibers in an area in each portion. Six specimens in 4 individuals (2 right, 4 left; age range, 62-87 years) included all 3 portions. The area of elastic fibers in the intrasac portion (mean area, 125.8±93.6 white dot) was not significantly different from that in the extrasac-extramuscular portion (p=0.637: mean area, 268.5±150.2 white dots) but was significantly smaller than the areas in the intramuscular portion (p<0.001: mean area, 796.3±278.1 white dots) and Horner's muscle fascia (p<0.001: mean area, 1052.8±250.1 white dots). The area of elastic fibers in the extrasac-extramuscular portion was also significantly smaller than areas in the intramuscular portion (p=0.001) and Horner's muscle fascia (p<0.001). There was no significant difference in the area between the intramuscular portion and Horner's muscle fascia (p=0.172). The elastic nature of the lacrimal canalicular wall was different in areas with or without Horner's muscle envelope.
25,105,525
[ -0.1788171, 0.06702106, -0.1772833, -0.05370206, 0.04778171, -0.1590318, 0.1209364, 0.04216685, 0.2437066, -0.06755367, 0.1000793, 0.1599746, -0.0855444, -0.1561615, -0.3990566, -0.04618087, -0.3143182, 0.2710912, -0.1266235, -0.2121779, 0.002709438, 0.2113898, -0.2153049...
Shear adhesion strength of aligned electrospun nanofibers.
Inspiration from nature such as insects' foot hairs motivates scientists to fabricate nanoscale cylindrical solids that allow tens of millions of contact points per unit area with material substrates. In this paper, we present a simple yet robust method for fabricating directionally sensitive shear adhesive laminates. By using aligned electrospun nylon-6, we create dry adhesives, as a succession of our previous work on measuring adhesion energies between two single free-standing electrospun polymer fibers in cross-cylinder geometry, randomly oriented membranes and substrate, and peel forces between aligned fibers and substrate. The synthetic aligned cylindrical solids in this study are electrically insulating and show a maximal Mode II shear adhesion strength of 27 N/cm(2) on a glass slide. This measured value, for the purpose of comparison, is 270% of that reported from gecko feet. The Mode II shear adhesion strength, based on a commonly known "dead-weight" test, is 97-fold greater than the Mode I (normal) adhesion strength of the same. The data indicate a strong shear binding on and easy normal lifting off. Anisotropic adhesion (Mode II/Mode I) is pronounced. The size and surface boundary effects, crystallinity, and bending stiffness of fibers are used to understand these electrospun nanofibers, which vastly differ from otherwise known adhesive technologies. The anisotropic strength distribution is attributed to a decreasing fiber diameter and an optimized laminate thickness, which, in turn, influences the bending stiffness and solid-state "wettability" of points of contact between nanofibers and surface asperities.
25,105,533
[ 0.1287042, 0.1584403, 0.1024885, 0.09268956, 0.2315086, -0.05686281, 0.1221459, 0.1573666, 0.07584365, -0.263315, -0.07753657, -0.3898935, 0.1243764, -0.1437034, -0.4607563, -0.0713036, -0.593913, 0.1127227, -0.2590737, -0.267254, -0.06087401, -0.07827681, -0.2834549, 0...
Oleic acid-induced hepatic steatosis is coupled with downregulation of aquaporin 3 and upregulation of aquaporin 9 via activation of p38 signaling.
Excess lipid deposition in hepatocytes is a hallmark feature of nonalcoholic fatty liver disease (NAFLD). The present study was designed to explore the expression and regulation of aquaporin (AQP) 3 and AQP9 in oleic acid-induced hepatic steatosis. HepG2 cells were incubated with oleic acid at different concentrations and time points. Oil-Red-O staining and triglyceride content measurement were done to assess the extent of hepatic steatosis. The expression of AQP3 and AQP9 was assessed using quantitative real-time PCR and Western blot analyses. The mitogen-activated protein kinase (MAPK) pathways involved in the regulation of AQP3 and AQP9 expression were checked. Compared to untreated control cells, oleic acid treatment significantly (p<0.05) induced hepatic steatosis in HepG2 cells in a dose- and time-dependent fashion. Oleic acid-treated cells showed a significant reduction in the AQP3 expression and a concomitant increase in the AQP9 expression. Oleic acid exposure led to enhanced phosphorylation of p38, but not ERK1/2 or JNK MAPK. Pharmacological inhibition of p38 rather than ERK1/2 signaling significantly blocked the regulation of AQP3 and AQP9 expression by oleic acid. Oleic acid-induced hepatic steatosis in HepG2 cells is associated with the coordinated regulation of AQP3 and AQP9 via activation of p38 signaling. These findings warrant functional studies of aquaglyceroporins in NAFLD.
25,105,540
[ -0.05892179, -0.1515883, -0.1562016, 0.173099, 0.07741579, 0.1184577, -0.09302316, 0.115635, 0.05430375, -0.1650307, 0.1964802, -0.08019037, 0.07268271, 0.1710832, -0.1907691, -0.07491293, -0.2582293, 0.3815362, -0.1567117, -0.3129132, -0.1475933, 0.1058788, -0.1580211, ...
Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.
Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.
25,105,556
[ 0.04130578, 0.08445808, 0.1539393, -0.311055, -0.1277345, 0.1608882, -0.007617989, -0.4747476, 0.06124778, -0.3455386, -0.04138416, 0.1483419, -0.3173129, 0.02938478, -0.5651236, 0.2335803, -0.03268453, 0.4064196, -0.09367178, 0.4340104, 0.0167831, -0.09376946, -0.258039,...
The diagnostic adaptive behavior scale: evaluating its diagnostic sensitivity and specificity.
The Diagnostic Adaptive Behavior Scale (DABS) was constructed with items across three domains--conceptual, social, and practical adaptive skills--and normed on a representative sample of American individuals from 4 to 21 years of age. The DABS was developed to focus its assessment around the decision point for determining the presence or absence of significant limitations of adaptive behavior for the diagnosis of Intellectual Disability (ID). The purpose of this study, which was composed of 125 individuals with and 933 without an ID-related diagnosis, was to determine the ability of the DABS to correctly identify the individuals with and without ID (i.e., sensitivity and specificity). The results indicate that the DABS sensitivity coefficients ranged from 81% to 98%, specificity coefficients ranged from 89% to 91%, and that the Area Under the Receiver Operating Characteristic Curve were excellent or good. These results indicate that the DABS has very good levels of diagnostic efficiency.
25,105,569
[ -0.1206162, -0.02961907, 0.115874, -0.1154301, 0.07839944, -0.2893875, -0.1461923, 0.190935, -0.02418996, -0.1315535, 0.08793721, 0.1819251, -0.4573171, -0.2340132, -0.05646598, -0.410199, -0.8984567, 0.2103756, -0.1189695, 0.0158102, 0.09886546, 0.2491778, -0.03681474, ...
Out of the F-box: reawakening the pancreas.
The adult pancreas lacks stem cells, and consequently, differentiation of pancreatic endocrine cells has been restricted to embryonic development or experimental manipulation. In this issue of Cell Stem Cell, Sancho et al. (2014) show that pancreas-specific loss of the ubiquitin ligase Fbxw7 stabilizes an endocrine-specific transcription factor, Ngn3, thus inducing in vivo β cell neogenesis.
25,105,572
[ 0.1305186, -0.3470481, -0.2193848, -0.3161848, 0.007138188, 0.0733856, 0.2425631, 0.0710277, -0.02392195, 0.2275839, 0.2907036, 0.2036384, -0.02434136, -0.3036302, -0.4871494, -0.2289261, -0.3230323, 0.08092012, -0.1713699, -0.162271, -0.03843462, 0.3096537, 0.007678613, ...
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
The adult pancreas is capable of limited regeneration after injury but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here, we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into α, δ, and β cells. Loss of Fbw7 stabilized the transcription factor Ngn3, a key regulator of endocrine cell differentiation. The induced β cells resemble islet β cells in morphology and histology, express genes essential for β cell function, and release insulin after glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
25,105,579
[ 0.2515365, -0.3418821, -0.2399925, -0.3121284, 0.01458739, -0.1721103, 0.1255099, 0.272358, 0.1939592, 0.3007377, 0.1683328, 0.05273065, -0.2532475, -0.227455, -0.3479516, -0.1049673, -0.3725609, -0.1216536, -0.1182151, 0.07459516, 0.07410574, 0.1552636, 0.04120506, 0.0...
Nanoporous silicon nitride membranes fabricated from porous nanocrystalline silicon templates.
The extraordinary permeability and manufacturability of ultrathin silicon-based membranes are enabling devices with improved performance and smaller sizes in such important areas as molecular filtration and sensing, cell culture, electroosmotic pumping, and hemodialysis. Because of the robust chemical and mechanical properties of silicon nitride (SiN), several laboratories have developed techniques for patterning nanopores in SiN using reactive ion etching (RIE) through a template structure. These methods however, have failed to produce pores small enough for ultrafiltration (<100 nm) in SiN and involve templates that are prone to microporous defects. Here we present a facile, wafer-scale method to produce nanoporous silicon nitride (NPN) membranes using porous nanocrystalline silicon (pnc-Si) as a self-assembling, defect free, RIE masking layer. By modifying the mask layer morphology and the RIE etch conditions, the pore sizes of NPN can be adjusted between 40 nm and 80 nm with porosities reaching 40%. The resulting NPN membranes exhibit higher burst pressures than pnc-Si membranes while having 5× greater permeability. NPN membranes also demonstrate the capacity for high resolution separations (<10 nm) seen previously with pnc-Si membranes. We further demonstrate that human endothelial cells can be grown on NPN membranes, verifying the biocompatibility of NPN and demonstrating the potential of this material for cell culture applications.
25,105,590
[ -0.3202576, -0.007029324, -0.06092407, 0.2278346, 0.1998571, 0.2008832, -0.3351869, 0.1148359, 0.3236865, 0.3009444, -0.04665048, -0.190256, -0.2392244, -0.1318435, -0.3251151, -0.2125611, -0.313136, 0.05049011, -0.1140688, -0.02846656, 0.1013118, 0.1018688, 0.1057468, ...
Phototoxic effect of na-pheophorbide a toward osteosarcoma cells in vitro using a laser diode.
The purpose of this study was to investigate the effectiveness of photodynamic therapy (PDT) with Na-pheophorbide A in anticancer treatment, using osteosarcoma cells in vitro. It has been reported that PDT with chlorophyll derivatives inhibits the proliferation of various cancer cells. However, there have been no reports that have evaluated the effectiveness of PDT in suppressing osteosarcoma cells. Uptake of Na-pheophorbide A into Hu09 cells (osteosarcoma cells) was assayed using fluorescence microscopy following incubation of the cells with 28 μmol/L of Na-pheophorbide A. The viability of Hu09 cells after PDT treatment was assessed using trypan blue dye staining and MTS assays. PDT-induced apoptosis was determined by evaluation of the activity of selected members of the caspase family and by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of cells. Na-pheophorbide A uptake by cells was rapid, being observed after 60 min of treatment, and Na-pheophorbide A persisted in cells for >24 h. PDT treatment decreased cell viability compared with the control group, indicating high cytocidal activity of PDT. This cytocidal effect was dependent upon drug concentration, light dose, and the number of irradiation times. An increase in the number of cells positive for TUNEL staining and increases in the activity of caspases-3, -8 and -9 were observed in the first 2 h after PDT treatment. A cytotoxic effect of PDT with Na-pheophorbide A on an osteosarcoma cell line in vitro was shown. Caspase activity assays suggested that PDT with Na-pheophorbide A induced an apoptotic change in HuO9 cells, mainly via activation of mitochondrial caspase -9 and -3 pathways.
25,105,597
[ -0.2192064, -0.04305499, -0.1166663, 0.08176447, -0.2128533, -0.2314717, -0.1959914, 0.04350294, 0.2001063, -0.02313392, -0.2259836, 0.3866717, -0.1020323, -0.1279874, -0.2452717, -0.03556621, 0.1408469, 0.2932405, 0.02927654, 0.260346, 0.4002066, 0.2100661, -0.05784044, ...
Experimental comparison of efficient tomography schemes for a six-qubit state.
Quantum state tomography suffers from the measurement effort increasing exponentially with the number of qubits. Here, we demonstrate permutationally invariant tomography for which, contrary to conventional tomography, all resources scale polynomially with the number of qubits both in terms of the measurement effort as well as the computational power needed to process and store the recorded data. We demonstrate the benefits of combining permutationally invariant tomography with compressed sensing by studying the influence of the pump power on the noise present in a six-qubit symmetric Dicke state, a case where full tomography is possible only for very high pump powers.
25,105,604
[ -0.06566971, 0.2964316, -0.1316915, 0.08913998, -0.04733792, -0.258675, -0.1955176, -0.1636934, 0.1715435, -0.0170873, -0.07808201, -0.0681954, -0.07871889, 0.2377394, -0.6999668, -0.02149857, -0.2434405, 0.08645882, -0.3091884, 0.08488001, 0.364834, 0.03063828, -0.134961...
Antineutrino monitoring for heavy water reactors.
In this Letter we discuss the potential application of antineutrino monitoring to the Iranian heavy water reactor at Arak, the IR-40, as a nonproliferation measure. An above ground detector positioned right outside the IR-40 reactor building could meet IAEA verification goals for reactor plutonium inventories. While detectors with the needed spectral sensitivity have been demonstrated below ground, additional research and development is needed to demonstrate an above-ground detector with this same level of sensitivity. In addition to monitoring the reactor during operation, observing antineutrino emissions from long-lived fission products could also allow monitoring the reactor when it is shut down, provided very low detector backgrounds can be achieved. Antineutrino monitoring could also be used to distinguish different levels of fuel enrichment. Most importantly, these capabilities would not require a complete reactor operational history and could provide a means to reestablish continuity of knowledge in safeguards conclusions should this become necessary.
25,105,612
[ -0.1111702, -0.06037135, 0.154505, -0.3090935, 0.07348209, 0.04463072, -0.2170164, 0.1997152, 0.05524805, -0.1367215, -0.05000764, -0.07305501, 0.1616652, -0.07124295, -0.3479301, -0.1108843, -0.4275939, 0.466623, 0.2119673, 0.07286975, 0.04070663, 0.1189438, 0.01878617, ...
Spin and valley noise in two-dimensional Dirac materials.
We develop a theory for optical Faraday rotation noise in two-dimensional Dirac materials. In contrast to spin noise in conventional semiconductors, we find that the Faraday rotation fluctuations are influenced not only by spins but also the valley degrees of freedom attributed to intervalley scattering processes. We illustrate our theory with two-dimensional transition-metal dichalcogenides and discuss signatures of spin and valley noise in the Faraday noise power spectrum. We propose optical Faraday noise spectroscopy as a technique for probing both spin and valley relaxation dynamics in two-dimensional Dirac materials.
25,105,640
[ -0.0830805, 0.1289641, -0.08717243, 0.001204735, 0.1863251, -0.1577015, -0.4687606, 0.0766114, 0.2382917, 0.003102994, -0.04709835, -0.367063, -0.1295109, -0.07303914, -0.647618, -0.2071176, -0.6277494, -0.03297248, -0.008094432, -0.04681252, 0.1350927, 0.03775623, -0.159...
Characterization of spin-orbit interactions of GaAs heavy holes using a quantum point contact.
We present transport experiments performed in high-quality quantum point contacts embedded in a GaAs two-dimensional hole gas. The strong spin-orbit interaction results in peculiar transport phenomena, including the previously observed anisotropic Zeeman splitting and level-dependent effective g factors. Here we find additional effects, namely, the crossing and the anticrossing of spin-split levels depending on subband index and magnetic field direction. Our experimental observations are reconciled in a heavy-hole effective spin-orbit Hamiltonian where cubic- and quadratic-in-momentum terms appear. The spin-orbit components, being of great importance for quantum computing applications, are characterized in terms of magnitude and spin structure. In light of our results, we explain the level-dependent effective g factor in an in-plane field. Through a tilted magnetic field analysis, we show that the quantum point contact out-of-plane g factor saturates around the predicted 7.2 bulk value.
25,105,641
[ 0.04507355, 0.02833977, 0.0150342, 0.003535773, 0.1343196, -0.04978832, -0.344972, -0.1031105, 0.07082944, -0.1331045, -0.2668244, -0.1949897, 0.02116487, 0.027453, -0.7289503, -0.1536285, -0.3325742, 0.06895696, 0.01658374, 0.1670991, 0.1744444, 0.07818471, -0.2250226, ...
Fractional quantum Hall effect in a curved space: gravitational anomaly and electromagnetic response.
We develop a general method to compute correlation functions of fractional quantum Hall (FQH) states on a curved space. In a curved space, local transformation properties of FQH states are examined through local geometric variations, which are essentially governed by the gravitational anomaly. Furthermore, we show that the electromagnetic response of FQH states is related to the gravitational response (a response to curvature). Thus, the gravitational anomaly is also seen in the structure factor and the Hall conductance in flat space. The method is based on an iteration of a Ward identity obtained for FQH states.
25,105,643
[ -0.3959538, 0.06291164, -0.1329877, 0.02952676, 0.476966, -0.2538154, -0.3396348, -0.1484783, 0.07010858, 0.03954444, -0.3184699, -0.04519508, 0.0134115, 0.2665721, -0.3086806, -0.3142778, -0.4049083, 0.2446101, -0.4568896, -0.2427706, 0.07224762, -0.02388531, -0.1168385,...
Superradiant decay of cyclotron resonance of two-dimensional electron gases.
We report on the observation of collective radiative decay, or superradiance, of cyclotron resonance (CR) in high-mobility two-dimensional electron gases in GaAs quantum wells using time-domain terahertz magnetospectroscopy. The decay rate of coherent CR oscillations increases linearly with the electron density in a wide range, which is a hallmark of superradiant damping. Our fully quantum mechanical theory provides a universal formula for the decay rate, which reproduces our experimental data without any adjustable parameter. These results firmly establish the many-body nature of CR decoherence in this system, despite the fact that the CR frequency is immune to electron-electron interactions due to Kohn's theorem.
25,105,654
[ 0.05820819, 0.07698671, -0.2704807, 0.1334796, 0.2550044, -0.2284902, -0.4542723, 0.001705571, 0.1244265, 0.06642166, -0.294981, 0.1441764, 0.1060009, 0.2223344, -0.6289613, -0.1837965, -0.25861, -0.08205938, 0.02761514, 0.1732526, 0.2390781, 0.05935674, -0.02268706, 0....
Active phase and amplitude fluctuations of flagellar beating.
The eukaryotic flagellum beats periodically, driven by the oscillatory dynamics of molecular motors, to propel cells and pump fluids. Small but perceivable fluctuations in the beat of individual flagella have physiological implications for synchronization in collections of flagella as well as for hydrodynamic interactions between flagellated swimmers. Here, we characterize phase and amplitude fluctuations of flagellar bending waves using shape mode analysis and limit-cycle reconstruction. We report a quality factor of flagellar oscillations Q = 38.0 ± 16.7 (mean ± s.e.). Our analysis shows that flagellar fluctuations are dominantly of active origin. Using a minimal model of collective motor oscillations, we demonstrate how the stochastic dynamics of individual motors can give rise to active small-number fluctuations in motor-cytoskeleton systems.
25,105,656
[ -0.1187791, 0.1275651, -0.3459162, 0.1429735, -0.1198459, -0.2979171, -0.306642, 0.239022, 0.04936153, -0.05944683, -0.03062707, -0.01370297, -0.267395, 0.07208627, -0.07420927, 0.1088744, -0.2198598, 0.07892698, -0.2883266, 0.1644867, 0.4054633, -0.06173803, -0.08725029,...
A new measure of functional evenness and some of its properties.
Functional evenness is increasingly considered an important facet of functional diversity that sheds light on the complex relationships between community assembly and ecosystem functioning. Nonetheless, in spite of its relevant role for ecosystem functioning, only a few measures of functional evenness have been proposed. In this paper we introduce a new measure of functional evenness that reflects the regularity in the distribution of species abundances, together with the evenness in their pairwise functional dissimilarities. To show how the proposed measure works, we focus on changes in functional evenness calculated from Grime's classification of plant strategies as competitors (C), stress-tolerators (S) and ruderals (R) along a post-fire successional gradient in temperate chestnut forests of southern Switzerland.
25,105,659
[ 0.07459816, 0.3009763, -0.09676938, -0.03606948, -0.05149469, -0.1916833, -0.1357086, 0.01697158, 0.1801049, 0.2123206, -0.2665402, -0.1654625, -0.08899905, -0.3166514, -0.6811489, -0.2424855, -0.0739724, 0.4418977, 0.04560107, 0.1592894, -0.07741645, 0.3241387, -0.007197...
Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease.
Left main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3-5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD. We enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups - with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes. We observed more complications with wound healing (40.5% vs. 12.8%, p<0.001) and sternal dehiscence (23.8% vs. 4.0%, p<0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p=0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p=0.014). Patients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.
25,105,661
[ -0.1039519, -0.1246243, 0.03734411, -0.1526933, -0.2957962, -0.1911294, 0.01525112, -0.1034579, 0.2331862, -0.02267214, 0.08622678, 0.2729666, -0.338755, -0.4357165, -0.03402806, -0.1864893, 0.06698954, 0.05013417, -0.04512263, -0.07550938, 0.4671148, 0.4209978, -0.107372...
[DHS osteosynthesis for proximal femoral fractures: infectious complications].
Evaluation of infectious complications in patients with proximal femoral fractures treated by osteosynthesis using dynamic hip screws (DHS). The group included 501 patients with 532 DHS procedures performed in the years 1996-2010. In 31 patients osteosynthesis was carried out bilaterally. Osteosynthesis was indicated for femoral neck fracture in 18 hips and for pertrochanteric fracture in 514 hips. Prophylactic antibiotic therapy was administered within 48 hours of surgery. The occurrence of infectious complications (surface and deep wound infection), presence of infectious agents, risk factors, and the course of treatment and its outcome were investigated. Of 532 fractures treated by DHS osteosynthesis, seven were infected (1.3%) as follows: one fracture of the femoral neck with methicillin-resistant Staphylococcus aureus, and, of six pertrochanteric fractures, four with Staphylococcus aureus, one with Escherichia coli and one with Staphylococcus epidermidis. Surface wound infection was diagnosed in one case (0.2%) and deep infection in six cases (1.1%). Five revision DHS procedures were carried out in five patients. One or more risk factors were found in each patient with infected DHS. The treatment of infection included wound dressing and abscess drainage without reoperation in two cases, implant removal in three, and implant removal with femoral head resection and spacer insertion in two cases. Second-stage total hip arthroplasty (THA) was performed in one case. Of the seven infected fractures, five (71%) healed successfully. DISCUSSION DHS osteosynthesis is a reliable method for treating proximal femoral fractures. The 1.3% infection rate in our group is comparable with other relevant studies. This complication is serious and requires prolonged treatment but is not as devastating as an infected THA. For the treatment of infected DHS osteosynthesis, standard methods from screw removal to second-stage THA were employed. Infectious complications following osteosynthesis with dynamic hip screws are rare events in the treatment of proximal femoral fractures. Staphylococcus aureus was the most frequently isolated infectious agent. Each infectious complacation was associated with one or more risk factors. Antibiotic prophylaxis is important particularly in patients at risk.
25,105,677
[ -0.06254358, -0.05333813, 0.004580768, 0.1795038, -0.1245002, -0.5057304, -0.06273721, 0.06761876, 0.05107534, 0.3463475, 0.04556475, -0.2901235, -0.2888679, -0.3841667, -0.09685276, -0.2030317, -0.04121166, -0.01864901, -0.2467618, -0.131564, 0.3921792, 0.08709801, -0.24...
Sexual Dimorphism of Endocranial, Facial and Limb Measurements in the Yellow Baboon (Papio cynocephalus).
The present study focused on the sexual dimorphism of yellow baboon (Papio cynocephalus) to clarify its relationship with social behaviour. The degree of sexual dimorphism in the endocranial volume is the lowest among the investigated measurements. Among the facial measurements, the degree value of sexual dimorphism was the maximum (38.4%) for palate length and the minimum for palate breadth at the upper second molar (M2) (16.8%). Reduced major axis (RMA) regression analysis indicated that most positive allometry in relation to body mass was barely shown in the endocranial volume, palate length, palate breadth at M2 and mandibular ramal width. On the other hand, most negative allometry in relation to body mass was barely indicated in the bizygomatic breadth, skull length, humeral length and femoral length. The plate breadth at M2 in males was smaller than that in females in equivalent to body mass. The results of the present study suggest that more males have longer pointed muzzles than females, which is considered to create an impressive view of large canine teeth. This contributes to display among males and agonistic encounters rather than to necessity of increased facial size due to larger body size or dietary influences.
25,105,681
[ 0.006211507, 0.2911816, 0.190479, -0.382611, -0.249487, -0.3576566, -0.3863065, 0.01775229, 0.143629, -0.1460201, 0.2254398, -0.2989026, 0.00007620167, -0.2475121, -0.4338576, 0.06073504, -0.2423725, 0.1007661, -0.1415672, -0.001387148, 0.37273, -0.05263988, 0.09238538, ...
Power maps and wavefront for progressive addition lenses in eyeglass frames.
To evaluate a method for measuring the cylinder, sphere, and wavefront of progressive addition lenses (PALs) in eyeglass frames. We examine the contour maps of cylinder, sphere, and wavefront of a PAL assembled in an eyeglass frame using an optical system based on a Hartmann test. To reduce the data noise, particularly in the border of the eyeglass frame, we implement a method based on the Fourier analysis to extrapolate spots outside the eyeglass frame. The spots are extrapolated up to a circular pupil that circumscribes the eyeglass frame and compared with data obtained from a circular uncut PAL. By using the Fourier analysis to extrapolate spots outside the eyeglass frame, we can remove the edge artifacts of the PAL within its frame and implement the modal method to fit wavefront data with Zernike polynomials within a circular aperture that circumscribes the frame. The extrapolated modal maps from framed PALs accurately reflect maps obtained from uncut PALs and provide smoothed maps for the cylinder and sphere inside the eyeglass frame. The proposed method for extrapolating spots outside the eyeglass frame removes edge artifacts of the contour maps (wavefront, cylinder, and sphere), which may be useful to facilitate measurements such as the length and width of the progressive corridor for a PAL in its frame. The method can be applied to any shape of eyeglass frame.
25,105,689
[ -0.4802846, 0.02787597, -0.1112325, 0.2275025, 0.3636395, -0.2869137, 0.03617747, -0.1461355, 0.7357727, 0.2748967, 0.08899385, -0.2586305, 0.1016357, 0.1659091, 0.02884723, 0.4556323, -0.7350103, 0.07733238, -0.2673682, -0.245565, 0.06720794, -0.2045798, -0.07451022, -...
The history of neurosurgery at the University of Rochester.
The Department of Neurosurgery at the University of Rochester has a long legacy of excellent patient care and innovation in the neurosciences. The department's founder, Dr. William Van Wagenen, was a direct pupil of Harvey Cushing and the first president of the Harvey Cushing Society. His successor, Dr. Frank P. Smith, was also a leader in organized neurosurgery and helped to permanently memorialize his mentor with an endowed fellowship that today is one of the most prestigious training awards in neurosurgery. The first 2 chiefs are honored every year by the department with memorial invited lectureships in their names. The department is home to a thriving multidisciplinary research program that fulfills the lifelong vision of its founder, Dr. Van Wagenen.
25,105,700
[ 0.006170331, -0.3173375, -0.02581395, -0.3550427, 0.3470813, -0.3795583, -0.2632134, 0.1318499, 0.09645825, 0.0132691, 0.1551944, 0.07614381, 0.05431334, -0.5924754, -0.2392419, 0.2079172, 0.1288845, 0.136307, 0.1963661, -0.0488772, -0.082309, -0.0683307, -0.1639913, 0....
Optimizing dosing of oncology drugs.
The purpose of this article is to acknowledge the challenges in optimizing the dosing of oncology drugs and to propose potential approaches to address these challenges in order to optimize effectiveness, minimize toxicity, and promote adherence in patients. These approaches could provide better opportunities to understand the sources of variability in drug exposure and clinical outcomes during the development and premarketing evaluation of investigational new drugs.
25,105,705
[ -0.2110645, -0.01128591, -0.1765658, -0.3652787, -0.07405139, -0.0797947, 0.00007539643, 0.2369999, 0.1330077, -0.2048995, 0.09992623, 0.1556093, 0.005725513, 0.03931624, -0.4938976, -0.04616301, -0.188818, 0.09811582, 0.01687016, 0.2160323, 0.02015001, 0.06861705, -0.059...
Keeping consumers safe: food providers' perspectives on pureed food.
Twelve focus groups were conducted in five sites with 80 allied health providers to identify their perspectives on providing pureed food to consumers. Thematic care analysis was completed to summarize and interpret these data. Providers' greatest concern was keeping consumers safe, and the right texture was prioritized over sensory appeal and acceptance. Providers recognized that these foods impacted the quality of life of consumers and worked to rationalize these diets with residents/patients and their families. In addition, offering foods they knew to be poorly accepted affected their self-concept as providers. As a result of these challenges, they did whatever they could in the kitchen and tableside to promote intake of pureed foods. Those in the "food chain" of pureed food provision suggested several ways to further improve these products. Greater communication between those who assist consumers with eating and those who produce the pureed food they consume is needed to promote acceptable pureed products.
25,105,713
[ -0.1904985, 0.2016192, 0.2023742, 0.03840651, 0.3702144, -0.01548575, -0.1963309, 0.08592451, 0.2815518, -0.1436879, 0.1186042, -0.08290714, -0.2988338, -0.2950307, -0.2213085, -0.03795024, -0.7651559, 0.06204865, -0.191674, -0.1607257, -0.1780211, 0.372913, 0.02772357, ...
Clinicopathologic features and treatment outcomes of primary extramammary Paget disease of the vulva.
The aim of this study was to identify the clinicopathologic features and treatment outcome of primary extramammary Paget disease of the vulva (EMPDV). We performed a retrospective analysis of 14 patients who were treated at our center from April 1994 to November 2010. The mean age of patients in our sample was 64.4 years (range = 47-83 y). We observed intraepithelial and invasive EMPDV in 11 (78.6%) and 3 (21.4%) patients, respectively. Moreover, we observed a positive incision margin in 9 patients (64.3%). During a median follow-up period of 69.5 months (range = 32-221 mo), we observed recurrence in 3 patients (21.4%), 2 of whom had invasive EMPDV and 1 had intraepithelial EMPDV. Time to recurrence was 16 and 18 months for patients with invasive EMPDV and 98 months for patients with intraepithelial EMPDV. The recurrence rate of intraepithelial EMPDV and invasive EMPDV was significantly different (9.1% and 66.7%, respectively, p < .028). Local recurrence occurred in all 3 patients, necessitating further surgical resection. One patient with recurrence of invasive EMPDV received adjuvant radiotherapy but died 101 months after the initial treatment. The other 2 patients remained alive without recurrence. We did not observe distant recurrence. The recurrence rate of invasive EMPDV was high. However, because distant metastasis is rare, repeat surgical excision for recurrent EMPDV and long-term observation are necessary for a good prognosis.
25,105,720
[ -0.1263638, -0.2414906, -0.2115975, -0.3370189, 0.007163126, -0.3254993, 0.05279011, -0.07054126, -0.01774454, -0.06694508, 0.1556869, -0.05093492, 0.06340863, -0.2197499, 0.2297202, -0.1064131, -0.312331, 0.1668023, 0.2835087, -0.159246, 0.3716457, 0.507825, -0.1101681, ...
Metabolic effects of glycerol supplementation and aerobic physical training on Wistar rats.
We evaluated the effects of oral glycerol supplementation on trained rats fed a normal diet. Wistar rats were distributed among 6 groups in a completely randomized 2 × 3 factorial design. The animals were subjected to 6 weeks of aerobic training. In the last 4 weeks, the animals' diet was supplemented with saline, glucose, or glycerol. Data were subjected to one-way analysis of variance (ANOVA) followed by a Student-Newmann-Keuls test, with values for P < 0.05 considered statistically significant. The change in body mass was lower in the trained groups, and their food and water consumption were higher. Glycerol supplementation resulted in an increase in the levels of triacylglycerol (TAG) and total cholesterol, as well as in the area and diameter of adipocytes. When associated with training, these parameters were similar to those of other trained groups. Levels of low-density lipoprotein + very-low-density lipoprotein cholesterol decreased in the trained animals that received glycerol compared with the non-trained ones. Glycerol consumption caused a reduction in food intake and increased the villous:crypt (V:C) ratio. No changes in glycemia, high density lipoproteins, or density of adipocytes were observed. Supplementation with glycerol together with aerobic physical training promoted beneficial metabolic effects. However, in non-trained rats glycerol increased the diameter and area of adipocytes, as well as the levels of TAG and total cholesterol.
25,105,723
[ -0.05102232, -0.1372585, 0.07103786, 0.07177048, 0.1004508, -0.468603, -0.3546419, -0.1857046, 0.08641773, -0.224995, 0.1811782, 0.007712096, -0.3961143, 0.02628473, -0.6790986, -0.09140217, -0.2457512, -0.2304579, -0.3152769, 0.1340834, -0.2883024, -0.03708775, -0.047772...
Identification of bacterial community composition in freshwater aquaculture system farming of Litopenaeus vannamei reveals distinct temperature-driven patterns.
Change in temperature is often a major environmental factor in triggering waterborne disease outbreaks. Previous research has revealed temporal and spatial patterns of bacterial population in several aquatic ecosystems. To date, very little information is available on aquaculture environment. Here, we assessed environmental temperature effects on bacterial community composition in freshwater aquaculture system farming of Litopenaeus vannamei (FASFL). Water samples were collected over a one-year period, and aquatic bacteria were characterized by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16S rDNA pyrosequencing. Resulting DGGE fingerprints revealed a specific and dynamic bacterial population structure with considerable variation over the seasonal change, suggesting that environmental temperature was a key driver of bacterial population in the FASFL. Pyrosequencing data further demonstrated substantial difference in bacterial community composition between the water at higher (WHT) and at lower (WLT) temperatures in the FASFL. Actinobacteria, Proteobacteria and Bacteroidetes were the highest abundant phyla in the FASFL, however, a large number of unclassified bacteria contributed the most to the observed variation in phylogenetic diversity. The WHT harbored remarkably higher diversity and richness in bacterial composition at genus and species levels when compared to the WLT. Some potential pathogenenic species were identified in both WHT and WLT, providing data in support of aquatic animal health management in the aquaculture industry.
25,105,725
[ -0.1091467, 0.2815199, -0.03843415, -0.214927, -0.02206248, -0.2398418, 0.02133238, 0.04223215, -0.04917501, -0.2231976, 0.05852744, -0.1140976, -0.1284442, -0.1497683, -0.09220628, 0.1227039, -0.2903283, 0.4503644, 0.2583101, 0.08149797, 0.03571688, 0.2967806, -0.4570963...
In vivo immunotoxicity of SiO2@(Y0.5Gd0.45Eu0.05)2O3 as dual-modality nanoprobes.
We have successfully synthesized SiO2@(Y0.5Gd0.45Eu0.05)2O3 nanocomposites as a potential dual-modality nanoprobe for molecular imaging in vitro. However, their immunotoxicity assessment in vivo remains unknown. In this article, the in vitro biocompatibility of our dual-modality nanoprobes was assayed in terms of cell viability and apoptosis. In vivo immunotoxicity was investigated by monitoring the generation of reactive oxygen species (ROS), cluster of differentiation (CD) markers and cytokines in Balb/c mice. The data show that the in vitro biocompatibility was satisfactory. In addition, the immunotoxicity data revealed there are no significant changes in the expression levels of CD11b and CD71 between the nanoprobe group and the Gd in a diethylenetriaminepentaacetic acid (DTPA) chelator (Gd-DTPA) group 24 h after injection in Balb/c mice (p>0.05). Importantly, there are significant differences in the expression levels of CD206 and CD25 as well as the secretion of IL-4 and the generation of ROS 24 h after injection (p<0.05). Transmission electron microscopy (TEM) images showed that few nanoprobes were localized in the phagosomes of liver and lung. In conclusion, the toxic effects of our nanoprobes may mainly result from the aggregation of particles in phagosomes. This accumulation may damage the microstructure of the cells and generate oxidative stress reactions that further stimulate the immune response. Therefore, it is important to evaluate the in vivo immunotoxicity of these rare earth-based biomaterials at the molecular level before molecular imaging in vivo.
25,105,724
[ -0.04621501, 0.0894604, -0.0462268, 0.4668317, 0.02250837, -0.06956963, 0.1018434, -0.3158752, -0.1740705, -0.08143713, -0.2607592, 0.1694046, 0.03564015, -0.2413466, -0.4599776, -0.0232388, -0.1419439, -0.0604129, 0.1542151, 0.2675357, 0.01681691, 0.621991, 0.07980236, ...
Bioactivity and Surface Characteristics of Titanium Implants Following Various Surface Treatments: An In Vitro Study.
This study compared the surface topography, hydrophilicity, and bioactivity of titanium implants after 3 different surface treatments (sandblasting and acid etching, modified sandblasting and acid etching, and thermal oxidation) with those of machined implants. One hundred indigenously manufactured threaded titanium implants were subjected to 3 methods of surface treatment. The surface roughness of the nontreated (Group A) and treated samples (Groups B through D) was evaluated with a scanning electron microscope (SEM) and profilometer. The wettability was visually examined using a colored dye solution. The calcium ions attached to the implant surface after immersing in simulated body fluid (SBF) were assessed on days 1, 2, and 7 with an atomic electron spectroscope. The data were analyzed statistically. The SBF test allowed the precipitation of a calcium phosphate layer on all surface-treated samples, as evidenced in the SEM analysis. A significantly higher amount of calcium ions and increased wettability were achieved in the thermally oxidized samples. The mean roughness was significantly lower in Group A (0.85 ± 0.07) compared to Group B (1.35 ± 0.17), Group C (1.40 ± 0.14), and Group D (1.36 ± 0.18). The observations from this in vitro study indicated that surface treatment of titanium improved the bioactivity. Moreover, results identified the implants that were sandblasted, acid etched, and then oxidized attracted more calcium ions.
25,105,748
[ 0.07592741, 0.08270338, -0.1213913, 0.08848097, -0.3455788, 0.06133024, 0.03473553, -0.2081046, 0.1789679, -0.1314264, 0.1527053, -0.09137236, -0.1782252, -0.26443, -0.09387638, -0.07584333, -0.3311504, -0.0684942, 0.02505674, -0.06451489, 0.2100594, 0.2313598, -0.0697374...
Individual and cumulative effects of agriculture, forestry and metal mining activities on the metal and phosphorus content of fluvial fine-grained sediment; Quesnel River Basin, British Columbia, Canada.
The impact of agriculture, forestry and metal mining on the quality of fine-grained sediment (<63 μm) was investigated in the Quesnel River Basin (QRB) (~11,500 km(2)) in British Columbia, Canada. Samples of fine-grained sediment were collected monthly during the snow-free season in 2008 using time-integrated samplers at replicate sites representative of agriculture, forestry and mining activities in the basin (i.e. "impacted" sites). Samples were also collected from replicate reference sites and also from the main stem of the Quesnel River at the downstream confluence with the Fraser River. Generally, metal(loid) and phosphorus (P) concentrations for "impacted" sites were greater than for reference sites. Furthermore, concentrations of copper (forestry and mining sites), manganese (agriculture and forestry sites) and selenium (agriculture, forestry and mining sites) exceeded upper sediment quality guideline (SQG) thresholds. These results suggest that agriculture, forestry and metal mining activities are having an influence on the concentrations of sediment-associated metal(loid)s and P in the Quesnel basin. Metal(loid) and P concentrations of sediment collected from the downstream site were not significantly greater than values for the reference sites, and were typically lower than the values for the impacted sites. This suggests that the cumulative effects of agriculture, forestry and mining activities in the QRB are presently not having a measureable effect at the river basin-scale. The lack of a cumulative effect at the basin-scale is thought to reflect: (i) the relatively recent occurrence of land use disturbances in this basin; (ii) the dominance of sediment contributions from natural forest and agriculture; and (iii) the potential for storage of contaminants on floodplains and other storage elements between the locations of disturbance activities and the downstream sampling site, which may be attenuating the disturbance signal.
25,105,754
[ 0.00237605, 0.09866766, 0.06002722, -0.1931565, -0.2861483, 0.01313418, -0.3125522, 0.04681398, -0.01529094, -0.003852115, -0.05511375, -0.07245293, -0.3840707, -0.09785049, -0.2856451, 0.1635298, 0.1764609, 0.04971411, 0.05713278, -0.04157339, 0.3444968, 0.5036207, -0.04...
Evolution of oleosin in land plants.
Oleosins form a steric barrier surface on lipid droplets in cytoplasm, preventing them from contacting and coalescing with adjacent droplets. Oleosin genes have been detected in numerous plant species. However, the presence of oleosin genes in the most basally diverging lineage of land plants, liverworts, has not been reported previously. Thus we explored whether liverworts have an oleosin gene. In Marchantia polymorpha L., a thalloid liverwort, one predicted sequence was found that could encode oleosin, possessing the hallmark of oleosin, a proline knot (-PX5SPX3P-) motif. The phylogeny of the oleosin gene family in land plants was reconstructed based on both nucleotide and amino acid sequences of oleosins, from 31 representative species covering almost all the main lineages of land plants. Based on our phylogenetic trees, oleosin genes were classified into three groups: M-oleosins (defined here as a novel group distinct from the two previously known groups), low molecular weight isoform (L-oleosin), and high molecular weight isoform (H-oleosin), according to their amino-acid organization, phylogenetic relationships, expression tissues, and immunological characteristics. In liverworts, mosses, lycophytes, and gymnosperms, only M-oleosins have been described. In angiosperms, however, while this isoform remains and is highly expressed in the gametophyte pollen tube, two other isoforms also occur, L-oleosins and H-oleosins. Phylogenetic analyses suggest that the M-oleosin isoform is the precursor to the ancestor of L-oleosins and H-oleosins. The later two isoforms evolved by successive gene duplications in ancestral angiosperms. At the genomic level, most oleosins possess no introns. If introns are present, in both the L-isoform and the M-isoform a single intron inserts behind the central region, while in the H-isoform, a single intron is located at the 5'-terminus. This study fills a major gap in understanding functional gene evolution of oleosin in land plants, shedding new light on evolutionary transitions of lipid storage strategies.
25,105,766
[ 0.2910573, 0.02944329, 0.03933443, -0.01604122, -0.03436859, -0.1091489, 0.06275144, -0.3569595, 0.4266421, -0.07260847, 0.1598646, -0.2466343, 0.01850661, 0.3227903, -0.5710217, 0.1804538, -0.2744292, -0.1090197, 0.04743497, 0.2122949, 0.2733394, 0.5849169, -0.1715594, ...
Co-occurrence of papillary thyroid cancer and MALT lymphoma of the thyroid with severe airway obstruction: A case report and review of the literature.
Co-occurrence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma resulting in severe airway obstruction is very rare. A 58-year-old woman visited our department because of enlargement of a neck mass. Computed tomography (CT) and ultrasonography showed 2 discrete hypoechoic nodules. Fine-needle aspiration biopsy revealed thyroid lymphoma in the left lobe and PTC in the right lobe. After 1 week, she returned to the emergency room at our hospital with shortness of breath and difficultly in swallowing. CT revealed enlargement of the left lobe, which was severely compressing the trachea. We performed emergency total thyroidectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged without any symptoms. The most common treatment for PTC is surgery; however, the treatment for thyroid lymphoma remains controversial. We propose that surgery be performed in the cases of symptoms such as shortness of breath and difficulty in swallowing. We performed emergency total thyroidectomy to relieve obstruction of the trachea and to remove the two malignant tumors. We suggest total thyroidectomy for a case of co-occurrence of two malignant tumors, causing severe airway obstruction.
25,105,773
[ -0.1725723, -0.2426241, -0.07501442, -0.2852342, -0.0677632, -0.3987352, -0.2101385, -0.1521072, 0.04680819, 0.4539248, 0.07634404, -0.009320972, -0.1557312, 0.01200463, 0.2068603, 0.06027655, -0.262942, 0.09596562, 0.1627621, -0.1476095, 0.2556154, 0.04890062, -0.3255506...
Femoral shaft fractures in adults: treatment options and controversies.
Antegrade reamed femoral nailing via the piriformis entry point is the technique of choice in treating femoral shaft fractures, with retrograde nailing as an alternative. The supine position is favored to reduce complications, especially rotational malalignment. With navigation and robotic assistance fracture reduction can be supported and the rate of rotational, axis and length malalignement can potentially further reduced. Careful reaming is the procedure of choice to optimize bony healing and reduce systemic and local complications. In multiply injured patients reamed nailing can be safely integrated in the DCO- or ETC-concept and can be performed in the majority of patients, even when additional severe chest and head injuries are present. Initial resuscitation should focus on general stabilization before definitive femur fixation. Plate osteosynthesis of the femur can be an option in selected patients.
25,105,784
[ -0.1600091, 0.5399395, 0.2711709, -0.1096468, 0.09331629, -0.3602782, -0.2119276, 0.3049945, -0.1971715, 0.1690473, 0.1441597, -0.2094997, -0.143034, -0.2308762, -0.2705783, -0.1139942, -0.4017958, -0.07694174, -0.2154986, -0.4634959, -0.08208423, 0.08386859, -0.1269673, ...
Differential effects of 670 and 830 nm red near infrared irradiation therapy: a comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury.
Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.
25,105,800
[ 0.11774, -0.03408192, -0.2893419, -0.005570034, -0.3386273, -0.3797722, -0.0351403, -0.1639083, 0.2346736, -0.01414071, 0.05347279, -0.0964125, -0.04349849, -0.2582974, -0.1110924, -0.123242, -0.4643403, 0.4244988, 0.03152279, -0.01139997, -0.2046708, 0.3080532, 0.1532486...
Shaping bacterial symbiosis with legumes by experimental evolution.
Nitrogen-fixing symbionts of legumes have appeared after the emergence of legumes on earth, approximately 70 to 130 million years ago. Since then, symbiotic proficiency has spread to distant genera of α- and β-proteobacteria, via horizontal transfer of essential symbiotic genes and subsequent recipient genome remodeling under plant selection pressure. To tentatively replay rhizobium evolution in laboratory conditions, we previously transferred the symbiotic plasmid of the Mimosa symbiont Cupriavidus taiwanensis in the plant pathogen Ralstonia solanacearum, and selected spontaneous nodulating variants of the chimeric Ralstonia sp. using Mimosa pudica as a trap. Here, we pursued the evolution experiment by submitting two of the rhizobial drafts to serial ex planta-in planta (M. pudica) passages that may mimic alternating of saprophytic and symbiotic lives of rhizobia. Phenotyping 16 cycle-evolved clones showed strong and parallel evolution of several symbiotic traits (i.e., nodulation competitiveness, intracellular infection, and bacteroid persistence). Simultaneously, plant defense reactions decreased within nodules, suggesting that the expression of symbiotic competence requires the capacity to limit plant immunity. Nitrogen fixation was not acquired in the frame of this evolutionarily short experiment, likely due to the still poor persistence of final clones within nodules compared with the reference rhizobium C. taiwanensis. Our results highlight the potential of experimental evolution in improving symbiotic proficiency and for the elucidation of relationship between symbiotic capacities and elicitation of immune responses.
25,105,803
[ 0.04842261, -0.1208112, 0.1356517, 0.0431506, 0.1676609, -0.2397497, -0.4225268, -0.1274265, 0.09936232, -0.07806123, -0.06888059, -0.3662433, -0.0257716, 0.3706709, -0.7672681, 0.04792188, -0.340002, -0.3738298, 0.1231483, -0.3199294, 0.07954006, 0.2484311, -0.06895308, ...
Cerebrovascular reactivity to carbon dioxide under anesthesia: a qualitative systematic review.
Controlling the arterial carbon dioxide tension (PaCO2) to reduce the cerebral blood flow (CBF) and the intracranial pressure is a common practice in neuroanesthesia. A change in CBF in response to change in PaCO2 is termed as cerebrovascular reactivity to carbon dioxide (CVR-CO2). Studies have shown that, both inhalational and intravenous anesthetic agents have variable effects on CVR-CO2 and the effect of anesthetic agents on CVR also varies with many physiological and pathologic conditions. The objectives of this review were to evaluate the effect of anesthetic agents on the CVR-CO2 in adults and to determine how this response is modified by other physiological and pathologic factors. We conducted a systematic search of the databases of Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews using related term components for both CVR-CO2 and anesthesia. Our primary outcome of this review was to determine whether the CVR-CO2 is maintained under anesthesia. The other endpoints of this review are to determine the effect of other factors (age, sex, medical comorbidities, and cerebrovascular pathology) on the CVR-CO2 under anesthesia. Because of the methodological heterogeneity in the primary studies, quantitative analysis of the data was not possible, and therefore, we have summarized the data qualitatively. Our search strategy yielded 1356 citations. After excluding nonpertinent papers, 38 studies were included for the systematic review. Nineteen randomized controlled trials and 19 observational studies met inclusion criteria and a total of 793 patients were studied. Transcranial Doppler was the most commonly used method for measuring CBF and changing the respiratory rate and/or minute ventilation were the most commonly used method to change the CO2 tension. CVR-CO2 is maintained with both inhalational and intravenous anesthetic agents within the range of concentrations used in clinical anesthesia. At doses leading to a broadly equivalent depth of anesthesia, the reactivity value was highest with isoflurane and the least with propofol. Individual agents differ in their degree of reactivity to hypercapnic and hypocapnic stimuli. CVR-CO2 is impaired in elderly patients when compared with young patients with both sevoflurane and propofol anesthesia. In patients with medical comorbidities, the CVR-CO2 impairment under anesthesia was associated with the severity of the underlying diseases and not the anesthetic agents. Our systematic review showed that within the clinical anesthesia concentrations, CVR-CO2 is maintained under both propofol and inhalational agents. However, most of the information available is from non-neurosurgical patients and these studies also suffer from significant methodological heterogeneity. Therefore, we were limited by the amount and the quality of data available for this review.
25,105,825
[ -0.02992314, -0.1321387, -0.1579126, -0.4017184, 0.06517823, -0.1642121, -0.1459478, -0.1142376, -0.03762243, -0.02847935, 0.03415136, -0.1215621, -0.05922332, -0.249445, -0.08127384, -0.2146672, -0.2971963, 0.3428812, -0.3690477, 0.3903575, -0.2552813, -0.03687572, 0.058...
Exploring Consumer Acceptance of Entomophagy: A Survey and Experiment in Australia and the Netherlands.
Insects are nutritious and suitable for human consumption. In this article an overview of research on consumer acceptance of entomophagy is given. This study furthermore provides insight into which factors are effective to influence consumer acceptance of entomophagy among Dutch and Australian participants. Based on the findings of this study, information about entomophagy and providing the participants with the opportunity to try insect food, both seem to be equally important when trying to positively influence their attitude toward entomophagy. The outcomes of this study show that "educating" consumers about entomophagy should be practiced in its broadest sense.
25,105,864
[ -0.2018145, -0.01897614, -0.0145278, -0.1341522, 0.1952006, -0.006840134, -0.113994, -0.2368762, 0.1754946, -0.2454586, 0.2804285, -0.09321529, 0.03723984, -0.3693642, -0.4056194, -0.04799391, -0.6273117, 0.2779838, -0.2049497, -0.2987863, -0.03277617, 0.6276913, -0.10843...
Weight loss by telemonitoring of nutrition and physical activity in patients with metabolic syndrome for 1 year.
Mobile technology can improve lifestyle programs, but the monitoring techniques and carer feedback need to be optimized. To this end, we investigated the efficacy of telemonitoring physical activity and nutrition over 12 months in patients with metabolic syndrome in a randomized, parallel-group, open trial. Screening all over Germany yielded 184 patients with metabolic syndrome. All patients attended a single 2-hour instruction meeting in their region concerning a combination diet and the importance of physical activity. Thereafter they were randomized into a control group (controls, n = 62) or one of 2 different intervention groups. Both intervention groups were issued accelerometers, which measured physical activity, recorded daily weight and calorie intake, and transmitted these data to a central server for use by patient carers. In the Active Body Control Program of University of Magdeburg (ABC) intervention group (n = 60), information and motivation was ensured by weekly letters. In the 4sigma telephone coaching (4S) intervention group (n = 58), this was accomplished by monthly telephone calls from the carers. Clinical and biochemical data for all patients were collected at 0, 4, 8, and 12 months without any regular face-to-face meetings between patients and carers. The primary endpoint was weight loss and the secondary endpoint was the presence of metabolic syndrome. After 12 months the dropout rates in the control, 4S, and ABC groups were respectively 35%, 17%, and 18%. The adjusted relative weight losses after 12 months were respectively 3.7%, 8.6%, and 11.4% (all p < 0.000 versus baseline). ABC was more effective than 4S (p = 0.041); 43% of the patients completing the study in the ABC group lost more than 15% of their baseline weight. The diagnosis of metabolic syndrome was no longer applicable in 58% of the cases in the ABC group, in 41% of the 4S group, and in 33% of the controls. Telemonitoring of physical activity and nutrition markedly improves weight loss and markers of metabolic syndrome.
25,105,874
[ 0.2706596, 0.2721404, 0.1176266, -0.1672138, 0.00364068, -0.09357567, 0.0912504, -0.1473383, 0.05410586, 0.06608506, 0.1574138, -0.06438994, 0.007280561, -0.1503324, -0.579723, 0.3268466, -0.4287828, 0.07867641, -0.1520869, 0.3004847, -0.04502554, 0.1010499, -0.01381581, ...
Mating damages the cuticle of C. elegans hermaphrodites.
Lifespan costs to reproduction are common across multiple species, and such costs could potentially arise through a number of mechanisms. In the nematode Caenorhabditis elegans, it has been suggested that part of the lifespan cost to hermaphrodites from mating results from physical damage owing to the act of copulation itself. Here, we examine whether mating damages the surface of the hermaphrodite cuticle via scanning electron microscopy. It is found that mated hermaphrodites suffered delamination of cuticle layers surrounding the vulva, and that the incidence of such damage depends on genetic background. Unmated hermaphrodites demonstrated almost no such damage, even when cultured in soil with potentially abrasive particles. Thus, a consequence of mating for C. elegans hermaphrodites is physical cuticle damage. These experiments did not assess the consequences of cuticle damage for lifespan, and the biological significance of this damage remains unclear. We further discuss our results within the context of recent studies linking the lifespan cost to mating in C. elegans hermaphrodites to male secretions.
25,105,881
[ 0.1560885, -0.02769054, 0.05141113, 0.05739126, 0.2284319, -0.2986439, 0.01394221, 0.002267676, 0.3078598, 0.09440622, 0.06275146, -0.0780684, -0.07055556, -0.2289042, -0.3078762, 0.04574931, -0.3637895, 0.03315555, 0.1788377, -0.3060648, 0.2438656, 0.4710602, -0.1202844,...
Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.
Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.
25,105,891
[ 0.2471645, -0.2615943, -0.541552, -0.2930343, 0.3836455, -0.662419, -0.07152729, -0.4498225, -0.2011717, 0.1530758, -0.2923022, 0.3667971, -0.03957817, 0.3882726, 0.2430951, -0.1043254, -0.6911337, 0.2027301, -0.3387377, -0.02635755, -0.0759443, 0.4546702, 0.1529514, 0....
The impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent.
Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism.
25,105,894
[ -0.0009163908, -0.01332446, 0.08018448, -0.4368741, -0.1149247, -0.1168874, -0.07801044, 0.004750103, 0.1290577, -0.08825108, -0.001077493, -0.09661049, -0.02377686, -0.166995, -0.5267597, 0.09474608, -0.3446125, -0.3981176, -0.2300932, 0.4065147, 0.1418273, 0.281638, 0.0...
Increased risk of Mycobacterium tuberculosis infection in household child contacts exposed to passive tobacco smoke.
Risk factors associated with Mycobacterium tuberculosis infection were investigated in a prospective cohort of household child tuberculosis contacts. A significantly increased risk of acquiring infection was associated with exposure to passive cigarette smoke, higher number of index cases, younger age and reduced household monthly income.
25,105,895
[ -0.250531, 0.2412616, 0.01146841, 0.399339, -0.112112, -0.1792896, -0.5458486, 0.09194704, -0.250112, -0.09369408, 0.1517163, 0.2265314, -0.02232362, -0.1112248, -0.08450162, 0.1321408, -0.1614361, 0.08666102, 0.1175206, -0.02448088, 0.1872292, 0.1329429, -0.007897533, ...
Synthesis and characterization of some new 4-hydroxy-coumarin derivatives.
Some novel coumarins were synthesized starting from 4-hydroxycoumarin and methyl bromoacetate. The structures of the newly obtained compounds were confirmed by elemental analysis, mass, IR and NMR spectra.
25,105,917
[ -0.168839, 0.501467, 0.03674982, 0.145981, 0.02395318, -0.01675587, -0.3675945, 0.1365887, 0.1662091, 0.09102194, 0.02258362, 0.1482514, 0.06509706, -0.399236, -0.529673, 0.04857733, -0.1645581, 0.381174, 0.1120834, 0.1613127, 0.1192866, -0.03108568, -0.1167662, -0.0659...
Reliable assessment of physical activity in disease: an update on activity monitors.
Physical activity is the main determinant of variability of individual energy expenditure. Reliable assessment of the activity level of an individual provides information on energy requirement and vital health. Here, evidence is presented on the validity of methods to assess physical activity as applied in health and disease. Improvement of technology has resulted in a growing number of physical activity monitors to evaluate the activity level of an individual. Outcome measures vary from raw data on body acceleration and posture to activity levels derived from proprietary algorithms based on body acceleration combined with sensor information on additional activity-induced physiological responses. Data interpretation is limited by evidence-based studies on the value of measured parameters for the assessment of physical activity. The optimal tool for reliable assessment of physical activity is an accelerometer providing a valid measure of body movement. Overall validity is derived from studies using doubly labelled water-assessed activity-induced energy as a reference. Thus, out of the large range of activity monitors, three came out with a better validity. The ultimate tool is a single unobtrusive device allowing valid and long-term monitoring of activity with regard to type and intensity.
25,105,926
[ -0.4069753, -0.02233659, -0.2507271, -0.2197744, -0.06725668, -0.3880371, -0.006830186, -0.04433949, -0.1597463, -0.4479708, -0.1148983, -0.2138395, 0.2595705, -0.3788909, -0.4732486, 0.01028392, -0.4996158, 0.283428, -0.4533208, 0.2507606, 0.01375477, 0.1553004, -0.23960...
HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.
Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.
25,105,936
[ -0.1399541, -0.002010301, -0.00875491, -0.1345647, -0.01854346, -0.265926, 0.0171684, 0.2781096, 0.5069622, 0.07814563, -0.01346824, -0.111534, -0.0615847, -0.57288, -0.4616154, -0.3968435, -0.1933765, 0.007410198, 0.2129988, -0.1723277, 0.02860899, 0.2182471, -0.3191149,...
Coping with college and inflammatory bowel disease: implications for clinical guidance and support.
Studies have shown that young adults with chronic diseases, including inflammatory bowel disease (IBD), experience greater difficulty during the transition to college, reaching lower levels of educational attainment and reporting greater levels of perceived stress than their otherwise-healthy peers. We performed a qualitative study to better understand how underlying illness shapes the college experience for patients with IBD and how the college experience, in turn, impacts disease management. Fifteen college students with IBD were recruited from the Boston Children's Hospital Center for IBD. We conducted an approximately 1 hour semistructured qualitative interview with each participant, and the interviews were thematically analyzed after an iterative and inductive process. Four primary themes were identified: (1) The transition experience of college students with IBD is shaped by their health status, perceived readiness, and preparedness, (2) Elements of the college environment pose specific challenges to young adults with IBD that require adaptive strategies, (3) College students with IBD integrate their underlying illness with their individual and social identity, and (4) College students navigate health management by conceptualizing themselves, their families, and providers as serving particular roles. For young adults with IBD, college is a proving ground for demonstrating self-care and disease management practices. Future initiatives aimed at this population should recognize the evolving roles of patients, parents, and providers in disease management. Increased attention should also be paid to the promotion of patient's self-management and the unique challenges of the structural and psychosocial college environment.
25,105,948
[ -0.3645478, 0.08592697, -0.2587652, 0.05013262, 0.1308203, -0.1535899, 0.1877141, 0.07975201, 0.02879433, -0.05617307, -0.1080045, -0.2274099, -0.02095029, -0.3935825, -0.4764707, 0.1442272, -0.4293202, 0.03419913, -0.07273535, -0.06192723, -0.3095742, 0.1165062, -0.03426...
A mother cell-to-forespore channel: current understanding and future challenges.
Formation of endospores allows some bacteria to survive extreme nutrient limitation. The resulting dormant cell, the spore, persists in the environment and is highly resistant to physical and chemical stresses. During spore formation, cells divide asymmetrically and the mother cell engulfs the developing spore, encasing it within a double membrane and isolating it from the medium. Communication between mother cell and isolated forespore involves a specialised connection system that allows nurturing of the forespore and continued macromolecular synthesis, required to finalise spore maturation. Here, we review current understanding of this feeding channel formed by a forespore protein, SpoIIQ, and a mother cell protein, SpoIIIAH, in the model organism Bacillus subtilis and the important human pathogen Clostridium difficile. We also analyse the presence of this channel across endospore-forming bacteria and highlight the main questions still remaining.
25,105,965
[ -0.1434387, -0.2432209, -0.08635809, -0.02524297, -0.3225205, -0.3610923, -0.2245404, 0.1255091, 0.2253949, -0.3250176, 0.08012972, -0.01188046, -0.1872536, -0.09217383, -0.6458992, -0.2086531, -0.5334418, -0.05902037, -0.003883406, -0.100109, 0.4224627, 0.2484637, -0.317...
Nitrogen fixed by cyanobacteria is utilized by deposit-feeders.
Benthic communities below the photic zone depend for food on allochthonous organic matter derived from seasonal phytoplankton blooms. In the Baltic Sea, the spring diatom bloom is considered the most important input of organic matter, whereas the contribution of the summer bloom dominated by diazotrophic cyanobacteria is less understood. The possible increase in cyanobacteria blooms as a consequence of eutrophication and climate change calls for evaluation of cyanobacteria effects on benthic community functioning and productivity. Here, we examine utilization of cyanobacterial nitrogen by deposit-feeding benthic macrofauna following a cyanobacteria bloom at three stations during two consecutive years and link these changes to isotopic niche and variations in body condition (assayed as C:N ratio) of the animals. Since nitrogen-fixing cyanobacteria have δ(15)N close to -2‰, we expected the δ(15)N in the deposit-feeders to decrease after the bloom if their assimilation of cyanobacteria-derived nitrogen was substantial. We also expected the settled cyanobacteria with their associated microheterotrophic community and relatively high nitrogen content to increase the isotopic niche area, trophic diversity and dietary divergence between individuals (estimated as the nearest neighbour distance) in the benthic fauna after the bloom. The three surface-feeding species (Monoporeia affinis, Macoma balthica and Marenzelleria arctia) showed significantly lower δ(15)N values after the bloom, while the sub-surface feeder Pontoporeia femorata did not. The effect of the bloom on isotopic niche varied greatly between stations; populations which increased niche area after the bloom had better body condition than populations with reduced niche, regardless of species. Thus, cyanobacterial nitrogen is efficiently integrated into the benthic food webs in the Baltic, with likely consequences for their functioning, secondary production, transfer efficiency, trophic interactions, and intra- and interspecific competition.
25,105,967
[ -0.09585641, -0.03249251, 0.1563618, -0.026474, 0.0188425, -0.187842, -0.001926048, 0.1116376, 0.1237172, 0.06600532, -0.1276553, -0.34381, 0.1083237, -0.2086538, -0.4866999, -0.289044, -0.51352, 0.1680537, 0.06956727, 0.1057228, 0.3121619, 0.4689696, 0.07852665, -0.188...
Environmental perchlorate exposure: potential adverse thyroid effects.
This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant intelligence quotient in groups who would be particularly susceptible to perchlorate effects. An update regarding the recently proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants.
25,106,002
[ -0.3864261, 0.09129205, 0.09740791, 0.09781627, -0.04983659, -0.1437276, -0.2515983, -0.2825322, -0.08543185, 0.2947293, 0.08887316, 0.1600649, -0.2238685, -0.1221427, 0.02787204, -0.3494603, -0.3565445, 0.2689684, 0.09212078, -0.4006146, -0.1113364, 0.5080535, -0.2182536...
Nitrogen-rich multinuclear ferrocenophanes as multichannel chemosensor molecules for transition and heavy-metal cations.
[m.n] Multinuclear ferrocenophanes prepared by aza-Wittig reaction of bisiminophosphoranes derived from 1,1'-diazidoferrocene and isophthaladelhyde or 2,5-diformylthiophene, behave as efficient electrochemical and chromogenic chemosensor molecules for Zn2+, Pb2+, and Hg2+ metal cations. Whereas the OSWV of receptor 3, bearing two m-phenylene units in the bridges, display one oxidation peak, receptor 4 incorporating two thiophene rings in the bridges, exhibits two well-separated oxidation peaks. In both receptors only the addition of Zn2+, Pb2+, and Hg2+ metal cations induced a remarkable anodic shift of ferrocene/ferrocenium redox couple. Likewise, in the absorption spectra of these receptors the low energy band is red-shifted by Δλ = 165 - 209 nm, and these changes promoted a significant color changes which could be used for the naked eye detection of these metal cations. The coordination modes for two representative cases were unveiled by DFT calculations that show an unsual coordination in the [42Pb]2+ complex with the Pb2+ cation in a distorted cubic N4S4 donor cage.
25,106,019
[ -0.1636043, 0.02189803, -0.1532698, -0.2996357, 0.1664742, -0.1346072, -0.4751642, 0.02107249, 0.2163137, -0.002550395, 0.1205836, -0.03472997, -0.1213718, -0.2457199, -0.6744293, -0.113526, -0.7252524, 0.2175906, 0.1339463, 0.2332586, 0.08137741, 0.3159044, -0.2562638, ...
Analysis of (7)Be behaviour in the air by using a multilayer perceptron neural network.
A multilayer perceptron artificial neural network (ANN) model for the prediction of the (7)Be behaviour in the air as the function of meteorological parameters was developed. The model was optimized and tested using (7)Be activity concentrations obtained by standard gamma-ray spectrometric analysis of air samples collected in Belgrade (Serbia) during 2009-2011 and meteorological data for the same period. Good correlation (r = 0.91) between experimental values of (7)Be activity concentrations and those predicted by ANN was obtained. The good performance of the model in prediction of (7)Be activity concentrations could provide basis for construction of models which would forecast behaviour of other airborne radionuclides.
25,106,024
[ -0.04690741, -0.153315, -0.2708248, 0.08081324, -0.07641125, -0.006861136, -0.351297, -0.1460445, 0.07719563, -0.2061618, -0.01672912, -0.1617823, 0.386181, -0.187509, -0.1222352, 0.08211806, -0.3077356, 0.4175753, 0.1967356, 0.5023899, 0.5810792, 0.3129516, 0.2617227, ...
Degradation and transformation of atrazine under catalyzed ozonation process with TiO2 as catalyst.
Degradation of atrazine by heterogeneously catalyzed ozonation was carried out with TiO2 in the form of rutile as the catalyst. Some experimental factors such as catalyst dose, ozone dose and initial concentration of atrazine were investigated for their influence on catalyzed ozonation process. Although atrazine was effectively removed from aqueous solution by catalyzed ozonation process, the mineralization degree only reached 56% at the experimental conditions. Five transformation products were identified by GC/MS analysis. The degradation of atrazine involved de-alkylation, de-chlorination and de-amination. Diaminotriazine and 5-azauracil were the de-chlorinated and de-aminated products, respectively. The evolution of concentration of transformation products during catalyzed ozonation process was compared with uncatalyzed ozonation to show the degradation pathway. Toxicity tests based on the inhibition of the luminescence emitted by Vibrio fisheri indicated the detoxification of atrazine by catalyzed ozonation.
25,106,044
[ -0.2102371, 0.1023432, 0.09352788, 0.1225968, 0.02931141, -0.2312541, -0.2945336, 0.2590292, -0.05352755, -0.3066379, 0.2854384, -0.01925757, -0.2864185, -0.04821162, -0.09286905, 0.05667338, -0.8326449, 0.2692091, 0.2911708, -0.01203444, 0.00658234, 0.3645483, -0.076703,...
Detection and molecular characterization of porcine circovirus type 2 from piglets with porcine circovirus associated diseases in Colombia.
The porcine circovirus-associated disease (PCVAD) has been known since 1991 in Canada, but the first outbreak of PCVAD in Colombia was reported in 2007. In order to understand the molecular epidemiology of the disease and to establish the origin of the virus in the country, the study presented here intended to evaluate the presence of PCV2-associated systemic infection in piglets from different geographical regions over a period of 9-years (2002-2010). The analysis included samples collected before, during and after outbreaks of PCVAD in pigs from Colombia. The PCV2 ORF2 from the positive samples was sequenced and used to determine the genotypes of the strains and to study the dynamic of these genotypes throughout the time. PCV2 DNA was detected in cases related to PCV2-associated systemic infection as well as in healthy pigs with a presumable persistent infection. The analysis of the ORF2 nucleotide full length sequence of twenty-three strains allowed to divide them into two groups: PCV2a and PCV2b. At the amino acid level the main variations in the sequence of the capsid protein were found in regions located within the immunoreactive areas. The results of this study demonstrated for the first time, that the two subgroups: PCV2a and PCV2b have been circulating in swine from Colombia. In addition, the study showed that genotype PCV2b is present in Colombian pigs suffering from both clinical and presumable persistent infection and that the PCV2b genotype was present in the Colombian pig population even before recognition of the disease in the country and it became predominant through time.
25,106,077
[ -0.0259026, -0.0657521, 0.3519109, -0.2601668, -0.04346088, -0.06280567, -0.0103846, 0.1168453, -0.05378486, -0.1903587, 0.01489779, -0.02743881, -0.03830251, -0.07383686, 0.05722584, -0.4508361, -0.3677519, -0.1172355, 0.3729768, -0.07199744, 0.1916512, 0.2363843, -0.223...
Long-term stability of return to work after a workplace-oriented intervention for patients on sick leave for burnout.
The period from the mid-1990s to the mid-2000s saw a rapid increase in long-term sick leave in Sweden, primarily due to mental illness and often related to job burnout. This led to an urge for effective treatment programs that could prevent the often long sick leaves. In 2010 we presented a newly developed work-place intervention method, showing that 89% of the intervention group had returned to work at a 1.5 year follow-up, compared to 73% of the control group. The main aim of this study was to assess the long-term stability of these promising results. Sick leave registry data from the Regional Social Insurance Office were analyzed for an additional year (50 weeks) beyond the original 1.5 year period (80 weeks). Data from 68 matched pairs of intervention participants (IP) and controls were available. The proportions of participants being on full-time sick leave versus having returned to work to any extent were computed for every 10th week. Generalized estimating equations were used with GROUP (IP versus controls) as between-subjects factor, WEEKS and AGE as covariates, and return-to-work (RTW) as dependent variable. Significant differences (Wald χ2 with α ≤ .05) was followed up with polynomial contrasts. Individual relapses to higher degrees of sick leave (e.g. from 50% to 100%) and whether partial RTW led to later full-time RTW, were also analyzed. The omnibus test over all 130 weeks showed a GROUP*WEEKS interaction effect (p = .02), indicating differential group developments in RTW, though similarly high at week 130 in both groups with 82.4% of the IP and 77.9% of the controls having RTW (p = .22; χ2-test). A significant interaction with age led to separate analyses of the younger and older subgroups, indicating a stable pattern of superior RTW only among younger IP (week 130: 88.6% vs. 69.7%, p = .054; χ2-test). There was no group difference in relapses into increased degree of sick leave. Part-time sick leave did not predict a later stable full-time RTW. The previously reported improvement in RTW with the newly developed workplace-oriented intervention showed a long-term stability only among younger participants.
25,106,094
[ 0.1942928, 0.1358973, -0.07728745, -0.06007782, 0.01955041, -0.2576301, 0.1374166, 0.1271913, -0.2300398, -0.1027984, 0.139443, -0.05224799, -0.02304314, -0.03904678, -0.4461047, -0.17066, 0.09937999, 0.1893147, -0.02455513, 0.1361128, -0.1092903, 0.4808117, -0.1050998, ...
Induction of the matricellular protein CCN1 through RhoA and MRTF-A contributes to ischemic cardioprotection.
Activation of RhoA, a low molecular-weight G-protein, plays an important role in protecting the heart against ischemic stress. Studies using non-cardiac cells demonstrate that the expression and subsequent secretion of the matricellular protein CCN1 is induced by GPCR agonists that activate RhoA. In this study we determined whether and how CCN1 is induced by GPCR agonists in cardiomyocytes and examined the role of CCN1 in ischemic cardioprotection in cardiomyocytes and the isolated perfused heart. In neonatal rat ventricular myocytes (NRVMs), sphingosine 1-phosphate (S1P), lysophosphatidic acid (LPA) and endothelin-1 induced robust increases in CCN1 expression while phenylephrine, isoproterenol and carbachol had little or no effect. The ability of agonists to activate the small G-protein RhoA correlated with their ability to induce CCN1. CCN1 induction by S1P was blocked when RhoA function was inhibited with C3 exoenzyme or a pharmacological RhoA inhibitor. Conversely overexpression of RhoA was sufficient to induce CCN1 expression. To delineate the signals downstream of RhoA we tested the role of MRTF-A (MKL1), a co-activator of SRF, in S1P-mediated CCN1 expression. S1P increased the nuclear accumulation of MRTF-A and this was inhibited by the functional inactivation of RhoA. In addition, pharmacological inhibitors of MRTF-A or knockdown of MRTF-A significantly diminished S1P-mediated CCN1 expression, indicating a requirement for RhoA/MRTF-A signaling. We also present data indicating that CCN1 is secreted following agonist treatment and RhoA activation, and binds to cells where it can serve an autocrine function. To determine the functional significance of CCN1 expression and signaling, simulated ischemia/reperfusion (sI/R)-induced apoptosis was assessed in NRVMs. The ability of S1P to protect against sI/R was significantly reduced by the inhibition of RhoA, ROCK or MRTF-A or by CCN1 knockdown. We also demonstrate that ischemia/reperfusion induces CCN1 expression in the isolated perfused heart and that this functions as a cardioprotective mechanism, evidenced by the significant increase in infarct development in response to I/R in the cardiac specific CCN1 KO relative to control mice. Our findings implicate CCN1 as a mediator of cardioprotection induced by GPCR agonists that activate RhoA/MRTF-A signaling.
25,106,095
[ -0.06794667, -0.2012031, -0.1470347, -0.3549232, 0.1181749, -0.03229356, 0.04957094, -0.1189372, -0.001593956, -0.1274817, -0.0002208974, 0.5685074, -0.2969862, -0.01655738, -0.3334332, 0.1009944, -0.2753411, -0.1194131, -0.0038158, 0.09947886, 0.060191, 0.009053314, -0.3...
Quantitative analysis of temperature dependent acoustic trapping characteristics by using concentric annular type dual element ultrasonic transducer.
This paper presents the temperature dependence of lateral acoustic trapping capability by probing the speed of sound in individual lipid droplets at a given temperature of water and measuring its corresponding displacement, a value for quantitatively evaluating a spring-like behavior of the acoustic trap with certain strength. A 20/40 MHz dual element LiNbO3 ultrasonic transducer is fabricated to simultaneously perform both transverse trapping and sound speed measurement for each droplet over a discrete temperature range from 20°C to 30°C. Time of flight method is employed for pulse tracking that determines the arrival time of an echo reflected back from either a trapped droplet or a mylar film. The estimated speeds of sound in water and droplets are 1484.8 m/s and 1431.6 m/s at 20°C, while 1506.0 m/s and 1400.6 m/s at 30°C, respectively. As the temperature rises, the sound speed in droplets decreases at an average rate of 3.1 m/s/°C, and the speed in water increases at 2.1 m/s/°C. The average displacement varies from 150.0 μm to 179.0 μm with an increasing rate of 2.9 μm/°C, and its standard deviation is obtained between 1.0 μm and 2.0 μm over the same temperature range. Reduced sound speed as a function of rising temperature results in increased displacement, indicating that the trapping strength is adjustable by regulating ambient temperature in water as well as by changing transducer excitation parameters. Therefore, the results suggest that the temperature dependence of this trapping technique can be exploited for developing a remote manipulation tool of micron-sized particles in a thermally fluctuating environment. It is also shown that any deviated trapping strength caused by thermal disturbance near the trap can be restored to its desired level by compensating either temperature difference or trapping system condition.
25,106,111
[ 0.05949973, 0.2423304, -0.1006203, -0.1626048, -0.2701276, -0.3349806, -0.2704952, 0.155838, 0.5291253, -0.3028754, -0.08617698, -0.3911316, 0.08139116, 0.1070721, -0.3899171, -0.06087238, -0.4739002, -0.1319294, -0.03960599, -0.1205586, 0.4299363, 0.05989663, -0.288795, ...
Role of astrocytic glycolytic metabolism in Alzheimer's disease pathogenesis.
Alzheimer's disease (AD) has historically been considered to arise due to the specific dysfunction and pathology of neurons in brain areas related to cognition. Recent progress indicates that astrocytes play an important role in neurodegenerative processes underlying AD. In this review, we focus on the different glucose metabolism profiles between astrocytes and neurons. In AD, a variety of CNS insults, such as the presence of amyloid protein, trigger reactive astrogliosis, which disrupts normal glycolytic activity in these cells. The compromise of the astrocytic metabolism in turn weakens the integrity of astrocytic-neuronal partnership, damages the normal brain homeostasis, impairs clearance of amyloid, promotes cytokine release and other inflammatory mediators, and over time, leads to neurodegeneration.
25,106,114
[ -0.1625213, -0.1543967, -0.03375231, -0.147988, -0.07470414, -0.2531113, -0.2388886, 0.1358883, 0.0369649, 0.1439115, -0.1564723, -0.1209975, -0.1079045, 0.1222259, -0.2348563, 0.1004618, -0.4127619, 0.195026, -0.08698367, -0.01595161, -0.1483508, 0.1804923, -0.03001563, ...
Chemical characterization of emissions from a municipal solid waste treatment plant.
Gaseous emissions are an important problem in municipal solid waste (MSW) treatment plants. The sources points of emissions considered in the present work are: fresh compost, mature compost, landfill leaks and leachate ponds. Hydrogen sulphide, ammonia and volatile organic compounds (VOCs) were analysed in the emissions from these sources. Hydrogen sulphide and ammonia were important contributors to the total emission volume. Landfill leaks are significant source points of emissions of H2S; the average concentration of H2S in biogas from the landfill leaks is around 1700 ppmv. The fresh composting site was also an important contributor of H2S to the total emission volume; its concentration varied between 3.2 and 1.7 ppmv and a decrease with time was observed. The mature composting site showed a reduction of H2S concentration (<0.1 ppmv). Leachate pond showed a low concentration of H2S (in order of ppbv). Regarding NH3, composting sites and landfill leaks are notable source points of emissions (composting sites varied around 30-600 ppmv; biogas from landfill leaks varied from 160 to 640 ppmv). Regarding VOCs, the main compounds were: limonene, p-cymene, pinene, cyclohexane, reaching concentrations around 0.2-4.3 ppmv. H2S/NH3, limonene/p-cymene, limonene/cyclohexane ratios can be useful for analysing and identifying the emission sources.
25,106,121
[ -0.09653202, 0.031681, 0.4132394, 0.09743836, -0.04360543, -0.05814236, -0.1192782, -0.1660808, 0.1251936, -0.1422818, 0.1562653, -0.04335083, -0.1546614, -0.08579819, -0.2533974, 0.06629043, -0.1774967, 0.07560112, 0.3125145, 0.2781299, 0.04730298, 0.5101884, -0.1311954,...
Mitochondrial DNA capture and divergence in Pinus provide new insights into the evolution of the genus.
The evolution of the mitochondrial (mt) genome is far from being fully understood. Systematic investigations into the modes of inheritance, rates and patterns of recombination, nucleotide substitution, and structural changes in the mt genome are still lacking in many groups of plants. In this study, we sequenced >11kbp mtDNA segments from multiple accessions of 36 pine species to characterize the evolutionary patterns of mtDNA in the genus Pinus. We found extremely low substitution rates and complex repetitive sequences scattered across different genome regions, as well as chimeric structures that were probably generated by multiple intergenomic recombinations. The mtDNA-based phylogeny of the genus differed from that based on chloroplast and nuclear DNA in the placement of several groups of species. Such discordances suggest a series of mtDNA capture events during past range shifts of the pine species and that both vertical and horizontal inheritance are implicated in the evolution of mtDNA in Pinus. MtDNA dating revealed that most extant lineages of the genus originated during Oligocene-Miocene radiation and subgenus Strobus diversified earlier than subgenus Pinus. Our findings illustrate a reticular evolutionary pathway for the mt genome through capture and recombination in the genus Pinus, and provide new insights into the evolution of the genus.
25,106,134
[ -0.07145195, 0.08476784, 0.2934482, 0.2152135, 0.2928911, -0.2087739, -0.278584, -0.03227433, 0.2795096, 0.2206661, -0.02123265, -0.08555035, -0.1018617, 0.1415079, -0.4976162, -0.01897159, -0.4923927, -0.0649505, 0.1839509, -0.1447079, 0.3133671, 0.3898487, -0.05171898, ...
Assessing item fit for unidimensional item response theory models using residuals from estimated item response functions.
Residual analysis (e.g. Hambleton & Swaminathan, Item response theory: principles and applications, Kluwer Academic, Boston, 1985; Hambleton, Swaminathan, & Rogers, Fundamentals of item response theory, Sage, Newbury Park, 1991) is a popular method to assess fit of item response theory (IRT) models. We suggest a form of residual analysis that may be applied to assess item fit for unidimensional IRT models. The residual analysis consists of a comparison of the maximum-likelihood estimate of the item characteristic curve with an alternative ratio estimate of the item characteristic curve. The large sample distribution of the residual is proved to be standardized normal when the IRT model fits the data. We compare the performance of our suggested residual to the standardized residual of Hambleton et al. (Fundamentals of item response theory, Sage, Newbury Park, 1991) in a detailed simulation study. We then calculate our suggested residuals using data from an operational test. The residuals appear to be useful in assessing the item fit for unidimensional IRT models.
25,106,393
[ 0.2463119, -0.3288749, -0.1906479, -0.3050616, 0.4653141, -0.311231, -0.09567047, 0.07095636, 0.3464321, -0.02629497, 0.14844, -0.3794788, -0.2158165, 0.07941452, -0.1588371, -0.06464914, -0.0404949, 0.1479186, -0.1001978, 0.02625478, 0.106339, 0.05952968, 0.1529112, -0...
CB2 Cannabinoid receptors as a therapeutic target-what does the future hold?
The past decades have seen an exponential rise in our understanding of the endocannabinoid system, comprising CB1 and CB2 cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that synthesize and degrade endocannabinoids. The primary focus of this review is the CB2 receptor. CB2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential for treating various pathologies while avoiding the adverse psychotropic effects that can accompany CB1 receptor-based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this review, we summarize our present knowledge of CB2 receptor signaling, localization, and regulation. We discuss the availability of genetic tools (and their limitations) to study CB2 receptors and also provide an update on preclinical data on CB2 agonists in pain models. Finally, we suggest possible reasons for the failure of CB2 ligands in clinical pain trials and offer possible ways to move the field forward in a way that can help reconcile the inconsistencies between preclinical and clinical data.
25,106,425
[ -0.04643673, -0.0248388, -0.1168966, -0.2544399, -0.1345598, -0.2019919, -0.08617259, 0.06199993, 0.04568711, -0.1986806, -0.02384284, -0.09285092, 0.1331704, -0.01571776, -0.3038304, -0.121772, -0.5052563, 0.2475978, -0.04003594, 0.1064861, -0.1404104, 0.3056812, -0.3513...
High matrix metalloproteinase levels are associated with dermal graft failure in diabetic foot ulcers.
The aim of our study is to analyze factors, including matrix metalloproteinase (MMP) levels, that could influence the integration of dermal grafts in diabetic foot ulcers. From September 2012 to September 2013, 35 diabetic patients with IIA lesion (Texas Wound Classification) and an extensive foot tissue loss were considered suitable for dermal graft. Before the enrollment we ensured the best local conditions: adequate blood supply, control of infection, and offloading. The MMP level of each lesion was evaluated blindly before the application of dermal substitutes. At 1-month follow-up, we analyzed the correlation between clinical patient characteristics, local wound features including MMP levels, dermal substitute applied, and the outcome expressed in terms of dermal graft integration. We observed dermal graft integration in 28/35 patients (80% of our population). In multivariate analysis high MMP level was the only negative predictor for dermal graft integration (P < .0007). In addition, we divided the patients into 2 groups according to MMP levels: group 1 with low protease activity (24 patients) and group 2 with elevated protease activity (11 patients). The integration of the dermal graft was 100% in group 1 (n = 24 patients) and 36.4% in group 2 (n = 4patients), P < .0001. According to our data, the evaluation of MMP levels may be useful to choose the right strategy to get the best results in terms of clinical success and cost saving. However, further studies are necessary to confirm these findings.
25,106,443
[ -0.05130837, 0.02648849, 0.09101362, -0.02173664, 0.0606745, -0.5750036, 0.1718011, 0.04615054, 0.1544363, -0.3725655, -0.2771208, -0.3842195, -0.2575703, -0.1183959, -0.2787841, -0.09193005, 0.3223354, -0.1821053, -0.004728518, -0.03015086, -0.202887, 0.07882345, -0.0907...
Isolation and characterization of a Sca-1+/CD31- progenitor cell lineage derived from mouse heart tissue.
Myocardial infarction remains the leading cause of mortality in developed countries despite recent advances in its prevention and treatment. Regenerative therapies based on resident cardiac progenitor cells (CPCs) are a promising alternative to conventional treatments. However, CPCs resident in the heart are quite rare. It is unclear how these CPCs can be isolated and cultured efficiently and what the effects of long-term culture in vitro are on their 'stemness' and differentiation potential, but this is critical knowledge for CPCs' clinical application. Here, we isolated stem cell antigen-1 positive cells from postnatal mouse heart by magnetic active cell sorting using an iron-labeled anti-mouse Sca-1 antibody, and cultured them long-term in vitro. We tested stemness marker expression and the proliferation ability of long-term cultured Sca-1+ cells at early, middle and late passages. Furthermore, we determined the differentiation potential of these three passages into cardiac cell lineages (cardiomyocytes, smooth muscle and endothelial cells) after induction in vitro. The expression of myocardial, smooth muscle and endothelial cell-specific genes and surface markers were analyzed by RT-PCR and IF staining. We also investigated the oncogenicity of the three passages by subcutaneously injecting cells in nude mice. Overall, heart-derived Sca-1+ cells showed CPC characteristics: long-term propagation ability in vitro, non-tumorigenic in vivo, persistent expression of stemness and cardiac-specific markers, and multipotent differentiation into cardiac cell lineages. Our research may bring new insights to myocardium regeneration, for which even a small number of biopsy-derived CPCs could be enriched and propagated long term in vitro to obtain sufficient seed cells for cell injection or cardiac tissue engineering.
25,106,452
[ -0.191475, 0.07370617, -0.3264391, -0.3033316, 0.07006112, -0.05157955, 0.09173752, 0.3990283, -0.06871711, -0.03534029, -0.04886504, 0.4885675, -0.05558947, -0.2330604, -0.3402091, 0.1113967, -0.2268324, -0.1688458, -0.3158821, 0.3583353, 0.2127378, 0.1330941, -0.1941848...
In vivo and in vitro evaluation of effects of Mg-6Zn alloy on apoptosis of common bile duct epithelial cell.
Biodegradable magnesium alloy implants have attracted much attention because of their excellent biocompatibility and good mechanical properties. However, effects of Mg alloy on cell apoptosis remain unclear. The aim of this study was to investigate the effects of the Mg-6Zn alloy on the apoptosis and necrosis of common bile duct (CBD) epithelial cells. In the in vitro experiments, primary mouse extrahepatic bile epithelial cells (MEBECs) were exposed to Mg-6Zn alloy extracts with different concentrations (0, 40, 80, and 100 %). Flow cytometry analysis indicated that low concentration Mg-6Zn extract can induce apoptosis of MEBECs, and high concentration Mg-6Zn extracts may relate to necrosis and/or 'apoptotic necrosis'. Real-time PCR results showed that when MEBECs were treated with 40 % extracts for 3 days, the relative apoptotic genes including Bax, Bax/Bcl-2 ratio, NF-κB and caspase-3 were higher than those in the control group. In the in vivo experiments, Mg-6Zn alloy stents were implanted into rabbits' CBD for 1, 2, 3 weeks, respectively. Based on the hematoxylin and eosin (H&E) staining of peri-implant CBD tissue, no apoptotic bodies and necrotic cells were observed. Results of immunohistochemical staining also showed Mg-6Zn stents did not increase expression levels of apoptosis related gene such as Bax, Bcl-2, Bax/Bcl-2 ratio, TNF-α, NF-κB and caspase-3 in CBD, which indicating Mg-6Zn did not induce significant apoptosis in the in vivo experiments. The different results of in vitro and in vivo experiment may result from the low corrosion rate of Mg-6Zn alloy stents in vivo and local Mg(2+) ion concentration in CBD.
25,106,461
[ -0.09788737, -0.08795049, -0.3001992, 0.4958832, -0.3707095, -0.1115037, 0.06331619, -0.001485308, -0.2565967, 0.04295531, -0.01016197, 0.2458682, -0.06789644, 0.01811683, -0.3300983, 0.01352417, 0.001715063, 0.338727, -0.1041, 0.6155912, 0.684666, 0.2439212, 0.06358598, ...
Pancreatic duct abnormalities in focal autoimmune pancreatitis: MR/MRCP imaging findings.
To evaluate the magnetic resonance (MR) imaging-MR cholangiopancreatographic (MRCP) findings of focal forms of autoimmune pancreatitis (AIP) to describe ductal involvement at diagnosis. MR examinations of 123 patients affected by AIP were analysed. We included 26 patients who satisfied International Consensus Diagnostic Criteria and were suffering from focal AIP. Image analysis included: site of parenchymal enlargement, main pancreatic duct (MPD) diameter, MPD stenosis, stricture length, presence of upstream dilation within the stricture, signal intensity, and pancreatic enhancement. Signal intensity abnormalities were localized in the head in 10/26 (38.5%) and in the body-tail in 16/26 (61.5%) patients. MRCP showed a single MPD stenosis in 12/26 (46.1%) and multiple MPD stenosis in 14/26 (53.8%) patients, without a dilation of the upstream MPD (mean: 3.83 mm). Lesions showed hypointensity on T1-weighted images in all patients, and hyperintensity on T2-weighted images in 22/26 (84.6%) patients. The affected parenchyma was hypovascular during the arterial phase in 25/26 (96.2%) patients with contrast retention. MR-MRCP are effective techniques for the diagnosis of AIP showing the loss of the physiological lobulation and the typical contrastographic appearance. The presence of multiple, long stenoses without an upstream MPD dilation at MRCP suggests the diagnosis of AIP, and can be useful in differential diagnosis of pancreatic adenocarcinoma. • MRI represents the gold standard in the diagnosis of AIP. • MRCP is an increasingly useful technique in the diagnosis of focal AIP. • MRCP could be a problem-solving tool in the differential diagnosis of AIP.
25,106,489
[ 0.1179526, -0.3214051, 0.09516152, -0.1883134, 0.0138343, -0.1665308, 0.2156205, -0.04387741, -0.077271, 0.1233196, -0.04752745, -0.1901428, -0.1999916, -0.3006684, -0.2446248, -0.2603312, -0.3973379, 0.1745958, 0.1156233, -0.1508853, -0.02887537, 0.2230046, 0.03561738, ...
A miniature quantitative PCR device for directly monitoring a sample processing on a microfluidic rapid DNA system.
We report a microfluidic device and measurement method to perform real-time PCR (or qPCR) in a miniaturized configuration for on-chip implementation using reaction volumes of less than 20 μL. The qPCR bioreactor is designed as a module to be embedded in an automated sample-in/profile-out system for rapid DNA biometrics or human identification. The PCR mixture is excited with a 505 nm diode-pumped solid-state laser (DPSSL) and the fluorescence build-up is measured using optical fibers directly embedded to the sidewalls of the microfluidic qPCR bioreactor. We discuss manufacturing and operating parameters necessary to adjust the internal surface conditions and temperature profiles of the bioreactor and to optimize the yield and quality of the PCR reaction for the amplification of 62 bp hTERT intron fragments using the commercial Quantifiler® kit (Life Technologies, Carlsbad, CA) commonly accepted for genotyping analysis. We designed a microfluidic device suitable for continuously processing a specimen by efficiently mixing the reagents from the kit to a set volume of DNA template on chip. Our approach relies on a calibration curve for the specific device using control DNA. We successfully applied this method to determine the concentration of genomic DNA extracted from a buccal swab on separate microfluidic devices which are operated upstream the qPCR device and perform buccal swab lysis and buccal DNA extraction. A precise correlation between the amount determined on chip and that obtained using a commercial cycler is demonstrated.
25,106,501
[ -0.04968485, 0.08189292, -0.02116495, 0.1278321, 0.02237767, -0.3775971, -0.01746496, 0.1945837, 0.4205064, 0.2871885, -0.01394955, -0.2758262, 0.1571461, -0.310708, -0.7334731, 0.1015125, -0.4227061, -0.1772551, -0.05898763, 0.2323595, 0.4609911, 0.08543993, -0.1182199, ...
Progress in stacking techniques based on field amplification of capillary electrophoresis.
Numerous strategies have been developed to mitigate the intrinsic low detection sensitivity that is a limitation of capillary electrophoresis. Among them, in-line stacking is an effective strategy to address the sensitivity challenge, and among the different stacking techniques, stacking based on field amplification is the most effective and simplest method of achieving high sensitivity without special complicated mechanisms or operations. This review introduces several stacking techniques based on field amplification. Field-amplified sample stacking, large-volume sample stacking, matrix field-amplified stacking injection (FASI), head-column FASI, matrix FASI combined with head-column FASI, FASI coupled with extraction and clean-up methods, electrokinetic supercharging, cation-anion selective exhaustive injection-sweeping-micellar electrokinetic chromatography, and newly developed techniques based on field amplification combined with other methods are included, and examples of straightforward methods for solving the sensitivity problem are provided. We also present a brief overview of the advantages, limitations, and future developments of these techniques.
25,106,543
[ -0.2831241, 0.2795543, -0.0460844, -0.06820334, 0.3114009, -0.007159345, -0.4420703, -0.06732494, -0.00707053, -0.02186579, 0.02356824, -0.08691621, 0.1138716, 0.3820263, -0.3751263, -0.2403731, -0.5422783, -0.009124802, -0.1572334, 0.1286291, 0.03141347, 0.01738326, -0.1...
Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms.
High production output of solid pharmaceutical formulations requires fast methods to ensure their quality. Likewise, fast analytical procedures are required in forensic sciences, for example at customs, to substantiate an initial suspicion. We here present the design and the optimization of an instrumental setup for rapid and non-invasive characterization of tablets by laser-induced fluorescence spectroscopy (with a UV-laser (λ ex = 266 nm) as excitation source) in reflection geometry. The setup was first validated with regard to repeatability, bleaching phenomena, and sensitivity. The effect on the spectra by the physical and chemical properties of the samples, e.g. their hardness, homogeneity, chemical composition, and granule grain size of the uncompressed material, using a series of tablets, manufactured in accordance with design of experiments, was investigated. Investigation of tablets with regard to homogeneity, especially, is extremely important in pharmaceutical production processes. We demonstrate that multiplicative scatter correction is an appropriate tool for data preprocessing of fluorescence spectra. Tablets with different physical and chemical characteristics can be discriminated well from their fluorescence spectra by subjecting the results to principal component analysis.
25,106,544
[ -0.04503166, 0.4150966, 0.1684288, 0.06074472, 0.192309, -0.3033229, -0.02972411, 0.202348, 0.4185088, -0.2181309, 0.04332921, 0.04342373, -0.05665985, -0.1130897, -0.4693181, 0.1894688, -0.1171558, 0.07107811, 0.01363285, 0.2561601, 0.5737619, 0.03859615, -0.1692564, 0...
Does change in hostility predict sexual recidivism?
The purpose of the study was to examine whether scores on a widely used measure of hostility--the Buss-Durkee Hostility Inventory (BDHI)--and change on this measure predicted sexual recidivism in a sample of 120 adult male incarcerated sexual offenders. Pre- and posttreatment scores, simple difference scores, and clinically significant change were examined. The majority of participants had functional scores on the BDHI prior to treatment. Of those who had dysfunctional pretreatment scores, the majority remained unchanged. Higher posttreatment scores on the Assault and Verbal Hostility subscales significantly predicted sexual recidivism. The remaining pre- and posttreatment scores as well as change scores and classifications did not significantly predict sexual recidivism. Our findings suggest that the Assault and Verbal Hostility subscales may be useful for predicting sexual recidivism but were not clearly consistent with the notion that the BDHI assesses a dynamic risk factor(s) for sexual recidivism. Due to a number of limitations of the current study, however, more rigorous research is needed before firm conclusions can be drawn.
25,106,554
[ -0.1900774, 0.1943693, -0.111677, -0.1665326, 0.2346067, -0.5141879, -0.05998785, -0.05861497, -0.02268952, -0.05729161, 0.1746984, -0.5234134, -0.04653377, -0.03500498, -0.2357787, -0.1531902, -0.3637563, -0.08257923, 0.4338602, -0.0245297, 0.009184654, 0.3136527, 0.0092...
A new perturbation theory for electrolyte solutions.
Developing physically based equations of state for electrolyte solutions is demanding due to the long range behaviour of the Coulombic interaction potentials. In this work, we present a new perturbation approach for nonprimitive model electrolyte solutions consisting of hard spheres with a positive or negative point charge or with point dipoles. We overcome the problem of diverging correlation integrals by separating the interaction potentials into short ranged parts and a long ranged contribution. For the point charges, the division is done like in most implementations of the Ewald sum. The perturbation expansion to 3rd order is formulated using the short ranged part of the potentials only, which results in converging correlation integrals for which we provide simple analytical expressions. The long range contribution to the Helmholtz energy is taken into account by a analytical term that has recently been presented by Rodgers and Weeks [J. M. Rodgers and J. D. Weeks, J. Chem. Phys. 131, 244108 (2009)]. In order to assess the proposed theory, we present molecular simulation data for Helmholtz energies of the same model electrolyte solutions. Predictions for the Helmholtz energy from the new theory are found to be in very good agreement with results from the molecular simulations for all state points we regarded.
25,106,566
[ -0.2044794, 0.1690241, 0.00834745, 0.07755689, 0.2673181, -0.3095964, -0.2084015, 0.126585, 0.3660342, 0.1380643, -0.1232341, 0.05772188, 0.1356332, 0.0247331, -0.4160203, -0.128964, -0.1643983, 0.1325115, -0.07143828, -0.1490134, -0.0007565585, -0.1675975, 0.06303518, ...
Insertion of liquid crystal molecules into hydrocarbon monolayers.
Atomistic molecular dynamics simulations were carried out to investigate the molecular mechanisms of vertical surface alignment of liquid crystals. We study the insertion of nCB (4-Cyano-4'-n-biphenyl) molecules with n = 0,…,6 into a bent-core liquid crystal monolayer that was recently found to provide good vertical alignment for liquid crystals. The results suggest a complex-free energy landscape for the liquid crystal within the layer. The preferred insertion direction of the nCB molecules (core or tail first) varies with n, which can be explained by entropic considerations. The role of the dipole moments was found to be negligible. As vertical alignment is the leading form of present day liquid crystal displays (LCD), these results will help guide improvement of the LCD technology, as well as lend insight into the more general problem of insertion of biological and other molecules into lipid and surfactant layers.
25,106,607
[ -0.1615527, 0.2526285, -0.1613026, -0.1218269, 0.12243, -0.09781784, -0.468725, 0.03532446, 0.06295693, -0.1099763, -0.02832177, -0.01420134, -0.07464065, 0.2857323, -0.5204949, -0.004420359, -0.5462792, 0.257743, -0.1415974, 0.1694465, 0.3661388, 0.4982449, -0.2124749, ...
Many-body effect in ion binding to RNA.
Ion-mediated electrostatic interactions play an important role in RNA folding stability. For a RNA in a solution with higher Mg(2+) ion concentration, more counterions in the solution can bind to the RNA, causing a strong many-body coupling between the bound ions. The many-body effect can change the effective potential of mean force between the tightly bound ions. This effect tends to dampen ion binding and lower RNA folding stability. Neglecting the many-body effect leads to a systematic error (over-estimation) of RNA folding stability at high Mg(2+) ion concentrations. Using the tightly bound ion model combined with a conformational ensemble model, we investigate the influence of the many-body effect on the ion-dependent RNA folding stability. Comparisons with the experimental data indicate that including the many-body effect led to much improved predictions for RNA folding stability at high Mg(2+) ion concentrations. The results suggest that the many-body effect can be important for RNA folding in high concentrations of multivalent ions. Further investigation showed that the many-body effect can influence the spatial distribution of the tightly bound ions and the effect is more pronounced for compact RNA structures and structures prone to the formation of local clustering of ions.
25,106,614
[ -0.1871694, 0.443798, -0.3719465, 0.1127294, 0.1012431, 0.06212719, -0.3094511, 0.1765414, 0.09956174, -0.170601, 0.1072794, 0.1727432, 0.3910783, 0.0484316, -0.3162125, 0.1400265, 0.00804484, 0.03996186, -0.01513837, 0.001794504, 0.384519, 0.2743593, -0.08419309, 0.029...
Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution.
The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5'-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to π* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5'-monophosphate, and adenosine 5'-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety.
25,106,615
[ -0.1704661, -0.003113445, -0.2778211, 0.1214616, 0.1435861, -0.03501786, -0.3160024, -0.08642895, 0.2082787, -0.02130886, -0.07349671, -0.04700161, 0.04846582, 0.2206666, -0.7503552, -0.2810991, -0.3793139, 0.1183601, 0.02570581, 0.1759092, 0.6404251, 0.08304439, -0.10207...
Unusual structural properties of water within the hydration shell of hyperactive antifreeze protein.
Many hypotheses can be encountered explaining the mechanism of action of antifreeze proteins. One widespread theory postulates that the similarity of structural properties of solvation water of antifreeze proteins to ice is crucial to the antifreeze activity of these agents. In order to investigate this problem, the structural properties of solvation water of the hyperactive antifreeze protein from Choristoneura fumiferana were analyzed and compared with the properties of solvation water present at the surface of ice. The most striking observations concerned the temperature dependence of changes in water structure. In the case of solvation water of the ice-binding plane, the difference between the overall structural ordering of solvation water and bulk water diminished with increasing temperature; in the case of solvation water of the rest of the protein, the trend was opposite. In this respect, the solvation water of the ice-binding plane roughly resembled the hydration layer of ice. Simultaneously, the whole solvation shell of the protein displayed some features that are typical for solvation shells of many other proteins and are not encountered in the solvation water of ice. In the first place, this is an increase in density of water around the protein. The opposite is true for the solvation water of ice - it is less dense than bulk water. Therefore, even though the structure of solvation water of ice-binding plane and the structure of solvation water of ice seem to share some similarities, densitywise they differ.
25,106,616
[ -0.196276, -0.04782785, -0.01558169, -0.0617898, -0.166875, -0.2265753, -0.3414532, -0.1364994, 0.1931341, 0.1244932, 0.04898504, 0.4076209, 0.1481324, 0.1815369, -0.1989933, 0.07878136, -0.2266827, -0.004721094, -0.1452307, 0.1803772, 0.4591248, 0.3219814, -0.2468524, ...
The role of melatonin in multiple sclerosis, Huntington's disease and cerebral ischemia.
Melatonin is produced and released by the pineal gland in a circadian rhythm. This neurohormone has proven to be an antioxidant and anti-inflammatory molecule able to reduce or mitigate cell damage associated with oxidative stress and inflammation, and this phenomenon underlies neurodegenerative disorders. These facts have drawn attention to this indole, triggering interest in evaluating its changes and in its relationship to the processes indicated, and analyzing its role in the mechanisms involved at the onset and development of neurodegenerative diseases, as well as its therapeutic potential. Multiple sclerosis, the most common cause of non-traumatic disability in young adults, is a chronic neuroinflammatory disease, characterized by demyelination, inflammation, and neuronal and oxidative damage. In its early diagnosis, it often requires a differential screening with other neurodegenerative diseases with similar symptoms, such as Huntington's disease, an autosomal dominant disorder. The onset of both diseases occurs in the second or third decade of life. On the other hand, cerebral ischemia is a major cause of human disability all over the world. Although a cerebral stroke can occur as the result of different damaging insults, severe ischemia produces the death of neuronal cells within minutes. Changes in melatonin levels have been observed in these processes (Huntington's disease, multiple sclerosis and cerebral ischemia) as part of their pathogenic features. This review aims to update and discuss the role played by melatonin during neurodegenerative processes, specifically in multiple sclerosis, Huntington's disease, and cerebral ischemia, and its possible therapeutic use. We also provide readers with an update on the many neuroprotective mechanisms exerted by this neurohormone in the Central Nervous System.
25,106,623
[ -0.4599289, -0.1001128, 0.2636391, -0.2193761, -0.0605335, -0.2563215, 0.08471096, -0.08358599, 0.08430073, -0.1010556, -0.01115611, 0.3963841, -0.01737396, -0.1049398, 0.2024273, -0.1953359, -0.1481162, 0.1522263, -0.2808281, -0.06149658, -0.1455435, 0.08316499, -0.12448...
Neuroprotection by association of palmitoylethanolamide with luteolin in experimental Alzheimer's disease models: the control of neuroinflammation.
Alzheimer's disease (AD) is the most common neurodegenerative disorder. Its neuropathological hallmarks include deposition of beta amyloid (Aβ) fibrils in senile plaques. Numerous biochemical events, leading to Aβ neurotoxicity in AD, have been proposed and it seems that neuroinflammation plays a prominent role among these. Thus, since inflammatory processes and oxidative stress are considered to play an important role in neuroinflammatory disorders and in AD pathology, in the present work we decided to test a new composite, which is a formulation constituted of an anti-inflammatory compound such as palmitoylethanolamide (PEA) and the well recognized antioxidant flavonoid luteolin (Lut), subjected to an ultra-micronization process, here designated co-ultraPEALut. We investigated the effect of co-ultraPEALut in both an in vitro and ex vivo organotypic model of AD. For the in vitro model, we used human neuronal cells, obtained by differentiating SH-SY5Y neuroblastoma cells into sustainable neuronal morphology. These well differentiated cells express features specific to mature neurons, such as synaptic structures and functional axonal vesicle transport, making this new concept for in vitro differentiation valuable for many neuroscientific research areas, including AD. Differentiated SH-SY5Y cells were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 µM PEA) for 2 h. AD features were induced by Aβ₁₋₄₂ stimulation (1 µM). Twenty-four hours later cell vitality was evaluated by the colorimetric MTT assay, whereas the neuroinflammation underling AD was observed by Western blot analysis for IκBα degradation and nuclear factor-κB traslocation, as well as glial fibrillary acidic protein expression. For the organotypic model of AD, hippocampal slice cultures were prepared from mice at postnatal day 6 and after 21 days of culturing the slices were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 µM PEA) for 2 h and then incubated with Aβ₁₋₄₂ (1 µg/ml) for 24 h. Pre-treatment with co-ultraPEALut significantly reduced inducible nitric oxide synthase and glial fibrillary acidic protein expression, restored neuronal nitric oxide synthase and brainderived neurotrophic factor and reduced the apoptosis. Taken together our results clearly showed that co-ultraPEALut is able to blunt Aβ-induced astrocyte activation and to exert a marked protective effect on glial cells. These findings suggest that the association of co-ultraPEALut may provide an effective strategy for AD.
25,106,636
[ -0.1938749, 0.07027242, 0.2127363, 0.0768482, -0.2513663, -0.2040662, 0.2038824, 0.1004028, 0.2709818, -0.0181801, -0.202661, -0.1040317, 0.1389273, -0.05357767, -0.1584846, 0.1731069, -0.04553486, -0.01501947, -0.234388, 0.2978679, 0.07861035, 0.2738534, -0.09054107, 0...
Potential targets for the development of novel antidepressants: future perspectives.
Depression is an affective disorder characterized by hallucination, delusion and increased social risk and is estimated to affect approximately 20 % of the population at some point during the lifetime. As per World Health Organization (WHO) it is predicted to be the leading cause of burden of disease by 2030. Effects of currently available antidepressants have explained the monoamine hypothesis of depression, which proposes that impaired release of serotonin, noradrenaline and dopamine, are thought to be responsible for the development of depressive symptoms. However, these drugs are not specific for their action, as they also inhibit other enzymes; this explains the side effects/drug interactions associated with these agents. The present review will familiarize the readers with novel targets being identified for depression which will be certainly beneficial for researcher, academician for the development of drugs for the management of depression and related behavior.
25,106,638
[ -0.3210907, -0.01194392, 0.1664245, -0.07809722, 0.0625784, -0.3116231, -0.3143375, -0.09096298, 0.001962432, -0.2258745, -0.1368984, 0.06266457, -0.03152453, 0.138163, -0.5361041, 0.0822094, -0.2158472, 0.2705845, 0.1158084, -0.08509804, -0.3098246, 0.3659446, -0.2270034...