title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Short-term effects of bright light therapy in adults with chronic nonspecific back pain: a randomized controlled trial. | The present trial evaluated incorporation of bright light therapy in the treatment of chronic nonspecific back pain (CNBP). A prospective, randomized, controlled, multicenter, open design with three parallel trial arms was used. Subjects received a novel therapeutic, an expected therapeutic ineffective low dose, or no light exposure at three different medical centers. A total of 125 CNBP patients reporting pain intensity of ≥3 points on item 5 of the Brief Pain Inventory (BPI) were included. Over 3 weeks, 36 active treatment, 36 placebo controls, and 33 controls received 3 or no supplementary light exposures of 5.000 lx or 230 lx, respectively. Changes in self-reported scores of pain intensity (BPI sub-score 1) and depression (Hospital Anxiety and Depression Questionnaire) were the primary outcome measures. Secondary outcome measures were changes in self-reported overall pain sensation (BPI total score), grade of everyday life impairment (BPI sub-score 2), mood (visual analog scale), and well-being (World Health Organization-Five Well-Being Index). Changes in pain intensity were higher (1.0 [0.8-1.6]) in the bright light group compared with controls (0.3 [-0.1-0.8]; effect size D = 0.46). Changes in the depression score were also higher in the intervention group (1.5 [0.0-2.5]) compared with controls (0.0 [0.0-2.0]; effect size D = 0.86). No differences were seen in change scores between intervention vs sham group. The present randomized controlled trial shows that light therapy even in low dose could improve depressive symptoms and reduce pain intensity in CNBP patients. Further research is needed for optimizing parameters of frequency, dose, and duration of therapeutic light exposure. | 25,159,085 | [
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In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo. | The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape-based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand-induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)- and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10(-7) M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy. | 25,159,092 | [
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Pharmacological blockade of the aromatase enzyme, but not the androgen receptor, reverses androstenedione-induced cognitive impairments in young surgically menopausal rats. | Androstenedione, the main circulating ovarian hormone present after menopause, has been shown to positively correlate with poor spatial memory in an ovary-intact rodent model of follicular depletion, and to impair spatial memory when administered exogenously to surgically menopausal ovariectomized rats. Androstenedione can be converted directly to estrone via the aromatase enzyme, or to testosterone. The current study investigated the hormonal mechanism underlying androstenedione-induced cognitive impairments. Young adult ovariectomized rats were given either androstenedione, androstenedione plus the aromatase inhibitor anastrozole to block conversion to estrone, androstenedione plus the androgen receptor blocker flutamide to block androgen receptor activity, or vehicle treatment, and were then administered a battery of learning and memory maze tasks. Since we have previously shown that estrone administration to ovariectomized rats impaired cognition, we hypothesized that androstenedione's conversion to estrone underlies, in part, its negative cognitive impact. Here, androstenedione administration impaired spatial reference and working memory. Further, androstenedione did not induce memory deficits when co-administered with the aromatase inhibitor, anastrozole, whereas pharmacological blockade of the androgen receptor failed to block the cognitive impairing effects of androstenedione. Anastrozole alone did not impact performance on any cognitive measure. The current data support the tenet that androstenedione impairs memory through its conversion to estrone, rather than via actions on the androgen receptor. Studying the effects of aromatase and estrogen metabolism is critical to elucidating how hormones impact women's health across the lifespan, and results hold important implications for understanding and optimizing the hormone milieu from the many endogenous and exogenous hormone exposures across the lifetime. | 25,159,107 | [
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Genomic organization, differential expression, and functional analysis of the SPL gene family in Gossypium hirsutum. | SQUAMOSA promoter binding protein-like (SPL) genes encode plant-specific transcription factors that are involved in many fundamental developmental processes. Certain SPL genes contain sequences complementary to miR156, a microRNA (miRNA) that plays a role in modulating plant gene expression. In this study, 30 SPL genes were identified in the reference genome of Gossypium raimondii and 24 GhSPLs were cloned from Gossypium hirsutum. G. raimondii is regarded as the putative contributor of the D-subgenome of G. hirsutum. Comparative analysis demonstrated sequence conservation between GhSPLs and other plant species. GhSPL genes could be classified into seven subclades based on phylogenetic analysis, diverse intron-exon structure, and motif prediction. Within each subclade, genes shared a similar structure. Sequence and experimental analysis predicted that 18 GhSPL genes are putative targets of GhmiR156. Additionally, tissue-specific expression analysis of GhSPL genes showed that their spatiotemporal expression patterns during development progressed differently, with most genes having high transcript levels in leaves, stems, and flowers. Finally, overexpression of GhSPL3 and GhSPL18 in Arabidopsis plants demonstrated that these two genes are involved in the development of leaves and second shoots and play an integral role in promoting flowering. The flowering integrator GhSOC1 may bind to the promoter of GhSPL3 but not GhSPL18 to regulate flowering. In conclusion, our analysis of GhSPL genes will provide some gene resources and a further understanding of GhSPL3 and GhSPL18 function in flowering promotion. Furthermore, the comparative genomics and functional analysis deepened our understanding of GhSPL genes during upland cotton vegetative and reproductive growth. | 25,159,110 | [
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Inferring population structure and demographic history using Y-STR data from worldwide populations. | The Y chromosome is one of the best genetic materials to explore the evolutionary history of human populations. Global analyses of Y chromosomal short tandem repeats (STRs) data can reveal very interesting world population structures and histories. However, previous Y-STR works tended to focus on small geographical ranges or only included limited sample sizes. In this study, we have investigated population structure and demographic history using 17 Y chromosomal STRs data of 979 males from 44 worldwide populations. The largest genetic distances have been observed between pairs of African and non-African populations. American populations with the lowest genetic diversities also showed large genetic distances and coancestry coefficients with other populations, whereas Eurasian populations displayed close genetic affinities. African populations tend to have the oldest time to the most recent common ancestors (TMRCAs), the largest effective population sizes and the earliest expansion times, whereas the American, Siberian, Melanesian, and isolated Atayal populations have the most recent TMRCAs and expansion times, and the smallest effective population sizes. This clear geographic pattern is well consistent with serial founder model for the origin of populations outside Africa. The Y-STR dataset presented here provides the most detailed view of worldwide population structure and human male demographic history, and additionally will be of great benefit to future forensic applications and population genetic studies. | 25,159,112 | [
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DEP domain-containing mTOR-interacting protein in the rat brain: distribution of expression and potential implication. | DEP domain-containing mTOR-interacting protein (DEPTOR) has been recently discovered as an endogenous regulator of the mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2. mTORC1 is present in the brain, and there is growing evidence that its dysregulation contributes to several brain alterations. This suggests the involvement of mTOR signaling and its modulators in neurobiological controls. Here, we characterized and mapped the expression of DEPTOR in the rat brain. We show that DEPTOR was widely expressed from the forebrain to the hindbrain, including the hippocampus, the mediobasal hypothalamus, and the circumventricular organs (CVOs). In the hippocampus, DEPTOR protein and Deptor mRNA were highly expressed in the dendate gyrus and CA3 field. In the CVOs, DEPTOR was expressed in the subfornical organ, the median eminence, and the area postrema. In the mediobasal hypothalamus, DEPTOR was expressed in neurons of the ventromedial nucleus (VMH) and colocalized with proopiomelanocortin (POMC) in the arcuate nucleus (ARC). The hypothalamic distribution suggested a role for DEPTOR in energy balance. Supporting this possibility, we observed that Deptor hypothalamic expression was modulated by the nutritional status in a context of diet-induced and genetic obesity; food deprivation increased Deptor mRNA in both the ARC and VMH of obese rats. In conclusion, the present results illustrate the presence of DEPTOR in the rat brain and suggest a role for DEPTOR in the hypothalamic regulation of energy balance, which further supports the role of mTOR in energy homeostasis. J. Comp. Neurol. 523:93-107, 2015. © 2014 Wiley Periodicals, Inc. | 25,159,114 | [
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Biochemical evaluation of virtual screening methods reveals a cell-active inhibitor of the cancer-promoting phosphatases of regenerating liver. | Computationally supported development of small molecule inhibitors has successfully been applied to protein tyrosine phosphatases in the past, revealing a number of cell-active compounds. Similar approaches have also been used to screen for small molecule inhibitors for the cancer-related phosphatases of regenerating liver (PRL) family. Still, selective and cell-active compounds are of limited availability. Since especially PRL-3 remains an attractive drug target due to its clear role in cancer metastasis, such compounds are highly demanded. In this study, we investigated various virtual screening approaches for their applicability to identify novel small molecule entities for PRL-3 as target. Biochemical evaluation of purchasable compounds revealed ligand-based approaches as well suited for this target, compared to docking-based techniques that did not perform well in this context. The best hit of this study, a 2-cyano-2-ene-ester and hence a novel chemotype targeting the PRLs, was further optimized by a structure-activity-relationship (SAR) study, leading to a low micromolar PRL inhibitor with acceptable selectivity over other protein tyrosine phosphatases. The compound is active in cells, as shown by its ability to specifically revert PRL-3 induced cell migration, and exhibits similar effects on PRL-1 and PRL-2. It is furthermore suitable for fluorescence microscopy applications, and it is commercially available. These features make it the only purchasable, cell-active and acceptably selective PRL inhibitor to date that can be used in various cellular applications. | 25,159,123 | [
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Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin. | Under physiological conditions, studies on the biology of naturally induced Foxp3(+) Treg cells of intra- and extrathymic origin have been hampered by the lack of unambiguous markers to discriminate the mature progeny of such developmental Treg-cell sublineages. Here, we report on experiments in double-transgenic mice, in which red fluorescent protein (RFP) is expressed in all Foxp3(+) Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3(+) Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP(+) GFP(+) ) and extrathymic (RFP(+) GFP(-) ) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3(+) Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3(+) Treg cells represent distinct phenotypic and functional sublineages. | 25,159,127 | [
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IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint destruction in a novel FcγRIIB-deficient rheumatoid arthritis mouse model. | We earlier found that TNFα but not interleukin (IL)-17 is indispensable in the pathogenesis of spontaneously occurring rheumatoid arthritis (RA)-like disease in our newly established FcγRIIB-deficient C57BL/6 (B6) mouse model, designated KO1. Here, we examined the role of IL-6 in the pathogenesis of RA features in KO1, with particular reference to cartilage and bone destruction in arthritic joints. To evaluate the preventive effect of MR16-1, a rat anti-mouse IL-6 receptor (IL-6R) mAb, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with MR16-1 for 6 months, the second treated with normal rat IgG, as a control, and the third left untreated. The incidence and severity of arthritis, immunological abnormalities, and transcription levels of receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines/chemokines in ankle joint tissues were compared among the three groups. The therapeutic effect of MR16-1 was examined by treating 7-month-old KO1 mice in the early stages of arthritis for 2 months. Compared with the findings in the KO1 mice left untreated or treated with normal rat IgG, the development of arthritis was markedly suppressed in mice with MR16-1 treatment started from preclinical stages. The suppression was associated with the decrease in production of autoantibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP). Histologically, marked synovitis, pannus formation, and cartilage and bone destruction associated with the increase in tartrate-resistant acid phosphatase (TRAP)-positive osteoclast generation were evident in the two control groups; however, these findings were virtually absent in MR16-1-treated mice. Real-time PCR analysis revealed that the up-regulated expression levels of MCP-1, IL-6, and TNFα, and the aberrantly high RANKL/OPG expression ratio in synovial joint tissues from the two control groups of mice with overt arthritis were significantly suppressed in MR16-1-treated mice. In mice with therapeutic MR16-1 treatment, there was no progression in arthritis score and the RANKL/OPG ratio in joint tissues was significantly suppressed. Administration of an anti-IL-6R mAb ameliorated spontaneously occurring RA-like disease features, indicating that IL-6, as well as TNFα, plays a pivotal role in the pathogenesis of RA in KO1 mice. Current studies showed that, in addition to the role in enhancing autoantibody production, IL-6 promotes synovial tissue inflammation and osteoclastogenesis, leading to the severe synovitis with pannus formation and the progressive cartilage and bone destruction in multiple joints. | 25,159,156 | [
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Highly magneto-responsive multilayer microcapsules for controlled release of insulin. | In this study, magneto-responsive polyelectrolyte multilayer microcapsules were successfully prepared by the formation of shell with biocompatible iron oxide nanoparticles (Fe₃O₄ NPs) and polyallylamine hydrochloride (PAH) by layer-by-layer (LbL) self-assembly technique. The self-assembled microcapsules were characterized by SEM, TEM and zeta-potential analyzer. According to the pH sensitivity of the microcapsule membrane permeability, insulin was encapsulated, with the encapsulation efficiency of 92.08±5.57%. The in vitro release behavior in an external alternating magnetic field indicated that once the magnetic field was applied, the drug release was greatly accelerated. In addition, according to the observed pulse release upon cyclic on-off operations of magnetic field, it could be assumed that the magneto-responsive microcapsules had an excellent "switching on" effect, which might be attributed to the rearrangement of shell structure caused by magnetic nanoparticles twisting and polyelectrolyte chains shaking, hence the increase of microcapsule membrane permeability and the enhancement of insulin release. | 25,159,178 | [
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Highlights from the ASCO Genitourinary Symposium 2014: focus on renal and prostate cancer. | The genitourinary cancer symposium is one of the most important conferences focused on cancers of the prostate, penis, urethra, testes, bladder and kidney. This year the genitourinary symposium celebrated 10 years – its theme was 'integrating biology into patient-centric care'. The conference offered educational sessions and oral and poster abstract presentations; the general sessions throughout the meeting focused on prevention, screening, diagnosis, multidisciplinary treatment, translational research and current controversies in the field. Here, we report the main news reported at the symposium about the treatment of metastatic renal cell carcinoma and castration resistant prostate cancer. | 25,159,199 | [
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Management of biliary complications in 412 patients with liver injuries. | Bile leaks occur in 4% to 23% of patients after major liver injuries. The role of conservative management versus internal biliary drainage has not been clearly defined. The safety and efficacy of nonoperative management of bile leaks were studied. Four hundred twelve patients with liver injuries were assessed in a prospective study between 2008 and 2013. All patients with clinically significant injuries to the intrahepatic biliary tract were evaluated. Bile leaks were classified as minor or major (>400 mL/d or persistent drainage >14 days). Minor leaks were managed conservatively, and major leaks underwent endoscopic retrograde cholangiogram and endoscopic biliary stenting. Fifty-one patients (12%) developed a bile leak after liver trauma. Eleven patients (22%) with an extrahepatic duct injury underwent open surgery. Forty patients (78%) had an intrahepatic bile leak. Twenty-six patients (65%) with minor bile leaks were treated conservatively, and 14 patients (35%) with major leaks underwent endoscopic retrograde cholangiogram and internal drainage. All bile leaks resolved. There was no significant difference in the two groups with respect to septic complications (p = 0.125), intensive care unit stay (p = 0.534), hospital stay (p = 0.164), or mortality (p = 1.000). Sixty-five percent of the intrahepatic bile leaks following trauma are minor and easily managed conservatively. Endoscopic retrograde cholangiogram and internal drainage should be reserved for major leaks. Therapeutic study, level IV. | 25,159,249 | [
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The multi-channel cochlear implant: multi-disciplinary development of electrical stimulation of the cochlea and the resulting clinical benefit. | This multi-disciplinary research showed sound could be coded by electrical stimulation of the cochlea and peripheral auditory nervous system. But the temporal coding of frequency as seen in the experimental animal, was inadequate for the important speech frequencies. The data indicated the limitation was due in particular to deterministic firing of neurons and failure to reproduce the normal fine temporo-spatial pattern of neural responses seen with sound. However, the data also showed the need for the place coding of frequency, and this meant multi-electrodes inserted into the cochlea. Nevertheless, before this was evaluated on people we undertook biological safety studies to determine the effects of surgical trauma and electrical stimuli, and how to prevent infection. Then our research demonstrated place of stimulation had timbre and was perceived as vowels. This led to our discovery in 1978 of the formant-extraction speech code that first enabled severely-profoundly deaf people to understand running speech. This result in people who had hearing before becoming severely deaf was an outcome not previously considered possible. In 1985 it was the first multi-channel implant to be approved by the US Food and Drug Administration (FDA). It was also the fore runner of our advanced formant and fixed filter strategies When these codes were used from 1985 for those born deaf or deafened early in life we discovered there was a critical period when brain plasticity would allow speech perception and language to be developed near- normally, and this required in particular the acquisition of place coding. In 1990 this led to the first cochlear implant to be approved by the FDA for use in children. Finally, we achieved binaural hearing in 1989 with bilateral cochlear implants, followed by bimodal speech processing in 1990 with a hearing aid in one ear and implant in the other. The above research has been developed industrially, with for example 250,000 people worldwide receiving the Cochlear device in 2013, and as of December 2012 the NIH estimated that approximately 324,200 people worldwide had received this and other implants (NIH Publication No. 11-4798). This article is part of a Special Issue entitled <Lasker Award>. | 25,159,273 | [
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Carbohydrate dynamics and mortality in a piñon-juniper woodland under three future precipitation scenarios. | Drought-induced forest mortality is an increasing global problem with wide-ranging consequences, yet mortality mechanisms remain poorly understood. Depletion of non-structural carbohydrate (NSC) stores has been implicated as an important mechanism in drought-induced mortality, but experimental field tests are rare. We used an ecosystem-scale precipitation manipulation experiment to evaluate leaf and twig NSC dynamics of two co-occurring conifers that differ in patterns of stomatal regulation of water loss and recent mortality: the relatively desiccation-avoiding piñon pine (Pinus edulis) and the relatively desiccation-tolerant one-seed juniper (Juniperus monosperma). Piñon pine experienced 72% mortality after 13-25 months of experimental drought and juniper experienced 20% mortality after 32-47 months. Juniper maintained three times more NSC in the foliage than twigs, and converted NSC to glucose and fructose under drought, consistent with osmoregulation requirements to maintain higher stomatal conductance during drought than piñon. Despite these species differences, experimental drought caused decreased leaf starch content in dying trees of both species (P < 0.001). Average dry-season leaf starch content was also a good predictor of drought-survival time for both species (R(2) = 0.93). These results, along with observations of drought-induced reductions to photosynthesis and growth, support carbon limitation as an important process during mortality of these two conifer species. | 25,159,277 | [
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Atrial fibrillation and coronary artery disease: which antithrombotic treatment strategy? | The optimal antithrombotic therapy in patients with atrial fibrillation and coronary artery disease is controversial. The benefit of the combination of antithrombotic therapies remains debatable, and, as the bleeding risk is substantial, this calls for knowledge of the duration, and which and how many agents should be used. The first randomized trial to challenge current recommendations of triple therapy (oral anticoagulation plus clopidogrel plus aspirin) examined patients on warfarin undergoing percutaneous coronary intervention with stent implantation. A reduced risk of any bleeding (hazard ratio 0.36) was found with combination of clopidogrel compared with triple therapy without increasing major cardiovascular events. In real-life patients, a nationwide Danish registry supported these findings, and, relative to triple therapy, no significant difference was found for recurrent myocardial infarction when adding only clopidogrel (hazard ratio 0.69) or aspirin (hazard ratio 0.96) to vitamin K antagonist. However, the latter regimen was associated with significantly increased risk of death. Within 1 year after myocardial infarction and/or percutaneous coronary intervention in patients with atrial fibrillation, current consensus papers endorse use of dual antiplatelet therapy on top of oral anticoagulation. A regimen consisting of oral anticoagulation and clopidogrel (without aspirin) could provide an alternative from a benefit and safety perspective. | 25,159,278 | [
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Hybrid approach for coronary artery revascularization: where do we stand? | Recently, hybrid coronary artery revascularization (HCAR), combining the benefits of both percutaneous coronary intervention and coronary artery bypass graft surgery (CABG) while minimizing their respective shortcomings, has been developed. This review is aimed to explore and discuss recent clinical outcomes and patient selection, and comment on surgical approaches for HCAR. Current forms of HCAR include off-pump mini-sternotomy or on-pump full sternotomy CABG [left internal mammary artery (LIMA)-to-left anterior descending artery(LAD) CABG followed by drug-eluting stents (DES) to non-LAD territories], robotic-assisted off-pump HCAR (robotic LIMA-to-LAD CABG and DES to non-LAD territories), and off-pump mini-thoracotomy single-vessel small thoracotomy (LIMA-to-LAD CABG), all of which have reported acceptable early to mid-term patency rates and freedom from major cardiac and cerebrovascular adverse events. As long-term effectiveness compared with conventional CABG remains to be demonstrated, especially in patients with diabetes and patients with higher SYNTAX scores, appropriate discussion between the 'Heart Team' and patient is needed prior to HCAR. HCAR presents an attractive alternative option for treating patients with multivessel coronary artery disease because it maximizes the clear survival benefits of LIMA-LAD grafting, improves quality assurance with completion angiography, and allows quicker patient recovery; furthermore, patients avoid the negative systemic inflammatory effects of cardiopulmonary bypass and delayed healing after sternotomy. | 25,159,279 | [
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The effects of constant flow bioreactor cultivation and keratinocyte seeding densities on prevascularized organotypic skin grafts based on a fibrin scaffold. | Organotypic full-thickness skin grafts (OTSG) are already an important technology for treating various skin conditions and are well established for skin research and development. These obvious benefits are often impaired by the need of laborious production, their noncomplete autologous composition, and, most importantly, their lack of included vasculature. Therefore, our study focused on combining a prevascularized dermal layer with an epidermis to cultivate full-thickness skin grafts incorporating capillary-like networks. It has been shown that prevascularization accelerates ingrowth of tissue-engineered grafts, and it is a prerequisite to circumvent diffusion limits due to graft thickness. To obtain such a graft, we chose a dermal layer incorporating human umbilical vein endothelial cells (HuVEC) amid human dermal fibroblasts within a fibrin-based scaffold, seeded apically with human foreskin keratinocytes (hfKC). Our research investigated the used concept's feasibility, as well as the effect of hfKC addition on the development of a well-connected capillary-like network after approximately 21 days. In addition, we evaluated the utilization of a custom-made constant flow bioreactor for simplified cultivation of these grafts, therefore possibly easing graft production and presumably increasing their cost effectiveness. Skin grafts were assessed by conventional two-dimensional histology. In addition, software-assisted three-dimensional evaluation of the capillary-like structure networks was performed by two-photon laser scanning microscopy (TPLSM) and subsequent image processing was done with ImagePro(®) Analyzer 7.0 software, thereby evaluating its platform technology power in the field of prevascularized skin grafts. All samples showed a capillary-like structure network, but we could report a significant reduction of its total length after 14 days of tri-culture with 5×10(5)/cm(2) seeded hfKC, possibly indicating nutritional deficiencies for this particular high cell density experimental setup. Lower concentrations of hfKC did not affect the formation of the capillary-like structures significantly. The developed bioreactor simplified cultivation of prevascularized OTSG. However, a flow-dependent reduction of capillary-like structures in 1 and 5 mL/min flow conditions occurred. We conclude that our technique for creating prevascularized OTSG is feasible. In addition, TPLSM is well suited for analyzing the prevascularization process. We hypothesize that the handling benefits of our bioreactor can be preserved by using considerably lower flow rates while not impairing the forming of capillary-like structure networks. | 25,159,286 | [
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Influence of pressure changes on recruitment pattern and neck muscle activities during Cranio-Cervical Flexion Tests (CCFTs). | The muscle activity of the deep cervical flexors is emphasized more than that of the superficial cervical flexors, and it has been reported that functional disorders of the longuscolli are found in patients who experience neck pain. The objective of this study was to analyze the recruitment patterns and muscle activities of the cervical flexors during Cranio-Cervical Flexion Tests (CCFTs) through real-time ultrasonography and surface electromyography with a view to presenting appropriate pressure levels for deep cervical flexor exercise protocols based on the results of the analysis. The twenty subjects without neck pain were trained until they became accustomed to CCFTs, and the pressure level was increased gradually from 20 mmHg to 40 mmHg by increasing the pressure level 5 mmHg at a time. Real-time ultrasonography images of the longuscolli and the sternocleidomastoid were taken to measure the amounts of changes in the thicknesses of these muscles, and surface electromyography was implemented to observe the muscle activity of the sternocleidomastoid. The measured value is RMS. According to the results of the ultrasonography, the muscle thicknesses of both the longuscolli and the sternocleidomastoid showed significant increases, as the pressure increased up to 40 mmHg (p< 0.05). The differences in the muscle thicknesses at all individual pressure levels showed significant increases (p< 0.05). According to the results of the electromyography, the muscle activity of the sternocleidomastoid gradually increased as the pressure increased up to 40 mmHg, the increases were significant between 20 mmHg and 25 mmHg, between 30 mmHg and 35 mmHg (p< 0.05). The pressure levels of exercise methods at which the muscle activity of the deep cervical flexors is maximally increased and the muscle activity of the superficial cervical flexors is minimally increased are 25 mmHg-30 mmHg. | 25,159,290 | [
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Circulating mitochondrial DNA level, a noninvasive biomarker for the early detection of gastric cancer. | Gastric cancer represents a major health burden worldwide and is often diagnosed at an advanced stage. Biomarkers for screening and prevention of gastric cancer are missing. Changes in peripheral blood mitochondrial DNA (mtDNA) have emerged as a potential preventive/diagnosis biomarker for cancer risk. We aimed to determine whether peripheral leukocytes mtDNA levels are associated with stages of the gastric carcinogenesis cascade. We measured mtDNA by quantitative real-time PCR assay in peripheral leukocytes of 28 patients with non-atrophic gastritis (NAG), 74 patients with gastric cancer, and 48 matched asymptomatic controls. In parallel, the serologic level of IL8 was determined. Mean mtDNA level was higher in patients with gastric cancer (P = 0.0095) than in controls, with values >8.46 significantly associated with gastric cancer (OR, 3.93). Three ranges of mtDNA values were identified: interval I, <2.0; interval II, 2.0-20; and interval III, >20. Interval I included mainly NAG cases, and few gastric cancer samples and interval III corresponded almost exclusively to patients with gastric cancer. All controls fell in interval II, together with some NAG and gastric cancer cases. IL8 levels were significantly higher in patients with gastric cancer (P < 0.05), with levels >50 pg/mL observed exclusively in patients with gastric cancer, allowing to distinguish them within interval II. We validated mtDNA results in a second cohort of patients, confirming that mtDNA was significantly higher in gastric cancer than in patients with preneoplasia. Circulating levels of mtDNA and IL8 constitute a potential biomarker for the early detection of gastric cancer. Our findings lead us to propose a new noninvasive method to detect patients with gastric cancer risk. | 25,159,292 | [
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Comparative genomics and transcriptomics in ants provide new insights into the evolution and function of odorant binding and chemosensory proteins. | The complex societies of ants and other social insects rely on sophisticated chemical communication. Two families of small soluble proteins, the odorant binding and chemosensory proteins (OBPs and CSPs), are believed to be important in insect chemosensation. To better understand the role of these proteins in ant olfaction, we examined their evolution and expression across the ants using phylogenetics and sex- and tissue-specific RNA-seq. We find that subsets of both OBPs and CSPs are expressed in the antennae, contradicting the previous hypothesis that CSPs have replaced OBPs in ant olfaction. Both protein families have several highly conserved clades with a single ortholog in all eusocial hymenopterans, as well as clades with more dynamic evolution and many taxon-specific radiations. The dynamically evolving OBPs and CSPs have been hypothesized to function in chemical communication. Intriguingly, we find that seven members of the conserved clades are expressed specifically in the antennae of the clonal raider ant Cerapachys biroi, whereas only one dynamically evolving CSP is antenna specific. The orthologs of the conserved, antenna-specific C. biroi genes are also expressed in antennae of the ants Camponotus floridanus and Harpegnathos saltator, indicating that antenna-specific expression of these OBPs and CSPs is conserved across ants. Most members of the dynamically evolving clades in both protein families are expressed primarily in non-chemosensory tissues and thus likely do not fulfill chemosensory functions. Our results identify candidate OBPs and CSPs that are likely involved in conserved aspects of ant olfaction, and suggest that OBPs and CSPs may not rapidly evolve to recognize species-specific signals. | 25,159,315 | [
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Physiology or psychic powers? William Carpenter and the debate over spiritualism in Victorian Britain. | This paper analyses the attitude of the British Physiologist William Benjamin Carpenter (1813-1885) to spiritualist claims and other alleged psychical phenomena in the second half of the Nineteenth Century. It argues that existing portraits of Carpenter as a critic of psychical studies need to be refined so as to include his curiosity about certain 'unexplained phenomena', as well as broadened so as to take into account his overarching epistemological approach in a context of theological and social fluidity within nineteenth-century British Unitarianism. Carpenter's hostility towards spiritualism has been well documented, but his interest in the possibility of thought-transference or his secret fascination with the medium Henry Slade have not been mentioned until now. This paper therefore highlights Carpenter's ambivalences and focuses on his conciliatory attitude towards a number of heterodoxies while suggesting that his Unitarian faith offers the keys to understanding his unflinching rationalism, his belief in the enduring power of mind, and his effort to resolve dualisms. | 25,159,318 | [
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Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits. | Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye. | 25,159,319 | [
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Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia. | Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2-4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l⁻¹·min, P < 0.001), with left-shifted insulin secretion (AUC(0-15): MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion. | 25,159,330 | [
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Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats. | The steroid receptor coactivator 1 (SRC1) regulates key metabolic pathways, including glucose homeostasis. SRC1(-/-) mice have decreased hepatic expression of gluconeogenic enzymes and a reduction in the rate of endogenous glucose production (EGP). We sought to determine whether decreasing hepatic and adipose SRC1 expression in normal adult rats would alter glucose homeostasis and insulin action. Regular chow-fed and high-fat-fed male Sprage-Dawley rats were treated with an antisense oligonucleotide (ASO) against SRC1 or a control ASO for 4 wk, followed by metabolic assessments. SRC1 ASO did not alter basal EGP or expression of gluconeogenic enzymes. Instead, SRC1 ASO increased insulin-stimulated whole body glucose disposal by ~30%, which was attributable largely to an increase in insulin-stimulated muscle glucose uptake. This was associated with an approximately sevenfold increase in adipose expression of lipocalin-type prostaglandin D2 synthase, a previously reported regulator of insulin sensitivity, and an approximately 70% increase in plasma PGD2 concentration. Muscle insulin signaling, AMPK activation, and tissue perfusion were unchanged. Although GLUT4 content was unchanged, SRC1 ASO increased the cleavage of tether-containing UBX domain for GLUT4, a regulator of GLUT4 translocation. These studies point to a novel role of adipose SRC1 as a regulator of insulin-stimulated muscle glucose uptake. | 25,159,329 | [
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Health status and health services utilization in elderly Koreans. | Korea is aging faster than any other country as the 'baby boomers' grow older. The purpose of this study is to describe the health status and health services utilization of older Koreans and examine the factors that are associated with effective health services utilization. Based on the 2008 Korean Longitudinal Study of Ageing which was conducted with Korean men and women aged 45 years or older, descriptive and logistic regression analysis was performed. The sample for this study was 4040 individuals who indicated they were 65 years or older. Bivariate analyses (chi-square tests) were used to examine the differences between men and women. Logistic regression analyses were then used to determine factors significantly associated with health services utilization. More women (29.3%) than men (14.5%) rated their health as poor or very poor. A significantly higher number of women than men reported having hypertension, arthritis or heart disease, while a larger number of men reported having cancer or lung problems. Age, education, income, and presence of chronic conditions significantly predicted the residents' self-rated health. Respondents with chronic conditions were twice as likely to report self-rated poor health (Odds Ratio: 2.26, 95% CI: 1.91-2.67) than residents with no chronic conditions. Those who were more likely to have used primary care services, such as a physician or traditional Korean medicine, included those 80 and older, men, those who had a chronic condition or poor health status, and lower-income individuals. Respondents with poor health status were significantly older, less-educated, poorer and had a higher rate of chronic conditions. Health-related need factors and income were important predictors of Korean elders using physician services and/or traditional Korean medicine. This study provides an important contribution to the knowledge base of Korean elders. The findings show that elders in poor health status were significantly older and poorer, with higher rates of chronic conditions and health services utilization, which should help in the health care planning required to address this issue. | 25,159,331 | [
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The use of rigid eye shields (Fox shields) at the point of injury for ocular trauma in Afghanistan. | Unlike hemorrhagic injuries in which direct pressure is indicated, any pressure placed on the eye after penetrating trauma can significantly worsen the injury by expulsing intraocular contents. The accepted first response measure for obvious or suspected penetrating ocular injury is placement of a rigid shield that vaults the eye so as to prevent accidental iatrogenic aggravation during transport to the ophthalmologist. Patching and placing intervening gauze between the shield and the eye are both contraindicated. Anecdotally, compliance with these recommendations is poor in the military and civilian communities alike; however, published studies documenting compliance are uniformly lacking. This study was undertaken to provide such an evaluation. In this retrospective observational study, the Department of Defense Trauma Registry was reviewed to identify eye injuries in Afghanistan from 2010 to 2012 and to examine compliance with eye shield recommendations. One hundred fifty-seven records of eye casualties were identified and categorized according to diagnostic codes, noting use of a shield. A subset of 30 records was further analyzed for compliance with other core treatment measures specified by the operant Clinical Practice Guideline. Because comparative studies do not exist, simple statistical analysis was performed. Overall, 39% of eye injuries received a shield at the point of injury (61% failure), ranging from 0% to 50% between diagnostic subgroups. Subset analysis revealed that only 4.2% of injuries were successfully mitigated at the point of injury (95.8% failure). In one of the few studies documenting the use of eye shields after ocular trauma, anecdotal reports of poor, inadequate, or incorrect compliance with basic recommendations were substantiated. Several factors may account for these findings. Corrective efforts should include enhanced educational emphasis and increased shield availability. Epidemiologic study, level IV. Therapeutic study, level IV. | 25,159,350 | [
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Continuous noninvasive respiratory volume monitoring for the identification of patients at risk for opioid-induced respiratory depression and obstructive breathing patterns. | Opioid-induced respiratory depression (OIRD) and postoperative apnea (POA) can lead to complications after surgery or traumatic injury. Previously, real-time monitoring of respiratory insufficiency and identification of apneic events have been difficult. A noninvasive respiratory volume monitor (RVM) that reports minute ventilation (MV), tidal volume, and respiratory rate is now available. The RVM was used to report the effect of opioids on respiratory status as well as demonstrate apneic breathing patterns in a hospital postanesthesia care unit. RVM traces were collected from 132 patients. Predicted MV (MVPRED) for each patient was used to calculate and the "percent predicted" MV (MVMEASURED / MVPRED × 100%) before opioid administration. Patients were stratified patients into two categories: "at risk," MV of less than 80% MVPRED, and "not at risk," MV of 80% MVPRED or greater. After opioid dosing, patients with MV of less than 40% MVPRED were categorized as "unsafe." POA was defined as more than five apneic or hypopneic events per hour. Of the 132 patients, 50 received opioids. Baseline MV was 7.2 ± 0.5 L/min. The MV-based protocol classified 18 of 50 patients as at risk before opioid administration. After the first opioid dose administration, at-risk patients experienced an average MV decrease (36.7% ± 8.5% MVPRED) and 13 of 18 decreased into unsafe; the 32 not at-risk patients experienced a lesser average MV decrease (76.9% ± 6.3% MVPRED). Only 1 of 32 not at-risk patients had a decrease in MV to unsafe. The proposed protocol had a sensitivity of 93% and a specificity of 86%. Of the 132 patients, 26 displayed POA. Of the 26 patients, 12 experienced POA without receiving opioids. Of the 26 patients with POA, 14 also received opioids, and of those, 6 were classified as unsafe. This investigation indicates that at risk and unsafe respiratory patterns occur frequently after procedure. RVM provides continuous noninvasive objective measurements of OIRD and POA. The RVM may prove a useful tool in opioid dosing and in recognition and management of POA and strong potential value in the rapid detection of OIRD and apnea in the contemporary combat casualty environment. Care management study, level V. | 25,159,358 | [
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Amnesic shellfish poisoning biotoxin detection in seawater using pure or amino-functionalized Ag nanoparticles and SERS. | Domoic acid (DA) biotoxin responsible for the amnesic shellfish poisoning (ASP) has been unambiguously detected in seawater in a broad range of concentration, with both pure and amino-functionalized Ag nanoparticles employed for surface enhanced Raman scattering (SERS). To achieve this, a comprehensive SERS study on DA dissolved in distilled water has been conducted. SERS of DA dissolved in seawater in concentrations ranging from 3.3 × 10(-4) to 3.3 × 10(-8) mol l(-1) exhibited specific signal, completely different to those of the corresponding DA aqueous solutions, due to the seawater interference in the overall SERS effect. In order to assess the capability of the technique as a cheaper alternative for rapid and unambiguous detection of the DA biotoxin in seawater, three detection schemes have been proposed. DA was detectable at 0.33 nmoll(-1) concentration (0.33) dissolved in distilled water and 0.033 nmol l(-1) (0.033 ppb) in seawater respectively, much lower than the admitted level by the current regulation. A solvent specific interaction of DA with the NPs was concluded, since DA aqueous solution added to Ag nanoparticles provided different SERS signal compared to that of DA directly dissolved in seawater. Employing amino-functionalized Ag nanoparticles with 4-aminothiophenol as SERS tag, SERS signal of DA on amino-AgNPs revealed significant specificity associated with the aromatic primary amine interaction of the SERS tag with DA, thus allowing DA detection in seawater at 4.16 × 10(-4) mol l(-1) concentration, much higher than in the case of pure NPs. To highlight the findings, a brief literature review to date on the DA biotoxin detection was also provided. | 25,159,386 | [
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In situ trapping of As, Sb and Se hydrides on nanometer-sized ceria-coated iron oxide-silica and slurry suspension introduction to ICP-OES. | A procedure is developed for the analysis of sub-μg L(-1) levels of arsenic, antimony and selenium after preconcentration of their hydrides. The study highlights the capability of an aqueous suspension of a nanometer-sized magnetic ceria, in the presence of iodide, to function as a sorbent for the in situ trapping and preconcentration of the hydrides of certain metalloids. After extraction, the material is magnetically separated from the trapping solution and analyzed. A slurry suspension sampling approach with inductively coupled plasma-optical emission spectrometry (ICP-OES) is employed for measurements, as the quantitative elution of the adsorbed metalloids is not feasible. The whole analytical procedure consists of five steps: (i) pre-reduction of As, Sb and Se, (ii) generation of the hydrides AsH3, SbH3 and SeH2, (iii) in situ collection in the trapping suspension of magnetic ceria, (iv) isolation of the particles by applying a magnetic field, and (v) measurement of As, Sb and Se concentrations using ICP-OES. Under the established experimental conditions, the efficiency of trapping accounted for 94 ± 2%, 89 ± 2% and 98 ± 3% for As, Sb and Se, respectively, signifying the effective implementation of the overall procedure. The applicability of the procedure has been demonstrated by analyzing tap and lake water and a reference material (soft drinking water). The obtained analytical figures of merit were satisfactory for the analysis of the above metalloids in natural waters by ICP-OES. | 25,159,391 | [
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Evaluation of total reducing power of edible oils. | The lipophilicity of untreated edible oils narrows the application of most published methods for the determination of antioxidant activity to hydrophilic extracts of oils. This research addresses the issue of the estimation of the total antioxidant properties of untreated edible oils by modifying two widely applied analytical methods, the Fe-Phenanthroline and the CUPRAC assays, to be used in untreated oils. The modifications pertain to the selection of mixture of solvents (ethanol-butanol in 3:1 v/v ratio), and the optimization of the reaction conditions (reagents concentration and reaction time). The developed methods were applied to a number of hydrophilic and lipophilic standard compounds and different types of commercial edible oils, as well as their corresponding aqueous or organic extracts. This implementation elucidated the differences in the antioxidant content of edible oils. All the results were compared to those of the DPPH and Folin-Ciocalteu methods and the analytical figures of merit for the methods have been estimated. Lastly, it was concluded that the modified CUPRAC assay has higher sensitivity compared to the Fe-Phenanthroline assay. | 25,159,404 | [
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Molecular interactions between some non-steroidal anti-inflammatory drugs (NSAID's) and bovine (BSA) or human (HSA) serum albumin estimated by means of isothermal titration calorimetry (ITC) and frontal analysis capillary electrophoresis (FA/CE). | The interactions between some non-steroidal anti-inflammatory drugs, NSAIDs, (naproxen, ibuprofen and flurbiprofen) and bovine (BSA) or human (HSA) serum albumin have been examined by means of two complementary techniques, isothermal titration calorimetry (ITC) and frontal analysis/capillary electrophoresis (FA/CE). It can be concluded that ITC is able to measure with high precision the strongest drug-albumin interactions but the higher order interactions can be better determined by means of FA/CE. Then, the combination of both techniques leads to a complete evaluation of the binding profiles between the selected NSAIDs and both kind of albumin proteins. When BSA is the binding protein, the NSAIDs show a strong primary interaction (binding constants: 1.5 × 10(7), 8 × 10(5) and 2 × 10(6) M(-1) for naproxen, ibuprofen and flurbiprofen, respectively), and also lower affinity interactions of the same order for the three anti-inflammatories (about 1.7 × 10(4) M(-1)). By contrast, when HSA is the binding protein two consecutive interactions can be observed by ITC for naproxen (9 × 10(5) and 7 × 10(4) M(-1)) and flurbiprofen (5 × 10(6) and 6 × 10(4) M(-1)) whereas only one is shown for ibuprofen (9 × 10(5) M(-1)). Measurements by FA/CE show a single interaction for each drug being the ones of naproxen and flurbiprofen the same that those evaluated by ITC as the second interaction events. Then, the ability of both techniques as suitable complementary tools to establish the whole interaction NSAIDs-albumin profile is experimentally demonstrated and allows foreseeing suitable strategies to establish the complete drug-protein binding profile. In addition, for the interactions analyzed by means of ITC, the thermodynamic signature is established and the relative contributions of the enthalpic and entropic terms discussed. | 25,159,405 | [
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Capillary electrophoresis coupled with automated fraction collection. | A fraction collector based on a drop-on-demand ink-jet printer was developed to interface capillary zone electrophoresis with a 96 well microtiter plate. We first evaluated the performance of the collector by using capillary zone electrophoresis to analyze a 1mM solution of tetramethylrhodamine; a fluorescent microtiter plate reader was then used to detect the analyte and characterize fraction carryover between wells. Relative standard deviation in peak height was 20% and the relative standard deviation in migration time was 1%. The mean and standard deviation of the tetramethylrhodamine peak width was 5 ± 1 s and likely limited by the 4-s period between droplet deposition. We next injected a complex mixture of DNA fragments and used real-time PCR to quantify the product in a CE-SELEX experiment. The reconstructed electrophoretic peak was 27 s in duration. Finally, we repeated the experiment in the presence of a 30-µM thrombin solution under CE-SELEX conditions; fractions were collected and next-generation sequencing was used to characterize the DNA binders. Over 25,000 sequences were identified with close matches to known thrombin binding aptamers. | 25,159,411 | [
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Near infrared spectral imaging for the analysis of dynamite residues on human handprints. | This study examines the utility of near infrared hyperspectral imaging (NIR-HSI) combined with chemometrics for the detection of dynamite residues on human handprints. Polyvinyl sheets containing dynamite residues were then analysed with the NIR-HSI system. A spectral library was developed by using partial least squares-discriminant analysis model (PLS-DA) to detect and classify the pixels contaminated with the dynamite residues. Values of sensitivity and specificity of 100% were obtained for both calibration and cross validation of dynamite and ammonium nitrate. The results were tested in real human handprints. Seven volunteers deposited their handprints into polyvinyl transparent sheets after the manipulation of a common type of dynamite which was mainly composed by ammonium nitrate. These results highlight the extremely high potential and capability of NIR-HSI combined with chemometrics for the fast and easy identification of explosive residues and additionally, its potential competence to detect the explosive manipulation. | 25,159,415 | [
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L-cysteine protected copper nanoparticles as colorimetric sensor for mercuric ions. | This report demonstrates a novel, simple and efficient protocol for the synthesis of copper nanoparticles in aqueous solution using L-cysteine as capping or protecting agent. UV-visible (UV-vis) spectroscopy was employed to monitor the LSPR band of L-cysteine functionalized copper nanoparticles (Cyst-Cu NPs) based on optimizing various reaction parameters. Fourier Transform Infrared (FTIR) spectroscopy provided information about the surface interaction between L-cysteine and Cu NPs. Transmission Electron Microscopy (TEM) confirmed the formation of fine spherical, uniformly distributed Cyst-Cu NPs with average size of 34 ± 2.1 nm. X-ray diffractometry (XRD) illustrated the formation of pure metallic phase crystalline Cyst-Cu NPs. As prepared Cyst-Cu NPs were tested as colorimetric sensor for determining mercuric (Hg(2+)) ions in an aqueous system. Cyst-Cu NPs demonstrated very sensitive and selective colorimetric detection of Hg(2+) ions in the range of 0.5 × 10(-6)-3.5 × 10(-6) mol L(-1) based on decrease in LSPR intensity as monitored by a UV-vis spectrophotometer. The developed sensor is simple, economic compared to those based on precious metal nanoparticles and sensitive to detect Hg(2+) ions with detection limit down to 4.3 × 10(-8) mol L(-1). The sensor developed in this work has a high potential for rapid and on-site detection of Hg(2+) ions. The sensor was successfully applied for assessment of Hg(2+) ions in real water samples collected from various locations of the Sindh River. | 25,159,429 | [
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Multivariate statistical comparison of analytical procedures for benzene and phenol determination with respect to their environmental impact. | The study describes the possibility of application of self-organizing maps technique to assess the greenness of analytical methodologies. The metrological and "environmental impact" parameters of procedures for benzene and phenol determination in water samples were sets of input data for chemometric analysis. Totally 47 objects and 8 variables formed the data used for analysis. The major factors responsible for non-green character of the methodology are the amount of organic solvent and amount of solid wastes formed. The results of the assessment methods with NEMI symbols and Eco-scale are in good agreement. Greener procedures for benzene and phenol determination are those based on SPME. In case of phenol the methodologies based on GC separation are much greener than those based on LC. The results also show that it is easier to apply green methodologies for benzene, as a compound with lower polarity and hence with less affinity to, than for phenol. The SOM assessment methodology can be useful in choosing the proper analytical procedures. | 25,159,434 | [
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Monte Carlo simulation of expert judgments on human errors in chemical analysis--a case study of ICP-MS. | Monte Carlo simulation of expert judgments on human errors in a chemical analysis was used for determination of distributions of the error quantification scores (scores of likelihood and severity, and scores of effectiveness of a laboratory quality system in prevention of the errors). The simulation was based on modeling of an expert behavior: confident, reasonably doubting and irresolute expert judgments were taken into account by means of different probability mass functions (pmfs). As a case study, 36 scenarios of human errors which may occur in elemental analysis of geological samples by ICP-MS were examined. Characteristics of the score distributions for three pmfs of an expert behavior were compared. Variability of the scores, as standard deviation of the simulated score values from the distribution mean, was used for assessment of the score robustness. A range of the score values, calculated directly from elicited data and simulated by a Monte Carlo method for different pmfs, was also discussed from the robustness point of view. It was shown that robustness of the scores, obtained in the case study, can be assessed as satisfactory for the quality risk management and improvement of a laboratory quality system against human errors. | 25,159,436 | [
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Simultaneous determination of dorzolomide and timolol in aqueous humor: a novel salting out liquid-liquid microextraction combined with HPLC. | A Snovel method for the simultaneous separation and determination of two antiglaucoma drugs namely, dorzolamide hydrochloride (DOR) and timolol maleate (TIM) in aqueous humor samples (AH) was developed by using salting-out assisted liquid-liquid microextraction (SALLME) combined with HPLC-UV method. Box-Behnken experimental design and response surface methodology were employed to assist the optimization of SALLME conditions, including salt concentration, the pH of sample solution and vortex time as variable factors. The optimal extraction conditions were as follows: to 50 µL of AH sample, 100 µL of phosphate buffer (100 mmol L(-1), pH 11.9), 90 µL of acetonitrile (ACN) and 0.11 g of (NH4)2SO4 salt were added into an Eppendorf vial (1 mL) then vortexed for 1.1 min. As an effort to miniaturize SALLE system, a 1 mL syringe adapted with a capillary tube was employed as the phase separation device. Once the phase separation occurred, the upper layer could be narrowed into the capillary tube by pushing the plunger; thus, the collection of the upper layer solvent was simple and convenient. By miniaturization, the consumption of the organic solvent was decreased as low as possible. The chromatographic separation was achieved on Gemini C18 column using a mobile phase of ACN: 30 mmol L(-1) potassium dihydrogen phosphate buffer containing 0.1% triethylamine, pH 3.5 (20:80, v/v) at a flow rate of 1 mL min(-1) and UV detection at 254 and 295 nm for DOR and TIM, respectively. Mepivacaine hydrochloride was used as an internal standard. The described method showed better separation with enhanced sensitivities than the previously reported methods with limits of quantitation of 8.75 and 10.32 ng mL(-1) in aqueous solution and 15.97 and 23.53 ng mL(-1) in AH for DOR and TIM, respectively. The simple, rapid and eco-friendly SALLME-HPLC method has been successfully applied for the simultaneous pharmacokinetic studies of DOR and TIM in rabbit AH. | 25,159,439 | [
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Nuclear fast red as highly sensitive "off/on" fluorescent probe for detecting guanine. | A novel fluorescence method for the determination of guanine was developed based on the fluorescence enhancement of Cu(2+)-nuclear fast red complex in the presence of guanine in Tris-HCl buffer. The complex of Cu(2+) with nuclear fast red resulted in a dramatic quenching of the fluorescence intensity. Nuclear fast red were dissociated from the complex with the addition of guanine due to the strong interaction between guanine and Cu(2+), which caused the fluorescence enhancement. The enhanced fluorescence intensity was well proportional to the concentration of guanine in the range of 4.96 × 10(-8)-1.09 × 10(-6)mol/L with the limit of detection 1.9 × 10(-8)mol/L. The method has been applied successfully to the determination of guanine in serum and DNA samples, and the recoveries were from 96.0% to 104.8%. | 25,159,443 | [
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Evaluation of image quality of DWIBS versus DWI sequences in thoracic MRI at 3T. | To compare diffusion weighted imaging with background suppression (DWIBS) sequence with classic spectral diffusion sequence (DWI) with and without respiratory gating in mediastinal lymph node analysis at 3T. 26 patients scheduled for mediastinoscopic lymph node analysis, prospectively undergone a thoracic 3T MRI with DWIBS (FatSat=STIR; TR/TE=6674.1/44.7ms; IR=260 ms) and DWI sequences (FatSat=SPIR; TR/TE=1291/59.6 ms) (b=0-400-800 s/mm2) with and without (free breathing) respiratory gating. Images at b=800 were analyzed by two radiologists. They performed qualitative analysis of fat-sat homogeneity and motion artifacts, rated from 0 to 4, and quantitative evaluation by studying signal to background (STB) of lymph nodes. Quality of fat suppression was significantly higher for DWIBS than for DWI both for free-breathing (score 3.48±0.65 vs. 1.76±0.96, p<0.0001) and respiratory-gated scans (3.17±0.77 vs. 1.72±0.73, p=0.0001). Similarly, artifacts were reduced with DWIBS (3.16±0.47 vs. 1.76±0.59, p<0.0001; 3.0±0.73 vs. 2.04±0.53, p=0.0001). Quantitative analysis showed higher STB with DWIBS (3.26±1.83 vs. 0.98±0.44, p<0.0001; 3.56±, 2.09 vs. 0.92±0.59, p<0.0001). Gating did not improve image quality and STB on DWIBS (p>0.05). In thoracic MRI, ungated DWIBS sequence improves fat-sat homogeneity, reduces motion artifacts and increases STB of lymph nodes. Respiratory gating does not improve DWIBS image quality. | 25,159,472 | [
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Cytochrome P450 2D6*10 genotype affects the pharmacokinetics of dimemorfan in healthy Chinese subjects. | This study aimed to investigate the effects of cytochrome P450 2D6*10 (100C > T, rs1065852) genotype on the pharmacokinetics of dimemorfan in healthy Chinese subjects. Data were evaluated from 24 subjects in two pharmacokinetic studies who received an oral dose of 40 mg of dimemorfan syrup (n = 12) or dimemorfan tablet (n = 12) after providing written informed consent and being divided into three groups: subjects with CYP2D6*10 CC (n = 5), CYP2D6*10 CT (n = 11) and CYP2D6*10 TT (n = 8). CC homozygotes and CT heterozygotes were defined to be C allele carriers. The CYP2D6*10 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Dimemorfan was measured by LC-MS/MS. There was significant difference in C max, AUC0-t , AUC0-inf, V z , and CL values of dimemorfan observed among the three CYP2D6*10 genotype groups (GLM, (a) P < 0.05, co-dominant model). CYP2D6*10 under the recessive model (CC + TC vs TT) was significantly associated with pharmacokinetics of dimemorfan ((c) P < 0.05). The C max values were significantly higher in subjects with CYP2D6*10 TT (8.06 ± 4.43 ng/mL) than CYP2D6*10 CC (3.41 ± 2.79 ng/mL), CYP2D6*10 CT (3.11 ± 2.47 ng/mL), so was AUC0-inf. V z /F and CL/F of subjects with CYP2D6*10 TT homozygotes were the lowest. We demonstrated that cytochrome P450 2D6*10 (100C > T, rs1065852) polymorphism can affect the pharmacokinetics of dimemorfan in humans, not dosage forms. | 25,159,483 | [
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Synthesis and reduction-responsive disassembly of PLA-based mono-cleavable micelles. | Stimuli-responsive block copolymers and their self-assembled nanostructures have been extensively studied as effective building blocks in construction of various nanomaterials in nanoscience and nanotechnology. A promising stimuli-responsive platform involves an incorportion of reduction-responsive disulfide linkages that can be cleaved to corresponding thiols when needed. Herein, we describe a novel approach utilizing a combination of ring-opening polymerization and a facile coupling reaction to synthesize a reduction-responsive triblock copolymer comprising biocompatible polylactide (PLA) and poly(ethylene glycol) (PEG) blocks, thus PEG-b(PLA-ss-PLA)-b-PEG (ssBCP). This copolymer self-assembles to form colloidally-stable mono-cleavable micelles having single disulfides in hydrophobic PLA cores surrounded with PEG coronas in aqueous solution. The reductive cleavage of the core disulfides results in changes in micelle morphologies to smaller nanostructures or larger aggregates, depending on the nature of reducing agents. In the presence of glutathione (a cellular reducing agent), the micelle size increases, which enhances the release of encapsulated anticancer drugs in vitro. For biological perspectives, the ssBCP micelles having hydrophilic PEG corona are non-cytotoxic and exhibit enhanced colloidal stability as well as non-specific interactions with proteins. | 25,159,511 | [
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A microarray platform and novel SNP calling algorithm to evaluate Plasmodium falciparum field samples of low DNA quantity. | Analysis of single nucleotide polymorphisms (SNPs) derived from whole-genome studies allows for rapid evaluation of genome-wide diversity, and genomic epidemiology studies of Plasmodium falciparum provide insights into parasite population structure, gene flow, drug resistance and vaccine development. In areas with adequate cold chain facilities, large volumes of leukocyte-depleted patient blood can be frozen for use in parasite genomic analyses. In more remote endemic areas smaller volumes of infected blood are taken by finger prick, and dried and stored on filter paper. These dried blood spots do not generally yield enough concentrated parasite DNA for whole-genome sequencing. A DNA microarray was designed for use on field samples to type a genome-wide set of SNPs which prior sequencing had shown to be variable in Africa, Southeast Asia, and Papua New Guinea. An algorithm was designed to call SNPs in samples with low parasite DNA. With this new algorithm SNP-calling accuracy of 98% was measured by hybridizing purified DNA from malaria lab strains and comparing calls with SNPs called from full genome sequences. An average accuracy of >98% was likewise obtained for DNA extracted from malaria field samples collected in studies in Southeast Asia, with an average call rate of > 82%. This new high-density microarray provided high quality SNP calls from a wide range of parasite DNA quantities, and represents a robust tool for genome-wide analysis of malaria parasites in diverse settings. | 25,159,520 | [
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Assessment of ovarian cancer conditions from exhaled breath. | We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor-free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC. | 25,159,530 | [
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Nanostructured porous Si optical biosensors: effect of thermal oxidation on their performance and properties. | The influence of thermal oxidation conditions on the performance of porous Si optical biosensors used for label-free and real-time monitoring of enzymatic activity is studied. We compare three oxidation temperatures (400, 600, and 800 °C) and their effect on the enzyme immobilization efficiency and the intrinsic stability of the resulting oxidized porous Si (PSiO2), Fabry-Pérot thin films. Importantly, we show that the thermal oxidation profoundly affects the biosensing performance in terms of greater optical sensitivity, by monitoring the catalytic activity of horseradish peroxidase and trypsin-immobilized PSiO2. Despite the significant decrease in porous volume and specific surface area (confirmed by nitrogen gas adsorption-desorption studies) with elevating the oxidation temperature, higher content and surface coverage of the immobilized enzymes is attained. This in turn leads to greater optical stability and sensitivity of PSiO2 nanostructures. Specifically, films produced at 800 °C exhibit stable optical readout in aqueous buffers combined with superior biosensing performance. Thus, by proper control of the oxide layer formation, we can eliminate the aging effect, thus achieving efficient immobilization of different biomolecules, optical signal stability, and sensitivity. | 25,159,537 | [
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Management of acute calcific tendinitis around the hip joint. | Although the natural history of calcific tendinitis within the rotator cuff of the shoulder is established, the natural history of calcific tendinitis around the hip joint remains unknown. To examine the duration of symptoms including pain, the location of calcific tendinitis around the hip joint, the radiologic course of calcium phosphate crystals, and the proportion of patients who required surgical treatment. Case series; Level of evidence, 4. Thirty hips (29 patients) with acute calcific tendinitis were treated between January 2010 and December 2012. Level of subjective hip pain using the visual analog scale pain score, radiologic type, and the location and size of calcium deposits were measured during a follow-up period of 12 to 32 months. The 29 patients included 7 men (24%) and 22 women (76%) with a mean age of 51.5 years (range, 28-78 years). All visual analog scale pain scores significantly improved from a mean of 7.1 to 0.8 at the latest follow-up (P < .001). The most common site of calcium deposition was the tendon of the gluteus medius. During follow-up, calcium deposition completely resolved in 5 of 20 hips. Symptoms in 23 patients (24 hips) responded to nonoperative treatment. Two patients (2 hips) were treated with ultrasound-guided local anesthetic and steroid injection. Four patients (4 hips) with long duration (>3 months) of severe pain, solid type, and large size (range, 96-416 mm(2)) were treated with arthroscopic excision. Nonoperative treatment in patients with acute calcific tendinitis of the hip joint might be successful in most patients. Surgical treatment is of value for patients experiencing prolonged severe pain, solid type, and large size. | 25,159,540 | [
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School-based prevention program associated with increased short- and long-term retention of safety knowledge. | Validation of program effectiveness is essential in justifying school-based injury prevention education. Although Risk Watch (RW) targets burn, fire, and life safety, its effectiveness has not been previously evaluated in the medical literature. Between 2007 and 2012, a trained fire service public educator (FSPE) taught RW to all second grade students in one public school district. The curriculum was delivered in 30-minute segments for 9 consecutive weeks via presentations, a safety smoke house trailer, a model-sized hazard house, a student workbook, and parent letters. A written pre-test (PT) was given before RW started, a post-test (PT#1) was given immediately after RW, and a second post-test (PT#2) was administered to the same students the following school year (ranging from 12 to 13 months after PT). Students who did not complete the PT or at least one post-test were excluded. Comparisons were made by paired t-test, analysis of variance, and regression analysis. After 183 (8.7%) were excluded for missing tests, 1,926 remaining students scored significantly higher (P = .0001) on PT#1 (mean 14.8) and PT#2 (mean 14.7) than the PT (mean 12.1). There was 1 FSPE and 36 school teachers with class size ranging from 10 to 27 (mean 21.4). Class size was not predictive of test score improvement (R = 0%), while analysis of variance showed that individual teachers trended toward some influence. This 6-year prospective study demonstrated that the RW program delivered by an FSPE effectively increased short-term knowledge and long-term retention of fire/life safety in early elementary students. Collaborative partnerships are critical to preserving community injury prevention education programs. | 25,159,554 | [
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Interest of functional foods for low-income countries. | To understand the interest of functional food in low-income countries by analyzing various necessary factors. Being on a low income would appear to relate most often to an unbalanced diet, both qualitatively and quantitatively, which may be damaging to health in the long term. Most chronic diseases of concern today are multifactorial in origin. For control, an approach in which medicines and nutrition are considered together and complement each other may produce most successful and cost-effective management of health risk factors and chronic diseases. Functional food may become an important player at the interface between pharma and nutrition, and merit attention from both public health and a marketing perspective. In general, the health benefit of functional food is well established and the attitude both to functional food and to their low socioeconomic consumers is positive. | 25,159,560 | [
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Synthesis of copper/nickel nanoparticles using newly synthesized Schiff-base metals complexes and their cytotoxicity/catalytic activities. | Transition metal complexes compounds with Schiff bases ligand representing an important class of compounds that could be used to develop new metal-based anticancer agents and as precursors of metal NPs. Herein, 2,3-bis-[(3-ethoxy-2-hydroxybenzylidene)amino]but-2-enedinitrile Schiff base ligand and its corresponding copper/nickel complexes were synthesized. Also, we reported a facile and rapid method for synthesis nickel/copper nanoparticles based on thermal reduction of their complexes. Free ligand, its metal complexes and metals nanoparticles have been characterized based on elemental analysis, transmission electron microscopy, powder X-ray diffraction, magnetic measurements and by various spectroscopic (UV-vis, FT-IR, (1)H NMR, GC-MS) techniques. Additionally, the in vitro cytotoxic activity of free ligand and its complexes compounds were assessed against two cancer cell lines (HeLa and MCF-7 cells)and one healthy cell line (HEK293 cell). The copper complex was found to be active against these cancer cell lines at very low LD50 than the free ligand, while nickel complex did not show any anticancer activity against these cell lines. Also, the antibacterial activity of as-prepared copper nanoparticles were screened against Escherichia coli, which demonstrated minimum inhibitory concentration and minimum bactericidal concentration values lower than those values of the commercial Cu NPs as well as the previous reported values. Moreover, the synthesized nickel nanoparticles demonstrated remarkable catalytic performance toward hydrogenation of nitrobenzene that producing clean aniline with high selectivity (98%). This reactivity could be attributed to the high degree of dispersion of Ni nanoparticles. | 25,159,596 | [
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Beneficial effect of splanchnic nerve transection and harmful effect of vagotomy on acute necrotizing pancreatitis in the dog. | The nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. However, the influence of visceral nerve (VN) on acute necrotizing pancreatitis (ANP) has drawn little attention. To investigate the influence of VN on the pathophysiological process of ANP in dogs. The dogs were divided into a sham operation (SO) group, ANP group, ANP + vagal nerve trunk transection (VNTT) group, and ANP + greater splanchnic nerve transection (GSNT) group. The VNTT and GSNT groups underwent VNTT and GSNT respectively immediately after ANP induction. The levels of serum pancreatic amylase (AMY), calcium, high-sensitivity C-reactive protein (HCRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were monitored dynamically and the pathological examinations of the pancreas was performed at postoperative day 7. All serum parameters among the four groups showed no differences before the experiment (p > 0.05). At different postoperative times, the serum TNF-α, IL-1β, HCRP, and AMY were significantly increased, however, the serum calcium and IL-10 had dropped in the ANP group versus SO group (p < 0.05); an alike variation trend occurred between the VNTT group and ANP group (p < 0.05); an opposite variation trend occurred between the GSNT group and the ANP group (p < 0.05). The pancreas pathological scoring of VNTT group was highest in the four groups (p < 0.05) and GSNT group was lower versus ANP group (p < 0.05). The GSNT has been shown to alleviate development of ANP, however, VNTT may exacerbate the ANP. | 25,159,609 | [
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How the misincorporation of ribonucleotides into genomic DNA can be both harmful and helpful to cells. | Ribonucleotides are misincorporated into replicating DNA due to the similarity of deoxyribonucleotides and ribonucleotides, the high concentration of ribonucleotides in the nucleus and the imperfect accuracy of replicative DNA polymerases in choosing the base with the correct sugar. Embedded ribonucleotides change certain properties of the DNA and can interfere with normal DNA transactions. Therefore, misincorporated ribonucleotides are targeted by the cell for removal. Failure to remove ribonucleotides from DNA results in an increase in genome instability, a phenomenon that has been characterized in various systems using multiple assays. Recently, however, another side to ribonucleotide misincorporation has emerged, where there is evidence for a functional role of misinserted ribonucleotides in DNA, leading to beneficial consequences for the cell. This review examines examples of both positive and negative effects of genomic ribonucleotide misincorporation in various organisms, aiming to highlight the diversity and the utility of this common replication variation. | 25,159,610 | [
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Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery. | The RNA component of signal recognition particle (SRP) is transcribed by RNA polymerase III, and most steps in SRP biogenesis occur in the nucleolus. Here, we examine processing and quality control of the yeast SRP RNA (scR1). In common with other pol III transcripts, scR1 terminates in a U-tract, and mature scR1 retains a U4-5 sequence at its 3' end. In cells lacking the exonuclease Rex1, scR1 terminates in a longer U5-6 tail that presumably represents the primary transcript. The 3' U-tract of scR1 is protected from aberrant processing by the La homologue, Lhp1 and overexpressed Lhp1 apparently competes with both the RNA surveillance system and SRP assembly factors. Unexpectedly, the TRAMP and exosome nuclear RNA surveillance complexes are also implicated in protecting the 3' end of scR1, which accumulates in the nucleolus of cells lacking the activities of these complexes. Misassembled scR1 has a primary degradation pathway in which Rrp6 acts early, followed by TRAMP-stimulated exonuclease degradation by the exosome. We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, potentially facilitating the decision between these alternative fates. | 25,159,613 | [
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40S recruitment in the absence of eIF4G/4A by EMCV IRES refines the model for translation initiation on the archetype of Type II IRESs. | Initiation of translation on Type II IRESs, such as those of EMCV and FMDV viruses, has been well documented in the recent years. For EMCV, the current model argues for a mechanism in which the key interaction necessary for the pre-initiation complex recruitment is eIF4G binding to the central J-K domains of EMCV-IRES. Here we demonstrate that, in contrast with the current model, the molecular mechanism of EMCV-IRES involves direct recruitment of the 40S subunit. Importantly, we identified a specific structural element that prevents the correct positioning of the initiation codon in the close vicinity of the ribosomal P site. This work clarifies how this interaction could not be anticipated by earlier studies and allows us to propose a new model for initiation complex assembly on EMCV-IRES. The role attributed to eIF4G/4A can thus be refined as stabilizing/promoting the conformational changes that are necessary for IRES function, thus resembling the role conventionally assigned to ITAFs. This raises the interesting possibility that IRESs are primarily ribosome binders, some of which having partly lost the ability to fold into the active structure without the help of proteins. | 25,159,618 | [
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Minimally invasive surgical techniques are safe in the diagnosis and treatment of pediatric malignancies. | Minimally invasive surgical (MIS) techniques have become an established part of the care of the adult oncology patient. As surgeons have become more experienced with these advances in technique, MIS has recently seen an expanding role in the diagnosis and treatment of pediatric malignancies. We hypothesize that MIS techniques can be used to provide reliable diagnosis and safe therapeutic resection of many pediatric malignancies. We performed a retrospective review of all patients who underwent a minimally invasive operation for diagnosis or treatment of a malignant solid tumor at the Children's Hospital Colorado over a ten-year period. A total of 105 minimally invasive procedures were performed in 98 patients, 61% of which were male. The majority of cases, 78 (74%) were thoracoscopic procedures and the remaining 27 (26%) were laparoscopic procedures. Twenty-one (27%) thoracoscopic procedures were performed for complete resection of primary tumor or metastases, with only three cases (14%) converted to open thoracotomy. Tumors that were successfully removed thoracoscopically include neuroblastomas (n = 8), metastatic disease (n = 7), and a schwannoma. Of the 28 laparoscopic procedures, nine were performed for tumor resection with one case converted to open. Tumors that were successfully removed laparoscopically include 6 adrenal neuroblastomas and one pseudopapillary pancreatic tumor. There were no major surgical complications. No port site or surgical site recurrences were reported. MIS techniques can be used safely and effectively for the diagnosis and resection of pediatric malignancies and treatment decisions can be made accurately based on tissue obtained. | 25,159,642 | [
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Robotic left colon cancer resection: a dual docking technique that maximizes splenic flexure mobilization. | Techniques for robotic resection of the left colon are not well defined and have not been widely adopted due to limited range of motion of the robotic arms. We have developed a dual docking technique for both the splenic flexure and the pelvis. We report our initial experience of robotic left colectomy using this technique for left-sided colon cancer. The study group comprised 61 patients who underwent robotic left colon cancer resection using our dual docking technique between July 2008 and January 2013. Operations comprised two stages: colon mobilization (stage 1) followed by pelvic dissection (stage 2). After completion of stage 1, the robot arms were undocked and the operating table was rotated 60° counterclockwise until a 45° angle was created between the patient cart and the operating table. All 61 procedures were technically successful without the need for conversion to laparoscopic or open surgery. Median total operation, 1st docking, and 2nd docking times were 227 min (range, 137-653 min), 4 min (range, 3-8 min), and 3 min (range, 3-9 min), respectively. Estimated blood loss was 20 ml (range, 20-2,000 ml). Median time to soft diet was 2 days (range, 2-12 days) and median length of hospital stay was 7 days (range, 4-20 days). Median total number of lymph nodes harvested was 17 (range, 3-61). According to the Clavien-Dindo classification, the numbers of complications for grades 1, 2, 3a, 3b, and 4 were 10, 2, 3, 3, and 1. There was no mortality within 30 days. Robotic left colon cancer resection using our dual docking technique is safe and feasible. This procedure can maximize splenic mobilization in robotic colorectal surgery. | 25,159,646 | [
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Laparoscopic limited Heller myotomy without anti-reflux procedure does not induce significant long-term gastroesophageal reflux. | Laparoscopic Heller myotomy with partial fundoplication is the gold standard treatment for achalasia. Laparoscopic limited Heller myotomy (LLHM) with no anti-reflux procedure is another possible option. A review of prospectively collected data was performed on patients who underwent LLHM from January 1998 to December 2012. Evaluation included gastroscopy, esophageal manometry, 24-h pH-metry, and the Short Form(36) Health Survey(SF-36) questionnaire at baseline and 6 months, as well as the global symptom score at baseline, 6 months, and 5 years post-surgery. Comparison between outcomes was performed with a paired t student's test. 126 patients underwent LLHM. Of these, 60 patients had complete pre and post-operative motility studies. 57 % were female, patient mean age was 45.7 years, with a mean follow-up of 10.53 months. Mean operative time was 56.1 min, and the average length of stay was 1.7 days. At 6 months, a significant decrease in the lower esophageal sphincter resting pressure (29.1 vs. 7.1 mmHg; p < 0.001) and nadir (16.4 vs. 4.3 mmHg; p < 0.001) was observed. Normal esophageal acid exposure (total pH < 4 %) was observed in 68.3 % patients. Nevertheless, of the remaining 31.7 % with abnormal pH-metry, only 21.6 % were clinically symptomatic and all were properly controlled with medical treatment without requiring anti-reflux surgery. Significant improvement in all pre-operative symptoms was observed at 6 months and maintained over 5 years. Dysphagia score was reduced from 9.8 pre-operatively to 2.6 at 5 years (p < 0.001), heartburn score from 3.82 to 2 (p < 0.01), and regurgitation score from 7.5 to 0.8 (p < 0.001). Only one patient (0.8 %) presented with recurrent dysphagia requiring reoperation. LLHM without anti-reflux procedure is an effective long-term treatment for achalasia and does not cause symptomatic GERD in three quarters of patients. The remaining patients are well controlled on anti-reflux medications. It is believed that similar clinical results would be obtained during a clinical investigation of the POEM procedure. | 25,159,656 | [
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Human ApoE ε4 alters circadian rhythm activity, IL-1β, and GFAP in CRND8 mice. | Disruptions to daily living, inflammation, and astrogliosis are characteristics of Alzheimer's disease. Thus, circadian rhythms, nest construction, IL-1β and TNF-α, and glial fibrillary acidic protein (GFAP) were examined in a mouse model developed to model late-onset Alzheimer's disease-the most common form of the disease. Mice carrying both the mutated human AβPP transgene found in the CRND8 mouse and the human apolipoprotein E ε4 allele (CRND8/E4) were compared with CRND8 mice and wildtype (WT) mice. Circadian rhythms were evaluated by wheel-running behavior. Activity of daily living was measured by nest construction. This study then examined mRNA levels of the inflammatory cytokines IL-1β and TNF-α as well as protein levels of GFAP. Behavioral outcomes were then correlated with cytokines and GFAP. Compared to WT controls, both CRND8 and CRND8/E4 mice showed significantly more frequent, but shorter, bouts of activity. In the three groups, the CRND8/E4 mice had intermediate disruptions in circadian rhythms. Both CRND8/E4 mice and CRND8 mice showed significant impairments in nesting behavior compared to WTs. While CRND8 mice expressed significantly increased IL-1β and GFAP expression compared to WT controls, CRND8/E4 mice expressed intermediate IL-1β and GFAP levels. Significant correlations between IL-1β, GFAP, and behavior were observed. These data are congruent with other studies showing that human ApoE ε4 is protective early in life in transgenic mice modeling Alzheimer's disease. | 25,159,669 | [
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Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease. | There is growing recognition that cerebral hypoperfusion is related to the pathogenesis of Alzheimer's disease (AD), implicating the measurement of cerebral blood flow (CBF) as a possible biomarker of AD. The ability to identify the earliest and most reliable markers of incipient cognitive decline and clinical symptoms is critical to develop effective preventive strategies and interventions for AD. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) measures CBF by magnetically labeling arterial water and using it as an endogenous tracer. Studies using ASL MRI in humans indicate that CBF changes are present several years before the development of the clinical symptoms of AD. Moreover, ASL-measured CBF has been shown to distinguish between cognitively normal individuals, adults at risk for AD, and persons diagnosed with AD. Some studies indicate that CBF may even be sensitive for predicting cognitive decline and conversion to mild cognitive impairment and AD over time. Taken together, evidence suggests that the current staging models of AD biomarker pathology should incorporate early changes in CBF as a useful biomarker, possibly present even earlier than amyloid-β accumulation. Though still a research tool, ASL imaging is a promising non-invasive and reliable method with the potential to serve as a future clinical tool for the measurement of CBF in preclinical AD. | 25,159,672 | [
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Waterpipe use and cognitive susceptibility to cigarette smoking among never-cigarette smoking Jordanian youth: analysis of the 2009 Global Youth Tobacco Survey. | Susceptibility to cigarette smoking, defined as lack of a firm decision to not initiate smoking, predicts youth smoking initiation and experimentation and is a first step in the transition to regular smoking. This study investigated whether waterpipe (WP) smoking, an increasingly prevalent form of tobacco use among Arab adolescents, was associated with increased susceptibility to cigarette smoking. A secondary analysis of the 2009 Jordan Global Youth Tobacco Survey was conducted to assess the association between WP use and cigarette susceptibility, after adjusting for important confounders. A total of 1,476 youth aged 13-15 years old who had never smoked cigarettes were identified and represented 166,593 never-cigarette smoking Jordanian youth. We found 40% of boys and 29% of girls were susceptible to cigarette smoking, and both boys (adjusted odds ratio [AOR] = 1.49, 95% confidence interval [CI] = 1.41-1.54) and girls (AOR = 1.95, 95% CI = 1.83-2.04) who had ever smoked WP were more susceptible to cigarette smoking than those who never smoked WP. This is the first study to report that WP use may increase youth's susceptibility to initiate cigarette smoking. | 25,159,679 | [
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Personalizing risk stratification by addition of PAK1 expression to TNM staging: improving the accuracy of clinical decision for gastroesophageal junction adenocarcinoma. | Gastroesophageal junction adenocarcinoma (GEJA) is an aggressive malignancy with an alarmingly rising incidence. TNM staging is widely used by oncologists to stratify prognosis as well as direct therapeutic strategies. However, inadequate lymphadenectomy is frequently encountered for GEJA and largely confounds prognosis resulting from TNM staging. Thus, a molecular biomarker, which can accurately forecast the risk of nodal metastasis in patients with inadequate lymphadenectomy, is required to guide precisely clinical decision. In this study, bioinformatics and pathological analysis identified that p21 protein-activated kinase 1 (PAK1) is associated with lymph nodal metastasis of GEJA. The PAK1 H-score was lower in the patients with negative lymph nodes than that in patients with positive (metastatic) lymph nodes (6.865 ± 3.376, 9.370 ± 2.530, respectively; p < 0.001). The PAK1 H-score in lymph nodes was positively correlated with that in primary tumors (PTs; p < 0.001; r = 0.475). PAK1 H-scores in PTs had the best performance based on its area under the receiver-operating characteristic (ROC) curve compared with PAK1 H-scores in lymph nodes, histological grade, lymph nodal metastasis status, tumor size, depth of tumor, TNM stage and number of resected lymph nodes. Multivariate Cox proportional hazard and Fine and Gray models showed that histological grade 3, Charlson comorbidity index > 7 and high PAK1 expression in PTs were associated with significantly increased risk of recurrence and cancer-related death. In conclusion, high PAK1 expression in PTs is predictive of node metastasis and can be easily integrated in the clinical decision process for personalized therapeutics of GEJA. | 25,159,681 | [
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Nursing Under the Old Poor Law in Midland and Eastern England 1780-1834. | This article uses data drawn from the overseers' accounts and supporting documentation in thirty-six parishes spread over four English counties, to answer three basic questions. First, what was the character, extent, structure, range of activities, and remuneration of the nursing labor force under the Old Poor Law between the late eighteenth century and the implementation of the New Poor Law in the 1830s? Second, were there regional and intra-regional differences in the scale and nature of spending on nursing care for the sick poor? Third, how might one explain such differences? The article suggests that nursing became an increasingly important category of spending for the poor law from the later eighteenth century, but that there were significant variations within and (particularly) between English counties in parochial attitudes toward the provision of nursing for the sick poor. These variations can be explained by applying a matrix of explanatory variables ranging from the minor (differences in how parishes defined "nursing") through to the major (long-standing cultural attitudes toward the responsibility of parishioners to their sick compatriots and the ingrained expectations of the sick poor). The article also throws new light on the hidden aspects of female labor force participation, pointing to the development of professional nursing networks long before the later nineteenth century. | 25,159,685 | [
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Improving the genetic representation of rare taxa within complex microbial communities using DNA normalization methods. | Complex microbial communities typically contain a large number of low abundance species, which collectively, comprise a considerable proportion of the community. This 'rare biosphere' has been speculated to contain keystone species and act as a repository of genomic diversity to facilitate community adaptation. Many environmental microbes are currently resistant to cultivation, and can only be accessed via culture-independent approaches. To enhance our understanding of the role of the rare biosphere, we aimed to improve their metagenomic representation using DNA normalization methods, and assess normalization success via shotgun DNA sequencing. A synthetic metagenome was constructed from the genomic DNA of five bacterial species, pooled in a defined ratio spanning three orders of magnitude. The synthetic metagenome was fractionated and thermally renatured, allowing the most abundant sequences to hybridize. Double-stranded DNA was removed either by hydroxyapatite chromatography, or by a duplex-specific nuclease (DSN). The chromatographic method failed to enrich for the genomes present in low starting abundance, whereas the DSN method resulted in all genomes reaching near equimolar abundance. The representation of the rarest member was increased by approximately 450-fold. De novo assembly of the normalized metagenome enabled up to 18.0% of genes from the rarest organism to be assembled, in contrast to the un-normalized sample, where genes were not able to be assembled at the same sequencing depth. This study has demonstrated that the application of normalization methods to metagenomic samples is a powerful tool to enrich for sequences from rare taxa, which will shed further light on their ecological niches. | 25,159,704 | [
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First-trimester screening biochemical markers (free beta-subunit human chorionic gonadotropin, pregnancy-associated plasma protein-A) and risk of early fetal loss. | The aim of this work was to assess the risk of early fetal loss (first trimester of pregnancy, 8-13 weeks of gestation) using the results of first-trimester screening (FTS) biochemical markers independently and combined. FTS results of 152 women who suffered early fetal loss were compared to a control group of 150 women with normal pregnancy outcomes. FTS biochemical markers were measured with a Delfia Xpress 6000 analyzer and biochemical risks for Down's and Edward's syndromes were calculated using Prenatal-Lifecycle version 3.0 software. Marker levels were standardized by calculating the gestational-specific multiple of the medians (MoM), further adjusted by maternal age, maternal weight, cigarette consumption and pre-existing type 1 diabetes mellitus. Receiver-operator curves were built to evaluate each marker and its combination. Our results show that values of biochemical risk of t21 of more than 1 in 310 have a poor sensitivity to predict early fetal loss (31.4%) with a positive predictive value (PPV) for fetal loss of 67.7%. Values of pregnancy-associated plasma protein A (PAPP-A) MoM of less than 0.48 show a sensitivity of 62.1% and a PPV of 84.5% for early fetal loss; whereas for free β-human chorionic gonadotropin, values of MoM of less than 0.44 have a sensitivity of 66.4% with a PPV of 85.3%. A novel algorithm, consisting in the multiplication of both markers, shows for values of less than 0.48 a sensitivity of 83.1%, a specificity of 78.7% and a PPV of 77.1%. Combined analysis of PAPP-A and free β-hCG appears to be a potential candidate to predict early fetal loss. | 25,159,705 | [
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International approaches to Indigenous dental care: what can we learn? | Indigenous populations around the world have significantly poorer oral health and inequalities in access to dental care largely attribute to the social determinants of health. Reviewing international literature offers an opportunity to better understand appropriate approaches for policy and practice in Australia. This article is a descriptive narrative review based on primary research literature discussing informative international approaches to Indigenous dental care. Approaches identified in the literature included integration of dentistry with primary health care and traditional practice, training and use of oral health professionals and approaches used at different stages of life, particularly in the management of early childhood caries. The international literature provides a range of approaches to Indigenous oral health. Tailored, culturally appropriate family and community based initiatives that address the multidisciplinary issues confronting Indigenous communities were most highly regarded. | 25,159,709 | [
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Examining the function in sitting test for validity, responsiveness, and minimal clinically important difference in inpatient rehabilitation. | To determine the responsiveness of the Function In Sitting Test (FIST), compare scores at admission and discharge from inpatient rehabilitation (IPR) with other balance and function measures, and determine the minimal clinically important difference (MCID). Prospective, nonblinded, reference-standard comparison study. Four accredited inpatient rehabilitation units. Population-based sample of adults (N=125) with sitting balance dysfunction, excluding persons with spinal cord injury, significant bracing/orthotics, and inability to perform testing safely. Not applicable. FIST, FIM, and Berg Balance Scale (BBS) at admission and discharge, and Global Rating of Change for function and balance at discharge. The FIST demonstrated good to excellent concurrent validity with the BBS and FIM at admission and discharge (Spearman ρ=.71-.85). Significant improvement (P<.000; 95% confidence interval [CI], 10.73-15.41) occurred in the FIST from admission (mean ± SD: 36.81±15.53) to discharge (mean ± SD: 49.88±6.90). The standard error of measurement for the FIST was 1.40, resulting in a minimal detectable change of 5.5 points. The receiver operator characteristic curve differentiated participants with meaningful balance changes (area under the curve, .78; P>.000; 95% CI, .66-.91), with a change in FIST score of ≥6.5 points designating the MCID. Findings support the strong responsiveness of the FIST during IPR as evidenced by the large effect size (.83), standardized response mean (1.04), and index of responsiveness (1.07). In this study, the FIST correlated well with balance and function measures (concurrent validity) and was responsive to change during IPR. A clinically meaningful change was indicated by an increase in score of ≥6.5 points. | 25,159,714 | [
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That eagle covering me: transitioning and connected autonomy for emerging adults with cystinosis. | Rare diseases pose transitioning challenges owing to limited provider expertise and changing healthcare systems. The timeframe and developmental changes of emerging adulthood overlap with the transition of patients with cystinosis from pediatric to adult-oriented healthcare. This study utilized techniques of qualitative grounded theory to explore the experiences of adults aged 18-47 with cystinosis, and their parents, with a focus on the transition to adulthood and adult-oriented care. Forty-six individuals from 21 families were recruited online and at cystinosis conferences to participate in focus groups and/or individual interviews. The constant comparative method was used to conduct both line-by-line and focused coding of verbatim transcripts. The following elements were reported to be critical to the transition to adulthood and adult-oriented care: gaining skills and responsibility for disease management, progressing toward autonomy while remaining connected to caregivers, and having strong communication with and between providers. Data analysis identified behaviors and relationships that support and/or threaten autonomy and treatment adherence. Participants described institutional, relational, and practical barriers to transition. Suggestions for improving transitioning include: identifying patient/family strengths and improving pediatric-adult provider partnerships and communication. Further research is needed into the experience of patients before and after transition to adult-oriented care. | 25,159,720 | [
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Nontraditional risk factors for cardiovascular disease and visceral adiposity index among different body size phenotypes. | Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities). We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01). Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies. | 25,159,728 | [
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Occurrence of decabromodiphenyl ethane in captive Chinese alligators (Alligator sinensis) from China. | Decabromodiphenyl ethane (DBDPE), a replacement for decabromodiphenyl ether (deca-BDE), was investigated in captive Chinese alligators from China. DBDPE was detected in adult tissues, neonates and eggs of Chinese alligators with concentrations ranging from 4.74-192, 0.24-1.94, and 0.01-0.51 ng g(-1) lipid weight, respectively. Compared to PBDEs and PCBs, DBDPE contamination was limited in Chinese alligators. Additionally, DBDPE concentrations in adult muscles were one to three orders of magnitude higher than those in neonates and eggs, suggesting the limited maternal transfer potential of DBDPE in Chinese alligators. This is the first study to report the occurrence of DBDPE in Chinese alligators. | 25,159,734 | [
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Comparing neuroprotective effects of CDNF-expressing bone marrow derived mesenchymal stem cells via differing routes of administration utilizing an in vivo model of Parkinson's disease. | The potential value of cerebral dopamine neurotrophic factor (CDNF) in treating Parkinson's disease (PD) remains controversial. To evaluate the therapeutic effects of CDNF-expressing bone marrow derived mesenchymal stem cell (CDNF-MSCs) injections in a rat model of Parkinson's disease, we chose three different routes of CDNF-MSC administration, including intra-striatal, intra-ventricular, and intravenous pathways. Parkinsonism was induced by intra-striatal unilateral injection of 6-OHDA and then rats were subsequently randomized into three groups for either intra-striatal, intra-ventricular or intravenous injection for CDNF-MSC grafting. Therapeutic effects were evaluated by observing dopaminergic (DA) neurons both in the substantia nigra compacta (SNc) and within the striatum and by monitoring apomorphine-induced rotational behavior (circling). Data show that one intra-venous administration of CDNF-MSCs was ineffective for treating Parkinson's disease-like neurodegeneration. Conversely, intra-striatal grafts can reduce loss of DA neurons both in the SNc and striatum with improvement of Parkinson's-related behaviors, compared to intra-ventricular injections. Thus, intra-striatal grafts composed of CDNF-MSCs may provide a strategy for therapeutic delivery to treat PD. | 25,159,816 | [
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Antioxidant, antibacterial and cytotoxic potential of the ripe fruits of Solanum lycocarpum A. St. Hil. (Solanaceae). | Ethanol extract (EE) and fractions obtained from the ripe fruits of Solanum lycocarpum were examined in order to determine their phenolic composition, antioxidant capacity, antibacterial activities and cytotoxic potential. High-performance liquid chromatography coupled with DAD analysis indicated that caffeic and chlorogenic acids were the main phenolic compounds present in the EE, dichloromethane (DCM) and ethyl acetate (Ac) fractions. The antioxidant activity assessed by the scavenging ability on 1,1-diphenyl-2-picrylhydrazyl radical was significantly more pronounced for DCM and Ac fractions than that of the commercial antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT). EE and fractions exhibited selective antibacterial activity against Gram-positive bacteria, especially the hexane (Hex) and DCM fractions. EE and fractions exhibited low toxicity towards the LLC-MK2 cell line, especially the Hex, DCM and Ac fractions. This work provides the knowledge of phenolic composition in the extract and fractions from the ripe fruits of S. lycocarpum and their antioxidant, antibacterial and cytotoxic activities. | 25,159,821 | [
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Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution. | Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity. | 25,159,823 | [
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Pulse-chase analysis of procollagen biosynthesis by azidohomoalanine labeling. | Disruptions in procollagen synthesis, trafficking and secretion by cells occur in multiple connective tissue diseases. Traditionally, these disruptions are studied by pulse-chase labeling with radioisotopes. However, significant DNA damage, excessive accumulation of reactive oxygen species and formation of other free radicals have been well documented in the literature at typical radioisotope concentrations used for pulse-chase experiments. Therefore, it is important to keep in mind that the resulting cell stress response might affect interpretation of the data, particularly with respect to abnormal function of procollagen-producing cells. In this study, we describe an alternative method of pulse-chase procollagen labeling with azidohomoalanine, a noncanonical amino acid that replaces methionine in newly synthesized protein chains and can be detected via highly selective click chemistry reactions. At least in fibroblast culture, this approach is more efficient than traditional radioisotopes and has fewer, if any, unintended effects on cell function. To illustrate its applications, we demonstrate delayed procollagen folding and secretion by cells from an osteogenesis imperfecta patient with a Cys substitution for Gly766 in the triple helical region of the α1(I) chain of type I procollagen. | 25,159,826 | [
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Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor. | Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders. | 25,159,846 | [
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Resistance through inhibition: ectopic expression of serine protease inhibitor offers stress tolerance via delayed senescence in yeast cell. | Protease inhibitors have been known to confer multiple stress tolerance in transgenic plants. We have assessed growth of yeast (Pichia pastoris GS115) strains expressing inhibitory repeat domains (PpIRD(+)) of previously characterized Capsicum annuum protease inhibitors under high salt, heavy metal and oxidative stress. PpIRD(+) strains exhibited multiple stress tolerance and showed differential molecular responses at transcriptional and translational level on exposure to stress inducing agents like heavy metal, high salt and H2O2. PpIRD(+) strains display significant reduction in metacaspase (Yca1) activity, the key enzyme in apoptosis, indicates the possibility of cross reactivity of IRDs (serine protease inhibitor) with cysteine proteases. PpIRD(+) and Saccharomyces cerevisiae knockout with Yca1 (ΔYca1) strain showed similar growth characteristics under stress, which indicated the delayed senescence due to cellular metacaspase inhibition. Molecular docking study showed a close proximity of IRDs reactive site and the active site of metacaspase in the complex that signified their strong interactions. Maintenance of GAPDH activity, primary target of metacaspase, in PpIRD(+) strain evidenced the inhibition of metacaspase activity and survival of these cells under stress. This report demonstrates a potential molecular mechanism of protease inhibitor-based multiple stress tolerance in yeast strains. | 25,159,848 | [
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Pyrene-based quantitative detection of the 5-formylcytosine loci symmetry in the CpG duplex content during TET-dependent demethylation. | Methylcytosine (5mC) is mostly symmetrically distributed in CpG sites. Ten-eleven-translocation (TET) proteins are the key enzymes involved in active DNA demethylation through stepwise oxidation of 5mC. However, oxidation pathways of TET enzymes in the symmetrically methylated CpG context are still elusive. Employing the unique fluorescence properties of pyrene group, we designed and synthesized a sensitive fluorescence-based probe not only to target 5-formylcytosine (5fC) sites, but also to distinguish symmetric from asymmetric 5fC sites in the double stranded DNA context during TET-dependent 5mC oxidation process. Using this novel probe, we revealed dominant levels of symmetric 5fC among total 5fC sites during in vitro TET-dependent 5mC oxidation and novel mechanistic insights into the TET-dependent 5mC oxidation in the mCpG context. | 25,159,856 | [
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Interrelationship between bone substitution materials and skeletal muscle tissue. | Bone density and quantity are primary conditions for the insertion and stability of dental implants. In cases of a lack of adequate maxillary or mandibulary bone, bone augmentation will be necessary. The use of synthetic bioactive bone substitution materials is of increasing importance as alternatives to autogenously bone grafts. It is well known that bone can influence muscle function and muscle function can influence bone structures. Muscles have a considerable potential of adaptation and muscle tissue surrounding an inserted implant or bone surrogate can integrate changes in mechanical load of the muscle and hereupon induce signaling cascades with protein synthesis and arrangement of the cytoskeleton. The Musculus latissimus dorsi is very often used for the analyses of the in vivo biocompatibility of newly designed biomaterials. Beside macroscopically and histologically examination, biocompatibility can be assessed by analyses of the biomaterial influence of gene expression. This review discusses changes in the fiber type distribution, myosin heavy chain isoform composition, histological appearance and vascularization of the skeletal muscle after implantation of bone substitution materials. Especially, the effects of bone surrogates should be described at the molecular-biological and cellular level. | 25,159,858 | [
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Sociodemographic and clinical correlates of migrant status in adults with psychotic disorders: data from the Australian Survey of High Impact Psychosis. | The links between migrant status and psychosis have attracted considerable attention in recent decades. The aim of the study was to explore the demographic and clinical correlates of migrant v. Australia-born status in individuals with psychotic disorders using a large community-based sample. Data were drawn from a population-based prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas in 2010. Logistic regression was used for the main analyses, examining associations of migrant status with sociodemographic and clinical variables. Of the 1825 participants with psychotic disorders, 17.8% (n = 325) were migrants, of whom 55.7% (n = 181) were male. Compared to Australia-born individuals with psychosis, migrants were more likely to be currently married, to have completed a higher level at school, to have left school later, and to be employed with full-time jobs. Migrants with psychosis were either no different from or less impaired or disadvantaged compared to their Australian-born counterparts on a range of clinical and demographic variables. In a sample of individuals with psychotic disorders, there was no evidence to suggest that migrant status was associated with worse clinical or socio-economic outcomes compared to their native-born counterparts. | 25,159,855 | [
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Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration. | To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action. | 25,159,861 | [
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Antecedent predictors of children's initiation of sipping/tasting alcohol. | Sipping or tasting alcohol is one of the earliest alcohol-use behaviors in which young children engage, yet there is relatively little research on this behavior. Previous cross-sectional analyses determined that child sipping or tasting is associated with the child's attitude toward sipping and with a family environment supportive of alcohol use, but not with variables reflecting psychosocial proneness for problem behavior as formulated in Problem Behavior Theory (Jessor and Jessor, Problem Behavior and Psychosocial Development: A Longitudinal Study of Youth, 1977, Academic Press, New York). This study extended these analyses longitudinally to identify antecedent predictors of the childhood initiation of sipping or tasting alcohol in a multiwave study. A sample of 452 children (238 girls) aged 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random digit dialing procedures. Children were interviewed using computer-assisted interviews. Antecedent variables collected at baseline (Wave 1) were examined as predictors of the initiation of sipping/tasting alcohol in childhood (before age 12) among Wave 1 abstainers (n = 286). Ninety-four children initiated sipping/tasting alcohol in a nonreligious context between baseline and turning age 12. Initiation of sipping/tasting did not generally relate to baseline variables reflecting psychosocial proneness for problem behavior. Instead, as found in the previous cross-sectional analyses, the variables most predictive of initiating sipping/tasting were perceived parents' approval for child sipping, parents' reported approval for child sipping, parents' current drinking status, and children's attitudes toward sipping/tasting alcohol. These longitudinal analyses replicate the earlier cross-sectional results. Young children's sipping/tasting of alcohol reflects parental modeling of drinking and parental approval of child sipping and does not represent a precocious manifestation of a psychosocial proneness to engage in problem behavior. | 25,159,887 | [
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Fidelity of delivery of a physical activity intervention: predictors and consequences. | Assessing fidelity of behavioural interventions is important, but demanding and rarely done. This study assessed adherence to behaviour change techniques used in an intervention to increase physical activity among sedentary adults ( ProActive ; N = 365). Transcripts of 108 sessions with a sub-sample of 27 participants were assessed. An independent assessor coded adherence of four 'facilitators' who delivered the intervention to 208 protocol-specified facilitator behaviours (e.g. 'elicit perceived advantages of becoming more active') in four key sessions. Four raters classified the 208 behaviours under 14 techniques (e.g., goal setting, use of rewards) to enable calculation of adherence to techniques. Observed adherence to techniques across participants was modest (median 44%, IQR 35-62%), and lower than that reported by facilitators. Adherence differed between facilitators (range: 26-63%) and decreased across the four sessions (mean drop 9% per session, 95% confidence interval 7-11%). In this small sample facilitator adherence was unrelated to (change in) participants' physical activity or its cognitive predictors: Attitudes, subjective norm, perceived behavioural control and intention. Future research should investigate causal pathways between fidelity indicators and outcomes in larger samples and develop and test less intensive measures of fidelity. | 25,159,904 | [
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School-based, randomised controlled trial of an evidence-based condom promotion leaflet. | A condom use promotion leaflet was designed for use with older teenagers in schools. The text targeted a series of cognitive and behavioural antecedents of condom use identified in the literature. Given previous evidence that motivational incentives can enhance the effectiveness of health promotion leaflets, the leaflet was presented in conjunction with a quiz and prize draw. Students were randomly assigned to either the intervention condition or a (no leaflet or incentive) control condition. Measures were taken immediately, pre-intervention and 4 weeks later from 404 students. The 20-min intervention successfully promoted six of the eight measured cognitions, namely (1) attitude towards using condoms with a new partner (2) attitude towards using condoms with a steady partner (3) normative beliefs in relation to preparatory actions (4) self-efficacy in relation to both preparatory actions and (5) condom use (6) intention to use condoms, as well as three measured preparatory actions, that is, purchasing condoms, carrying condoms and discussing condom use. The intervention did not increase condom use with steady or new partners but power to test intervention impact on condom use was curtailed. | 25,159,906 | [
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Drawing ability in typical and atypical development; colour cues and the effect of oblique lines. | Individuals with Williams syndrome (WS) have poor drawing ability. Here, we investigated whether colour could be used as a facilitation cue during a drawing task. Participants with WS and non-verbal ability matched typically developing (TD) children were shown line figures presented on a 3 by 3 dot matrix, and asked to replicate the figures by drawing on an empty dot matrix. The dots of the matrix were either all black (control condition), or nine different coloured dots (colour condition). In a third condition, which also used coloured dots, participants were additionally asked to verbalise the colours of the dots prior to replicating the line drawings (colour-verbal condition). Performance was stronger in both WS and TD groups on the two coloured conditions, compared with the control condition. However, the facilitation effect of colour was significantly weaker in the WS group than in the TD group. Replication of oblique line segments was less successful than replication of non-oblique line segments for both groups; this effect was reduced by colour facilitation in the TD group only. Verbalising the colours had no additional impact on performance in either group. We suggest that colour acted as a cue to individuate the dots, thus enabling participants to better ascertain the spatial relationships between the parts of each figure, to determine the start and end points of component lines, and to determine the correspondence between the model and their replication. The reduced facilitation in the WS group is discussed in relation to the effect of oblique versus non-oblique lines, the use of atypical drawing strategies, and reduced attention to the model when drawing the replication. | 25,159,922 | [
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Nurses' involvement in developing NICE guidelines. | This article discusses the development of National Institute for Health and Care Excellence guidelines, the contribution made by nurses to the guidelines and the importance of continuing to take an active role in this work. The challenges nurses face and the support provided to nurses involved in this work by the Royal College of Nursing are outlined. It is intended the article will stimulate interest and encourage nurses to contribute to guideline development. | 25,159,976 | [
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Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKβ. | The transcription factor NF-κB is one of the main players involved in inflammatory responses during which NF-κB becomes rapidly activated. However to maintain homeostasis, this NF-κB activation profile is only transient. Nevertheless deregulation of NF-κB activity is often observed and can lead to chronic inflammatory diseases as well as cancer. Therefore various research projects focus on the development of therapeutics that target the NF-κB activation pathway. One such compound is Withaferin A from the Ayurvedic plant Withania somnifera. Several reports already described the NF-κB inhibiting, anti-inflammatory capacity of WA, either in vitro as well as in vivo. However the underlying molecular mechanism remains largely unknown. In this paper we demonstrate a direct interaction of WA with the IKK-complex, more specifically with IKKβ, a kinase which is indispensable for the nuclear translocation of NF-κB. Hereby WA directly inhibits IKK catalytic activity. By mutation of Cys179 in IKKβ we could demonstrate loss of interaction between IKKβ and WA indicating that WA exerts its anti-inflammatory effects by targeting the crucial Cys179 residue located in the catalytic site of IKKβ. Upon docking of WA to a IKKβ homology structure model, WA was found to fit nicely into the groove of IKKβ where it can form hydrogen bond to stabilize its interaction with Cys179. | 25,159,986 | [
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Genetic and epigenetic variation in vulvar cancer: current research and future clinical practice. | Vulvar cancer is a relatively rare gynaecological malignancy, the treatment of which is associated with significant patient morbidity. With reports that the incidence of vulvar cancer is increasing, there is a rising need for improved preventive, diagnostic and therapeutic tools. Recent advances within genetics and epigenetics present possible approaches for addressing this need, by contributing to the clarification of the aetiology of this disease, identifying screening and drug targets and introducing the potential for personalised treatments. This paper reviews the genetic and epigenetic research undertaken to date within vulvar cancer, evaluates its potential for clinical application and identifies directions for future research. | 25,159,988 | [
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Antigenic homogeneity of male Müllerian gland (MG) secretory proteins of a caecilian amphibian with secretory proteins of the mammalian prostate gland and seminal vesicles: evidence for role of the caecilian MG as a male accessory reproductive gland. | Whereas in all other vertebrates the Müllerian ducts of genetic males are aborted during development, under the influence of Müllerian-inhibiting substance, in the caecilian amphibians they are retained as a pair of functional glands. It has long been speculated that the Müllerian gland might be the male accessory reproductive gland but there has been no direct evidence to this effect. The present study was undertaken to determine whether the caecilian Müllerian gland secretory proteins would bear antigenic similarity to secretory proteins of the prostate gland and/or the seminal vesicles of a mammal. The secretory proteins of the Müllerian gland of Ichthyophis tricolor were evaluated for cross-reactivity with antisera raised against rat ventral prostate and seminal vesicle secretory proteins, adopting SDS-PAGE, two-dimensional electrophoresis and immunoblot techniques. Indeed there was a cross-reaction of five Müllerian gland secretory protein fractions with prostatic protein antiserum and of three with seminal vesicle protein antiserum. A potential homology exists because in mammals the middle group of the prostate primordia is derived from a diverticulum of the Müllerian duct. Thus this study, by providing evidence for expression of prostatic and seminal vesicle proteins in the Müllerian gland, substantiates the point that in caecilians the Müllerian glands are the male accessory reproductive glands. | 25,160,003 | [
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Incidence and associated factors of difficult tracheal intubations in pediatric ICUs: a report from National Emergency Airway Registry for Children: NEAR4KIDS. | To evaluate the incidence and associated risk factors of difficult tracheal intubations (TI) in pediatric intensive care units (PICUs). Using the National Emergency Airway Registry for Children (NEAR4KIDS), TI quality improvement data were prospectively collected for initial TIs in 15 PICUs from July 2010 to December 2011. Difficult pediatric TI was defined as TIs by direct laryngoscopy which failed or required more than two laryngoscopy attempts by fellow/attending-level physician providers. A total of 1,516 oral TIs were reported with a median age of 2 years. A total of 97% of patients were intubated with direct laryngoscopy. The incidence of difficult TI was 9%. In univariate analysis, patients with difficult TI were younger [median 1 year (0-4) vs. 2 (0-8) years, p = 0.046], and had a reported history of difficult TI (22 vs. 8%, p < 0.001). Multivariate analysis showed that history of difficult airway and signs of upper airway obstruction are significantly associated with difficult TI. The advanced airway provider was more involved as a first provider in difficult TI (81 vs. 58%, p < 0.001). The presence of difficult TI was associated with higher incidence of oxygen desaturation below 80% (48 vs. 15%, p < 0.001), adverse TI associated events (53 vs. 20%, p < 0.001), and severe TI associated events (13 vs. 6%, p = 0.003). Difficult TI was reported in 9% of all TIs and was associated with increased adverse TI events. History of difficult airway and sign of upper airway obstruction were associated with difficult TIs. | 25,160,031 | [
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Introduction to RNA-Seq and its applications to drug discovery and development. | Preclinical Research RNA sequencing (RNA-Seq) is a novel high-throughput technology for comprehensive transcriptome study. It can measure the expression levels of thousands of genes simultaneously and provide insight into functional pathways and regulations in biological processes. In addition, RNA-Seq can provide copious information on alternative splicing, allele-specific expression, unannotated exons, and novel transcripts (gene or noncoding RNAs). This technology has revolutionized the way biologists examine transcriptomes and has been successfully applied in drug discovery and development, being able to identify drug-related genes, microRNAs, and fusion proteins. In this overview, we will review this technology including data analysis, and its recent applications in drug discovery and development. | 25,160,072 | [
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Congenital vulnerability of cutaneous segments arising from skin mosaicism: A genetic basis for locus minoris resistentiae. | Mosaicism is a biologic phenomenon that describes an individual who has two or more populations of cells with distinct genotypes and concomitant patterned phenotypes (eg, lines of Blaschko). It is distinguished from chimerism by its derivation from a single fertilized egg rather than multiple cell lineages derived from distinct fertilized eggs. With respect to dermatologic disorders, it is the strongest genetic example of how a cutaneous site, being populated by cells with distinct antigenic or immunologic properties, differs in its susceptibility or resistance to skin disorders, being preferentially affected in the former (ie, locus minoris resistentiae). We review patterns and mechanisms of skin mosaicism and discuss examples of segmental/mosaic dermatologic disorders that have been superimposed on a background of a nonsegmental eruption of the same disease or dermatologic disorders that have arisen secondarily on segmental cutaneous disorders. | 25,160,099 | [
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Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas. | Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD. | 25,160,106 | [
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Between students' instrumental goals and how they learn: goal content is the gap to mind. | Experimental/correlational studies have consistently demonstrated that the contents of an individual's goals play an important role within future motivations, learning processes, and outcomes. The aim of the study was to extend past findings by employing a three-point, cross-lagged latent simultaneous structural model in the examination of the role of intrinsic/extrinsic goals' effects on key proximal motivations, learning variables, and achievement in the context of a Japanese university. This study consisted of first-year students within seven departments, attending one university (n = 584). Employing three data points, separated by 8 and 7 months, this study tests the effects of students' instrumental goals on future motivations, approaches to learning and learning outcomes. Three goals were the focus of this study: Distal internally regulated, distal externally regulated, and proximal externally regulated. Internally regulated goals were hypothesized to be broadly adaptive, while externally regulated goals were hypothesized to be maladaptive. Findings reflected the broad importance of internal regulation for goals. Internally regulated goals positively predicted mastery goals and negatively predicted task valuation and effort belief deficits 8 months later. While not predicting achievement directly, internally regulated goals were the strongest predictor of future deep approaches to learning despite the lag of 15 months. Proximal externally regulated goals had no significant cross-lagged effects, and distal externally regulated goals had a negative predictive effect on future deep approaches to learning. This study extends intrinsic/extrinsic goal research both within education broadly and in the context of Japan. Furthermore, instrumental goals were found to play important roles supporting students in overcoming future motivation deficits and the pursuit of deep approaches to learning. | 25,160,115 | [
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The sarcoidal granuloma: A unifying hypothesis for an enigmatic response. | Although the cause of sarcoidosis is unknown, there is growing support for the concept that sarcoidal granulomas result from a hypersensitivity reaction producing a nonspecific response to an extrinsic or intrinsic (autoimmune) antigen in genetically susceptible individuals. The immune milieu associated with these antigens, localized in a specific cutaneous area, produces a variant of Ruocco's "immunocompromised district." This may explain the predilection for sarcoidal granulomas in association with foreign bodies, tattoos, herpes zoster-affected dermatomes, and scars. Similar antigenic stimulation produces sarcoidal granulomas surrounding internal tumors. Finally, systemic sarcoidosis, as manifested by hilar adenopathy, may reflect the lymphatic spread of foreign antigens. | 25,160,107 | [
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0.4996246,
-0.4418232,
-0.02898257,
0.1229606,
-0.2053183,
... |
Embracing case management for computerization of care pathways. | The computerization of care pathways (CPs) has drawn considerable attention, for improving quality of health care and reducing costs. A well-known big challenge of implementing CPs is their flexibility and ad hoc variations in execution of clinical tasks. We observe that case management suits well to address this problem, and this paper proposes a CMMN-based CP model, where CMMN (Case Management Model and Notation) is becoming an industry standard. Via an experimental experience on modelling CHF (congestive heart failure) ambulatory CP, we illustrate that the usage of case management paves the way to popularize CPs, particularly for its quick deployment and execution in industrial products. | 25,160,134 | [
-0.4404182,
0.1742385,
-0.06669533,
0.01013115,
0.04165563,
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-0.2247839,
0.1628457,
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0.07326483,
0.02468349,
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0.1166108,
-0.248... |
Towards evidence-based CDSSs implementing the medical reasoning contained in CPGs: application to antibiotic prescription. | Clinical practice guidelines (CPGs) are documents giving recommendations based on expert reasoning, weighing up the pros and cons of treatments on the basis of the available evidence. We propose a new approach to the construction of clinical decision support systems (CDSS), making use of the evidence-based medical reasoning used by experts in CPGs. In this study, we determined whether this approach could retrieve the recommendations for antibiotic prescription for empirical treatment in primary care. We manually extracted, from CPGs, all the properties of antibiotics underlying recommendations for their prescription or non-prescription. We then used these properties to establish an algorithm in the form of a sequence of conditions, leading to a list of recommended antibiotics. The optimal sequence was determined by studying, for each sequence, the degree of similarity between the list of antibiotics recommended in CPGs and the list obtained with the algorithm. 12 antibiotic properties were used in the form of conditions in an algorithm. For 95% of clinical situations, 10 sequences retrieved the recommended treatment. This algorithm could be used in a CDSS for antibiotic treatment and would be useful for experts drawing up CPGs. | 25,160,136 | [
-0.2680065,
0.1341287,
0.1494454,
0.2046982,
0.165763,
0.0005010546,
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0.1252021,
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0.1622156,
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0.1552396,
0.1318243,
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... |
Arranging ISO 13606 archetypes into a knowledge base. | To enable the efficient reuse of standard based medical data we propose to develop a higher level information model that will complement the archetype model of ISO 13606. This model will make use of the relationships that are specified in UML to connect medical archetypes into a knowledge base within a repository. UML connectors were analyzed for their ability to be applied in the implementation of a higher level model that will establish relationships between archetypes. An information model was developed using XML Schema notation. The model allows linking different archetypes of one repository into a knowledge base. Presently it supports several relationships and will be advanced in future. | 25,160,140 | [
-0.3153104,
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0.3616449,
0.03316503,
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-0.2134248,
... |
Explicit evidence for prognostic Bayesian network models. | Many prognostic models are not adopted in clinical practice regardless of their reported accuracy. Doubts about the basis of the model is considered to be a major reason for this as the evidence behind clinical models is often not clear to anyone other than their developers. We propose a framework for representing the evidence behind Bayesian networks (BN) developed for prognostic decision support. The aim of this evidence framework is to be able to present all the evidence alongside the BN itself. We illustrate this framework by a BN developed with clinical evidence to predict coagulation disorders in trauma care. | 25,160,144 | [
0.0811324,
0.01131571,
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0.09069768,
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0.07242615,
0.09863233,
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0.3843652,
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0.3624077,
0.1885543,
0.1807054,
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0... |
A novel personal health system with integrated decision support and guidance for the management of chronic liver disease. | A personal health system platform for the management of patients with chronic liver disease that incorporates a novel approach to integrate decision support and guidance through care pathways for patients and their doctors is presented in this paper. The personal health system incorporates an integrated decision support engine that guides patients and doctors through the management of the disease by issuing tasks and providing recommendations to both the care team and the patient and by controlling the execution of a Care Flow Plan based on the results of tasks and the monitored health status of the patient. This Care Flow Plan represents a formal, business process based model of disease management designed off-line by domain experts on the basis of clinical guidelines, knowledge of care pathways and an organisational model for integrated, patient-centred care. In this way, remote monitoring and treatment are dynamically adapted to the patient's actual condition and clinical symptoms and allow flexible delivery of care with close integration of specialists, therapists and care-givers. | 25,160,150 | [
-0.2253731,
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0.1799963,
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0.1426179,
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0.05005799,
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0.1097988,
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-0.2074217,
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0.12623,
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Plug-and-play Integration of dual-model based Knowledge Artefacts into an Open Source Ehr System. | In this paper we present our experiences with extending an existing approach for an archetype-compliant collection and export of data according to the openEHR specifications within the open source EHR system OpenMRS. It allows an automatic generation of forms from templates, which were introduced by openEHR as an extension of the dual-model approach. Data entered in these forms can be exported in form of standardized EHR extracts. The use of templates allowed us to solve problems reported for the original archetype-based version of the approach, which were caused by the high optionality within archetypes. | 25,160,154 | [
-0.1776155,
0.06036705,
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0.3545892,
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0.1830308,
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0.3359458,
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-0.... |
Interpretable associations over DataCubes: application to hospital managerial decision making. | The world concern about the costs of the health care systems has raised the importance of counting on precise and interpretable tools, that help the health care institution's managers to make decisions to optimize the use of health resources. In this paper we propose a new Classification based on Association Rules (CAR) algorithm that improves the interpretability of the results, making it specially useful for decision making. Changing the usual way to obtain the rules we follow four goals: first to improve the interpretability of the result by obtaining rules meaningful and interpretable by themselves, secondly to reduce the complexity of the result obtaining a lower number of rules; thirdly, to obtain simpler rules, with less size in number of antecedents; and finally to avoid the usual over-fitting problem of the classification methods by obtaining a generic final result set, where specific rules for specific cases are avoided unless they are necessary. To prove the utility of our proposal we have used it in an example of decision support regarding the planning of the surgery rooms. | 25,160,160 | [
-0.07229895,
0.2051516,
0.289325,
0.3104814,
0.05420561,
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0.006530218,
0.1348652,
0.06951969,
0.1175257,
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0.02162271,
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0.07645699,
0.03842263,
-0.02239015,
0.09246838,
-0.06516442,
-0.206131... |
Preservation of information in terminology transcoding. | Linking interface terminologies (IT) to reference terminologies (RT) in flow of terminologies may allow health information system to be both usable and interoperable. Two French university hospitals worked independently on such a flow from the prescription of lab-test to the display of the corresponding results. The aim of this study was to evaluate the transmission of information in these two hospitals communication. An expert, supported by natural language processing tool, created the gold standard link between the 2 prescription ITs i.e. the terms that share the same meaning. A semantic pathway was defined to allow the mapping of one prescription IT to the other, through LOINC® and SNOMED®, the RT chosen by each hospital, respectively. The capacity of the semantic pathway to identify the correct links was computed. The expert found 218 links between the 2 prescription ITs (containing 580 and 374 terms that are linked to RT). The semantic pathway correctly identifies 96 of these links (44.0% [37.4-50.6]). The recall was not as good as expected, even though the semantic pathway was created in order to maximize it. Using different RT in different hospitals is not an efficient solution. The use of LOINC® seems to be preferable as a RT for prescription. | 25,160,165 | [
0.03177598,
0.1155667,
0.3342138,
0.2216752,
0.1442529,
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0.1018638,
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0.06180842,
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-0.08123158,
-0.1015602,
0.05632267,
0.3100486,
-0.03051513,
-0.1986635... |
An approach for utilizing clinical statements in HL7 RIM to evaluate eligibility criteria. | The HL7 RIM (Reference Information Model) is a commonly used standard for the exchange of clinical data and can be employed for integrating the patient care and clinical research domains. Yet it is not sufficiently well specified to ensure a canonical representation of structured clinical data when used for the automated evaluation of eligibility criteria from a clinical trial protocol. We present an approach to further constrain the RIM to create a common information model to hold clinical data. In order to demonstrate our approach, we identified 132 distinct data elements from 10 rich clinical trails. We then defined a taxonomy to (i) identify the types of data elements that would need to be stored and (ii) define the types of predicate that would be used to evaluate them. This informed the definition of a pattern used to represent the data, which was shown to be sufficient for storing and evaluating the clinical statements required by the trials. | 25,160,189 | [
-0.2028394,
0.241291,
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0.1612005,
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0.0559991,
0.1914276,
0.08238225,
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0.05886366,
0.09601738,
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-0.3302782,
0.09916855,
-0.02777369,
0.01163179,
0.144915,
0.2811568,
0.1086283,
... |
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