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Survival benefit of primary deceased donor transplantation with high-KDPI kidneys.
The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating deceased donor kidney offers, but the relative benefit of high-KDPI kidney transplantation (KT) versus the clinical alternative (remaining on the waitlist until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71-80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult registrants, adjusting for candidate characteristics. High-KDPI KT was associated with increased short-term but decreased long-term mortality risk. Recipients of KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a survival benefit thereafter. Cumulative survival at 5 years was better in all three high-KDPI groups than the conservative approach (p < 0.01 for each comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and patients at centers with median wait time ≥33 months. Recipients of high-KDPI KT can enjoy better long-term survival; a high-KDPI score does not automatically constitute a reason to reject a deceased donor kidney.
25,139,729
[ -0.04975888, 0.1257998, -0.2681946, -0.1531412, 0.2520132, -0.243105, 0.1643434, 0.1393751, -0.08886465, -0.3064803, 0.01230818, 0.2917699, -0.0008948324, -0.1228202, -0.5597726, -0.4390541, -0.1350172, 0.09850186, 0.1714175, -0.04844032, -0.0256962, 0.5900397, -0.131412,...
Importance of intense male sexual behavior for inducing the preovulatory LH surge and ovulation in seasonally anovulatory female goats.
The present study was carried out to determine whether the presence of photostimulated sedated male goats could stimulate the LH preovulatory surge and ovulation in seasonal anestrous goats. Sexually experienced male goats were treated with artificial long days (16 hours light per day) from 1 November to 15 January to stimulate their sexual activity in March and April, corresponding to the natural sexual rest. A female group of goats (n=20) was exposed to non-sedated males who displayed an intense sexual behavior and provided strong odor (non-sedated group). Another female group of goats (n=20) was exposed to the photo-stimulated male goats, but these males were sedated with Xylazine 2% to prevent the expression of sexual behavior (sedated group). The sedated males also provided a strong odor. Females of both groups had full physical and visual contact with non-sedated or sedated males. In both groups, the males remained with females during 4 days. The LH preovulatory surge of 10 female goats per group was measured by determination of LH plasma concentrations in samples taken every 3 hours. In addition, in all goats, (n=20 by group), ovulation was determined by measuring plasma concentrations of progesterone. The proportion of female goats showing a preovulatory LH surge was higher in goats exposed to non-sedated (10/10) than in those exposed to sedated bucks (0/10; P<0.0001). Similarly, most of does in contact with non-sedated males ovulated (19/20), but none of those in contact with sedated males did so (0/20; P<0.0001). We conclude that the expression of an intense sexual behavior by male goats is necessary to induce LH preovulatory surge and ovulation in seasonally anovulatory goats.
25,139,756
[ 0.1651523, 0.1957974, -0.1267688, -0.1049396, 0.05297295, -0.4270492, 0.03368224, -0.2513362, -0.03947546, -0.5173076, -0.04272502, -0.0946638, 0.07312301, -0.2690745, -0.07885807, 0.05725094, -0.7711457, 0.1049684, 0.4309886, -0.2425887, 0.1587416, 0.2157311, -0.1015695,...
Extracavitary primary effusion lymphoma: clinical, morphological, phenotypic and cytogenetic characterization using nuclei enrichment technique.
Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma, which typically manifests as malignant effusion in the body cavities. However, extracavitary solid variants are also described. The aim of this study was to investigate copy number aberrations in two cases of solid PEL at their first occurrences and relapse by applying a newly developed methodology of tumour nuclei enrichment. Using histological and genetic techniques, a novel protocol for tumour nuclei enrichment by flow sorting and array-comparative genomic hybridization, we characterized two cases of extracavitary PEL, one of which later relapsed as effusion. Both primary tumours were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B-cell origin. Cytogenetic characterization of primary tumours revealed modest number of aberrations, partially overlapping with previously reported affected loci. The effusional relapse in case 1 was cytogenetically related to the primary tumour but showed dramatic increase of chromosomal instability. We for the first time demonstrate a cytogenetic relationship between solid and effusional presentations of PEL. Moreover, we provide an indirect evidence of multiple malignant clones, which gave rise to clonally-related, yet karyotypically different relapsing lymphoma manifestations.
25,139,766
[ -0.1818459, 0.138611, 0.1835767, -0.1413605, 0.07534727, -0.3419324, -0.2033924, -0.1741766, 0.1074862, 0.4224201, 0.1362715, 0.1139788, 0.04649112, 0.07282396, -0.1934583, -0.1474117, -0.267618, -0.06644075, 0.1661242, -0.1463639, 0.3474942, 0.264491, -0.1885212, 0.056...
Psychosocial risk factors for hypertension: an update of the literature.
A growing body of research demonstrates that psychosocial factors play an important role in the development of hypertension. Previous reviews have identified several key factors (i.e., occupational stress) that contribute to the onset of hypertension; however, they are now outdated. In this review, we provide an updated synthesis of the literature from 2010 to April 2014. We identified 21 articles for inclusion in the review, of which there were six categories of psychosocial stressors: occupational stress, personality, mental health, housing instability, social support/isolation, and sleep quality. Sixteen of the studies reported an association between the psychosocial stressor and blood pressure. While several findings were consistent with previous literature, new findings regarding mediating and moderating factors underlying the psychosocial-hypertension association help to untangle inconsistencies reported in the literature. Moreover, sleep quality is a novel additional factor that should undergo further exploration. Areas for future research based on these findings are discussed.
25,139,781
[ -0.3827957, 0.1528801, 0.01876262, -0.1952985, -0.05219704, -0.1691505, -0.1005364, -0.1394941, -0.02698941, -0.2374011, 0.06799374, -0.4316575, -0.06922886, -0.2161713, -0.4088746, 0.003554687, -0.1335932, 0.1121342, 0.3490888, 0.1193495, -0.6322901, 0.2535009, -0.322214...
Assessment of a fluorescent antibody test for the detection of antibodies against epizootic bovine abortion.
The current study was directed at developing and validating an indirect fluorescent antibody test (IFAT) capable of detecting antibodies specific for the agent of epizootic bovine abortion (aoEBA). Sensitivity and specificity was determined by comparing antibody titers from 114 fetuses infected with aoEBA with 68 fetuses diagnosed with alternate infectious etiologies. Data established specificity at 100% and sensitivity at 94.7% when cutoff criteria for a positive test were assigned at a titer of ≥1,000. Potential cross-reactivity was noted in samples from 3 fetuses with antibody titers of 10 or100; all were infected with Gram-positive organisms. The remaining 65 fetuses infected with microbes other than aoEBA, and an additional 12 negative reference sera, did not have detectable titers. The IFAT-based serology assay is rapid, reproducible, and unaffected by fluid color or opacity. Total fetal immunoglobulin (Ig)G was also evaluated as an aid for diagnosing EBA. Significantly higher concentrations of IgG were identified in fetuses infected with aoEBA as compared to those with alternate infectious etiologies. The presence of IgG is a sensitive indicator of EBA and increases the specificity of FAT-based serologic diagnosis when titers are 10 or 100. Taken together, serology and IgG analyses suggest that the incidence of EBA may be underestimated.
25,139,792
[ 0.078453, -0.1888334, 0.08973677, -0.1814446, -0.0649709, -0.06895667, -0.1760695, 0.284176, 0.1767344, -0.3559338, -0.04981608, 0.2260305, 0.1474286, 0.02995737, -0.04964818, -0.3191957, -0.5729187, -0.06291035, -0.155466, 0.1900199, 0.07468136, 0.1831915, -0.2835609, ...
A rare disorder mimics otitis media: Langerhans cell histiocytosis of the temporal bone in a child with interstitial pulmonary fibrosis.
Langerhans cell histiocytosis (LCH) is a rare disease ranging from a benign to a rapidly fatal condition affecting young children predominantly, and is characterized by an abnormal clonal proliferation of Langerhans cells. We report a case of a 3-year-old child presenting with a 1-year history of otorrhea and otorrhagia followed by a 6-month history of postauricular swelling in the right ear. Imaging demonstrated a large mass of organized tissue. A biopsy was conducted, and the diagnosis of LCH was confirmed by histopathological and immunohistochemical examination. The child was treated with a 12-month course of vinblastine chemotherapy with prednisolone. No clinical evidence of recurrence was noticed after 3 years of follow-up. This rare case highlights the importance for otolaryngologists to keep LCH in mind for differential diagnosis in very young patients with symptoms and signs suggestive of acute mastoiditis or chronic otitis media.
25,139,821
[ -0.1784674, -0.3072746, 0.004887807, -0.1839995, 0.1933998, -0.2662072, -0.2953961, -0.1487195, -0.00685874, -0.2052864, 0.1689577, 0.3612395, -0.4834625, 0.07624375, -0.2706456, -0.1483377, 0.1069406, 0.1937745, 0.1505378, -0.2914625, 0.1587617, 0.3204566, -0.2958925, ...
Efficient quantification and characterization of bacterial outer membrane derived nano-particles with flow cytometric analysis.
There currently exists no efficient and easy method for size profiling and counting of membranous nano-scale particles, such as bacterial outer membrane vesicles (OMVs). We present here a cost-effective and fast method capable of profiling and counting small sample volumes of nano-scale membranous vesicles with standard laboratory equipment without the need for any washing steps. OMV populations of different bacterial species are compared and even subpopulations of OMVs can be identified after a simple labelling procedure. Counting is possible over three orders of magnitude without any changes to the protocol. Protein contaminations do not alter the described measurements.
25,139,826
[ -0.06604106, 0.2979754, -0.1506758, 0.1732914, -0.2882065, -0.2563597, -0.07919072, 0.2082849, 0.1720231, -0.0137905, -0.154643, -0.1942168, -0.1608506, -0.05581564, -0.3253363, -0.02333639, -0.2615104, 0.08647501, -0.1018892, -0.09799731, 0.2511218, 0.07033192, 0.0978913...
MicroRNA-145 as one negative regulator of astrogliosis.
Astrogliosis occurs at the lesion site within days to weeks after spinal cord injury (SCI) and involves the proliferation and hypertrophy of astrocytes, leading to glia scar formation. Changes in gene expression by deregulated microRNAs (miRNAs) are involved in the process of central nervous system neurodegeneration. Here, we report that mir-145, a miRNA enriched in rat spinal neurons and astrocytes, was downregulated at 1 week and 1 month after SCI. Our in vitro studies using astrocytes prepared from neonatal spinal cord tissues indicated that potent inflammagen lipopolysaccharide downregulated mir-145 expression in astrocytes, suggesting that SCI-triggered inflammatory signaling pathways could play the inhibitory role in astrocytic mir-145 expression. To induce overexpression of mir-145 in astrocytes at the spinal cord lesion site, we developed a lentivirus-mediated pre-miRNA delivery system using the promoter of glial fibrillary acidic protein (GFAP), an astrocyte-specific intermediate filament. The results indicated that astrocyte-specific overexpression of mir-145 reduced astrocytic cell density at the lesion border of the injured spinal cord. In parallel, overexpression of mir-145 reduced the size of astrocytes and the number of related cell processes, as well as cell proliferation and migration. Through a luciferase reporter system, we found that GFAP and c-myc were the two potential targets of mir-145 in astrocytes. Together, the findings demonstrate the novel role of mir-145 in the regulation of astrocytic dynamics, and reveal that the downregulation of mir-145 in astrocytes is a critical factor inducing astrogliosis after SCI. GLIA 2015;63:194-205.
25,139,829
[ -0.00331972, -0.1745247, 0.1369389, 0.2490955, -0.06159941, -0.0453655, -0.05304511, 0.1475006, 0.2573406, 0.2231691, -0.1022687, -0.3042651, 0.2102098, 0.2944573, 0.02622819, 0.1472221, -0.1819494, 0.1073606, -0.07272763, -0.06687101, 0.173876, 0.2509984, 0.1090335, -0...
Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate the neuronal microtubule cytoskeleton.
Drosophila neuromuscular junctions (NMJs) represent a powerful model system with which to study glutamatergic synapse formation and remodeling. Several proteins have been implicated in these processes, including components of canonical Wingless (Drosophila Wnt1) signaling and the giant isoforms of the membrane-cytoskeleton linker Ankyrin 2, but possible interconnections and cooperation between these proteins were unknown. Here, we demonstrate that the heterotrimeric G protein Go functions as a transducer of Wingless-Frizzled 2 signaling in the synapse. We identify Ankyrin 2 as a target of Go signaling required for NMJ formation. Moreover, the Go-ankyrin interaction is conserved in the mammalian neurite outgrowth pathway. Without ankyrins, a major switch in the Go-induced neuronal cytoskeleton program is observed, from microtubule-dependent neurite outgrowth to actin-dependent lamellopodial induction. These findings describe a novel mechanism regulating the microtubule cytoskeleton in the nervous system. Our work in Drosophila and mammalian cells suggests that this mechanism might be generally applicable in nervous system development and function.
25,139,856
[ 0.1010025, -0.1708356, -0.3500152, -0.3966149, 0.03637365, -0.2583961, 0.1534076, 0.1462322, -0.07996745, -0.005325306, -0.07511397, 0.3679647, -0.1095025, -0.3084101, -0.457017, 0.2355838, -0.8193782, 0.1200446, 0.2001667, -0.335228, 0.3434781, 0.3052314, -0.1204212, 0...
Isolated talonavicular fusion with tension band for Müller-Weiss syndrome.
There are still controversies with regard to the operative treatment in advanced Müller-Weiss syndrome (MWS), where the navicular undergoes avascular necrosis and the talonavicular (TN) joint becomes arthritic. Most authors advocate extended fusion, sacrificing hindfoot mobility. To restore TN alignment and to achieve stable fixation, we developed a new isolated TN fusion technique applying the principles of a static tension band. The aim of the present study was to report the midterm results of a preliminary series of patients and their clinical and radiographic outcomes. Ten feet (10 patients; 8 females, 2 males; age 63 ± 16.7 [range, 34-83] years) with advanced deformity of MWS (3 Maceira's stage III and 7 stage IV) were treated with isolated TN arthrodesis using the tension band technique. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used to evaluate the functional outcome. Standard angles were measured to determine the amount of correction achieved through the operative treatment. The minimum follow-up was 24 (range, 24-43) months. Trabeculation was seen to cross the fusion site on radiographs in 8 patients after 2 and in 1 patient after 3 months. One case needed revision after 13 months due to implant failure; after additional screw fixation, bony healing was achieved 2 months later. At last follow-up, all cases described a high level of satisfaction. Postoperatively, the AOFAS score improved from 33 (range, 18-48) to 88.3 (range, 79-100) (P < .0001) points, the AP talocalcaneal angle increased from 14.2 (range, 1-22) to 22.7 (range, 12-30) degrees (P = .0007), and the calcaneal pitch increased from 10.3 (range, 3-22) to 14.7 (range, 8-22) degrees (P = .0006). The static tension band technique is a new, promising technique to treat MWS patients, providing stability against the counteracting deforming forces. Therefore, we consider this technique as our treatment of choice in patients with stage III and stage IV MWS. Level IV, prospective case series.
25,139,862
[ -0.346529, 0.1683814, 0.2252288, -0.4226869, 0.1069053, -0.4205506, -0.2110448, -0.2370705, 0.1780401, -0.2000447, -0.2562416, -0.4087528, -0.3446595, -0.3418958, -0.476065, -0.2795767, -0.04270987, 0.05507884, -0.35063, 0.00286888, 0.2146597, -0.01008705, -0.4128866, 0...
Facile fabrication of a well-ordered porous Cu-doped SnO2 thin film for H2S sensing.
Well-ordered Cu-doped and undoped SnO2 porous thin films with large specific surface areas have been fabricated on a desired substrate using a self-assembled soft template combined with simple physical cosputtering deposition. The Cu-doped SnO2 porous film gas sensor shows a significant enhancement in its sensing performance, including a high sensitivity, selectivity, and a fast response and recovery time. The sensitivity of the Cu-doped SnO2 porous sensor is 1 order of magnitude higher than that of the undoped SnO2 sensor, with average response and recovery times to 100 ppm of H2S of ∼ 10.1 and ∼ 42.4 s, respectively, at the optimal operating temperature of 180 °C. The well-defined porous sensors fabricated by the method also exhibit high reproducibility because of the accurately controlled fabrication process. The facile process can be easily extended to the fabrication of other semiconductor oxide gas sensors with easy doping and multilayer porous nanostructure for practical sensing applications.
25,139,871
[ -0.0980871, 0.05916969, 0.1416669, -0.02694752, 0.01417453, -0.06741235, -0.5645427, 0.1052873, 0.1767086, -0.1238057, -0.01154082, 0.02581698, 0.0211112, -0.1005459, -0.5521964, -0.2609104, -0.2715131, 0.1864456, -0.08035285, 0.1821243, 0.0974397, 0.008593444, -0.2139444...
Association of interleukin-6 with the progression of carotid atherosclerosis: a 9-year follow-up study.
Limited information is available on the long-term effects of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present study was to clarify the relationship between chronic elevation of IL-6 and the long-term progression of carotid atherosclerosis. We prospectively evaluated 210 patients with ≥1 vascular risk factors for 9.0±1.0 years. Carotid mean-maximal intima-media thickness (mmIMT), the serum high-sensitivity C-reactive protein (hs-CRP) level, and the serum IL-6 level were measured at baseline and every 3 years. The associations between the progression of mmIMT and the long-term average levels of hs-CRP and IL-6 were analyzed. Carotid mmIMT increased throughout the study period (0.031±0.026 mm/y). Baseline mmIMT was significantly associated with baseline hs-CRP (P=0.002) and baseline IL-6 (P<0.001) levels. Progression of mmIMT was positively correlated with average hs-CRP (P=0.001) and average IL-6 (P<0.001) levels. When adjusted for age, sex, traditional risk factors, and baseline mmIMT, mmIMT progression remained significantly associated only with the average IL-6 level (standardized β=0.17; P=0.02), but not with the average hs-CRP level (standardized β=0.10; P=0.18). Chronic elevation of serum IL-6 was associated with the progression of atherosclerosis in patients with vascular risk factors. IL-6 could be used as a quantitative marker and a potential therapeutic target for accelerated atherosclerosis.
25,139,874
[ -0.2672488, 0.08576986, -0.3483125, -0.1496865, 0.1097452, -0.3476186, -0.02432615, 0.1144829, 0.1730389, -0.2629308, -0.1049791, 0.03390388, 0.1500901, -0.1848575, -0.07778293, 0.107476, -0.1697599, 0.3350679, -0.1597852, 0.288784, -0.09637224, 0.05243306, -0.1938346, ...
Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke.
Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1-p53 interaction is therapeutically effective against stroke. We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke. We showed that Tat-p53DM blocked DAPK1-p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions. DAPK1-p53 interaction is a preferred target for therapeutic intervention of stroke.
25,139,875
[ -0.28869, 0.03753848, 0.09401768, -0.03802441, 0.2978786, -0.07781806, 0.01940965, 0.1532099, 0.1427984, -0.01173484, 0.06580532, 0.242301, -0.01989061, -0.1468417, -0.1389927, 0.04263053, -0.6352025, -0.1161194, -0.1026992, -0.1328658, 0.2529709, 0.03127398, -0.17277, ...
Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities study.
Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke.
25,139,878
[ -0.03567333, 0.3542076, 0.21844, -0.04700633, -0.2356446, -0.1914963, 0.1496669, 0.202889, -0.180114, -0.2746097, -0.4699034, 0.3047974, -0.09604291, -0.1896141, 0.1943127, -0.06045846, -0.3238432, 0.2746618, 0.5476792, 0.1957414, -0.3888326, 0.4055583, 0.06947637, -0.1...
Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study.
Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.
25,139,879
[ -0.02553653, -0.05952997, -0.5763, -0.07894739, -0.0001790424, -0.3542124, 0.03045158, 0.1623147, 0.02269872, 0.0768306, -0.2086861, 0.4738409, 0.02057184, -0.1782466, 0.2588955, -0.4317678, -0.08864491, -0.0674846, 0.2132063, -0.0373988, 0.01048562, 0.2681941, -0.2529461...
Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.
In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D.
25,139,883
[ -0.0121775, -0.01092858, -0.1719124, 0.1340063, 0.440716, -0.3526962, -0.1452296, 0.05263268, 0.1748259, 0.02350265, 0.1170767, 0.4428346, -0.3618769, -0.3667087, -0.3207769, -0.346835, 0.08053771, 0.3138167, 0.1006522, 0.02222586, 0.02172954, 0.3223042, -0.2725128, -0....
Acquisition and evolution of SXT-R391 integrative conjugative elements in the seventh-pandemic Vibrio cholerae lineage.
SXT-R391 Integrative conjugative elements (ICEs) are self-transmissible mobile genetic elements able to confer multidrug resistance and other adaptive features to bacterial hosts, including Vibrio cholerae, the causative agent of cholera. ICEs are arranged in a mosaic genetic structure composed of a conserved backbone interspersed with variable DNA clusters located in conserved hot spots. In this study, we investigated ICE acquisition and subsequent microevolution in pandemic V. cholerae. Ninety-six ICEs were retrieved from publicly available sequence databases from V. cholerae clinical strains and were compared to a set of reference ICEs. Comparative genomics highlighted the existence of five main ICE groups with a distinct genetic makeup, exemplified by ICEVchInd5, ICEVchMoz10, SXT, ICEVchInd6, and ICEVchBan11. ICEVchInd5 (the most frequent element, represented by 70 of 96 elements analyzed) displayed no sequence rearrangements and was characterized by 46 single nucleotide polymorphisms (SNPs). SNP analysis revealed that recent inter-ICE homologous recombination between ICEVchInd5 and other ICEs circulating in gammaproteobacteria generated ICEVchMoz10, ICEVchInd6, and ICEVchBan11. Bayesian phylogenetic analyses indicated that ICEVchInd5 and SXT were independently acquired by the current pandemic V. cholerae O1 and O139 lineages, respectively, within a period of only a few years. SXT-R391 ICEs have been recognized as key vectors of antibiotic resistance in the seventh-pandemic lineage of V. cholerae, which remains a major cause of mortality and morbidity on a global scale. ICEs were acquired only recently in this clade and are acknowledged to be major contributors to horizontal gene transfer and the acquisition of new traits in bacterial species. We have reconstructed the temporal dynamics of SXT-R391 ICE acquisition and spread and have identified subsequent recombination events generating significant diversity in ICEs currently circulating among V. cholerae clinical strains. Our results showed that acquisition of SXT-R391 ICEs provided the V. cholerae seventh-pandemic lineage not only with a multidrug resistance phenotype but also with a powerful molecular tool for rapidly accessing the pan-genome of a large number of gammaproteobacteria.
25,139,901
[ -0.254126, 0.005144254, 0.07929829, -0.2171866, -0.166046, -0.2938777, -0.2521434, -0.09489146, 0.05172492, 0.01387712, 0.1545269, 0.07579724, -0.08271087, -0.1317004, -0.5173051, -0.2449673, -0.3810232, 0.06372365, 0.1559235, 0.2817194, 0.0215652, 0.1780264, -0.08056726,...
Remodeling of the intestinal brush border underlies adhesion and virulence of an enteric pathogen.
Intestinal colonization by Vibrio parahaemolyticus-the most common cause of seafood-borne bacterial enteritis worldwide-induces extensive disruption of intestinal microvilli. In orogastrically infected infant rabbits, reorganization of the apical brush border membrane includes effacement of some microvilli and marked elongation of others. All diarrhea, inflammation, and intestinal pathology associated with V. parahaemolyticus infection are dependent upon one of its type 3 secretion systems (T3SS2); however, translocated effectors that directly mediate brush border restructuring and bacterial adhesion are not known. Here, we demonstrate that the effector VopV is essential for V. parahaemolyticus intestinal colonization and therefore its pathogenicity, that it induces effacement of brush border microvilli, and that this effacement is required for adhesion of V. parahaemolyticus to enterocytes. VopV contains multiple functionally independent and mechanistically distinct domains through which it disrupts microvilli. We show that interaction between VopV and filamin, as well as VopV's previously noted interaction with actin, mediates enterocyte cytoskeletal reorganization. VopV's multipronged approach to epithelial restructuring, coupled with its impact on colonization, suggests that remodeling of the epithelial brush border is a critical step in pathogenesis. Colonization of the small bowel by Vibrio parahaemolyticus, the most common bacterial agent of seafood-borne enteric disease, induces extensive structural changes in the intestinal epithelium. Here, we show that this diarrheal pathogen's colonization and virulence depend upon VopV, a bacterial protein that is transferred into host epithelial cells. VopV induces marked rearrangement of the apical epithelial cell membrane, including elimination of microvilli, by two means: through interaction with actin and through a previously unrecognized interaction with the actin-cross-linking protein filamin. VopV-mediated "effacement" of microvilli enables V. parahaemolyticus to adhere to host cells, although VopV may not directly mediate adhesion. VopV's effects on microvillus structure and bacterial adhesion likely account for its essential role in V. parahaemolyticus intestinal pathogenesis. Our findings suggest a new role for filamin in brush border maintenance and raise the possibility that microvillus effacement is a common strategy among enteric pathogens for enhancing adhesion to host cells.
25,139,905
[ -0.1601308, -0.1324238, 0.08775063, -0.2003328, 0.03826192, -0.4275234, 0.1611374, 0.4596925, 0.1523795, 0.2017554, 0.07847334, -0.2031038, -0.4342235, -0.1486878, -0.3280593, -0.1491426, -0.7353699, -0.05115241, 0.09971829, -0.1387495, -0.1368794, 0.4536312, -0.3445322, ...
A new trick for an ancient drug: quinine dissociates antiphospholipid immune complexes.
Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial properties that has been phased out by more effective synthetic candidates. In previous studies we discovered that hydroxychloroquine (HCQ), a synthetic antimalarial with structural similarities to quinine, reduced the binding of antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed ellipsometry and atomic force microscopy (AFM) studies to measure the effect of quinine on dissociation of anti-β2-glycoprotein I (anti-β2GPI) immune complexes. We found that quinine desorbed pre-formed β2GPI-aPL immunoglobulin (Ig)G complexes from phospholipid bilayers at significantly lower molar concentrations than HCQ. Quinine also inhibited the formation of immune complexes with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml (0.192 ± 0.025 µg/cm(2) for quinine vs. 0.352 ± 0.014 µg/cm(2) for HCQ, p < 0.001). Furthermore, AFM imaging experiments revealed that addition of quinine disintegrated immune complexes bound to planar phospholipid layers. The desorptive and inhibitory effects of the old drug, quinine, toward β2GPI-aPL IgG complexes and β2GPI were significantly more pronounced compared to the synthetic antimalarial, HCQ. The results suggest that the quinoline core of the molecule is a critical domain for this activity and that side chains may further modulate this effect. The results also indicate that there may yet be room for considering new activities of very old drugs in devising clinical trials on potential non-anticoagulant treatments for antiphospholipid syndrome (APS).
25,139,939
[ 0.003942898, 0.2056632, -0.3262573, 0.247109, -0.1062499, 0.00563979, 0.02984068, 0.3123231, 0.2833103, -0.06371248, -0.01710552, 0.2432826, 0.05774869, 0.1473344, -0.5138592, -0.1631411, -0.4881402, 0.1278984, -0.1859565, 0.1973996, -0.06677416, 0.1179603, -0.3152324, ...
Autism and attention-deficit/hyperactivity disorder among individuals with a family history of alcohol use disorders.
Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we examine here whether the risks of autism and ADHD are increased among individuals with a family history of alcohol use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and 2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed.
25,139,954
[ -0.02925461, 0.01525975, -0.2343206, 0.1514175, 0.2346646, -0.09138241, -0.230754, 0.2707101, -0.1469421, 0.07606834, 0.2274673, 0.2897126, -0.05550411, 0.2000815, -0.1407148, 0.1470671, -0.3902639, 0.157981, 0.1285559, -0.3005451, 0.09077108, 0.3978541, -0.142342, -0.2...
Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis.
Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and are exquisitely sensitive to FGF signals. However, whether the EC or another vascular cell type requires FGF signaling during development, homeostasis, and response to injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), which results in deletion in endothelial and hematopoietic cells, is compatible with normal embryonic development. As adults, Fgfr1/2(Flk1-Cre) mice maintain normal blood pressure and vascular reactivity and integrity under homeostatic conditions. However, neovascularization after skin or eye injury was significantly impaired in both Fgfr1/2(Flk1-Cre) and Fgfr1/2(Tie2-Cre) mice, independent of either hematopoietic cell loss of FGFR1/2 or vascular endothelial growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired neovascularization was associated with delayed cutaneous wound healing. These findings reveal a key requirement for cell-autonomous EC FGFR signaling in injury-induced angiogenesis, but not for vascular homeostasis, identifying the EC FGFR signaling pathway as a target for diseases associated with aberrant vascular proliferation, such as age-related macular degeneration, and for modulating wound healing without the potential toxicity associated with direct manipulation of systemic FGF or VEGF activity.
25,139,991
[ -0.06001349, -0.4191341, -0.4336015, -0.4888296, 0.2231203, -0.02440134, 0.1967665, 0.1319801, 0.03495217, 0.1509981, 0.1656769, 0.06451069, -0.4277211, -0.09955929, -0.31756, -0.2020105, -0.08176778, 0.05942143, -0.137571, 0.1780382, 0.1044296, 0.04483474, -0.1938315, ...
Axl kinase as a key target for oncology: focus on small molecule inhibitors.
Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily, Axl regulates key processes such as cell growth, migration, aggregation, and apoptosis through several pathways. Its overexpression/overactivation has been underlined in several conditions, especially cancers, and in both chemotherapy and targeted therapy sensitivity loss. In this review, we propose to highlight the therapeutic implication of Axl, starting with the pathways it regulates, validating its interest as a therapeutic target, and defining the tools available to develop strategies for its inhibition. We especially focus on small molecule inhibitors, their structure, inhibition profile, and development stages.
25,139,999
[ -0.09175941, 0.1702943, 0.1818328, -0.3730756, -0.005579521, -0.1290016, 0.007156699, 0.1863366, -0.04350059, -0.03273912, 0.1021186, -0.006397299, -0.2690113, -0.1416304, -0.3278407, -0.01906895, -0.5464337, 0.2208586, -0.01727304, 0.1253771, 0.3320586, 0.235242, -0.2356...
Invincible DNA tethers: covalent DNA anchoring for enhanced temporal and force stability in magnetic tweezers experiments.
Magnetic tweezers are a powerful single-molecule technique that allows real-time quantitative investigation of biomolecular processes under applied force. High pulling forces exceeding tens of picoNewtons may be required, e.g. to probe the force range of proteins that actively transcribe or package the genome. Frequently, however, the application of such forces decreases the sample lifetime, hindering data acquisition. To provide experimentally viable sample lifetimes in the face of high pulling forces, we have designed a novel anchoring strategy for DNA in magnetic tweezers. Our approach, which exploits covalent functionalization based on heterobifunctional poly(ethylene glycol) crosslinkers, allows us to strongly tether DNA while simultaneously suppressing undesirable non-specific adhesion. A complete force and lifetime characterization of these covalently anchored DNA-tethers demonstrates that, compared to more commonly employed anchoring strategies, they withstand 3-fold higher pulling forces (up to 150 pN) and exhibit up to 200-fold higher lifetimes (exceeding 24 h at a constant force of 150 pN). This advance makes it possible to apply the full range of biologically relevant force scales to biomolecular processes, and its straightforward implementation should extend its reach to a multitude of applications in the field of single-molecule force spectroscopy.
25,140,010
[ -0.1379792, -0.03799162, -0.02455357, -0.004528012, 0.212536, -0.1514875, -0.1994787, 0.1588248, 0.1928469, 0.118758, -0.03136491, -0.139354, 0.1689893, -0.2652135, -0.7940022, 0.1043607, -0.4096979, 0.0361209, -0.4197132, 0.1620993, 0.4408761, -0.05587248, -0.2184453, ...
Open-mouthpiece ventilation versus nasal mask ventilation in subjects with COPD exacerbation and mild to moderate acidosis: a randomized trial.
Open mouthpiece ventilation is efficacious in patients with neuromuscular disease. We used this ventilation technique in patients with exacerbations of COPD with mild to moderate acidosis. The study was performed in 2 respiratory monitoring care units. Fifty subjects with exacerbations of COPD, breathing frequency > 25, PaCO2 > 45, and pH between 7.25 and 7.30, as well as Kelly scale ≤ 2 were enrolled. Subjects were randomly assigned to receive noninvasive ventilation (NIV) via nasal mask or mouthpiece ventilation. The primary outcome was improvement in arterial blood gases. Arterial blood gases and breathing frequency were recorded 2 h after the start of the enrollment and then after 12, 24, and 48 h. The duration of NIV, hospital stay, and acceptability of the interface (mouthpiece or nasal mask) using a Likert scale were assessed. No subjects had deterioration of gas exchange. The 2 groups had similar trends in arterial blood gases and breathing frequency. No differences in duration of NIV or hospital stay were noted. However, a significant difference in acceptability was found: subjects preferred mouthpiece ventilation (P < .01). Open mouthpiece ventilation is a useful technique and may prevent further deterioration of gas exchange in COPD patients with mild to moderate acidosis (similar to traditional NIV delivered by a nasal mask). www.chictr.org registration ChiCTR-TRC-12002672.
25,140,033
[ -0.06403997, -0.1462041, 0.1071824, 0.2322635, -0.06895944, 0.04553718, -0.04412456, 0.04348253, -0.3074674, -0.47022, -0.05281896, 0.02987159, 0.01215679, 0.01390703, 0.1160609, -0.3175149, -0.5419788, 0.06346475, 0.1641273, -0.3400742, -0.3091264, -0.07791829, 0.1786044...
Efficacy of cabazitaxel in mouse models of pediatric brain tumors.
There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.
25,140,037
[ -0.05499226, -0.1186165, -0.08941663, -0.6536084, 0.1863167, -0.1706678, -0.1013313, 0.1465088, -0.07125714, -0.08387518, 0.2665748, 0.5467045, 0.04987017, -0.1648287, -0.196702, 0.07041522, -0.4585834, 0.06701283, -0.1190784, 0.1754465, 0.4952768, 0.04001924, -0.1658545,...
Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events.
Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1S transcripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1S transcripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.
25,140,042
[ -0.1395296, -0.08654504, -0.04487852, -0.4357983, 0.09579176, 0.05291965, 0.0946155, 0.05301302, 0.1839798, 0.439224, 0.05604168, 0.4269165, -0.4642717, 0.08646559, 0.09312904, 0.04626984, -0.4339233, -0.0446248, 0.1231135, -0.3436809, 0.7369496, 0.3293516, 0.1395508, 0...
Assessing the performance of two lung age equations on the Australian population: using data from the cross-sectional BOLD-Australia study.
Lung age, a simple concept for patients to grasp, is frequently used as an aid in smoking cessation programs. Lung age equations should be continuously updated and should be made relevant for target populations. We observed how new lung age equations developed for Australian populations performed when utilizing the Burden of Obstructive Lung Disease (BOLD)-Australia dataset compared to more commonly used equations. Data from a cross-sectional population study of noninstitutionalized Australians aged ≥40 years with analysis restricted to Caucasians <75 years. Lung age calculated using equations developed by Newbury et al. and Morris and Temple was compared with chronological age by smoking status and within smoking status. There were 2,793 participants with a mean age of 57 (±10 SD) years. More than half (52%) ever smoked, and 10.4% were current smokers. Prevalence of chronic obstructive pulmonary disease stage I or higher was 13.4% (95% confidence interval = 12.2, 14.7). For both genders, newer Newbury equations estimated lung ages significantly higher than actual age across all smoking groups (p < .05). Morris and Temple equations resulted in lung age estimates significantly lower than chronological age for nonsmokers (p < .05) but no difference among current smokers. Both equations showed exposure to smoking had lung ages higher than never-smokers (p < .001). Lung age also increased with increased pack-years. This supports the use of updated equations suited to the population of interest. The Australian Newbury equations performed well in the BOLD-Australia dataset, providing more meaningful lung age profile compared to chronological age among smokers. Using equations not developed or ideally suited for our population is likely to produce misleading results.
25,140,044
[ 0.0240055, -0.1801576, -0.1432325, -0.05878006, -0.07061238, -0.2588598, 0.02998506, -0.200144, -0.01412411, 0.1186031, -0.2060838, 0.5048103, 0.05938994, 0.1393011, -0.07625096, -0.1140931, -0.134796, 0.03272872, -0.2123412, -0.1094555, -0.1274439, 0.475708, -0.1567461, ...
Effects of Low-intensity Pulsed Ultrasound and Cryotherapy on Recovery of Joint Function and C-reactive Protein Levels in Patients after Total Knee Replacement Surgery.
[Purpose] We investigated the effect of low-intensity pulsed ultrasound and cryotherapy on joint function recovery and C-reactive protein (CRP) levels of patients with total knee replacement. [Subjects] Forty-six patients with total knee replacement were recruited and allocated to either low-intensity pulsed ultrasound therapy (n=15), cryotherapy (n=15), or a combination of both (n=16). Therapy was administered once a day, 5 times a week for 3 weeks. To determine functional joint recovery and reduction of inflammation, changes in the Korean Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), range of motion (ROM), and CRP were assessed postsurgically and four times over a 3-week period. Using one-way analysis of variance (ANOVA), homogeneity tests were performed based on participants' general characteristics. To recognize changes in time-variant K-WOMAC, ROM, and CRP values between groups, repeated measures ANOVA was performed, and Tukey's test was used for post-test analysis. Values at α=0.05 were considered significant. [Results] We found a difference between groups and times, and the group that received the combined therapies showed greater changes in outcomes than the group that received low-intensity pulsed ultrasound therapy alone. [Conclusion] Applying both low-intensity pulsed ultrasound and cryotherapy can relieve inflammation and enhance joint function in patients who undergo total knee replacement.
25,140,090
[ 0.05170837, 0.04910457, -0.2977632, -0.2560107, 0.04489271, -0.3662457, -0.0235605, 0.257023, -0.08891034, -0.2021987, 0.3695616, 0.2161236, -0.2769945, -0.1429712, 0.2708327, -0.09425134, 0.1460737, 0.04272645, -0.1036498, 0.006683932, -0.3446306, 0.02744673, 0.0184287, ...
Peak torque and average power at flexion/extension of the shoulder and knee when using a mouth guard in adults with mild midline discrepancy.
[Purpose] This study was conducted to investigate the changes in torque and power during flexion and extension of the shoulder and the knee joints caused by midline correction using mouth guards made from different materials in adults with mild midline discrepancy. [Subjects] The subjects of this study were males (n=12) in their 20s who showed a 3-5 mm difference between the midlines of the upper and lower teeth but had normal masticatory function. [Methods] The torque and average power of the lower limb and upper limb were measured during flexion and extension according to various types of mouth guard. [Results] There were significant differences in relative torque and average power between three conditions (no mouth guard, soft-type mouth guard, and hard-type mouth guard) at shoulder flexion and extension. There were no significant differences in relative torque and average power between the three conditions at knee flexion and extension. [Conclusions] These results suggest that use of a mouth guard is a method by which people with a mild midline discrepancy can improve the stability of the entire body.
25,140,095
[ -0.05281454, 0.6565715, -0.008893925, -0.2238098, 0.07207378, -0.1599143, -0.1078344, -0.09477162, 0.01533796, -0.1154747, 0.0248958, -0.401302, 0.2654273, 0.4173564, -0.1733378, -0.01500298, -0.3711547, -0.08144874, -0.07568777, 0.1335171, 0.171651, -0.1676772, 0.2907131...
Tumor necrosis factor is a therapeutic target for immunological unbalance and cardiac abnormalities in chronic experimental Chagas' heart disease.
Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. To challenge the hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas' heart disease. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNγ levels; diminished the frequency of IL-17A(+) but increased IL-10(+) CD4(+) T-cells; reduced TNF(+) but augmented IL-10(+) Ly6C(+) and F4/80(+) cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNγ-producing VNHRFTLV-specific CD8(+) T-cells in spleen and reduced the number of perforin(+) cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. Our data support that TNF is a crucial player in the pathogenesis of Chagas' heart disease fueling immunological unbalance which contributes to cardiac abnormalities.
25,140,115
[ -0.02879579, 0.004238502, -0.199362, -0.3177672, 0.2955191, -0.1892646, 0.489816, 0.1093824, -0.05360678, 0.06039404, -0.07250516, 0.03772007, 0.07672931, -0.1426775, -0.5677382, -0.3149554, -0.2554888, -0.07606944, -0.1228129, 0.2752277, -0.06860198, 0.1924294, -0.301291...
Cell death-associated molecular-pattern molecules: inflammatory signaling and control.
Apoptosis, necroptosis, and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury, and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-κB multiprotein complexes. Current studies show that the nonprotein thiols and thiol-regulating enzymes as well as highly diffusible prooxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells.
25,140,116
[ -0.4708699, -0.1103462, 0.1674269, -0.02510281, -0.1128936, -0.2668988, -0.1955638, 0.2157046, 0.0855209, 0.3324334, -0.204584, 0.03954381, 0.04742521, 0.05632304, -0.5433998, 0.1291278, -0.368498, -0.2274794, 0.1176918, 0.04201715, 0.1851577, 0.239857, -0.2565743, -0.0...
Changes in complex spike activity during classical conditioning.
The cerebellar cortex is necessary for adaptively timed conditioned responses (CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause responses or "Purkinje cell CRs" to the conditioned stimuli (CS), resulting in disinhibition of the cerebellar nuclei (CN), allowing them to activate motor nuclei that control eyeblinks. This disinhibition also causes inhibition of the inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO, which relays the unconditional stimulus (US) to the cortex, elicits characteristic complex spikes in Purkinje cells. Although Purkinje cell activity, as well as stimulation of the CN, is known to influence IO activity, much remains to be learned about the way that learned changes in simple spike firing affects the IO. In the present study, we analyzed changes in simple and complex spike firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate ferrets undergoing training in a conditioning paradigm. In agreement with the N-O feedback hypothesis, acquisition resulted in a gradual decrease in complex spike activity during the conditioned stimulus, with a delay that is consistent with the long N-O latency. Also supporting the feedback hypothesis, training with a short interstimulus interval (ISI), which does not lead to acquisition of a Purkinje cell CR, did not cause a suppression of complex spike activity. In contrast, observations that extinction did not lead to a recovery in complex spike activity and the irregular patterns of simple and complex spike activity after the conditioned stimulus are less conclusive.
25,140,129
[ -0.05615217, 0.07556815, -0.1853822, -0.2321142, 0.2571886, -0.4121102, 0.2678841, -0.08383831, 0.1731575, 0.09660076, -0.2727211, 0.2262303, -0.05277725, -0.5509983, -0.1098995, -0.07632715, -0.3627875, -0.002688992, -0.0573651, -0.002988747, 0.04476137, 0.08659291, 0.05...
Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds.
In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain.
25,140,130
[ -0.1082018, 0.0003815194, -0.1749448, -0.3064485, 0.2093815, -0.5126872, -0.02110678, -0.2660874, -0.2413713, 0.04848656, 0.01445032, 0.1526169, 0.132164, -0.06798834, -0.5474876, -0.2764663, -0.4458451, 0.118976, -0.2015561, 0.003724297, -0.08738089, 0.1244476, -0.149658...
Changes in scalp potentials and spatial smoothing effects of inclusion of dura layer in human head models for EEG simulations.
The dura layer which covers the brain is less conductive than the CSF (cerebrospinal fluid) and also more conductive than the skull bone. This could significantly influence the flow of volume currents from cortex to the scalp surface which will also change the magnitude and spatial profiles of scalp potentials. This was examined with a 3-D finite element method (FEM) model of an adult subject constructed from 192 segmented axial magnetic resonance (MR) slices with 256×256 pixel resolution. The voxel resolution was 1×1×1 mm. The model included the dura layer. In addition, other major tissues were also identified. The electrical conductivities of various tissues were obtained from the literature. The conductivities of dura and CSF were 0.001 S/m and 0.06 S/m, respectively. The electrical activity of the cortex was represented by 144,000 distributed dipolar sources with orientations normal to the local cortical surface. The dipolar intensity was in the range of 0.0-0.4 mA meter with a uniform random distribution. Scalp potentials were simulated for two head models with an adaptive finite element solver. One model had the dura layer and in the other model, dura layer was replaced with the CSF. Spatial contour plots of potentials on the cortical surface, dural surface and the scalp surface were made. With the inclusion of the dura layer, scalp potentials decrease by about 20%. The contours of gyri and sulci structures were visible in the spatial profiles of the cortical potentials which were smoothed out on the dural surface and were not visible on the scalp surface. These results suggest that dura layer should be included for an accurate modeling of scalp and cortical potentials.
25,140,148
[ -0.1498991, 0.04295593, 0.01641237, 0.145699, -0.1742358, -0.3226254, -0.2324189, -0.322403, -0.01743648, 0.1750797, -0.171586, 0.00507193, -0.08745886, 0.2059656, -0.4817714, -0.109083, -0.3921565, 0.07460616, -0.2898743, 0.06105226, -0.04095357, 0.1271693, 0.30933, -0...
Phonological and lexical influences on phonological awareness in children with specific language impairment and dyslexia.
Children with dyslexia and/or specific language impairment have marked deficits in phonological processing, putting them at an increased risk for reading deficits. The current study sought to examine the influence of word-level phonological and lexical characteristics on phonological awareness. Children with dyslexia and/or specific language impairment were tested using a phoneme deletion task in which stimuli differed orthogonally by sound similarity and neighborhood density. Phonological and lexical factors influenced performance differently across groups. Children with dyslexia appeared to have a more immature and aberrant pattern of phonological and lexical influence (e.g., favoring sparse and similar features). Children with SLI performed less well than children who were typically developing, but followed a similar pattern of performance (e.g., favoring dense and dissimilar features). Collectively, our results point to both quantitative and qualitative differences in lexical organization and phonological representations in children with SLI and in children with dyslexia.
25,140,161
[ -0.02252862, 0.3716658, -0.001094032, 0.06226335, 0.3138603, -0.2364738, -0.369339, -0.1686954, 0.2779367, -0.06465694, 0.1712385, 0.1317337, -0.3894132, -0.2655633, -0.1717514, 0.08824644, -0.3504563, 0.1778188, -0.1670071, -0.1730802, 0.4506809, 0.2655984, 0.1162594, ...
Multidrug resistance: an emerging crisis.
The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistance mechanisms and decrease in efficiency of treating common infectious diseases, it results in failure of microbial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as "super bugs." Although the development of MDR is a natural phenomenon, the inappropriate use of antimicrobial drugs, inadequate sanitary conditions, inappropriate food-handling, and poor infection prevention and control practices contribute to emergence of and encourage the further spread of MDR. Considering the significance of MDR, this paper, emphasizes the problems associated with MDR and the need to understand its significance and mechanisms to combat microbial infections.
25,140,175
[ -0.351333, -0.2284646, -0.01730537, -0.1355236, 0.01863454, -0.1428621, -0.2123557, 0.1663727, -0.08693393, -0.1868881, 0.01018732, -0.02176948, -0.1413996, 0.4819433, -0.4813589, -0.2300418, -0.2014886, 0.09119361, 0.2134871, -0.03371785, -0.2060203, 0.1290984, -0.200103...
Navigating diabetes-related immune epitope data: resources and tools provided by the Immune Epitope Database (IEDB).
The Immune Epitope Database (IEDB), originally focused on infectious diseases, was recently expanded to allergy, transplantation and autoimmunity diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We utilize a combined tutorial and meta-analysis format, which demonstrates how common questions, related to diabetes epitopes can be answered. A total of 409 references are captured in the IEDB describing >2,500 epitopes from diabetes associated antigens. The vast majority of data were derived from GAD, insulin, IA-2/PTPRN, IGRP, ZnT8, HSP, and ICA-1, and the experiments related to T cell epitopes and MHC binding far outnumbers B cell assays. We illustrate how to search by specific antigens, epitopes or host. Other examples include searching for tetramers or epitopes restricted by specific alleles or assays of interest, or searching based on the clinical status of the host. The inventory of all published diabetes epitope data facilitates its access for the scientific community. While the global collection of primary data from the literature reflects potential investigational biases present in the literature, the flexible search approach allows users to perform queries tailored to their preferences, including or excluding data as appropriate. Moreover, the analysis highlights knowledge gaps and identifies areas for future investigation.
25,140,192
[ -0.007133382, -0.6534938, -0.3121199, 0.1186409, -0.06329972, -0.1247583, 0.1562652, 0.2589601, 0.155979, 0.05419474, 0.2984441, -0.1543437, 0.09804072, -0.2320344, -0.2788444, -0.1154812, -0.3796647, 0.2275992, 0.005051522, 0.1028771, 0.008767567, 0.3226241, -0.0128029, ...
Isolated dissection of the superior mesenteric artery treated using open emergency surgery.
Isolated dissection of the superior mesenteric artery (IDSMA) remains a rare diagnosis. However, new diagnostic means such as computed tomography makes it possible to detect even asymptomatic patients. If patients present symptomatic on admission, the risk of bowel infarction makes immediate therapy necessary. Today, endovascular techniques are often successfully used; however, open surgery remains important for special indications. In this paper, we present two cases with IDSMA and show why open surgical repair is still important in current treatment concepts. Two cases with ISDMA that presented in our department from January 1, 2014 to June 1, 2014 are described. Data collection was performed retrospectively. Additionally, a review of articles which reported small cases series on patients with IDSMA within the past five years is provided. Both patients underwent open surgical repair following interdisciplinary consultation. Both patients were transferred to the intensive care unit after surgical repair and needed bowel rest, nasogastric suction and intravenous fluid therapy. CT scans were performed within the first week after operation. Platelet aggregation inhibitors were used in both cases as postoperative medication. Both patients survived and are able to participate in everyday activities. Open surgical repair remains important in cases of anatomic variants of visceral arteries and suspected bowel infarction. Therefore, it is important that knowledge about open surgical techniques still be taught and trained.
25,140,196
[ -0.5029052, 0.2050976, -0.277911, -0.4456626, 0.1540767, -0.1375612, 0.007408213, -0.2787749, -0.02069785, 0.2043949, 0.3338286, -0.2244201, -0.02929466, -0.5243506, -0.3914301, 0.1445091, -0.294805, -0.3407303, -0.1367576, 0.3930544, 0.2622949, -0.009522491, 0.1491383, ...
Use of Martius flap in the complex female urethral surgery.
Objectives were to evaluate safety and patient reported perception of the Martius fibroadipose flap for complex female urethra reconstruction. Patients operated with a Martius flap were contacted again via telephone to rate their self-perception on cosmetic appearance, pain or numbness of the flap harvest site. 37 women (mean age of 46.8 yrs.) were operated with Martius flaps. Complications were limited to bleeding from the flap bed in 19% (7/37); hematomas - 5.4% (2/37); and lymphorrhea from the labial incision in 13.5% (5/37) and labial wound infection in 5.4% of cases (2/37). For self-perception 65% of patients (24/37) were phone interviewed (mean follow up - 54.2 months). Only 17% of women (4/24) complained to cosmetic problems. Two patients (8%) complained to a periodical mild pain. And 12.5% (3/24) of the women had decreased sensation or numbness at the labia. Martius flap is safe and it is not causing significant complications during female urethral reconstruction. However, an informed consent for decreased sensation and numbness at the flap harvesting area should be obtained.
25,140,241
[ 0.07803399, -0.2395842, -0.1679653, -0.1883215, -0.24986, -0.5232323, -0.06477178, -0.007907555, 0.02510938, -0.01603653, 0.2120206, -0.04552122, -0.0266873, 0.003638122, -0.2376516, -0.2612107, -0.174944, -0.0136283, -0.03710565, -0.1819371, 0.303653, 0.3368219, -0.09751...
Knowledge and perception on long acting and permanent contraceptive methods in adigrat town, tigray, northern ethiopia: a qualitative study.
Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice.
25,140,252
[ 0.0326626, 0.1791963, 0.03438661, -0.01322523, 0.4155072, -0.1652089, -0.03932893, -0.2392413, 0.07485157, -0.05924092, 0.07516993, 0.008398085, -0.04074921, 0.2031363, -0.2296487, 0.164589, -0.3492476, 0.07137462, -0.4468529, -0.1811509, 0.1844705, 0.08913219, -0.0608356...
High Steroid Sensitivity among Children with Nephrotic Syndrome in Southwestern Nigeria.
Recent reports from both Caucasian and black populations suggest changes in steroid responsiveness of childhood nephrotic syndrome. This study was therefore undertaken to determine the features and steroid sensitivity pattern of a cohort of black children with nephrotic syndrome. Records of children managed for nephrotic syndrome from January 2008 to April 2013 were reviewed. Details including age, response to treatment, and renal histology were analysed. There were 108 children (median age: 5.9 years, peak: 1-2 years), 90.2% of whom had idiopathic nephrotic syndrome. Steroid sensitivity was 82.8% among children with idiopathic nephrotic syndrome but 75.9% overall. Median time to remission was 7 days. Median age was significantly lower in steroid sensitive compared with resistant patients. The predominant histologic finding in resistant cases was focal segmental glomerulosclerosis (53.3%). No cases of quartan malaria nephropathy or hepatitis B virus nephropathy were diagnosed. Overall mortality was 6.5%. In conclusion, unusually high steroid sensitivity is reported among a cohort of black children. This is likely attributable to the lower age structure of our cohort as well as possible changing epidemiology of some other childhood diseases. Surveillance of the epidemiology of childhood nephrotic syndrome and corresponding modifications in practice are therefore recommended.
25,140,253
[ 0.2269618, 0.3269593, -0.1683246, -0.1784991, -0.02313548, -0.1737461, 0.2163911, -0.05519268, 0.215018, 0.1100208, 0.04891573, -0.2073975, 0.1180243, 0.181262, -0.238241, -0.4109998, 0.08785237, 0.3027802, 0.2132735, 0.2340397, 0.170105, 0.1572698, -0.2439095, -0.01352...
Pleomorphic adenomas of the parapharyngeal space.
Background. Parapharyngeal space is one of potential facial planes for neoplasms and infections and represents less than 1% of all head and neck tumours. Occurrence of the pleomorphic adenoma in the parapharyngeal space is a rarity. Case Presentation. Here, three giant pleomorphic adenomas of different sizes occupying the parapharyngeal space in three patients are reported. Extensive preoperative diagnostic workup was done in order to verify the nature and size of the tumour and the proximity to the large vessels. Review of the literature, clinical features, pathology, radiological findings, and treatment of these tumours are discussed. Conclusion. The excision of the tumor through submandibular transcervical approach, without cutting the mandible, turned out to be a safe and radical approach in all three cases.
25,140,265
[ -0.3829855, -0.1951528, -0.3903022, -0.5141338, -0.09691732, -0.4248579, -0.2459693, -0.1109577, -0.08499335, 0.1074502, 0.2504659, -0.19956, -0.1766863, -0.3753379, -0.2249689, -0.1419432, -0.3910219, 0.09310605, -0.01274706, -0.08469547, 0.2272481, 0.1200539, -0.0803198...
Comparison of generalist predators in winter-flooded and conventionally managed rice paddies and identification of their limiting factors.
Winter-flooding of rice paddies without the application of agricultural chemicals is attracting attention as a new agricultural method for enhancing the habitat conditions of wintering waterfowl in rice paddy ecosystems throughout Japan and east Asia. Conditions in these paddies are expected to result in restoration of not only the winter habitats of waterfowl but also those of other taxonomic groups during the rice growing season. In this study, we tested whether the diversity of summer spiders--ubiquitous predators in rice paddies--was higher in the winter-flooded paddies than in the conventional ones by conducting field measurements in 31 winter-flooded and 7 conventional paddies. Limiting factors of spiders in the winter-flooded paddies were then examined. Results revealed that both the density and species richness of spiders were significantly higher in the winter-flooded paddies than in the conventional ones both before and after the insecticide application against pecky rice bug Stenotus rubrovittatus (Matsumura)(Hemiptera: Miridae) to conventional paddies. In addition, spider density and species richness in the winter-flooded paddies correlated with the availability of two prey groups--chironomids and other nematocera. These findings suggest that in the winter-flooded paddies the diversity of generalist predators is higher than in the conventional ones during the rice-growing season and that the combination of management at both the landscape and field level is likely more effective for increasing spider abundance in winter-flooded paddies.
25,140,294
[ 0.1088406, 0.3935308, 0.2543198, -0.287592, -0.120849, -0.1982327, 0.01179151, -0.1853474, 0.2543443, 0.003429065, -0.07768182, -0.1180298, 0.1067884, 0.03671646, -0.2310194, 0.02139252, -0.3961107, 0.450202, 0.1632957, 0.03582441, -0.3945065, 0.2600691, -0.07364377, -0...
Trimodality therapy for bladder preservation in the elderly population with invasive bladder cancer.
Bladder cancer is considered as primarily a disease of the elderly, typically aged in their 70s or 80s and often with associated medical comorbidities. Unfortunately, fewer elderly patients receive radical treatment for muscle-invasive bladder cancer (MIBC) that their younger counterparts. Over the last decades, several studies have shown that the use of trimodality therapy consisting of transurethral bladder resection followed by concomitant chemotherapy and radiation therapy results in comparable outcomes to radical cystectomy, considered the gold standard for this disease. In this review, we revised the literature on bladder-preservation treatments using the trimodality approach in the elderly population with MIBC.
25,140,295
[ -0.2466201, 0.0865567, -0.1072462, -0.3336858, 0.05538882, -0.3743935, -0.1250608, -0.1721794, -0.04560744, 0.03764908, 0.03137751, 0.2607612, -0.06239535, -0.04231065, -0.3581527, -0.3109392, -0.01846956, 0.2213545, -0.248426, -0.3317961, -0.1149056, 0.2870881, 0.0068792...
Self-Medication Practices among a Sample of Latino Migrant Workers in South Florida.
Although the literature on self-medication among Latino migrant workers (LMWs) is sparse, a few existing studies indicate that this practice is common in this community. The purpose of this paper is to estimate health status, access to health care, and patterns of self-medication practices of a cohort of LMWs in South Florida. A stratified network-based sample was utilized to recruit 278 LMWs in the Homestead area. After screening for eligibility, participants were administered a structured questionnaire that collected data on their health status, access to health care services, and self-medication practices. A convenience sample of 24 LMWs, who participated in the parent study were invited back to participate in 3 focus groups to look more in depth into self-medication practices in the LMW community. Study findings indicate that LMWs are affected by a vast array of health problems yet lack access to health care services. Participants already engaged in self-medication practices in the countries of origin and, upon their arrival in the US, these practices continue and, in many cases, increase. Long-held traditions and lack of access to the formal health care system in the US contribute to the high prevalence of self-medication among LMWs. Self-medication practices such as the use of prescription medications without a prescription and lay injection are high risk practices that can have harmful consequences. Prevention interventions that address self-medication in the LMW community are likely to be most effective if they are culturally adapted to the community and facilitate access to health care services.
25,140,297
[ -0.08196893, 0.3046461, -0.07680455, -0.1650966, 0.2275002, -0.3077106, -0.2308751, 0.3253377, -0.0892785, -0.2580974, 0.1271443, -0.237565, -0.03807964, -0.5101189, 0.05207419, 0.2445179, -0.223678, 0.331094, 0.2048439, -0.03439903, 0.1245984, 0.2253196, -0.1008792, 0....
Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in Hemagglutinin Gene in H1N1 Subtype of Influenza A Virus.
It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. Influenza A virus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenza A viruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenza A virus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences were A redundant with most codons preferring nucleotide A over others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus.
25,140,301
[ -0.08410434, 0.1873792, -0.06664768, 0.06581516, 0.1441826, -0.227455, 0.08055736, -0.09441727, 0.1765869, -0.1059568, -0.2214475, -0.2601429, 0.1124194, 0.2486399, -0.2204563, -0.09016924, 0.05824009, 0.003076685, 0.1025338, -0.1799051, 0.315968, 0.2028232, -0.3566422, ...
The antileukemia activity of natural product HQ17(3) is possibly associated with downregulation of miR-17-92 cluster.
The compound 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)] was purified from the sap of the lacquer tree Rhus succedanea. HQ17(3) has cytotoxic effect on cancer cells and can inhibit topoisomerase (topo) IIα activity. We treated various cancer cells with different doses of HQ17(3) and found that leukemia cells were most sensitive to HQ17(3). After analysis of microRNA (miRNA) profiling, we found that treatment with HQ17(3) caused downregulation of miR-17-92 cluster in some leukemia cells. These changes partially restored the normal levels from leukemia-specific miRNA expression signature. Messenger RNAs of tumor suppressor proteins, such as pRB, PTEN, and Dicer, are targets of miR-17-92 cluster. Their protein levels were increased after the treatment. c-Myc is a regulatory protein for miR-17-92 gene. Similar to topo IIα, we found that c-Myc decreased its activity after the HQ17(3) treatment, which may explain the downregulation of miR-17-92 cluster. Combined with 5-fluorouracil, NaAsO2, or ABT-737, HQ17(3) elicited additive inhibitory effects on leukemia cells. In conclusion, the high sensitivity of leukemia cells to HQ17(3) may be associated with the reduction of topo IIα and c-Myc activities, as well as with the downregulation of the miR-17-92 cluster expression.
25,140,305
[ -0.0576275, 0.1483921, 0.2065432, 0.2454001, 0.2493713, -0.01337796, -0.1515823, 0.06600698, 0.4686821, 0.1796982, 0.3729215, 0.1914141, -0.05561743, 0.07352608, -0.3952329, -0.2525298, -0.218347, 0.3548853, 0.09448992, 0.2429612, 0.7863902, 0.4032967, 0.04392305, -0.00...
The nonglycemic actions of dipeptidyl peptidase-4 inhibitors.
A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.
25,140,306
[ -0.1658677, -0.399641, -0.2949059, -0.04774445, -0.09667542, -0.07067677, 0.3178782, 0.288997, 0.1640132, -0.04522463, 0.02293124, -0.323718, -0.2468188, -0.1046954, -0.3332722, -0.1367072, -0.3090853, 0.1737664, 0.03692095, 0.1573026, -0.05882074, 0.2343738, -0.09610791,...
Treatment of bilateral varicocele and other scrotal comorbidities using a single scrotal access: our experience on 34 patients.
Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities.
25,140,311
[ 0.3827667, 0.09218939, -0.02582628, -0.2835529, 0.1323918, -0.3125711, -0.2751388, -0.06850456, -0.2628318, -0.09830413, 0.3385044, 0.3392719, -0.2707368, -0.1492142, -0.01429226, -0.2871701, -0.3847559, 0.02883358, 0.4083095, -0.6187471, -0.1409936, -0.009137502, -0.2999...
Effect of prenatal polycyclic aromatic hydrocarbons exposure on birth outcomes: the Polish mother and child cohort study.
The aim of this study was to assess the impact of PAH exposure on various anthropometric measures of birth outcomes. The study population consisted of 210 nonsmoking pregnant women. Urine samples collected between 20th and 24th week of pregnancy were used for analysis of the following PAH metabolites: 1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene (1-, 2-, 3-, 4-, and 9-OH-PHE), 1-hydroxypyrene (1-OH-PYR), 1,6 + 1,8-dihydroxypyrene (DI-OH-PYR), phenanthrene trans-1,2-dihydrodiol (PHE-1,2-diol), and phenanthrene trans-9,10-dihydrodiol (PHE-9,10-diol) by gas chromatography-mass spectrometry. Environmental tobacco smoke exposure (ETS) was assessed by cotinine level in saliva using a stable isotope dilution LC-ESI-MS/MS method. The mean PAH metabolite concentrations were in the range of 0.15 µg/g creatinine for 9-OH-PHE to 5.9 µg/g creatinine for PHE-9,10-diol. It was shown that none of the individual PAH exposure markers demonstrate a statistically significant influence on birth outcomes. Interestingly a statistically significant association was found between the sum of OH-PHE along with cotinine level and the cephalization index after adjusting for potential confounders (P = 0.04). This study provides evidence that combined exposure of pregnant women to common environmental pollutants such as PAH and ETS might adversely affect fetal development. Thus, reduction of human exposure to these mixtures of hazardous compounds would in particular result in substantial health benefits for newborns.
25,140,312
[ 0.05794369, 0.1114499, -0.2102024, 0.4865104, 0.0682718, -0.2056226, -0.2926612, -0.007792563, 0.1784045, 0.3557566, 0.03765681, -0.06725755, 0.01097811, -0.25222, -0.5956156, -0.04719946, -0.1960559, 0.3699921, 0.1514798, 0.09427012, -0.1097732, 0.4319478, -0.3045902, ...
On the coupling of two models of the human immune response to an antigen.
The development of mathematical models of the immune response allows a better understanding of the multifaceted mechanisms of the defense system. The main purpose of this work is to present a scheme for coupling distinct models of different scales and aspects of the immune system. As an example, we propose a new model where the local tissue inflammation processes are simulated with partial differential equations (PDEs) whereas a system of ordinary differential equations (ODEs) is used as a model for the systemic response. The simulation of distinct scenarios allows the analysis of the dynamics of various immune cells in the presence of an antigen. Preliminary results of this approach with a sensitivity analysis of the coupled model are shown but further validation is still required.
25,140,313
[ -0.01177396, -0.307481, -0.1742639, 0.1992339, 0.1128136, -0.3416631, 0.02905876, 0.2339883, 0.2553075, 0.04774489, -0.1346243, -0.3061399, 0.01259015, 0.005740994, -0.5593444, -0.3517671, -0.4845238, -0.08070923, -0.1496184, 0.3184487, 0.1997634, 0.06429369, -0.1206343, ...
Autophagy in alcohol-induced multiorgan injury: mechanisms and potential therapeutic targets.
Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy.
25,140,315
[ -0.278299, -0.2161174, -0.1091303, -0.2016687, 0.01210923, -0.1973198, -0.2440389, -0.001018137, -0.1826434, 0.2007626, 0.1212103, -0.04114909, -0.01041611, 0.04911138, -0.3023401, 0.1677937, -0.5116416, -0.06107712, -0.05415006, -0.07580205, -0.1679227, 0.4976916, -0.184...
Screening of cognitive function and hearing impairment in older adults: a preliminary study.
Previous research has found that hearing loss is associated with poorer cognitive function. The question is that when a hearing impairment is being compensated for by appropriately fitted monaural hearing aids, special precautions are still needed when screening cognitive function in older adults. This research examined cognitive function in elderly hearing aid users who used monaural hearing aids and whether the presence of a hearing impairment should be accounted for when screening cognitive function in these individuals. Auditory thresholds, sentence reception thresholds, and self-reported outcomes with hearing aids were measured in 34 older hearing aid users to ensure hearing aids were appropriately fitted. Mini-Mental State Examination (MMSE) results obtained in these participants were then compared to normative data obtained in a general older population exhibiting similar demographic characteristics. Stepwise multiple regression analyses were used to examine the effects of demographic and auditory variables on MMSE scores. Results showed that, even with appropriately fitted hearing aids, cognitive decline was significant. Besides the factors commonly measured in the literature, we believed that auditory deprivation was not being fully compensated for by hearing aids. Most importantly, screening of cognitive function should take into account the effects of hearing impairment, even when hearing devices have been appropriately fitted.
25,140,321
[ 0.03815107, 0.1731475, 0.2483402, -0.1062376, -0.01562376, -0.2113573, -0.4662967, -0.03347624, 0.1224401, -0.07483937, 0.2875189, -0.02736236, -0.0522572, 0.2079599, 0.04951008, 0.2622995, -0.4386151, 0.03004133, -0.4599802, -0.2875075, -0.05545804, 0.002273089, 0.307259...
Approach to the patient: transgender youth: endocrine considerations.
Compelling studies have demonstrated that "gender identity"--a person's inner sense of self as male, female, or occasionally a category other than male or female--is not simply a psychosocial construct, but likely reflects a complex interplay of biological, environmental, and cultural factors. An increasing number of preadolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"--ie, the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including the use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender-dysphoric in early or middle childhood and who still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"--clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender." Studies have shown that such distress may be ameliorated by a "gender-affirming" model of care. Although endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development, many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a disorder of sex development. The goals of this article are to review studies that shed light on the biological underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth.
25,140,398
[ -0.1851496, 0.131371, -0.2444964, -0.3267061, 0.001289205, -0.04444857, -0.1920617, 0.1080088, 0.1625281, -0.06770288, -0.07715476, 0.02563893, -0.2191837, -0.3095231, -0.2223381, 0.02687583, -0.1791847, 0.3032514, 0.01881345, -0.1613969, 0.05894534, 0.1903552, -0.3783584...
An active oscillator model describes the statistics of spontaneous otoacoustic emissions.
Even in the absence of external stimulation, the cochleas of most humans emit very faint sounds below the threshold of hearing, sounds that are known as spontaneous otoacoustic emissions. They are a signature of the active amplification mechanism in the cochlea. Emissions occur at frequencies that are unique for an individual and change little over time. The statistics of a population of ears exhibit characteristic features such as a preferred relative frequency distance between emissions (interemission intervals). We propose a simplified cochlea model comprising an array of active nonlinear oscillators coupled both hydrodynamically and viscoelastically. The oscillators are subject to a weak spatial disorder that lends individuality to the simulated cochlea. Our model captures basic statistical features of the emissions: distributions of 1), emission frequencies; 2), number of emissions per ear; and 3), interemission intervals. In addition, the model reproduces systematic changes of the interemission intervals with frequency. We show that the mechanism for the preferred interemission interval in our model is the occurrence of synchronized clusters of oscillators.
25,140,416
[ -0.1628149, 0.0301421, -0.1885641, 0.02774056, 0.03723503, -0.460245, -0.5424196, -0.0570366, 0.402649, -0.2283663, -0.124405, 0.03132182, -0.2001742, -0.1935466, 0.09131841, 0.1779523, -0.5109583, 0.01526657, -0.08885915, -0.2077319, 0.1788996, 0.126358, -0.03505844, 0...
Membrane interactions of phylloseptin-1, -2, and -3 peptides by oriented solid-state NMR spectroscopy.
Phylloseptin-1, -2, and -3 are three members of the family of linear cationic antimicrobial peptides found in tree frogs. The highly homologous peptides encompass 19 amino acids, and only differ in the amino acid composition and charge at the six most carboxy-terminal residues. Here, we investigated how such subtle changes are reflected in their membrane interactions and how these can be correlated to their biological activities. To this end, the three peptides were labeled with stable isotopes, reconstituted into oriented phospholipid bilayers, and their detailed topology determined by a combined approach using (2)H and (15)N solid-state NMR spectroscopy. Although phylloseptin-2 and -3 adopt perfect in-plane alignments, the tilt angle of phylloseptin-1 deviates by 8° probably to assure a more water exposed localization of the lysine-17 side chain. Furthermore, different azimuthal angles are observed, positioning the amphipathic helices of all three peptides with the charged residues well exposed to the water phase. Interestingly, our studies also reveal that two orientation-dependent (2)H quadrupolar splittings from methyl-deuterated alanines and one (15)N amide chemical shift are sufficient to unambiguously determine the topology of phylloseptin-1, where quadrupolar splittings close to the maximum impose the most stringent angular restraints. As a result of these studies, a strategy is proposed where the topology of a peptide structure can be determined accurately from the labeling with (15)N and (2)H isotopes of only a few amino acid residues.
25,140,425
[ -0.006239741, 0.2610744, -0.2129343, -0.05018127, -0.2816593, 0.016322, 0.2277849, 0.11723, 0.4184727, 0.1544987, -0.02256401, 0.07502618, -0.05972396, 0.07249157, -0.4926276, -0.2751259, -0.5453928, 0.250869, -0.2447832, 0.06413471, 0.2819, 0.1246698, -0.1694781, -0.18...
Temperature and electrolyte optimization of the α-hemolysin latch sensing zone for detection of base modification in double-stranded DNA.
The latch region of the wild-type protein pore α-hemolysin (α-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the α-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12-35°C) and KCl concentration (0.15-1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ∼ 8 kJ mol(-1) decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ∼ 2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes.
25,140,427
[ -0.1293849, -0.2579916, -0.2063964, 0.103814, 0.08772822, -0.03937616, 0.000765387, 0.05778413, 0.3323717, -0.1893259, -0.01464914, 0.02644568, -0.07874168, -0.08681115, -0.3444849, -0.35484, -0.7152808, -0.3393015, -0.1725721, 0.0693296, 0.5375953, 0.3016326, -0.2835864,...
Azobenzene photoisomerization-induced destabilization of B-DNA.
Molecular photoswitches provide a promising way for selective regulation of nanoscaled biological systems. It has been shown that conformational changes of azobenzene, one of the widely used photoswitches, can be used to reversibly control DNA duplex formation. Here, we investigate the conformational response of DNA upon azobenzene binding and isomerization, using a threoninol linker that has been experimentally investigated recently. To this end, nonequilibrium molecular dynamics simulations are carried out using a switching potential describing the photoinduced isomerization. Attachment of azobenzene leads to a distortion of the DNA helical conformation that is similar for the trans and cis forms. However, the trans form is stabilized by favorable stacking interactions whereas the cis form is found to remain flipped out of the basepair-stacked position. Multiple azobenzene attachment augments the distortion in DNA helical conformation. The distorted DNA retains nativelike pairing of bases at ambient temperatures, but shows weaker basepairing compared to native DNA at an elevated temperature.
25,140,428
[ -0.2055755, 0.0308603, -0.2240081, 0.0941348, 0.3060807, -0.1632556, -0.4232356, 0.2334362, 0.206027, 0.06176684, -0.03449702, 0.08895741, 0.1962831, 0.1301581, -0.5797561, 0.02050301, -0.7060918, -0.04637917, -0.2546747, 0.1314268, 0.4103973, 0.1487346, -0.3152566, -0....
Cucurbitane glycosides derived from mogroside IIE: structure-taste relationships, antioxidant activity, and acute toxicity.
Mogroside IIE is a bitter triterpenoid saponin which is the main component of unripe Luo Han Guo fruit and a precursor of the commercially available sweetener mogroside V. In this study, we developed an enzymatic glycosyl transfer method, by which bitter mogroside IIE could be converted into a sweet triterpenoid saponin mixture. The reactant concentration, temperature, pH and buffer system were studied. New saponins with the α-glucose group were isolated from the resulting mixtures, and the structures of three components of the extract were determined. The structure-taste relationships of these derivatives were also studied together with those of the natural mogrosides. The number and stereoconfiguration of glucose groups present in the mogroside molecules were found to be the main factor to determine the sweet or bitter taste of a compound. The antioxidant and food safety properties were initially evaluated by their radical scavenging ability and via 7 day mice survival tests, respectively. The results showed that the sweet triterpenoid saponin mixture has the same favorable physiological and safety characteristics as the natural mogrosides.
25,140,446
[ -0.04189152, 0.04064086, -0.1673959, 0.1901714, 0.2578379, -0.1901504, 0.1229623, 0.1593111, 0.3161364, 0.04894578, -0.1043755, -0.06451578, 0.01776805, -0.07608334, -0.3913671, 0.23288, -0.6381586, 0.2718306, 0.1119623, 0.3139976, 0.04903175, 0.362386, -0.1073637, -0.1...
Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system.
Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes.
25,140,455
[ -0.3862228, 0.4471347, -0.08709402, -0.02731489, 0.04857308, -0.23971, -0.4365895, -0.1126759, 0.3236361, 0.2635627, 0.07761782, -0.3785069, 0.0390747, 0.08700183, -0.1967856, 0.1728178, -0.0374487, 0.08409772, 0.5615734, -0.03743816, 0.1079293, 0.2001997, -0.1459928, -...
Analysis of transit time flow of the right internal thoracic artery anastomosed to the left anterior descending artery compared to the left internal thoracic artery.
We evaluated with transit time flow the performance of the right and left thoracic arteries when used as a graft for the left anterior descending artery. Fifty patients undergoing surgery for myocardial revascularization without cardiopulmonary bypass were divided into two groups. In group A patients received graft of right internal mammary artery to the anterior interventricular branch. In group B patients received graft of left internal mammary artery to the same branch. At the end of the operation the flow was assessed by measuring transit time. In group A, mean age was 60.6 ± 9.49 years. The average height and weight of the group was 80.4 ± 10.32 kg and 169.2 ± 6.86 cm. The average number of grafts per patient in this group was 3.28 ± 1.49. The mean flow and distal resistance obtained in right internal thoracic artery was 42.1 ± 23.4 ml/min and 2.8 ± 0.9 respectively. In group B, the mean age was 59.8 ± 9.7 years. The average height and weight of this group was 77.7 ± 14.22 kg and 166.0 ± 8.2 cm. The average number of grafts per patient in this group was 3.08 ± 0.82. The mean flow and distal resistance observed in this group was 34.2 ± 19.1 ml/min and 2.0 ± 0.7. There were no deaths in this series. Right internal mammary artery presented a similar behavior to left internal mammary artery when anastomosed to the anterior interventricular branch of the left coronary artery. There was no statistical difference between the measured flow obtained between both arteries.
25,140,463
[ -0.182552, -0.268971, -0.4120128, -0.3687135, -0.1198213, -0.1817391, 0.2393004, -0.2956493, -0.3208902, 0.0292347, 0.1388604, 0.1811974, -0.4108693, -0.305987, -0.02959819, -0.1873642, -0.3492515, 0.152015, -0.03553697, 0.02724997, 0.5051827, 0.1757107, 0.09004437, 0.2...
Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate.
Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental model, considering the caspase markers, IL-8 and KI-67. Twenty male Wistar rats were anesthetized and heparinized. The chest was opened, the heart was withdrawn and 40 ml/kg of cardioplegia (with histidine-tryptophan-cetoglutarate or histidine-tryptophan-glutamate solution) was infused. The hearts were kept for 2 hours at 4ºC in the same solution, and thereafter placed in the Langendorff apparatus for 30 min with Ringer-Locke solution. Analyzes were performed for immunohistochemical caspase, IL-8 and KI-67. The fractal dimension and Shannon entropy were not different between groups histidine-tryptophan-glutamate and histidine-tryptophan-acetoglutarate. The amount of information measured by Shannon entropy and the distribution thereof (given by fractal dimension) of the slices treated with histidine-tryptophan-cetoglutarate and histidine-tryptophan-glutamate were not different, showing that the histidine-tryptophan-glutamate solution is as good as histidine-tryptophan-acetoglutarate to preserve myocytes in isolated rat heart.
25,140,464
[ 0.103341, 0.1074672, -0.171848, 0.2657374, 0.1240195, -0.5027446, 0.1207055, 0.01028547, -0.04796848, -0.3209925, -0.08649657, 0.7746717, -0.05699254, 0.1177386, -0.3489703, 0.1224072, -0.08687535, 0.03824316, -0.02260289, 0.3971252, 0.05721452, 0.3691642, -0.2341311, 0...
Comparative analysis of the patency of the internal thoracic artery in the CABG of left anterior descending artery: 6-month postoperative coronary CT angiography evaluation.
To assess the patency of the pedicled right internal thoracic artery with an anteroaortic course and compare it to the patency of the left internal thoracic artery , in anastomosis to the left anterior descending artery in coronary artery bypass grafting by using coronary CT angiography at 6 months postoperatively. Between December 2008 and December 2011, 100 patients were selected to undergo a prospective coronary artery bypass grafting procedure without cardiopulmonary bypass. The patients were randomly divided by a computer-generated list into Group-1 (G-1) and Group-2 (G-2), comprising 50 patients each, the technique used was known at the beginning of the surgery. In G-1, coronary artery bypass grafting was performed using the left internal thoracic artery for the left anterior descending and the free right internal thoracic artery for the circumflex, and in G-2, coronary artery bypass grafting was performed using the right internal thoracic artery pedicled to the left anterior descending and the left internal thoracic artery pedicled to the circumflex territory. The groups were similar with regard to the preoperative clinical data. A male predominance of 75.6% and 88% was observed in G-1 and G-2, respectively. Five patients migrated from G-1 to G-2 because of atheromatous disease in the ascending aorta. The average number of distal anastomoses was 3.48 (SD=0.72) in G-1 and 3.20 (SD=0.76) in G-2. Coronary CT angiography in 96 re-evaluated patients showed that all ITAs, right or left, used in situ for the left anterior descending were patent. There were no deaths in either group. Coronary artery bypass grafting surgery involving anastomosis of the anteroaortic right internal thoracic artery to the left anterior descending artery has an outcome similar to that obtained using the left internal thoracic artery for the same coronary site.
25,140,469
[ -0.1060492, 0.354939, -0.4583636, -0.3397095, -0.03789615, -0.1760376, -0.02156119, -0.2992977, -0.120164, 0.03648601, 0.04372565, -0.1376659, -0.1278445, -0.02706207, -0.03276018, -0.09865853, -0.5572842, -0.03420426, 0.02157887, 0.09026799, 0.2844571, 0.3019251, -0.0945...
Probiotics protect the intestinal wall of morphological changes caused by malnutrition.
This study sought to morphometrically analyze the jejunal wall of protein-malnourished rats administered a probiotic supplement. The sample consisted of recently weaned Wistar rats (Rattus norvegicus) distributed among four groups: animals given a commercial diet (G1, n = 4); animals given the same ration as G1 plus a probiotic supplement (G2, n = 4); animals given a 4% protein diet (G3, n = 4); and animals given the same ration as G3 plus a probiotic supplement (G4, n = 4). After 12 weeks, part of the jejunum was harvested and subjected to routine histological processing. Transverse sections with a thickness of 3 µm were stained with HE, and histochemical techniques were used to assay for glycoconjugates, including staining with periodic acid-Schiff (PAS) + diastase, Alcian Blue (AB) solution at pH 2.5, and Alcian Blue solution at pH 1.0. Morphometric analysis of the bowel wall showed that the probiotic culture used in this study induced hypertrophy of several layers of the jejunal wall in well-nourished animals and reduced the bowel wall atrophy usually observed in protein-malnourished animals. Neither malnutrition nor the use of probiotics altered the relationship between the number of goblet cells and the number of enterocytes.
25,140,504
[ -0.01621192, -0.5729076, 0.1562358, 0.2380578, 0.1220141, 0.01735586, 0.3306998, 0.06467091, 0.2970832, -0.2586856, 0.06498478, 0.007551588, -0.1231903, 0.07064608, -0.07763891, 0.1865186, -0.3094746, 0.1503875, -0.02906743, -0.09743878, -0.3406171, 0.1504691, -0.107944, ...
Re-induction of desiccation tolerance after germination of Cedrela fissilis Vell. seeds.
This work aimed to characterize the re-induction of desiccation tolerance (DT) in germinated seeds, using polyethylene glycol (PEG 8000). Cell changes were investigated through cytological assays (cell viability and transmission electronic microscopy) as well as DNA integrity during loss and re-establishment of DT. The loss of DT was characterized by drying germinated seeds with different radicle lengths (1, 2, 3, 4 and 5 mm) in silica gel, decreasing the moisture content to ten percentage points intervals, followed by pre-humidification (100% RH / 24 h) and rehydration. To re-induce DT, germinated seeds were treated for 72 h with PEG (-2.04 MPa) and PEG (-2.04 MPa) + ABA (100 µM) before dehydration. Germinated seeds did not tolerate desiccation to 10% moisture content, irrespectively of the radicle length. However, when incubated in PEG, those with 1 and 2 mm long radicle attained 71% and 29% survival, respectively. The PEG+ABA treatment was efficient to re-establish DT in seeds with 1 mm long radicles (100% survival). The ultrastructural assays of the cells of germinated seeds with 2 and 5 mm length confirmed the obtained physiological results. Germinated seeds of C. fissilis constitute a useful tool for desiccation tolerance investigations.
25,140,505
[ 0.1806721, 0.04050387, 0.3294507, -0.01142009, 0.1802647, -0.2589436, -0.1975028, -0.3038834, 0.180779, 0.1560812, -0.02465262, 0.3710174, -0.2471713, -0.2271859, -0.5431934, -0.1786919, 0.1337137, 0.2129788, -0.1126641, 0.1066387, -0.005887614, 0.2773988, -0.01377286, ...
An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features.
Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD) from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI). The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC) using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous, this approach could stratify the large amount of data rapidly and could be combined with more detailed subsequent analyses based on non-linear transformation.
25,140,532
[ -0.1156562, 0.4899568, 0.1725308, -0.1999545, 0.07652672, -0.2651166, -0.04779711, 0.05170847, 0.271449, 0.09865575, -0.1669055, 0.023236, 0.159215, -0.05000024, -0.4294143, 0.3479514, -0.01479351, 0.2770115, -0.1160404, -0.07709164, -0.1514178, 0.09323075, -0.132201, -...
Detection of a right carotid focus of 18F-FDG predicted an ischemic stroke.
A 60-year-old woman was referred into our department for staging of an endometrial carcinoma. In addition to peritoneal and nodes metastases, F-FDG PET/CT showed a calcified plaque of the right carotid with focal uptake. One month later, the patient presented left hemiparesis, suggesting a right hemisphere stroke. MRI confirmed frontal infarction in the anterior cerebral artery territory. F-FDG is suggested to be a valuable tool to detect vessel wall inflammation; detection of focal arterial uptake on PET/CT suggests unstable plaque and requires urgent patient's management to prevent vascular events in a population already weakened by both disease and therapy.
25,140,539
[ -0.148024, 0.373118, -0.2457967, -0.2993193, -0.00420398, -0.3829856, -0.003877177, -0.1613307, -0.1043709, 0.09661531, -0.1165749, 0.04927663, -0.111746, -0.3335925, -0.02070097, -0.2166882, -0.3479016, 0.4478056, -0.1871993, 0.05841459, -0.1233438, 0.1577474, -0.2848303...
CT, MRI, and 18F-FDG PET/CT in a patient with nested stromal epithelial tumor of the liver.
An 11-year-old girl presented with abnormal weight gain and was found to have hepatomegaly. MRI of the abdomen revealed a 20-cm hepatic mass. F-FDG PET/CT showed a large hypermetabolic calcified hepatic mass and couple of mildly hypermetabolic pulmonary nodules with associated intrathoracic lymphadenopathy. Liver biopsy was consistent with nested stromal epithelial tumor of the liver, a rare nonhepatocytic, nonbiliary primary neoplasm of the liver associated with variable calcification and ossification.
25,140,542
[ -0.2951794, -0.007800479, -0.3001373, -0.1658096, 0.04967083, -0.3059555, -0.2670029, -0.09223922, 0.03980704, 0.1499574, 0.161553, 0.03793904, -0.2174698, 0.133098, -0.6755765, -0.006276643, -0.412628, -0.002560992, 0.09828603, 0.07154389, -0.2758775, 0.2295198, -0.26969...
Sister Mary Joseph Nodules on 99mTc HYNIC-TOC scintigraphy in patients with neuroendocrine tumors.
A Sister Mary Joseph nodule represents an umbilical metastasis, which is more commonly caused by a primary malignancy in gastrointestinal tract or from reproductive system. We report Sister Mary Joseph nodules caused by neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy.
25,140,559
[ 0.05101822, -0.2954133, 0.1208425, -0.5762459, 0.04869156, -0.1163614, -0.2562248, -0.2963676, 0.4296359, 0.2058969, 0.02396788, 0.3676814, 0.08672133, 0.00363686, -0.4910811, -0.26487, -0.5177971, 0.07367808, 0.5108491, -0.3371643, 0.4459813, 0.1827995, -0.2189319, 0.1...
The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease.
Platelets of patients with sickle cell disease (SCD) show evidence of mild activation in the non-crisis steady state and greater activation during vaso-occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet activation and aggregation, may be useful in attenuating VOC. We compared platelet responses to ADP stimulation in patients with SCD and healthy subjects before and after treatment with prasugrel. In a phase 1 study, platelet biomarker levels were assessed in 12 adult patients with SCD and 13 healthy subjects before and after 12 ± 2 days of 5.0 or 7.5 mg/day prasugrel. The following were determined in whole blood samples stimulated with 20 µM ADP: (i) percentages of monocytes and neutrophils with adherent platelets (cell-platelet aggregates); (ii) the relative number (mass) of platelets associated with each monocyte and neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte-platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets positive for surface expression of CD40 ligand (CD40L), P-selectin (CD62p) and activated glycoprotein IIb-IIIa (GPIIb-IIIa); and (iv) the percentages of platelets and monocyte-platelet aggregates positive for surface tissue factor (TF) expression. At baseline, there were no significant differences between cohorts in the percentages of platelets expressing activation biomarkers. Following 12 days of prasugrel administration, the percentages of platelets expressing activation biomarkers following ADP stimulation were reduced in both cohorts, and there were no significant differences between groups. Both patients with SCD and healthy subjects had significant reductions in the monocyte-platelet and neutrophil-platelet aggregate MFI and the percentage of platelets expressing P-selectin and activated GPIIb-IIIa (all p < 0.05). Healthy subjects also had significant reductions in monocyte-platelet aggregate percentages (p = 0.004), neutrophil-platelet aggregate percentages (p = 0.011) and the percentage of CD40L-positive platelets (p = 0.044) that were not observed in patients with SCD. Prasugrel administration to SCD patients attenuates ex vivo ADP-stimulated platelet activation as measured by the percentage of platelets positive for P-selectin and GPIIb-IIIa, thus reducing the proportion of platelets that may participate in aggregates. Furthermore, prasugrel decreases ex vivo ADP-stimulated platelet aggregation with monocytes and neutrophils as measured by the monocyte-platelet and neutrophil-platelet aggregate MFI. This implies that in the presence of prasugrel, fewer platelets adhere to monocytes and neutrophils, which may result in reducing cell-platelet aggregate size. Therefore, reduced platelet reactivity and decreased size of leukocyte-platelet aggregates suggest additional mechanisms by which prasugrel may provide benefit to patients with SCD and support further investigation of possible therapeutic benefits of prasugrel in this population.
25,140,584
[ -0.02165546, 0.170597, -0.02034336, -0.2653655, 0.1831792, -0.4076478, 0.2150334, 0.1054187, -0.0575311, -0.3276693, -0.2329072, 0.1004854, -0.1842404, -0.3431541, -0.1728026, -0.2566389, -0.2183953, -0.03692327, 0.1314748, 0.5891897, 0.08160507, 0.3419647, -0.2317716, ...
Impact of lifetime psychiatric diagnosis on long-term retention and survival of former opiate addicts in methadone maintenance treatment.
To characterize lifetime psychiatric diagnosis groups among methadone maintenance treatment (MMT) patients and associations of diagnosis to long-term (up to 20 years) retention and survival either during treatment or post discontinuation. A total of 758 patients with available psychiatric diagnosis (98% of those ever admitted between June 1993 and June 2012) were followed-up until June 2013. Lifetime psychiatric diagnosis was assessed according to DSM-IV-TR (Axis I, II, I & II, or none). Observed urine samples at 1 and 13 months were positive for drugs if at least one was positive. Survival data were based on the Israel National Population Registry. Survival and retention in MMT were compared (Kaplan Meier) between groups. The Axis II (personality disorders) group had the worst mean long-term retention (5.8 years, 95% Confidence Interval (CI) 5.0-6.5) compared with the Axis I, Axis I & II or no psychiatric diagnosis groups (9.6 years, 95% CI 8.8-10.4) (P < 0.0005). Mean survival since admission (16.4 years, 95% CI 15.9-16.9) was similar for all groups. Axis II patients included more males, more drug injectors, were younger at initial opiate use and more likely left treatment before 1 year. Personality and coping mechanisms (Axis II) could be significant obstacles to the success of MMT, warranting special interventions to overcome them.
25,140,586
[ 0.09071406, -0.0623585, 0.01729231, -0.3746412, 0.1297954, -0.3486911, -0.1591002, -0.083836, -0.1932393, -0.02136659, 0.06783142, 0.2879247, 0.1291688, 0.3897339, -0.2613944, -0.1246433, -0.01922249, 0.2225387, 0.04523568, -0.125333, -0.07603709, 0.07254335, -0.1977924, ...
The establishment and evaluation of rabbit model for peripherally inserted central catheter.
To establish a model to simulate the clinical specific process of peripherally inserted central catheter (PICC) on rabbits, and detect how long the catheter can be indwelled. Seventeen healthy New Zealand white rabbits were inserted the PICC according to the clinical specific procedure. With the principle of random, the rabbits were divided into four groups (14d, 21d, 28d, 35d). Each group contains four rabbits, and Group 1 was served as blank control group. When finishing the experiment, we took the blood vessels which was inserted the catheter and observed the changes of vascular endothelium using the Hematoxylin-Eosin (HE) staining. 90% animals were succeeded in inserting PICC. Early signs of endovascular inflammation were predominantly neutrophils, then mainly monocytes, visible fibrous tissue hyperplasia of the vessel wall, vascular endothelial proliferation and granuloma formation. And after that the irreversible changes in the blood vessels could be observed, especially five weeks after catheterization. We have succeeded in establishing the rabbit model for peripherally inserted central catheter, and provided a new way for nursing teaching and training. Since the irreversible changes of the vascular endothelium, it is recommended that the time of indwelling is not more than five weeks on animal.
25,140,590
[ 0.1562397, 0.3568638, -0.1887274, 0.2471585, 0.3359379, -0.08195863, 0.1615502, 0.04016708, -0.111142, 0.06249688, 0.1904982, -0.1769972, -0.2502274, -0.2691855, -0.1728219, -0.3179591, -0.5482028, 0.5285082, -0.2215901, 0.2672957, -0.08283541, 0.6122152, 0.2593811, -0....
Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus.
To evaluate bladder histology in healing and biochemical analysis of rats with single kidney in ischemia/reperfusion, treated with tacrolimus. Fifty rats randomized into five groups. Three rats died in surgery, 47 rats divided in groups: Control (non-operated, n=10), Sham (operated without drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus 0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was: laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy followed by bladder suture. After that, rats were submited to gavage daily (Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses already mentioned). On the 14th day, after death induction, cystectomy was performed and bladder was histologicaly analysed. The serum urea, creatinine and tacrolimus were analysed too. There was difference in serum tacrolimus in T3 compared to the other groups (p<0.05). There was higher doses of creatinine in T3 group and higher urea in groups with tacrolimus. There were significant differences among all histologic variables comparing groups with and without tacrolimus (p<0.05). Tacrolimus associated with ischemia/reperfusion is nephrotoxic, suppresses inflammation and seems to delay the healing bladder.
25,140,592
[ 0.1707115, 0.08663552, 0.0840207, -0.327445, 0.2428264, -0.5087596, -0.2210066, -0.1426363, 0.1634993, -0.2775866, 0.07638548, -0.1158918, -0.1681715, -0.1096284, -0.4445659, -0.1719549, 0.05673302, -0.1065932, 0.1455126, 0.210585, -0.3502332, 0.2270561, -0.2128088, 0.0...
A Cu(II) complex of an imidazolium-based ionic liquid: synthesis, X-ray structure and application in the selective electrochemical sensing of guanine.
An imidazolium-based ionic liquid containing a carboxylic acid group was synthesized and complexed with Cu(II). The resulting complex R1 was fully characterized using various techniques, including IR spectroscopy and X-ray crystallography. Binding studies of the complex R1 were performed with anions and biomolecules using cyclic voltammetry, which showed no change in its voltammogram upon the addition of various anions and most biomolecules. However, a shift in the reduction peak from +0.20 to -0.15 was observed upon the addition of guanine. This selective determination of guanine by R1 was extended by using R1 as an electrochemical sensor for guanine in various voltammetric techniques, including cyclic voltammetry, LSV and DPV. The proposed sensor showed excellent reproducibility and high selectivity and sensitivity towards guanine, with a linear range of 0-20 μM and a detection limit of 45 nM.
25,140,610
[ 0.1229241, -0.03858337, -0.02289413, -0.1287329, 0.3851574, 0.06768481, -0.3919116, 0.01486385, 0.1197917, 0.06685665, -0.1546572, 0.1693763, -0.05470985, 0.236976, -0.5644252, -0.2667958, -0.3690666, 0.2475892, -0.0504614, 0.2577805, 0.277649, -0.06683337, -0.08994717, ...
Transparent metallic fractal electrodes for semiconductor devices.
Nanostructured metallic films have the potential to replace metal oxide films as transparent electrodes in optoelectronic devices. An ideal transparent electrode should possess a high, broadband, and polarization-independent transmittance. Conventional metallic gratings and grids with wavelength-scale periodicities, however, do not have all of these qualities. Furthermore, the transmission properties of a nanostructured electrode need to be assessed in the actual dielectric environment provided by a device, where a high-index semiconductor layer can reflect a substantial fraction of the incident light. Here we propose nanostructured aluminum electrodes with space-filling fractal geometries as alternatives to gratings and grids and experimentally demonstrate their superior optoelectronic performance through integration with Si photodetectors. As shown by polarization and spectrally resolved photocurrent measurements, devices with fractal electrodes exhibit both a broadband transmission and a flat polarization response that outperforms both square grids and linear gratings. Finally, we show the benefits of adding a thin silicon nitride film to the nanostructured electrodes to further reduce reflection.
25,140,611
[ -0.04354398, 0.202861, -0.06053412, -0.002415665, 0.005283449, -0.1240304, -0.2006688, -0.1028775, -0.02059183, 0.0006888198, -0.14094, -0.1358905, -0.05295934, 0.04549987, -0.3650154, -0.08314948, -0.696282, 0.01014081, -0.1645585, -0.2097484, 0.1064843, -0.05152759, -0....
Facile surface functionalization of hydrophobic magnetic nanoparticles.
Nonpolar phase synthesized hydrophobic nanocrystals show attractive properties and have demonstrated prominent potential in biomedical applications. However, the preparation of biocompatible nanocrystals is made difficult by the presence of hydrophobic surfactant stabilizer on their surfaces. To address this limitation, we have developed a facile, high efficiency, single-phase and low-cost method to convert hydrophobic magnetic nanoparticles (MNPs) to an aqueous phase using tetrahydrofuran, NaOH and 3,4-dihydroxyhydrocinnamic acid without any complicated organic synthesis. The as-transferred hydrophilic MNPs are water-soluble over a wide pH range (pH = 3-12), and the solubility is pH-controllable. Furthermore, the as-transferred MNPs with carboxylate can be readily adapted with further surface functionalization, varying from small molecule dyes to oligonucleotides and enzymes. Finally, the strategy developed here can easily be extended to other types of hydrophobic nanoparticles to facilitate biomedical applications of nanomaterials.
25,140,614
[ -0.1709944, 0.2251828, 0.1270893, -0.007166805, -0.02291629, -0.06546357, -0.2215228, 0.1559535, 0.1421945, 0.1271978, -0.08806663, 0.003620898, -0.001803624, -0.1032925, -0.6087832, 0.03230134, -0.5203183, 0.1444854, -0.1041025, 0.1268289, 0.164884, 0.04978776, -0.336992...
Association between peripheral arterial disease and C-reactive protein in the Japanese-Brazilian population.
To evaluate the relationship between peripheral arterial disease and elevated levels of C-reactive protein in the Japanese-Brazilian population of high cardiovascular risk. We conducted a cross-sectional study derived from a population-based study on the prevalence of diabetes and associated diseases in the Japanese-Brazilian population. One thousand, three hundred and thirty individuals aged e" 30 underwent clinical and laboratory examination, including measurement of ultrasensitive C-reactive protein. The diagnosis of peripheral arterial disease was performed by calculating the ankle-brachial index. We considered with peripheral arterial disease patients who had ankle-brachial index d" 0.9. After applying the exclusion criteria, 1,038 subjects completed the study. The mean age of the population was 56.8 years; 46% were male. The prevalence of peripheral arterial disease was 21%, with no difference between genders. Data analysis showed no association between peripheral arterial disease and ultrasensitive C-reactive protein. Patients with ankle-brachial index d" 0.70 showed higher values of ultrasensitive C-reactive protein and worse cardiometabolic profile. We found a positive independent association of peripheral arterial disease with hypertension and smoking. The association between low levels of ankle-brachial index and elevated levels of ultrasensitive C-reactive protein may suggest a relationship of gravity, aiding in the mapping of high-risk patients.
25,140,647
[ -0.1809263, 0.01550345, 0.09882408, 0.1585229, -0.220874, -0.2742246, -0.1699738, 0.1140028, 0.01522875, -0.1526142, -0.09717043, -0.3138653, 0.1070537, -0.2131177, 0.00948886, -0.1426143, -0.07232091, 0.1248, 0.01007434, -0.05488397, -0.2743919, -0.01303491, -0.01379269,...
Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia.
To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volume-controlled ventilator. Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation. BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N- groups could be successfully ventilated using a tidal volume of 75 ìl, but the failure of ventilation in the CDH group decreased only when ventilated with 50 ìl. Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology.
25,140,649
[ 0.01821944, 0.2846439, -0.2533576, -0.1090751, 0.3894551, -0.3591653, 0.03019466, -0.4320803, 0.1407643, -0.1135675, 0.1530208, 0.1013409, -0.1110674, -0.2349903, -0.1142838, -0.137649, -0.264787, 0.2929578, -0.2606177, 0.08674558, -0.2970151, 0.1251013, -0.01912602, 0....
Surgical treatment of cleft lip.
We performed a systematic review of the literature on the surgical treatment of cleft lip, emphasizing the prevalence, complications associated with the treatment and the points of disagreement between authors. We conducted a literature cross-sectional search that analyzed publications in books, articles and on the databases SciELO - Scientific Electronic Library Online, PubMed, of the National Center for Biotechnology Information. We conclude that: 1) the severity of the cleft will indicate the technique presenting more advantages; 2) the different approaches indicate that there is no consensus on the optimal technique; and 3) the surgeon experience contributes to choosing the best option.
25,140,654
[ 0.02915444, -0.2296979, 0.1866578, -0.1845181, -0.1243627, -0.1741313, -0.4232987, -0.326351, 0.2399574, -0.1824633, 0.3220521, -0.0367899, -0.1860184, -0.2201648, -0.2759093, -0.3087385, -0.03184964, -0.1194932, -0.07428872, -0.1262765, 0.1467829, 0.2507066, -0.3409063, ...
Four-arm single docking full robotic surgery for low rectal cancer: technique standardization.
The authors present the four-arm single docking full robotic surgery to treat low rectal cancer. The eight main operative steps are: 1- patient positioning; 2- trocars set-up and robot docking; 3- sigmoid colon, left colon and splenic flexure mobilization (lateral-to-medial approach); 4-Inferior mesenteric artery and vein ligation (medial-to-lateral approach); 5- total mesorectum excision and preservation of hypogastric and pelvic autonomic nerves (sacral dissection, lateral dissection, pelvic dissection); 6- division of the rectum using an endo roticulator stapler for the laparoscopic performance of a double-stapled coloanal anastomosis (type I tumor); 7- intersphincteric resection, extraction of the specimen through the anus and lateral-to-end hand sewn coloanal anastomosis (type II tumor); 8- cylindric abdominoperineal resection, with transabdominal section of the levator muscles (type IV tumor). The techniques employed were safe and have presented low rates of complication and no mortality.
25,140,655
[ -0.1093222, -0.1178166, -0.1030207, -0.1809202, -0.06108022, -0.4194657, -0.3216527, -0.2488562, 0.08545169, -0.03190148, 0.1417673, -0.1113114, -0.02614564, -0.2497548, -0.2564536, 0.05564564, -0.6508808, 0.01427789, -0.1747004, -0.1412143, -0.3075139, 0.2631085, -0.1691...
Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms.
Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.
25,140,675
[ -0.1005917, 0.08772244, 0.02167619, -0.407358, -0.1003955, -0.3660456, -0.3131213, 0.0337138, 0.1170604, -0.07787675, 0.03508344, -0.0666194, -0.3442224, -0.3047785, -0.209989, 0.002280218, -0.279489, 0.1201373, -0.07231905, -0.1425819, 0.3204744, 0.03364312, -0.1647472, ...
Synergistic effect of viral load and alcohol consumption on the risk of persistent high-risk human papillomavirus infection.
This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection. Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated. Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05-8.18) and 2-year persistence (OR 8.08, CI 2.36-27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05) and 2-year persistence (OR 6.61, CI 2.09-20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75 or OR 2.05, CI 0.87-4.83) and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR 4.14, CI 1.18-14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63). The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.
25,140,695
[ 0.01241845, -0.0141052, -0.2879185, 0.06450938, 0.02588291, -0.3898773, -0.4228515, -0.04884749, 0.3766643, 0.04341944, -0.03950763, 0.2774317, -0.2818233, 0.07451531, 0.0502706, -0.2970474, -0.05189113, 0.2348389, 0.4074029, -0.2191282, 0.05158392, 0.2430345, 0.0709128, ...
Extent of mangrove nursery habitats determines the geographic distribution of a coral reef fish in a South-Pacific archipelago.
Understanding the drivers of species' geographic distribution has fundamental implications for the management of biodiversity. For coral reef fishes, mangroves have long been recognized as important nursery habitats sustaining biodiversity in the Western Atlantic but there is still debate about their role in the Indo-Pacific. Here, we combined LA-ICP-MS otolith microchemistry, underwater visual censuses (UVC) and mangrove cartography to estimate the importance of mangroves for the Indo-Pacific coral reef fish Lutjanus fulviflamma in the archipelago of New Caledonia. Otolith elemental compositions allowed high discrimination of mangroves and reefs with 83.8% and 98.7% correct classification, respectively. Reefs were characterized by higher concentrations of Rb and Sr and mangroves by higher concentrations of Ba, Cr, Mn and Sn. All adult L. fulviflamma collected on reefs presented a mangrove signature during their juvenile stage with 85% inhabiting mangrove for their entire juvenile life (about 1 year). The analysis of 2942 UVC revealed that the species was absent from isolated islands of the New Caledonian archipelago where mangroves were absent. Furthermore, strong positive correlations existed between the abundance of L. fulviflamma and the area of mangrove (r = 0.84 for occurrence, 0.93 for density and 0.89 for biomass). These results indicate that mangrove forest is an obligatory juvenile habitat for L. fulviflamma in New Caledonia and emphasize the potential importance of mangroves for Indo-Pacific coral reef fishes.
25,140,697
[ 0.2339277, 0.004546463, 0.2299968, -0.1649304, -0.1921678, -0.2126417, -0.112555, 0.126177, 0.3562883, -0.09492029, -0.1460959, -0.0165754, -0.2465097, -0.3344848, -0.3943619, -0.3772135, -0.3348679, 0.4777642, 0.3365822, -0.004004225, 0.3776281, 0.1047593, -0.08449753, ...
Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.
Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.
25,140,699
[ -0.05014134, -0.001847289, -0.2520309, -0.2214458, 0.1291714, -0.5246484, 0.1664985, -0.3165797, -0.1129618, -0.03087802, -0.06082636, 0.02801117, -0.002734166, -0.486198, -0.2525457, -0.1369465, -0.342828, 0.1682872, -0.0213061, -0.4256961, -0.2936863, 0.04013249, -0.248...
Antimicrobial activity and synergism of lactoferrin and lysozyme against cariogenic microorganisms.
The present study evaluated the antimicrobial in vitro effects of the salivary proteins lactoferrin and lysozyme on microorganisms involved in the carious process, obtaining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Streptococcus mutans (ATCC 25175) and Lactobacillus casei (ATCC 7469) were submitted to broth macrodilution of lysozyme at 80 mg/mL and lactoferrin at 200 mg/mL. The tubes were read in a spectrophotometer after they had been incubated at 37 °C for 18 h, in a carbon dioxide chamber, in order to read the MIC. A new subculture was carried on agar plates to obtain the MBC. The agar diffusion method was also tested, using BHI agar with 100 µL of the standardized microbial inocula. Filter-paper disks soaked in 10 µL of the solutions lactoferrin (200 µg/mL) and lysozyme (80 µg/mL) were placed on the agar surface. Inhibition halos were not observed on the plates, showing the absence of the antimicrobial effects of these proteins in this method. The bactericidal and bacteriostatic effects of lysozyme on L. casei were 50.3 mg/mL and 43.1 mg/mL respectively. The bactericidal and bacteriostatic effects on S. mutans were 68.5 mg/mL and 58.7 mg/mL. Lactoferrin did not induce any inhibitory effects on any microorganism, even in the concentration of 200 mg/mL. There was not a synergic antimicrobial effect of proteins, when they were tested together, even in the concentration of 42.8 mg/mL of lysozyme and 114 mg/mL of lactoferrin (the highest values evaluated). S. mutans and L. casei were only inhibited by lysozyme, not affected by lactoferrin and by the synergic use of both proteins.
25,140,723
[ -0.1176113, 0.08863547, 0.2889492, 0.1990728, -0.1980415, 0.08305705, -0.5243731, -0.2556158, 0.4477828, -0.4964019, -0.03582912, 0.2605516, -0.5405204, -0.1409931, 0.2512134, 0.04840855, -0.2865063, -0.4190496, -0.1193327, -0.1682122, 0.177974, 0.2376571, 0.294196, 0.4...
Anteroposterior and vertical changes in skeletal class II patients treated with modified Thurow appliance.
The aim of this study was to evaluate the post-treatment anteroposterior and vertical alterations in skeletal Class II malocclusion with different maxillary patterns in patients treated with modified Thurow appliance. Forty-five patients (22 girls and 23 boys) with skeletal Class II and angle SN.GoGn ≤ 35 and different maxillary patterns (n = 15), as follows: retrusive (SNA<80°), normal (SNA = 80°- 84°) or protrusive (SNA>84°) maxilla; mean age 9 years at pre-treatment (T1) and 9 years and 10 months at post-treatment (T2), were treated with modified Thurow cervical traction appliance, with expander screw and extraoral face bow with 10° to 20° fold in relation to the intraoral arch. Force of 500 gf was applied and use for 12 to 14 h/day, with fortnightly adjustments. Analysis of variance ANOVA followed by post-hoc Tukey and Kruskal-Wallis test, followed by Mann-Whitney were used (α = 5%). In changes obtained from stage T1 to T2, no statistically significant differences were found among the groups Protrusive, normal and retrusive maxilla for the variables SNB, SN.GoGn, 1.NA, overjet, overbite and Class II discrepancy (right and left) (p>0.05). Angular measurements SNA and ANB in the protrusive maxilla group were significantly greater than in the normal and retrusive maxilla groups (p<0.01). However, in the normal maxilla group these values did not differ significantly from those of the retrusive maxilla group (p>0.05). Within the limits of this study, it may be concluded that the modified Thurow cervical traction appliance was efficient for the correction of skeletal Class II irrespective of the maxillary pattern. The mandible had no significant rotation during treatment.
25,140,724
[ 0.05543697, 0.1666122, -0.2864203, -0.4273256, 0.04875576, -0.2563555, -0.1461363, -0.257366, -0.1189077, -0.1818855, -0.00969184, -0.2787196, -0.3076211, -0.3967773, -0.5870757, -0.2175303, 0.05703092, 0.1211249, -0.3043617, -0.1456615, 0.009580976, 0.1021559, -0.3661512...
Properties of lignin, cellulose, and hemicelluloses isolated from olive cake and olive stones: binding of water, oil, bile acids, and glucose.
A process based on a steam explosion pretreatment and alkali solution post-treatment was applied to fractionate olive stones (whole and fragmented, without seeds) and olive cake into their main constitutive polymers of cellulose (C), hemicelluloses (H), and lignin (L) under optimal conditions for each fraction according to earlier works. The chemical characterization (chromatographic method and UV and IR spectroscopy) and the functional properties (water- and oil-holding capacities, bile acid binding, and glucose retardation index) of each fraction were analyzed. The in vitro studies showed a substantial bile acid binding activity in the fraction containing lignin from olive stones (L) and the alkaline extractable fraction from olive cake (Lp). Lignin bound significantly more bile acid than any other fraction and an amount similar to that bound by cholestyramine (a cholesterol-lowering, bile acid-binding drug), especially when cholic acid (CA) was tested. These results highlight the health-promoting potential of lignin from olive stones and olive cake extracted from olive byproducts.
25,140,731
[ 0.111971, 0.3493334, 0.02686115, 0.08718856, -0.03683693, -0.1447202, -0.002234263, -0.02971495, 0.2417869, 0.04801713, -0.04184324, -0.01558216, -0.1919405, -0.1376685, -0.3760679, 0.2677204, -0.5934213, 0.1147294, -0.006673785, -0.004061244, 0.4170813, -0.0128317, -0.05...
Plasmonic imaging of electrochemical oxidation of single nanoparticles.
Measuring electrochemical activities of nanomaterials is critical for creating novel catalysts, for developing ultrasensitive sensors, and for understanding fundamental nanoelectrochemistry. However, traditional electrochemical methods measure a large number of nanoparticles, which wash out the properties of individual nanoparticles. We report here a study of transient electrochemical oxidation of single Ag nanoparticles during collision with an electrode and voltammetry of single nanoparticles immobilized on the electrode using a plasmonic-based electrochemical current microscopy. This technique images both electrochemical reaction and size of the same individual nanoparticle, enabling quantitative examination of size-dependent electrochemical activities at single nanoparticle level. The imaging capability further allows detection of the reaction kinetics of each individual nanoparticle and analysis of the average behaviors of multiple nanoparticles. The average kinetics and size dependence can be accurately described by the Tafel equation, but there is a large variability between different nanoparticles, which underscores the importance of single nanoparticle analysis.
25,140,732
[ 0.03975105, 0.0579528, -0.1125488, -0.04597508, 0.05940033, 0.03464079, -0.385421, -0.1878534, 0.1545553, 0.06285389, -0.149359, 0.01215271, -0.138935, -0.05684657, -0.1671103, 0.09400829, -0.3985061, 0.07505981, 0.116068, -0.003130697, -0.1315535, 0.04599831, -0.03819399...
Enhancement of open-circuit voltage and the fill factor in CdTe nanocrystal solar cells by using interface materials.
Interface states influence the operation of nanocrystal (NC) solar cell carrier transport, recombination and energetic mechanisms. In a typical CdTe NC solar cell with a normal structure of a ITO/p-CdTe NCs/n-acceptor (or without)/Al configuration, the contact between the ITO and CdTe is a non-ohm contact due to a different work function (for an ITO, the value is ~4.7 eV, while for CdTe NCs, the value is ~5.3 eV), which results in an energetic barrier at the ITO/CdTe interface and decreases the performance of the NC solar cells. This work investigates how interface materials (including Au, MoO(x) and C₆₀) affect the performance of NC solar cells. It is found that devices with interface materials have shown higher V(oc) than those without interface materials. For the case in which we used Au as an interface, we obtained a high open-circuit voltage of 0.65 V, coupled with a high fill factor (62%); this resulted in a higher energy conversion efficiency (ECE) of 5.3%, which showed a 30% increase in the ECE compared with those without the interlayer. The capacitance measurements indicate that the increased V(oc) in the case in which Au was used as the interface is likely due to good ohm contact between the Au's and the CdTe NCs' thin film, which decreases the energetic barrier at the ITO/CdTe interface.
25,140,734
[ -0.2641391, -0.007250241, 0.09401655, -0.02230486, 0.1264764, -0.1684423, -0.1880911, 0.1826152, 0.1983143, 0.1239707, -0.2534499, 0.09370613, 0.03655862, 0.1072007, -0.8034398, -0.4936625, -0.475072, 0.05033703, 0.1580367, 0.1748317, 0.2853675, 0.09022536, -0.2913941, ...
Where do you want to give report?
Traditionally, nurses have met in a conference room to give each other end-of-shift report. Many hospitals are now moving to bedside report. Which does the research support as best practice? What are the ethical and practical issues of each? This article answers those questions.
25,140,744
[ -0.1245258, -0.1069888, -0.376529, -0.20016, 0.07319675, 0.2712539, -0.1133513, 0.1029456, 0.01201439, -0.07213306, -0.01791115, -0.0593039, -0.1952173, 0.1530314, -0.2861879, -0.4391293, -0.1855573, 0.2146856, -0.07158987, 0.04103383, 0.2039082, 0.1302743, 0.2365343, -...
Model for heart failure education.
Heart failure (HF) is the heart's inability to meet the body's need for blood and oxygen. According to the American Heart Association 2013 update, approximately 5.1 million people are diagnosed with HF in the United States in 2006. Heart failure is the most common diagnosis for hospitalization. In the United States, the HF direct and indirect costs are estimated to be US $39.2 billion in 2010. To address this issue, nursing educators designed innovative teaching frameworks on HF management both in academia and in clinical settings. The model was based on 2 resources: the American Association of Heart Failure Nurses (2012) national nursing certification and the award-winning Pierce County Responsive Care Coordination Program. The HF educational program is divided into 4 modules. The initial modules offer foundational levels of Bloom's Taxonomy then progress to incorporate higher-levels of learning when modules 3 and 4 are reached. The applicability of the key components within each module allows formatting to enhance learning in all areas of nursing, from the emergency department to intensive care units to the medical-surgical step-down units. Also applicable would be to provide specific aspects of the modules to nurses who care for HF patients in skilled nursing facility, rehabilitation centers, and in the home-health care setting.
25,140,745
[ -0.2126405, 0.06244633, -0.09359668, -0.213015, 0.162277, -0.1002801, 0.388749, -0.1335312, 0.009371637, 0.3876618, -0.04084671, 0.001952416, -0.07742435, -0.3491814, -0.2327069, -0.02525861, -0.001179982, -0.03756367, 0.08667833, -0.660877, -0.11921, -0.02635176, -0.0849...
Effect of Ganoderma applanatum mycelium extract on the inhibition of adipogenesis in 3T3-L1 adipocytes.
Ganoderma applanatum (GA) and related fungal species have been used for over 2000 years in China to prevent and treat various human diseases. However, there is no critical research evaluating the functionality of GA grown using submerged culture technology. This study aimed to evaluate the effects of submerged culture GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1 cells were treated with differentiation inducers in the presence or absence of GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay showed that the GAM extract (0.01-1 mg/mL) was not toxic to 3T3-L1 preadipocyte. Treatment of cells with GAM extracts and its active components significantly decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Western blot analysis results showed that the protein expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract. In addition, adipogenic-specific genes such as perilipin, fatty acid synthase (FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4 (FABP4) decreased in a dose-dependent manner. Quantitative high-performance liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part, through altered regulation of PPARγ, C/EBPα, and SREBP1. These results suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting differentiation of preadipocytes.
25,140,758
[ -0.2568437, -0.06623478, -0.2196049, -0.1452875, 0.1100935, -0.001548094, -0.3252846, 0.3736618, 0.3178225, 0.0003184443, 0.09498215, -0.04785887, -0.01883088, 0.05879458, -0.3918286, 0.4052984, -0.5411155, 0.1908996, -0.08818927, 0.559313, -0.0852455, 0.49825, -0.23239, ...
Structural insights of JAK2 inhibitors: pharmacophore modeling and ligand-based 3D-QSAR studies of pyrido-indole derivatives.
In this study we have performed pharmacophore modeling and built a 3D QSAR model for pyrido-indole derivatives as Janus Kinase 2 inhibitors. An efficient pharmacophore has been identified from a data set of 51 molecules and the identified pharmacophore hypothesis consisted of one hydrogen bond acceptor, two hydrogen bond donors and three aromatic rings, i.e. ADDRRR. A powerful 3D-QSAR model has also been constructed by employing Partial Least Square regression analysis with a regression coefficient of 0.97 (R(2)) and Q(2) of 0.95, and Pearson-R of 0.98.
25,140,764
[ 0.1354095, -0.0103061, 0.1890181, -0.05567608, 0.03839176, 0.04695943, 0.1132132, 0.4571871, 0.2514605, 0.04662619, 0.296939, 0.1939182, -0.1396136, 0.4051407, -0.578436, -0.06503386, 0.1241621, 0.3473807, -0.07027694, 0.304315, 0.16985, -0.2223148, -0.07387985, 0.09034...
[Risk factors for invasive pulmonary fungal infection in children].
To analyze the risk factors for invasive pulmonary fungal infection (IPFI) and to provide a theoretical basis for the early prevention and treatment of IPFI. A retrospective case-control study was conducted on the clinical data of children hospitalized in the pediatric intensive care unit between January 2012 and March 2013. These children consisted of 48 patients with a clinical diagnosis of IPFI (IPFI group) and 106 pneumonia patients without a clinical diagnosis of IPFI (non-IPFI group). The clinical date of the two groups were compared and analyzed. The main risk factors for the development of IPIF were identified by unconditional multivariate logistic regression analysis. Compared with the non-IPIF group, the IPIF group had significantly lower mean age and serum albumin level (P<0.01), significantly longer mean length of hospital stay, duration of antibiotic use, and duration of corticosteroid use (P<0.01), and significantly higher rates of malnutrition, invasive mechanical ventilation, indwelling catheter use, oropharyngeal fungal infection, and diarrhea (P<0.05). Multivariate logistic regression analysis showed that invasive mechanical ventilation, diarrhea, long duration of corticosteroid use, long duration of antibiotic use, young age, and low serum albumin level were independent risk factors for the development of IPFI. For the infants with suspected IPFI for whom pathogenic examination is difficult to perform, IPFI should be considered in cases of invasive mechanical ventilation, diarrhea, long-time uses of broad-spectrum antibiotics and corticosteroids and hypoalbuminemia, and empirical antifungal therapy should be performed as soon as possible.
25,140,766
[ -0.09379619, -0.2631363, 0.2931424, -0.06268646, 0.2657498, 0.008095711, -0.1331926, 0.2678965, 0.006783117, -0.1927054, 0.2260687, 0.06024121, -0.0662207, -0.01216013, 0.2296296, -0.1248851, -0.1903956, 0.3352288, -0.2151448, -0.1338142, -0.2286736, -0.1331044, -0.024242...
[Pathogenic analysis of ventilator-associated pneumonia in the pediatric intensive care unit in high-altitude areas].
To investigate the pathogens of ventilator-associated pneumonia (VAP) and their drug resistance in the pediatric intensive care unit (PICU) in high-altitude areas and to provide a clinical basis for the prevention and treatment of VAP. A total of 94 children with VAP hospitalized in the PICU in high-altitude areas between June 2011 and June 2013 were recruited. Their lower respiratory tract secretions were collected for bacterial culture and drug sensitivity test. Of the 94 children with VAP, 22 (23%) had a single bacterial infection, and 72 (77%) had mixed infections, mostly with Klebsiella pneumoniae and Acinetobacter baumannii (17 cases, 27%). Of the 178 isolated strains of pathogens, 139 (78%) were Gram-negative bacteria (G⁻ bacteria), mainly including Klebsiella pneumoniae, Stenotrophomonas maltophilia, Acinetobacter baumannii, and Pseudomonas aeruginosa, 26 (15%) were Gram-positive bacteria (G⁺ bacteria), mainly including Staphylococcus aureus, and 13 (7%) were fungi, mainly including Candida albicans. Most G⁻ bacteria had a high drug resistance. Pseudomonas aeruginosa was extensively drug-resistant. Acinetobacter baumannii was only highly sensitive to cefoperazone/sulbactam and imipenem. Multidrug resistance (methicillin resistance) was found in G⁺ bacteria, for which vancomycin was effective. The pathogens of VAP in high-altitude areas are mostly G- bacteria, which may cause mixed infections and develop drug resistance. This provides guidance for the rational use of antimicrobial drugs and the development of key prevention and control measures for VAP.
25,140,768
[ 0.1825101, -0.1809692, -0.2375386, 0.02969233, -0.05534896, 0.2228769, -0.3348491, 0.1551384, -0.1307776, 0.04693503, 0.0950271, 0.1286784, -0.2806373, 0.3239791, 0.2976522, 0.2158316, -0.5963189, 0.5279911, -0.09169373, 0.08660434, 0.3309537, -0.1419169, 0.05415489, 0....
[Clinical analysis of 10 cases of pediatric Crohn's disease].
To study the clinical features and treatment of pediatric Crohn's disease (CD). Clinical data of 10 children with active CD diagnosed between 2005 and 2013 were retrospectively reviewed. Abdominal pain, diarrhea, and bloody stools were the most common symptoms in these patients, usually accompanied by different degrees of growth retardation and nutritional disorders. Fever was the main extraintestinal manifestation. Enteroscopy showed discontinuous and segmental mucosal hyperaemia and erosion, cobblestone appearance and mucosal ulceration. Abdominal ultrasound revealed uneven and segmental thickening of the intestinal wall. The pathological esamination showed many lymphocytes, eosinophils and plasma cells infiltrating into the lamina propria and partial atrophy of mucosal gland. C-reactive protein (CRP) level was significantly lower in the remission stage than in the acute stage and the recurrence stage (P<0.05). The erythrocyte sedimentation rate (ESR) was significantly lower in the remission stage than in the recurrence stage (P<0.05). Among mild cases identified by the pediatric Crohn's disease activity index (PCDAI) in the early stage of disease, the induced remission rate and maintained remission rate were 100% and 67%, respectively, with oral 5-aminosalicylic acid (5-ASA) and adrenocortical hormone. Among moderate and severe cases identified by the PCDAI, the partial remission rate was 100% with 5-ASA and adrenocortical hormone, but the maintained remission rate was not so good and the recurrence rate of disease was high. Pediatric CD has no specific clinical manifestations and laboratory test results. ESR and CRP can be used as the markers for evaluating the disease progression. 5-ASA has certain efficacy in inducing and maintaining remission of pediatric CD. There is a certain correlation between treatment outcome and the PCDAI score in the early stage of disease.
25,140,776
[ 0.1776917, 0.0006407436, 0.1885206, 0.0490813, -0.1768491, -0.04862893, 0.1378171, 0.1768066, 0.2584426, -0.240492, 0.1910565, -0.02324934, -0.00787204, 0.1664103, 0.1175901, 0.4635588, -0.3818699, -0.1443139, 0.2254089, 0.3651198, 0.3427299, 0.1028364, -0.3327651, -0.1...
Attitudes to aging in midlife are related to health conditions and mood.
Health is an important aspect of individuals' lives as they age. The aim of this study was to examine the relationship of sociodemographic factors, diagnosed chronic health conditions, and current depression with attitudes to aging in midlife. A cross-sectional baseline analysis was conducted on the first 300 participants from the Canterbury Health, Ageing and Life Course study in New Zealand, a stratified randomized community longitudinal study of adults recruited between 49 and 51 years. Attitudes were measured using the Attitudes to Aging Questionnaire (AAQ) and analyzed with a range of prevalent diagnosed chronic conditions, current depression, and sociodemographic variables. Individuals perceived their physical aging more negatively after a diagnosis of hypertension, arthritis or asthma. Diagnosed lifetime depression and anxiety, and current depression, showed strong relationships with attitudes to aging across domains. After controlling for sociodemographic factors and current depression, individuals with diagnosed hypertension, arthritis, asthma, lifetime depression or anxiety continued to report significantly more negative attitudes to aging. Current depression showed the strongest associations with attitudes to aging and mediated relationships of health on attitudes to aging. Physical and mental health are related to attitudes to aging. Most chronic conditions examined are significantly associated with attitudes toward aging in the physical change domain. Diagnosed lifetime depression and anxiety, and current depression, are negatively related across attitudinal domains. Individuals can feel positive about aging while experiencing poorer health, but this is more difficult in the presence of low mood.
25,140,789
[ -0.1158324, -0.03249482, -0.2673106, -0.08420981, -0.2457763, -0.1065269, -0.4844005, 0.2338475, 0.05153444, -0.07590329, 0.1120986, 0.05255454, 0.134211, -0.09979445, 0.02157399, -0.02095957, 0.006577773, 0.3232445, -0.1075445, -0.1321081, -0.1394112, 0.2017492, -0.10907...
High-throughput screening system to identify small molecules that induce internalization and degradation of HER2.
Overexpression of growth factor receptors in cancers, e.g., human epidermal growth factor receptor 2 (HER2) in ovarian and breast cancers, is associated with aggressiveness. A possible strategy to treat cancers that overexpress those receptors is blockade of receptor signaling by inducing receptor internalization and degradation. In this study, we developed a cell-based high-throughput screening (HTS) system to identify small molecules that induce HER2 internalization by employing our recently developed acidic-pH-activatable probe in combination with protein labeling technology. Our HTS system enabled facile and reliable quantification of HER2 internalization with a Z' factor of 0.66 and a signal-to-noise ratio of 44.6. As proof of concept, we used the system to screen a ∼155,000 small-molecule library and identified three hits that induced HER2 internalization and degradation via at least two distinct mechanisms. This HTS platform should be adaptable to other disease-related receptors in addition to HER2.
25,140,805
[ 0.1460306, -0.176688, 0.1174375, -0.0296741, 0.1205904, 0.04468484, -0.01961257, 0.3961026, 0.1849176, -0.03119895, -0.03926982, -0.0109461, -0.153506, -0.06228282, -0.1791918, 0.02957905, -0.4893002, 0.09700939, 0.2315427, -0.2119217, 0.3390065, 0.2472528, -0.3454271, ...
Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain.
O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2 ± 2 vs 7.9 ± 1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4 ± 2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3 ± 2 vs 7.5 ± 2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1 ± 2 vs 7.4 ± 2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca(2+)/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.
25,140,811
[ 0.1605447, -0.1390695, -0.5319195, -0.1950684, 0.1394222, 0.1339661, -0.1566223, 0.2856663, 0.1226827, -0.2773465, -0.0506008, 0.004225855, 0.01292732, -0.3156266, -0.9260217, -0.1071067, -0.8101876, 0.1713317, -0.04692157, 0.2024922, 0.4212555, 0.160761, -0.2201189, 0....
Effect of drainage on postoperative pain after laparoscopic ovarian cystectomy.
The aim of this prospective study was to investigate the effect of drainage on postoperative shoulder and abdominal pain after uncomplicated laparoscopic ovarian cystectomy (LOC). Allocation to drain or not to drain was non-randomised. There were 55 patients with drainage and 56 patients without drainage. Postoperative shoulder and abdominal pain was assessed using a 10-point visual analogue scale. Postoperative hospital stay in the drainage group was longer than the non-drainage group (p = 0.040). Postoperative shoulder pain scores at 6 h and 24 h were similar between the drainage and non-drainage groups (p = 0.376 and p = 0.847, respectively). Postoperative abdominal pain was higher in the drainage group at 6 h (p = 0.009), but was similar at 24 h (p = 0.097) between the groups. These data suggest that for LOC, drainage may not be useful to prevent postoperative shoulder pain and also increases postoperative abdominal pain and length of hospital stay.
25,140,836
[ -0.02943429, 0.1679965, 0.05541614, -0.2145295, -0.361785, -0.4752701, -0.05662471, -0.316301, -0.07626002, -0.3618625, 0.1738259, -0.04136974, 0.01488482, -0.2712696, -0.09721446, -0.2147792, -0.2082061, 0.2373658, 0.1355686, -0.4473698, -0.09126342, -0.1902286, 0.084914...