title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The role of exercise in reducing the risks of gestational diabetes mellitus in obese women. | The global obesity epidemic continues unabated, now rapidly expanding to developing countries. Multiple comorbidities and premature mortality are associated with obesity, most frequently diabetes. The associated financial and economical burden is escalating as well. The sedentary lifestyle adopted by many pregnant women because of traditional practices and the current recommendation for gestational weight gain are contributing factors to the obesity and diabetes epidemic. Physical inactivity is recognized as an independent risk factor for obesity insulin resistance and type 2 diabetes; the physiological and hormonal changes associated with pregnancy magnify this risk. Conversely, evidence and accumulated experience indicate that antenatal lifestyle interventions that include physical activity and judicious dieting could improve the pregnancy outcome and reduce the risk of gestational diabetes and is effective as an adjunctive therapy for diabetes in pregnancy. All major professional organizations, among them American Congress of Obstetricians and Gynecologists (ACOG), American Diabetes Association (ADA), Royal College of Obstetricians and Gynaecologists (RCOG), and Society of Obstetricians and Gynaecologists of Canada (SOGC), recommend lifestyle interventions that include diet and exercise to prevent or manage gestational diabetes or diabetes mellitus. | 25,240,421 | [
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Lessons from the atomic bomb about secondary MDS. | Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed. | 25,240,475 | [
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Ultrasensitivity part I: Michaelian responses and zero-order ultrasensitivity. | Quantitative studies of signal transduction systems have shown that ultrasensitive responses - switch-like, sigmoidal input/output relationships - are commonplace in cell signaling. Ultrasensitivity is important for various complex signaling systems, including signaling cascades, bistable switches, and oscillators. In this first installment of a series on ultrasensitivity we survey the occurrence of ultrasensitive responses in signaling systems. We review why the simplest mass action systems exhibit Michaelian responses, and then move on to zero-order ultrasensitivity, a phenomenon that occurs when signaling proteins are operating near saturation. We also discuss the physiological relevance of zero-order ultrasensitivity to cellular regulation. | 25,240,485 | [
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Transcriptomic analysis of the myometrium during peri-implantation period and luteolysis--the study on the pig model. | In pigs, implantation begins with the attachment of embryos to the endometrium. As the process is regulated by the expression of numerous genes, endometrial transcriptomic profiles have been extensively studied in early gravid pigs. However, the myometrium, a secretory tissue, should not be neglected, as it can also participate in the regulation of implantation in early pregnant pigs. To clarify this issue, the transcriptomic profile of the porcine myometrium during the peri-implantation period (i.e. on days 15 to 16 of pregnancy) was compared with the profile observed during luteolysis (i.e. on days 15 to 16 of the oestrous cycle) with an Agilent's Porcine (V2) Two-Colour Gene Expression Microarray 4 × 44 (Agilent, USA). Analysis of the microarray data revealed that of 526 unique, accurately annotated genes, the expression of 271 unique genes was upregulated, while the expression of 255 genes was downregulated in pregnant versus cyclic myometrium. The in-depth data analysis revealed differential expression of genes encoding for factors involved in immunomodulation, tissue growth and differentiation, and prostaglandin and steroid biosynthesis and action. Moreover, the comparison of the obtained data on the myometrial transcriptome with our previously published results on the endometrial transcriptome allowed us to determine substantial differences in the regulatory function of both tissues. The new insights into the function of the myometrium of early pregnant pigs obtained here are in agreement with our previous results that suggest that this tissue plays an important role in providing optimal conditions for developing embryos. Therefore, the importance of the myometrium as an active embryo signal-responsive tissue during early pregnancy cannot be underestimated. | 25,240,502 | [
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Social-, age- and gender differences in testing and positive rates for Chlamydia trachomatis urogenital infection - a register-based study. | Chlamydia trachomatis is suspected of causing female infertility. It is the most widespread sexually transmitted infection with an estimated general prevalence of ~5-10% with a peak in younger individuals. C. trachomatis infection is more prevalent among lower social classes. In this study, the association between age, gender, social status and testing and positive rates is investigated in the age group 15-24 years. Case-control study linked to data from Statistics Denmark. Data from the Department of Microbiology, Hvidovre University Hospital, Copenhagen were used and included 21887 people tested by general practitioners (GPs) and 3177 people tested at a venereological clinic. The age range was 15-24 years in 2011. These data were linked with the parental educational status delivered by Statistics Denmark, which also delivered a matched control group. The data were analysed using a case-control design. Testing was more frequent in the following groups: age range 20-24 years, females and patients with higher parental educational status. About 87.3% of patient had been tested by GPs. Positive rates were highest among males at the general practice constituting 17.1% versus females 10.6%, younger individuals and patients with lower parental educational status. The C. trachomatis testing pattern and positive rates highlight a need for a greater focus on males, younger patients and individuals with a lower social status. | 25,240,514 | [
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Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion. | The aim of this meta-analysis was to evaluate and compare the efficacy of the 2 different neuroprotection systems in preventing embolization during carotid artery stenting (CAS), as detected by diffusion-weighted magnetic resonance imaging (DW-MRI). Data from randomized and nonrandomized studies comparing both types of embolic protection devices revealed contrasting evidence about their efficacy in neuroprotection, as assessed by the incidence of new ischemic lesions detected by DW-MRI. Eight studies, enrolling 357 patients, were included in the meta-analysis. Our study analyzed the incidence of new ischemic lesions/patient, comparing filter cerebral protection and proximal balloon occlusion. Following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: -0.43; 95% confidence interval [CI]: -0.84 to -0.02, I(2) = 70.08, Q = 23.40). Furthermore, following CAS, the incidence of lesions at the contralateral site was significantly lower in the proximal protection group (ES: -0.50; 95% CI: -0.72 to -0.27, I(2) = 0.00, Q = 3.80). Our meta-analysis supports the concept that the use of proximal balloon occlusion compared with filter cerebral protection is associated with a reduction of the amount of CAS-related brain embolization. The data should be confirmed by a randomized clinical trial. | 25,240,544 | [
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Decline of compound muscle action potentials and statistical MUNEs during Wallerian degeneration. | In two previous studies, we found that the compound muscle action potential (CMAP) amplitude loss was significantly higher than the loss of estimated motor unit numbers in the course of Wallerian degeneration (WD). In order to overcome some drawbacks of the method previously used, we performed a similar CMAP vs MUNE comparison by using the statistical motor unit number estimation (MUNE) method. Initial electrophysiological studies on 6 patients were performed between 22 and 98 hours after the injuries; it was possible to make repeated examinations, four times in 1 nerve, twice in 1 nerve and three times in 4 nerves, before the eventual complete disappearance of the CMAPs. The transected/intact (T/I) side CMAP ratios declined steeply as WD evolved. They were significantly lower than the relatively stable MUNE ratios 48 hours after the injury. This study, performed with the use of statistical MUNE, strengthens our previous observation by the incremental method that might have some relevance to the pathophysiology of early WD. CMAP amplitude loss that is more than expected from the amount of axonal degeneration may indicate a considerable amount of inactive muscle fibers in the motor units innervated by the nerve fibers, which are undergoing degeneration but still retain their excitability. Although technical sources of error cannot be totally excluded, our findings could more likely be explained by the failing of neuromuscular synapses in an asynchronous order before complete unresponsiveness of the motor unit ensues. | 25,240,559 | [
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Dual versus single antiplatelet therapy in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis. | Although dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve replacement (TAVR), this approach is not evidence based. We therefore sought to systematically review the current evidence for this practice in terms of 30-day outcome looking at stroke, MI, bleeding, and death. Relevant studies were identified through electronic literature search. Studies involving single antiplatelet therapy (SAPT) and DAPT in patients undergoing TAVR were included. Study specific risk ratios were calculated and combined using random-effects model meta-analysis. Analysis of data from 410 patients, stroke occurred in seven (3.16%) of SAPT and six (3.17%) of DAPT RR=1.03 (95% CI, 0.36-2.96, P=0.96). In analysis of 530 patients, MI occurred in three (1.07%) of SAPT and one (0.40%) of DAPT RR=1.97 (95% CI, 0.29-13.29, P=0.49), significant bleeding (major, life threatening and bleeding requiring transfusion) occurred in 20 (7.11%) of SAPT and 43 (17.27%) of DAPT RR=0.41 (95% CI, 0.25-0.69, P=0.0006). Number needed to harm for major or life threatening bleeding was 10. Death occurred in 15 (6.78%) of SAPT and 15 (7.94%) of DAPT (RR 0.91; 95% CI 0.46-1.79, P=0.78). Our meta-analysis suggests that at 30 days following TAVR there is no difference between post-procedural SAPT versus DAPT for the risk of stroke or MI and DAPT may have a higher bleeding risk. Adequately powered RCTs are warranted to clarify the optimal antiplatelet treatment strategy following TAVR. | 25,240,570 | [
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Inhibition of prolyl oligopeptidase increases the survival of alpha-synuclein overexpressing cells after rotenone exposure by reducing alpha-synuclein oligomers. | α-Synuclein (aSyn) aggregation, mitochondrial dysfunction and oxidative damage has been shown to be related to the death of dopaminergic neurons in Parkinson's disease (PD). Prolyl oligopeptidase (PREP) is proposed to increase aSyn aggregation, and PREP inhibition has been shown to inhibit the aggregation process in vitro and in vivo. In this study, we investigated the effects of a specific PREP inhibitor, KYP-2047, on rotenone induced aSyn aggregation and increased the production of reactive oxygen species (ROS) in cells overexpressing A53T mutation of aSyn. Rotenone, a mitochondrial toxin that induces oxidative damage and aSyn aggregation, associated with PD pathology, was selected as a model for this study. The results showed that rotenone induced the formation of high-molecular-weight aSyn oligomers, and this was countered by simultaneous incubation with KYP-2047. Inhibition of PREP also decreased the production of ROS in [A53T]aSyn overexpressing cells, leading to improved cell viability. | 25,240,592 | [
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Migraine and nosebleed in children case series and literature review. | The presence of nose bleeding during a migraine attack as a single occurrence is so far rarely reported. Therefore, we have decided to report such occurrences we have noticed to further improve and build upon possible existing knowledge of such incidences. 728 children with an average age of 11.5 years, suffering from migraine were examined for nose bleeding. All structural, trauma, coagulation and medical causes were excluded. A computer-based literature search was also conducted to identify other cases of such sort. Eight cases (1.1%) of nose bleeding during attacks of migraine with no other known causes were identified. An additional 3 cases were identified in literature, though the presenting age was 25 years or above. In our case series, nose bleeding exclusively occurred during the attacks of headaches, although it was not considerably related to aura, frequency, location or intensity of migraine attacks. The presence of nose bleeding associated with migraine is an uncommon phenomenon and its mechanism is still unknown. | 25,240,603 | [
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The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors. | Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents. | 25,240,614 | [
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Safety of a nasal vaccine against Streptococcus pneumoniae using heat-killed Lactobacillus casei as adjuvant. | Streptococcus pneumoniae is a highly important respiratory pathogen that causes infections in children, elderly people and immunocompromised people around the world. Pneumococcal vaccines licensed did not reach to eradicate the pneumococcal infection. In a previous study was demonstrated the effectiveness of a nasal experimental vaccine that consisted in a pneumococcal protective protein A (PppA) co-administrated with heat-killed-Lactobacillus casei (LcM), in mice model of respiratory pneumococcal challenge. In the present work the safety of the experimental vaccine LcM+PppA and its components were evaluated through hematological, biochemical and immune parameters in a model infection with S. pneumoniae. Thus, alanine transaminase activity, creatinine levels, lactate dehydrogenase activity, C reactive protein levels, corticosterone levels in serum, total and differential leukocyte counts in blood and bronchoalveolar lavages (BAL) and IgE in BAL, were evaluated. Experimental vaccine: LcM+PppA nasally administered does not induce harmful effects in our vaccination-infection model. Studied parameters showed LcM+PppA's safety in liver, kidney, pulmonary and systemic levels. Although studies in experimental animals do not guarantee security for the application of the vaccine on humans, they are important evidence for the planning and subsequent clinical trials in humans. | 25,240,632 | [
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Differences in lens optical plasticity in two gadoid fishes meeting in the Arctic. | Arctic and boreal/temperate species are likely to be evolutionary adapted to different light regimes. Currently, the boreal/temperate Atlantic cod (Gadus morhua) is coexisting with the native polar cod (Boreogadus saida) in the Arctic waters around Svalbard, Norway. Here, we studied light/dark adaptative optical plasticity of their eye lenses by exposing fish to bright light during the polar night. Schlieren photography, high-definition laser scanning and ray tracing were used to determine the optical properties of excised crystalline lenses. Both species have multifocal lenses, an optical adaptation for improved color vision. In polar cod, the optical properties of the lens were independent of light exposure. In the more southern Atlantic cod, the optical properties of the lens changed within hours upon exposure to light, even after months of darkness. Such fast optical adjustment has previously only been shown in a tropical cichlid. During the polar night the Atlantic cod lens seems to be unregulated and dysfunctional since it had an unsuitable focal length and severe spherical aberration. We present a system, to our knowledge unique, for studying visual plasticity on different timescales in relation to evolutionary history and present the first study on the polar cod visual system. | 25,240,636 | [
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Eating behaviour among undergraduate students. Comparing nutrition students with other courses. | Our main aim was to compare eating behaviour between Portuguese undergraduate nutrition students and students attending other courses. Several eating behaviour dimensions were compared between 154 nutrition students and 263 students from other areas. Emotional and external eating were assessed by the Dutch Eating Behavior Questionnaire, dietary restraint was measured using the flexible and rigid control of eating behaviour subscales, binge eating was measured using the Binge Eating Scale, and eating self-efficacy using the General Eating Self-Efficacy Scale. Higher levels of flexible and rigid control were found in nutrition students from both sexes when compared to students from other courses. Female nutrition students also presented higher binge eating levels than their colleagues from other courses. To our knowledge no other work has previously assessed all eating behaviour dimensions considered in the current study among nutrition students. Besides the results by themselves, the data obtained from this study provide several clues to further studies to be developed regarding the still rarely approached issue of eating behaviour among nutrition students. | 25,240,638 | [
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Nerve blocks for chronic pain. | Nerve blocks are often performed as therapeutic or palliative interventions for pain relief. However, they are often performed for diagnostic or prognostic purposes. When considering nerve blocks for chronic pain, clinicians must always consider the indications, risks, benefits, and proper technique. Nerve blocks encompass a wide variety of interventional procedures. The most common nerve blocks for chronic pain and that may be applicable to the neurosurgical patient population are reviewed in this article. This article is an introduction and brief synopsis of the different available blocks that can be offered to a patient. | 25,240,668 | [
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Successful aging, dietary habits and health status of elderly individuals: a k-dimensional approach within the multi-national MEDIS study. | The definition and determinants of successful aging is still controversial. Although dietary habits have long been associated with aging, eating habits and behaviors have rarely been included in various proposed indices of successful aging. The aim of this work was to evaluate determinants of successful aging together with assessment of dietary habits in relation to healthcare facility use among elders living in the Mediterranean basin. During 2005-2011, 2663 elderly (aged 65-100 years) individuals from 21 Mediterranean islands and rural Mani region (Peloponnesus) were voluntarily enrolled in the study. A successful aging index ranging from a score of 0 to a score of 10 was constructed using 10 attributes, i.e., education, financial status, physical activity, body mass index, depression, participation in social activities with friends and family, number of yearly excursions, number of cardiovascular disease risk factors and adherence to the Mediterranean diet. The applied factor analysis on the components of the index extracted three main components for successful aging: psychosocial-economic, bioclinical and lifestyle; confirming the multiple dimensions of aging. After adjusting for confounders, a 1/10-unit increase in the successful aging index was associated with 0.8 less annual visits to healthcare centers (95% CI -1.3 to-0.2). Stratified analysis by gender revealed heterogeneity of factors predicting successful aging. These findings suggest that successful aging is a multidimensional and complex concept that exhibits gender heterogeneity. Annual use of health care services by the elders was found to be related to level of successful aging. | 25,240,688 | [
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Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. | Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events. The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector). In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response. NCT01644175 ( NCT01644175). NCT01644188 ( NCT01644188). | 25,240,705 | [
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Socio-cognitive influences on the domain-specificity of prosocial behavior in the second year. | The main aim of this study was to explain the domain-specificity of early prosocial behavior in different domains (i.e., helping, comforting, and cooperation) by simultaneously assessing specific socio-cognitive factors (i.e., self-other-differentiation and joint attentional skills) that were hypothesized to be differentially related to the three domains of prosocial behavior. Based on a longitudinal study design, observational and parental report data were collected when toddlers (N=42) from German urban middle-class families were 15 and 18 months of age. At 15 months, regression analyses indicated differential relationships between socio-cognitive development and prosocial behavior (i.e., joint attentional skills were positively related with helping and, as hypothesized, both joint attentional skills and self-other differentiation were positively related with cooperation). Furthermore, self-other differentiation at 15 months predicted increases in coordination between 15 and 18 months. Finally, between 15 and 18 months, parental reports of socio-cognitive measures increased significantly while behavioral measures of both socio-cognitive concepts and prosocial behavior were stable across time. In sum, these results support the theoretical assumption of domain-specific socio-cognitive influences that constitute differential development of prosocial behavior. Implications of the results for theory and future studies are discussed from different perspectives with a focus on an interference interpretation calling for the integration of socialization approaches to the study of prosocial development. | 25,240,709 | [
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Determination of oxidative stress and effect of erdosteine on rhinitis medicamentosa in a rat model. | We aimed to determine the presence of oxidative stress in rhinitis medicamentosa (RM) and to evaluate the effect of erdosteine (ED) on mucosal changes in a rat model. Twenty-four male rats were used in this experimental study. Three groups were created. Group 1 (n=8) was the control group. Two puffs of 0.05% oxymetazolin were sprayed into the nasal cavities of the remaining rats (n=16) three times daily for eight weeks. One of these 16 rats was scarified at the end of the eight weeks and examined to confirm the presence of RM. Seven of the remaining 16 rats were killed, and venous blood samples were taken (Group 2). Group 3 (n=8) received 10mg/kg of an ED suspension orally for seven days. All rats were put on formalin for light microscopy. The total antioxidant status (TAS) was similar in all groups (p=0.073). The total oxidative status (TOS) of the RM group was significantly higher than that of the control group and RM+ED group (Group 3) (p=0.003 and p=0.011, respectively). The pathological recovery of the nasal mucosa of the rats was similar in the RM+ED and control groups. The TOS was high in this RM rat model, and oxidative stress was associated with RM. ED significantly ameliorated nasal mucosal changes induced by RM, suggesting that oxidative stress may play an important role in the pathophysiology of this condition. | 25,240,710 | [
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8-Hydroxy-2'-deoxyguanosine expression predicts outcome of esophageal cancer. | Esophageal cancer is characterized by increased oxidative stress and the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the main mutagenic modifications of DNA. We analyzed the predictive value of 8-OHdG expression on postoperative survival of patients with esophageal cancer with univariate and multivariate analysis. The high levels of 8-OHdG are associated with significantly shorter survival time by log-rank test using Kaplan-Meier methods. Moreover, the level of 8-OHdG expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 0.294; 95% confidence interval, 0.178-0.487; P = .000). These results suggest that oxidative damage marker of 8-OHdG is a useful prognostic marker in esophageal cancer. The analysis of 8-OHdG levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes. | 25,240,715 | [
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Activity-guided isolation, identification and quantification of biologically active isomeric compounds from folk medicinal plant Desmodium adscendens using high performance liquid chromatography with diode array detector, mass spectrometry and multidimentional nuclear magnetic resonance spectroscopy. | The antioxidant activity of the crude extract (60% ethanol) from the leaves of Desmodium adscendens (Sw.) DC. (Fabaceae) was observed in DPPH, xanthine/xanthine oxidase, lipid peroxydation and neutrophils burst tests. Further activity-guided fractionation on C18 column (water, 20% methanol, 50% methanol and 100% methanol) resulted in the separation of the fraction (50% methanol) with the highest antioxidant capacity. HPLC-DAD analysis of biologically active fraction revealed the presence of two pairs of flavonoid isomers as the dominant constituents. Those compounds were isolated and purified by multi-step liquid column chromatography (Sephadex LH20). Their structures were elucidated by various spectroscopic techniques, including NMR, UV and MS. Based on 1D and 2D NMR spectra as well as ion fragmentation, flavonoids were identified as: isovitexin 2''-O-xyloside (1), vitexin 2''-O-xyloside (2), vitexin (3) and isovitexin (4). The hybrid HSQC-DEPT technique provided very fast determination of the glycosylation positions in aglycone and the type of glycosidic bond in the flavonoid isomers. This study provides novel information concerning identity of the major compounds present in the leaves of D. adscendens cultivated in Ghana, which broadens the knowledge about anti-inflammatory, antiallergic and antioxidant properties of their extracts. | 25,240,729 | [
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The functional role of Cys3-Cys4 loop in hydrophobin HGFI. | Hydrophobins are a large group of low-molecular weight proteins. These proteins are highly surface-active and can form amphipathic membranes by self-assembling at hydrophobic-hydrophilic interfaces. Based on physical properties and hydropathy profiles, hydrophobins are divided into two classes. Upon the analysis of amino acid sequences and higher structures, some models suggest that the Cys3-Cys4 loop regions in class I and II hydrophobins can exhibit remarkable difference in their alignment and conformation, and have a critical role in the rodlets structure formation. To examine the requirement for the Cys3-Cys4 loop in class I hydrophobins, we used protein fusion technology to obtain a mutant protein HGFI-AR by replacing the amino acids between Cys3 and Cys4 of the class I hydrophobin HGFI from Grifola frondosa with those ones between Cys3 and Cys4 of the class II hydrophobin HFBI from Trichoderma reesei. The gene of the mutant protein HGFI-AR was successfully expressed in Pichia pastoris. Water contact angle (WCA) and X-ray photoelectron spectroscopy (XPS) measurements demonstrated that the purified HGFI-AR could form amphipathic membranes by self-assembling at mica and hydrophobic polystyrene surfaces. This property enabled them to alter the surface wettabilities of polystyrene and mica and change the elemental composition of siliconized glass. In comparison to recombinant class I hydrophobin HGFI (rHGFI), the membranes formed on hydrophobic surfaces by HGFI-AR were not robust enough to resist 1 % hot SDS washing. Atomic force microscopy (AFM) measurements indicated that unlike rHGFI, no rodlet structure was observed on the mutant protein HGFI-AR coated mica surface. In addition, when compared to rHGFI, no secondary structural change was detected by Circular Dichroism (CD) spectroscopy after HGFI-AR self-assembled at the water-air interface. HGFI-AR could not either be deemed responsible for the fluorescence intensity increase of Thioflavin T (THT) and the Congo Red (CR) absorption spectra shift (after the THT(CR)/HGFI-AR mixed aqueous solution was drastically vortexed). Remarkably, replacement of the Cys3-Cys4 loop could impair the rodlet formation of the class I hydrophobin HGFI. So, it could be speculated that the Cys3-Cys4 loop plays an important role in conformation and functionality, when the class I hydrophobin HGFI self-assembles at hydrophobic-hydrophilic interfaces. | 25,240,738 | [
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Structural basis of the pH-dependent assembly of a botulinum neurotoxin complex. | Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and releases it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent conformation with limited domain flexibility. Intriguingly, the free form NTNHA-A adopts pH-dependent conformational changes due to a torsional motion of its C-terminal domain. Once forming a complex at acidic pH, they each adopt a stable conformation that is similar to that observed in the crystal structure of the M-PTC. Our results suggest that assembly of the M-PTC depends on the environmental pH and that the complex form of BoNT/A is induced by interacting with NTNHA-A at acidic pH. | 25,240,768 | [
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Adding a "GRADE" to the quality appraisal of rheumatoid arthritis guidelines identifies limitations beyond AGREE-II. | To assess how well treatment recommendations for rheumatoid arthritis (RA) address Grading of Recommendations Assessment, Development and Evaluation (GRADE) steps and determine whether these steps can be adequately appraised using Appraisal of Guidelines Research & Evaluation II (AGREE-II). We systematically reviewed English-language treatment recommendations for the pharmacologic management of RA since 2000, assessed how well GRADE steps were addressed, rated AGREE-II quality, and compared the findings. GRADE steps were poorly addressed by the 44 included guidelines. Few guidelines discussed study limitations and/or risk of bias (23%), inconsistency (50%), indirectness (39%), imprecision (23%), or potential for publication bias (0%). Observational evidence was cited in 96% but rarely evaluated systematically. Only one guideline considered evidence on patients' preferences for health outcomes, and few provided an explicit justification for the strength of evidence or recommendation. The five GRADE steps that overlapped with AGREE-II questions were addressed more frequently (by 54-100% of guidelines) than the 13 GRADE steps not directly assessed by AGREE-II (0-50%). Among the nine guidelines rated as "Recommended for use" by AGREE-II, 8 of 13 GRADE steps were not addressed consistently by any guideline. GRADE's steps are poorly addressed by RA recommendations. AGREE-II provides a broad assessment of quality but lacks sufficient granularity to assess how well a guideline addresses GRADE's steps. | 25,240,769 | [
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Ultraviolet B radiation-stimulated urocortin 1 is involved in tyrosinase-related protein 1 production in human melanoma HMV-II cells. | Ultraviolet B (UVB) radiation stimulates cutaneous melanin pigmentation. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in the modulation of pigment production in response to this stressor. Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1), together with their corresponding receptors, in mammalian skin. Although CRF and Ucn1 are thought to have potent effects on the skin system, their possible roles and regulations have yet to be determined fully. Our previous findings in human melanoma HMV-II cells suggest that both CRF and Ucn1 regulate TRP1 gene expression via Nurr-1/Nur77, transcription factors that constitute the nuclear receptor 4a subgroup of orphan nuclear receptors. HMV-II cells were found to express mainly Ucn1 mRNA. This study aimed to explore the effects of UVB on Ucn1 mRNA and TRP1 protein levels in HMV-II cells. UVB (30 mJ/cm(2)) increased Nurr-1, Nur77, and Ucn1 mRNA levels. UVB also increased TRP1 protein levels. Ucn1 knockdown inhibited the UVB-induced increases in TRP1 protein levels. These data suggest that UVB-stimulated Ucn1 contributes to TRP1 production via the transcription of both Nurr-1 and Nur77. Ucn1, produced in melanoma cells, acts on melanoma cells themselves in an autocrine manner. | 25,240,771 | [
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Epigenetics of cancer stem cells: Pathways and therapeutics. | Epigenetic alterations including DNA methylation and histone modifications are the key factors in the differentiation of stem cells into different tissue subtypes. The generation of cancer stem cells (CSCs) in the process of carcinogenesis may also involve similar kind of epigenetic reprogramming where, in contrast, it leads to the loss of expression of genes specific to the differentiated state and regaining of stem cell-specific characteristics. The most important predicament with treatment of cancers includes the non-responsive quiescent CSC. The distinctive capabilities of the CSCs make cancer treatment even more difficult as this population of cells tends to remain quiescent for longer intervals and then gets reactivated leading to tumor relapse. Therefore, the current review is aimed to focus on recent advances in understanding the relation of epigenetic reprogramming to the generation, self-renewal and proliferation of CSCs. CSC-targeted therapeutic approaches would improve the chances of patient survival by reducing the frequency of tumor relapse. Differentiation therapy is an emerging therapeutic approach in which the CSCs are induced to differentiate from their quiescent state to a mature differentiated form, through activation of differentiation-related signalling pathways, miRNA-mediated alteration and epigenetic differentiation therapy. Thus, understanding the origin of CSC and their epigenetic regulation is crucial to develop treatment strategy against not only for the heterogeneous population of cancer cells but also to CSCs. Characterizing the epigenetic marks of CSCs and the associated signalling cascades might help in developing therapeutic strategies against chemo-resistant cancers. | 25,240,776 | [
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IL-10-overexpressing B cells regulate innate and adaptive immune responses. | Distinct human IL-10-producing B-cell subsets with immunoregulatory properties have been described. However, the broader spectrum of their direct cellular targets and suppressive mechanisms has not been extensively studied, particularly in relation to direct and indirect IL-10-mediated functions. The aim of the study was to investigate the effects of IL-10 overexpression on the phenotype and immunoregulatory capacity of B cells. Primary human B cells were transfected with hIL-10, and IL-10-overexpressing B cells were characterized for cytokine and immunoglobulin production by means of specific ELISA and bead-based assays. Antigen presentation, costimulation capacity, and transcription factor signatures were analyzed by means of flow cytometry and quantitative RT-PCR. Effects of IL-10-overexpresing B cells on Toll-like receptor-triggered cytokine release from PBMCs, LPS-triggered maturation of monocyte-derived dendritic cells, and tetanus toxoid-induced PBMC proliferation were assessed in autologous cocultures. IL-10-overexpressing B cells acquired a prominent immunoregulatory profile comprising upregulation of suppressor of cytokine signaling 3 (SOCS3), glycoprotein A repetitions predominant (GARP), the IL-2 receptor α chain (CD25), and programmed cell death 1 ligand 1 (PD-L1). Concurrently, their secretion profile was characterized by a significant reduction in levels of proinflammatory cytokines (TNF-α, IL-8, and macrophage inflammatory protein 1α) and augmented production of anti-inflammatory IL-1 receptor antagonist and vascular endothelial growth factor. Furthermore, IL-10 overexpression was associated with a decrease in costimulatory potential. IL-10-overexpressing B cells secreted less IgE and potently suppressed proinflammatory cytokines in PBMCs, maturation of monocyte-derived dendritic cells (rendering their profile to regulatory phenotype), and antigen-specific proliferation in vitro. Our data demonstrate an essential role for IL-10 in inducing an immunoregulatory phenotype in B cells that exerts substantial anti-inflammatory and immunosuppressive functions. | 25,240,783 | [
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Evolution and function of light harvesting proteins. | Photosynthetic eukaryotes exhibit very different light-harvesting proteins, but all contain membrane-intrinsic light-harvesting complexes (Lhcs), either as additional or sole antennae. Lhcs non-covalently bind chlorophyll a and in most cases another Chl, as well as very different carotenoids, depending on the taxon. The proteins fall into two major groups: The well-defined Lhca/b group of proteins binds typically Chl b and lutein, and the group is present in the 'green lineage'. The other group consists of Lhcr/Lhcf, Lhcz and Lhcx/LhcSR proteins. The former are found in the so-called Chromalveolates, where they mostly bind Chl c and carotenoids very efficient in excitation energy transfer, and in their red algae ancestors. Lhcx/LhcSR are present in most Chromalveolates and in some members of the green lineage as well. Lhcs function in light harvesting, but also in photoprotection, and they influence the organisation of the thylakoid membrane. The different functions of the Lhc subfamilies are discussed in the light of their evolution. | 25,240,794 | [
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Medical specialty-related adherence to anti-osteoporotic regimens in fragility hip fracture patients. | There is poor adherence in the management of osteoporotic fractures. We designed a study to investigate adherence to osteoporotic regimens among osteoporotic hip fracture patients and to analyze the risk factors associated with poor compliance. This retrospective chart-review study was carried out using a database of osteoporotic hip fracture patients at a medical center in Taiwan for the period 2001-2007. Adherence was assessed using compliance and persistence. Compliance was calculated by the medication possession ratio (MPR) and persistence by the time from treatment initiation to discontinuation. The MPR and corresponding risk factors for poor compliance (MPR < 80 %) were evaluated for year 1. The year 2 results were analyzed only for those subjects with good compliance (MPR ≥ 80 %) at the end of year 1. There were 366 osteoporotic hip fracture patients (323 women, 43 men) with a mean age of 73.9 ± 7.6 years. Of these, 53.8 % had good compliance for year 1 and 68.5 % for year 2. During 2 years of follow-up, the overall persistence ratio was 33.1 %. The risk factor associated with poor compliance in the first year was index prescription by orthopedists [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.10-2.59]. Subjects with hypertension (OR 0.69, 95 % CI 0.46-0.99) had good compliance. Index prescription by orthopedists (OR 2.44, 95 % CI 1.31-4.51) was the sole risk factor for poor compliance in year 2. In conclusion, although adherence to osteoporotic regimens was sub-optimal in hip fracture patients, the majority of patients' decreased adherence occurred within the first year. Medical specialties showed different adherences in both year 1 and year 2. | 25,240,801 | [
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Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. | Cyclophosphamide's lack of hematopoietic stem cell toxicity and its unique effects on the immune system have prompted several investigators to explore its potential for the prevention of graft-versus-host disease (GVHD). In haploidentical hematopoietic stem cell transplants, post-transplant cyclophosphamide together with standard prophylaxis reduces the incidence of GVHD to acceptable rates without the need for T cell depletion. In matched related and unrelated donor settings, cyclophosphamide alone has produced encouraging results. In particular, the low incidence of chronic GVHD is noteworthy. Here, we present a review of the current understanding of the mechanism of action of post-transplant cyclophosphamide and summarize the clinical data on its use for the prevention of GVHD. | 25,240,817 | [
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Serum thymus and activation-regulated chemokine level monitoring may predict disease relapse detected by PET scan after reduced-intensity allogeneic stem cell transplantation in patients with Hodgkin lymphoma. | Patients with relapsed and refractory Hodgkin lymphoma (HL) may experience long-term survival after allogeneic stem cell transplantation (alloSCT), but disease recurrence represents the main cause of treatment failure. Positron-emission tomography (PET)-positive patients after alloSCT have a dismal outcome. Serum thymus and activation-regulated chemokine (TARC) is produced by Reed-Sternberg cells and may be a marker of disease. Our study aimed at assessing whether TARC levels after alloSCT correlated with disease status and whether TARC monitoring could increase the ability to predict relapse. Twenty-four patients were evaluated in a prospective observational study. TARC serum level and PET were assessed before and after alloSCT during the follow-up (median, 30 months; range, 2 to 54). Before alloSCT, the median TARC level was 721 pg/mL (range, 209 to 1332) in PET-negative patients and 2542 pg/mL (range, 94 to 13,870) in PET-positive patients. After alloSCT, TARC was 620 pg/mL (range, 12 to 4333) in persistently PET-negative patients compared with 22,397 pg/mL (range, 602 to 106,578) in PET-positive patients (P < .0001). In 7 patients who relapsed after alloSCT, TARC level increased progressively even before PET became positive, with a median fold increase of 3.19 (range, 1.66 to 7.11) at relapse. The cut-off value of 1726 pg/mL had a sensitivity of 100% and a specificity of 71% for PET positivity. Patients with at least 1 TARC value above 1726 pg/mL during the first year after alloSCT had a worse progression-free survival (P = .031). In conclusion, TARC was correlated with disease status and its monitoring may be able to predict PET positivity after alloSCT, thus potentially allowing an early immune manipulation. | 25,240,818 | [
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The evolving field of kinase inhibitors in thyroid cancer. | Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC). | 25,240,824 | [
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Structural, optical, mechanical and dielectric studies of pure and doped L-Prolinium trichloroacetate single crystals. | In the present work, pure and metal substituted L-Prolinium trichloroacetate (LPTCA) single crystals were grown by slow evaporation method. The grown crystals were subjected to single crystal X-ray diffraction (XRD), powder X-ray diffraction, FTIR, UV-Visible-NIR, hardness, photoluminescence and dielectric studies. The dopant concentration in the crystals was measured by inductively coupled plasma (ICP) analysis. Single crystal X-ray diffraction studies of the pure and metal substituted LPTCA revealed that the grown crystals belong to the trigonal system. Ni(2+) and Co(2+) doping slightly altered the lattice parameters of LPTCA without affecting the basic structure of the crystal. FTIR spectral analysis confirms the presence of various functional groups in the grown crystals. The mechanical behavior of pure and doped crystals was analyzed by Vickers's microhardness test. The optical transmittance, dielectric and photoluminescence properties of the pure and doped crystals were analyzed. | 25,240,832 | [
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Pathophysiology of the hepoxilins. | There is increasing evidence from various scientific groups that hepoxilins represent novel inflammatory mediators. In vitro studies have shown that the hepoxilins cause mobilization of intracellular calcium in human neutrophils, cause plasma leakage, and potently stimulate chemotaxis of human neutrophils. In vivo, the hepoxilin pathway is activated in conditions of inflammation, e.g. after pathogen infection, in inflamed conditions (psoriasis, arthritis), and hepoxilins promote inflammatory hyperalgesia and allodynia. Although much work has demonstrated an effect of hepoxilins on neutrophils, the hepoxilin pathway has been demonstrated in a variety of tissues, including the lung, brain, pituitary, pancreatic islets, skin, etc. A genetic defect linked to a deficiency in hepoxilin formation has been described and believed to be responsible for the scaly skin observed in ichthyosis. Despite their biological and chemical instability, the involvement of the hepoxilin pathway in pathology has been demonstrated in vitro and in vivo through either isolation of the hepoxilins themselves (or their metabolites) or implied through the use of stable hepoxilin analogs. These analogs have additionally shown efficacy in animal models of lung fibrosis, cancer, thrombosis and diabetes. Research on these compounds has merely scratched the surface, but results published to date have suggested that the hepoxilin pathway is a distinct and novel pathway leading to inflammation and hepoxilin antagonists may provide the means of controlling early aspects of the acute inflammatory phase. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". | 25,240,838 | [
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The association of suicide-related Twitter use with suicidal behaviour: a cross-sectional study of young internet users in Japan. | Infodemiology studies for suicide prevention have become increasingly common in recent years. However, the association between Twitter use and suicide has only been partially clarified. This study examined the association between suicide-related tweets and suicidal behaviour to identify suicidal young people on the Internet. A cross-sectional survey was conducted using Internet survey panels (n=220,848) comprising users in their 20s, through a major Japanese Internet survey company. Final analyses included the data of 1000 participants. Of the participants (n=1000) used in the final analysis, 61.3% were women and the mean age was 24.9 years (SD=2.9, range=20-29). Logistic regression analyses showed that tweeting "want to die" and "want to commit suicide" was significantly related to suicidal ideation and behaviour. Lifetime suicide attempts, the most powerful predictor of future suicide out of all suicidal behaviours, were more strongly associated with tweeting "want to commit suicide" than tweeting "want to die". Having a Twitter account and tweeting daily were not associated with suicidal behaviour. An online panel survey has some inherent biases, such as coverage bias. Respondents were already registered as members of a particular Internet survey company in Japan, which limits the possibility of generalization. Twitter logs may be used to identify suicidal young Internet users. This study provides a basis for the early identification of individuals at high risk for suicide. | 25,240,843 | [
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Water treatment of hexavalent chromium by gelatin-impregnated-yeast (Gel-Yst) biosorbent. | A method is described for biosorption and water treatment of Cr(VI) from aqueous and real water samples by using gelatin-impregnated-yeast as a novel biosorbent. Gelatin and yeast materials (Gel-Yst) were combined together to form a novel eco-friendly, non-toxic, non-carcinogenetic, biodegradable, biocompatible and inexpensive biosorbent to enhance the extraction and biosorption of Cr(VI) from water. The potential affinity characters of Gel-Yst for biosorption of Cr(VI) were studied by the static technique in various buffer solutions. Other controlling experimental factors were also examined and evaluated. The effect of initial concentration of Cr(VI) was also evaluated to follow the postulates of Langmuir, Brunauer-Emmer-Teller (BET) and Dubinin-Radushkevich (D-R) adsorption isotherms. The potential applications of Gel-Yst biosorbent in water treatment processes of Cr(VI) from real acidic and neutral water samples by using multi-stage micro-column techniques were successfully accomplished. | 25,240,854 | [
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[Pliability and deflection of diagnostic catheters]. | The cardiac catheter is an intravascular catheter, which is introduced or implanted into the heart for diagnostic or therapeutic reasons. The catheters may break or king during their introduction and/or removal. The aim of the authors was to study the pliability of two catheters with the same material but different diameters according to the Food and Drug Administration's recommendation. The bending points, diameter decrease, deflection, and their correlation and dependence on the distance from the tip, as well as the influence of the initial diameter of the catheters were determined. The bending of catheters was performed on 9 bending points (120-280 mm from the tip by 20 mm) on 16 gauges with different radius (10-2.5 mm by 0.5 mm). A linear dependency between the diameter decrease and deflection was observed, which was independent from the placement of the measurement in both catheters examined. The larger initial diameter had significant (p = 0.05) greater diameter decrease than the smaller, but the curves characteristic of the diameter decrease and deflection were similar. The applied method seems to be useful for the examination of weak points of cardiac catheters. | 25,240,876 | [
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A biochemical approach to identify direct microRNA targets. | We have recently developed a biochemical approach to isolate miRNA-bound mRNAs and have used this method to identify the genome-wide mRNAs regulated by the tumor suppressor miRNA miR-34a. This method involves transfection of cells with biotinylated miRNA mimics, streptavidin pulldown, RNA isolation, and qRT-PCR. The protocol in this chapter describes these steps and the issues that should be considered while designing such pulldown experiments. | 25,240,884 | [
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Identification and validation of miRNA target sites within nontraditional miRNA targets. | miRNAs are endogenous small RNAs that regulate gene expression through recognition of complementary RNA sequences. While miRNAs have generally been understood to repress gene expression posttranscriptionally through recognition of 3'-untranslated regions (3'-UTRs) of mRNA transcripts, they have the potential to target additional classes of RNAs. Understanding the expanding pool of potential miRNA targets has been hindered by the lack of tools for predicting target sites within these RNAs. Here, the principles for developing computational algorithms for identifying putative miRNA target sites outside of mRNA are discussed. Laboratory techniques for validating computational miRNA target predictions are described. | 25,240,886 | [
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A new microcolumn-type microchip for examining the expression of chimeric fusion genes using a nucleic acid sandwich hybridization technique. | We report a new type of microcolumn installed in a microchip. The architecture allows use of a nucleic acid sandwich hybridization technique to detect a messenger RNA (mRNA) chain as a target. Data are presented that demonstrate that the expression of a chimeric fusion gene can be detected. The microcolumn was filled with semi-transparent microbeads made of agarose gel that acted as carriers, allowing increased efficiency of the optical detection of fluorescence from the microcolumn. The hybrid between the target trapped on the microbeads and a probe DNA labeled with a fluorescent dye was detected by measuring the intensity of the fluorescence from the microcolumn directly. These results demonstrate an easy and simple method for determining the expression of chimeric fusion genes with no preamplification. | 25,240,923 | [
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Lehr's fields of campaniform sensilla in beetles (Coleoptera): functional morphology. I. General part and allometry. | In this first of three articles we show the construction of the articular part of the elytron, the root. The root bears a conspicuous field of campaniform sensilla. This field was studied using light and scanning electron microscopes. The diversity of shape of the field among beetles, types of orientation of elongated sensilla within the field, individual variability of their number among conspecifics are demonstrated. Elongated sensilla point to the junction of the elytron with the second axillary plate. Presumably, they monitor twist movement in this junction, which is possible if the elytron is open. The goal of the whole project is to reveal the effect of both structure and function of the hind wings and elytra on the morphology of this mechanosensory field. Our data on allometric relationships between the animal size and quantitative characteristics of the field in normally flying beetles provide an important background for further functional analysis of this sensory organ. We selected 14 series of several species belonging to the same taxon but differing in size from big to small. It is revealed that the area of the sensory field is directly proportional to the elytral area, whereas the number of sensilla is proportional to the square root of the elytral area. Despite the great range in the elytral area (1500 times) in series of selected species the area of an external pit or cap of a single sensillum varies only 25-fold. The density of sensilla per unit area of the sensory field increases with decrease of the elytral area. | 25,240,964 | [
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Self-reported adult footwear and the risks of lower limb osteoarthritis: the GOAL case control study. | Biomechanical factors may play a role in osteoarthritis (OA) development and progression. Previous biomechanical studies have indicated that types of footwear may modulate forces across the knee joint, and high heeled womens' shoes in particular are hypothesised to be detrimental to lower limb joint health. This analysis of data from a case control study investigated persistent users of different adult footwear for risks of knee and hip OA. Our underlying hypotheses were that high heeled, narrow heeled, and hard soled shoe types were putative risk factors for lower limb OA. Data on footwear were initially obtained from participants during the Genetics of Osteoarthritis and Lifestyle (GOAL) hospital-based, case control study using standardised interview-delivered questionnaires. An additional questionnaire was later sent to GOAL study participants to verify findings and to further investigate specific shoe use per decade of life. Persistent users of footwear types (high or narrow heel; sole thickness or hardness) were identified from early adulthood. Participants were grouped into single sex knee OA, hip OA or control groups. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were calculated. Univariate analysis of persistent users of women's high heeled and narrow heeled shoes during early adulthood showed negative associations with knee OA and hip OA. After logistic regression, persistent narrow heel users were associated with less risk of OA (knee OA aOR 0.59, 95% CI 0.35 - 1.00 and hip aOR: 0.50, 95% CI 0.30 - 0.85), and other analyses were not statistically significant. Further analysis suggested that women with hip OA may have stopped wearing high and narrow heeled footwear to attenuate hip pain in early adulthood. Consistent associations between shoe soles and OA were not found. In general, persistent users of high and narrow heeled shoes during early adulthood had a negative association with knee or hip OA. This does not necessarily imply a causal relationship, as changing footwear during early adulthood to modulate index joint pain may provide a possible explanation. Despite the findings of previous biomechanical studies of high heels, we did not find a positive association between women's shoes and lower limb osteoarthritis. | 25,240,981 | [
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The use of high-speed, continuous, T2-weighted magnetic resonance sequences and saline for the evaluation of swallowing. | To introduce a new high-speed, continuous, T2-weighted magnetic resonance imaging (MRI) technique for the evaluation of swallowing by visualizing the flow of saline. In 20 healthy participants, high-speed (10 frames per second), continuous MRI of the pharynx and larynx was performed during administration of 5 mL of saline. The extent to which fluid flow and swallowing (including flow to the esophagus or trachea) could be visualized was determined for all 20 participants. Solution flow was visualized, and swallowing events, including the direction of flow to the esophagus, could be visualized with high-speed, continuous MRI for all 20 participants. This initial study suggests that the visualization of saline flow using our method may facilitate functional evaluation of swallowing without side effects. | 25,240,997 | [
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Direct optimization of signal-to-noise ratio of CPMG-like sequences in inhomogeneous fields. | The performance of the standard CPMG sequence in inhomogeneous fields can be improved with the use of broadband excitation and refocusing pulses. In previous work we have developed short composite broadband refocusing pulses together with practical excitation pulses to realize such performance gains, and quantified them using the ratio of signal to noise power (SNR). In this work we systematically explore the performance of refocusing pulses as a function of the overall pulse length up to ten times the length of the regular 180° pulse. This is in the regime of non-adiabatic pulses. We introduce a new performance functional for numerical pulse optimization that directly maximizes SNR and study the effect of symmetry constraints on the pulses. We find that for the optimal pulses, the SNR per asymptotic echo increases with pulse length but, for typical echo spacings, the SNR per unit time is maximized for refocusing pulses that are between two and four times longer than the duration of the standard rectangular 180° pulse. The performance is limited by the control bandwidth and the inability of finding the global maximum. The best performance was obtained with symmetric phase-alternating (SPA) refocusing pulses optimized with our novel performance functional. To test them in the CPMG sequence, we also developed axis-matching excitation (AMEX) pulses for use with these SPA refocusing pulses and tested the new AMEX-SPA sequences experimentally in a grossly inhomogeneous field, observing excellent agreement with the theoretical expectations. One of these sequences produced over 4.5 times higher SNR per asymptotic echo and 3.9 times higher SNR per unit time than the standard CPMG sequence with the same instantaneous RF power level. We also found that the new sequences are at least as robust to changes in the RF field strength as the standard CPMG sequence. | 25,241,006 | [
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Assessment of pretend play in Prader-Willi syndrome: a direct comparison to autism spectrum disorder. | Children with Prader-Willi syndrome (PWS) are at risk for autism spectrum disorder (ASD), including pervasive social deficits. While play impairments in ASD are well documented, play abilities in PWS have not been evaluated. Fourteen children with PWS and ten children with ASD were administered the Autism Diagnostic Observation Schedule (ADOS) (Lord et al. in Autism Diagnostic Observation Schedule manual. Western Psychological Services, Los Angeles, 2006) as part of a larger project. A modified Affect in Play Scale (APS; Russ in Play in child development and psychotherapy: toward empirically supported practice. Lawrence Erlbaum Associates Publishers, Mahwah, 2004; Pretend play in childhood: foundation of adult creativity. APA Books, Washington, 2014) was used to score ADOS play activities. Results indicate both groups scored below normative data on measures of imagination, organization, and affective expression during individual play. In addition, the inclusion of a play partner in both groups increased all scaled scores on the APS. These findings suggest children with PWS show impaired pretend play abilities similar to ASD. Further research is warranted and should focus on constructing and validating programs aimed at improving symbolic and functional play abilities within these populations. | 25,241,008 | [
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New devices and technology in interventional cardiology. | There have been substantial improvements made in the tools and techniques used since the advent of percutaneous coronary intervention. What was primarily developed as a treatment of coronary artery disease is now used to address a variety of structural heart disease problems. The outcomes have been remarkably successful with relatively low complication rates that rival the results of open-heart surgery. This article will review some of the new devices available for management of structural cardiac conditions including congenital defects and acquired valvular abnormalities. Transcatheter treatment offers advantages over surgical intervention in recovery time, improved patient satisfaction, lower procedural risk, and avoidance of cardio-pulmonary bypass especially in high-risk patients. We will discuss different medical conditions and introduce the devices used to treat these conditions. Each device or technique has benefits and risks, and familiarity with the devices along with patient selection will best optimize the outcome. | 25,241,014 | [
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Mechanical changes in human dental pulp stem cells during early odontogenic differentiation. | Cell adhesion and migration in bioactive scaffolds require actin cytoskeleton remodeling and focal adhesion formation. Additionally, human dental pulp stem cells (hDPSCs) undergo several changes in their mechanical properties during odontogenic differentiation. The effect of factors essential for odontogenesis on actin stress fiber elasticity and focal adhesion formation is not known. Live hDPSCs cultured in odontogenic media were imaged for cytoskeleton changes using an atomic force microscope. The Young's modulus (kPa) of the cytoskeleton was recorded as a function of culture medium for 10 days. Focal adhesion formation was assessed using immunofluorescence. Cultured hDPSCs were incubated with a monoclonal vinculin antibody, and filamentous actins were visualized using 0.5 μmol/L phalloidin. Cytoskeletal elasticity significantly increased in response to odontogenic media. Both the number and physical size of focal adhesions in hDPSCs also increased. Up-regulation of vinculin expression was evident. The increase in the formation of focal adhesions was consistent with actin remodeling to stress fibers. Our findings suggest that hDPSCs firmly attach to the glass substrate in response to odontogenic media. Successful regeneration of pulp-dentin tissue using biomimetic scaffolds will likely require cell-extracellular matrix interactions influenced by biochemical induction factors. | 25,241,024 | [
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Psychical research in the history and philosophy of science. An introduction and review. | As a prelude to articles published in this special issue, I sketch changing historiographical conventions regarding the 'occult' in recent history of science and medicine scholarship. Next, a review of standard claims regarding psychical research and parapsychology in philosophical discussions of the demarcation problem reveals that these have tended to disregard basic primary sources and instead rely heavily on problematic popular accounts, simplistic notions of scientific practice, and outdated teleological historiographies of progress. I conclude by suggesting that rigorous and sensitively contextualized case studies of past elite heterodox scientists may be potentially useful to enrich historical and philosophical scholarship by highlighting epistemologies that have fallen through the crude meshes of triumphalist and postmodernist historiographical generalizations alike. | 25,241,025 | [
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Attention and recognition biases associated with stature dissatisfaction among young men in China. | This research evaluated information-processing biases related to height dissatisfaction among young Chinese men. In Study 1, 32 highly stature dissatisfied (HSD) men and 36 less stature dissatisfied (LSD) men performed a dot probe task featuring height-related words and neutral words. HSD men were significantly slower than LSD men were in responding to probes that followed short stature words, but the groups did not differ in response speeds to probes that followed tall stature or neutral words. In Study 2, 33 HSD men and 34 LSD men completed an implicit learning task followed by a word recognition task. HSD men recognized significantly more short stature words from the initial task, but recognition accuracy for other word types did not differ between groups. Together, these findings suggest that HSD men are more inclined than LSD men to selectively avoid cues that reflect shortness in stature and to selectively recognize such cues later. | 25,241,032 | [
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Vertical expandable prosthetic titanium rib (VEPTR): a review of indications, normal radiographic appearance and complications. | Vertical expandable prosthetic titanium rib (VEPTR) is increasingly used in the treatment of thoracic insufficiency, idiopathic and neuromuscular scoliosis and chest wall defects in children. In contrast to spinal fusion surgery, the VEPTR allows for growth while stabilizing the deformity. We illustrate the common indications and normal radiographic appearance of the three common configurations of VEPTR (cradle-to-cradle assembly, cradle with lumbar extension assembly, cradle-to-ala hook assembly). There is a relatively high rate of reported complications with VEPTR in the literature. We discuss the potential complications of VEPTR, including infection, rib fracture, dislodged hardware and neurological injury, with an emphasis on imaging diagnosis. | 25,241,040 | [
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Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for reduced neuronal integrity in the anterior cingulate. | Neuroimaging studies have suggested that dysfunction of the cortico-striatal-thalamo-cortical (CSTC) circuit is a key pathophysiologic feature of obsessive-compulsive disorder (OCD). Several studies using proton magnetic resonance spectroscopy ((1)H MRS) have found abnormal neural metabolite concentrations among OCD patients. The aim of this study was to investigate the metabolic integrity of the anterior cingulate, caudate and putamen in OCD. In the present study, 32 unmedicated patients with OCD, including 23 who were drug-naïve, were compared using MRS with 32 healthy controls. Metabolite levels of N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) were measured in terms of their ratios to creatine (Cr). The ratio of NAA/Cr was significantly lower in OCD patients than in healthy controls in the anterior cingulate. There was a tendency for levels of NAA/Cr to be lower in the caudate and the putamen in patients with OCD compared with healthy controls. NAA/Cr ratios were negatively correlated with the total scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in the anterior cingulate in patients with OCD. Our results support the significance and biochemical involvement of the anterior cingulate cortex (ACC) in the pathophysiology of OCD. | 25,241,042 | [
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Fingerprinting sedimentary and soil units by their natural metal contents: a new approach to assess metal contamination. | One of the major issues when assessing soil contamination by inorganic substances is reliable determination of natural metal concentrations. Through integrated sedimentological, pedological and geochemical analyses of 1414 (topsoil/subsoil) samples from 707 sampling stations in the southern Po Plain (Italy), we document that the natural distribution of five potentially toxic metals (Cr, Ni, Cu, Zn and Pb) can be spatially predicted as a function of three major factors: source-rock composition, grain size variability and degree of soil weathering. Thirteen genetic and functional soil units (GFUs), each reflecting a unique combination of these three variables, are fingerprinted by distinctive geochemical signatures. Where sediment is supplied by ultramafic (ophiolite-rich) sources, the natural contents of Cr and Ni in soils almost invariably exceed the Italian threshold limits designated for contaminated lands (150 mg/kg and 120 mg/kg, respectively), with median values around twice the maximum permissible levels (345 mg/kg for Cr and 207 mg/kg for Ni in GFU B5). The original provenance signal is commonly confounded by soil texture, with general tendency toward higher metal concentrations in the finest-grained fractions. Once reliable natural metal concentrations in soils are established, the anthropogenic contribution can be promptly assessed by calculating metal enrichments in topsoil samples. The use of combined sedimentological and pedological criteria to fingerprint GFU geochemical composition is presented here as a new approach to enhance predictability of natural metal contents, with obvious positive feedbacks for legislative purposes and environmental protection. Particularly, natural metal concentrations inferred directly from a new type of pedogeochemical map, built according to the international guideline ISO 19258, are proposed as an efficient alternative to the pre-determined threshold values for soil contamination commonly established by the national regulations. | 25,241,058 | [
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Prefrontal dopamine in associative learning and memory. | Learning to associate specific objects or actions with rewards and remembering the associations are everyday tasks crucial for our flexible adaptation to the environment. These higher-order cognitive processes depend on the prefrontal cortex (PFC) and frontostriatal circuits that connect areas in the frontal lobe with the striatum in the basal ganglia. Both structures are densely innervated by dopamine (DA) afferents that originate in the midbrain. Although the activity of DA neurons is thought to be important for learning, the exact role of DA transmission in frontostriatal circuits during learning-related tasks is still unresolved. Moreover, the neural substrates of this modulation are poorly understood. Here, we review our recent work in monkeys utilizing local pharmacology of DA agents in the PFC to investigate the cellular mechanisms of DA modulation of associative learning and memory. We show that blocking both D1 and D2 receptors in the lateral PFC impairs learning of new stimulus-response associations and cognitive flexibility, but not the memory of highly familiar associations. In addition, D2 receptors may also contribute to motivation. The learning deficits correlated with reductions of neural information about the associations in PFC neurons, alterations in global excitability and spike synchronization, and exaggerated alpha and beta neural oscillations. Our findings provide new insights into how DA transmission modulates associative learning and memory processes in frontostriatal systems. | 25,241,063 | [
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In vivo mitochondrial inhibition alters corticostriatal synaptic function and the modulatory effects of neurotrophins. | Experimental evidence has revealed the role of mitochondria in various aspects of neuronal physiology. Mitochondrial failure results in alterations that underlie the pathogeneses of many neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease (HD) and amyotrophic lateral sclerosis. The mitochondrial toxin 3-nitropropionic acid (3-NP) has been used to model failure; for example, systemic administration of 3-NP imitates the striatal degeneration that is exhibited in the postmortem tissue of patients afflicted with HD. We have demonstrated that low, sub-chronic doses of 3-NP are sufficient to initiate the damage to striatal neurons that is associated with changes in neurotrophin expression levels. However, the mechanisms underlying the alterations in neuronal activity and neurotransmission due to 3-NP-induced mitochondrial dysfunction remain to be elucidated. In this paper, we focus on how corticostriatal transmission and its modulation by neurotrophins are altered in vivo after 5 days of mitochondrial inhibition with 3-NP. Recordings of population spikes and a paired pulse (PP) stimulation protocol were used to document changes in corticostriatal synapses in 3-NP-treated brain slices. The corticostriatal synapses were modulated by neurotrophins but displayed differential amplitude increases in the presence of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) under control conditions. Neurotrophin-mediated synaptic modulation was decreased in slices from 3-NP-treated mice. The protein and mRNA levels of neurotrophins and their receptors were also modified in the 3-NP-treated tissue. Neuronal structural evaluation demonstrated that synaptic length and density were reduced in the 3-NP-treated mice, which partially explained the changes in the amplitudes of the synaptic field responses. Our results demonstrate that corticostriatal synapses are differentially modulated by neurotrophins and that this modulation is altered by mitochondrial failure. Mitochondrial dysfunction also affects neurotransmitter release in corticostriatal synapses, neurotrophin availability, dendritic arborization and the lengths of the striatal medium spiny neurons (MSNs). | 25,241,069 | [
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Striatal circuits, habits, and implications for obsessive-compulsive disorder. | Increasing evidence implicates abnormalities in corticostriatal circuits in the pathophysiology of obsessive-compulsive disorder (OCD) and OC-spectrum disorders. Parallels between the emergence of repetitive, compulsive behaviors and the acquisition of automated behaviors suggest that the expression of compulsions could in part involve loss of control of such habitual behaviors. The view that striatal circuit dysfunction is involved in OC-spectrum disorders is strengthened by imaging and other evidence in humans, by discovery of genes related to OCD syndromes, and by functional studies in animal models of these disorders. We highlight this growing concordance of work in genetics and neurobiology suggesting that frontostriatal circuits, and their links with basal ganglia, thalamus and brainstem, are promising candidates for therapeutic intervention in OCD. | 25,241,072 | [
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Complex lymphatic anomalies. | Complex lymphatic anomalies include several diagnoses with overlapping patterns of clinical symptoms, anatomic location, imaging features, hematologic alterations, and complications. Lymphatic malformations likely arise through anomalous embryogenesis of the lymphatic system. Analysis of clinical, imaging, histologic, and hematologic features is often needed to reach a diagnosis. Aspiration of fluid collections can readily define fluid as chylous or not. The presence of chyle indicates dysfunction at the mesenteric or retroperitoneal level or above the cisterna chyli due to reflux. The imaging patterns of generalized lymphatic anomaly (GLA) and Gorham-Stout disease have been segregated with distinctive bone lesions and peri-osseous features. More aggressive histology (spindled lymphatic endothelial cells), clinical progression, hemorrhage, or moderate hematologic changes should raise suspicion for kaposiform lymphangiomatosis. Biopsy may be needed for diagnosis, though avoidance of rib biopsy is advised to prevent iatrogenic chronic pleural effusion. Lymphangiography can visualize the anatomy and function of the lymphatic system and may identify dysfunction of the thoracic duct in central conducting lymphatic anomalies. Local control and symptom relief are targeted by resection, laser therapy, and sclerotherapy. Emerging data suggest a role for medical therapies for complications of complex lymphatic anomalies. Outcomes include recurrent effusion, infection, pain, fracture, mortality, and rarely, malignancy. Complex lymphatic anomalies present significant diagnostic and therapeutic challenges. Results from a phase 2 study of sirolimus in these and other conditions are expected in 2014. Improved characterization of natural history, predictors of poor outcomes, responses to therapy, and further clinical trials are needed for complex lymphatic anomalies. | 25,241,096 | [
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Arteriovenous malformations. | Arteriovenous malformations (AVMs) are fast-flow vascular malformations composed of a complex vessel network directly connecting feeding arteries to draining veins. The intervening normal capillary network is absent. Proper diagnosis and treatment of AVMs is challenging and in need of an interdisciplinary team of experienced physicians. Careful analysis of the clinical features and evaluation of therapeutic options represent the basis for successful management of AVMs. This article will focus on the clinical and radiological findings and in particular on interdisciplinary management strategies of AVMs including minimally invasive endovascular and surgical treatment. | 25,241,099 | [
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Antibacterial effect of crude extract and metabolites of Phytolacca americana on pathogens responsible for periodontal inflammatory diseases and dental caries. | The oral cavity is the store house of different species of microorganisms that are continuously engaged in causing diseases in the mouth. The present study was conducted to evaluate the antibacterial potential of crude extracts of the aerial parts of Phytolacca americana and its natural compounds against two oral pathogens, Porphyromonas gingivalis and Streptococcus mutans, which are primarily responsible for periodontal inflammatory diseases and dental caries, as well as a nonpathogenic Escherichia coli. Crude extract and fractions from the aerial parts of P. americana (0.008-1.8 mg/mL) were evaluated for their potential antibacterial activity against two oral disease causing microorganisms by micro-assays. The standard natural compounds present in P. americana, kaempferol, quercetin, quercetin 3-glucoside, isoqueritrin and ferulic acid, were also tested for their antibacterial activity against the pathogens at 1-8 μg/mL. The crude extract was highly active against P. gingivalis (100% growth inhibition) and moderately active against S. mutans (44% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fraction controlled the growth of P. gingivalis with 91% and 92% growth inhibition at a concentration of 0.2 mg/mL, respectively. Kaempferol exerted antibacterial activity against both the pathogens, whereas quercetin showed potent growth inhibition activity against only S. mutans in a concentration dependent manner. The crude extract, chloroform fraction, and hexane fraction of P. americana possesses active natural compounds that can inhibit the growth of oral disease causing bacteria. Thus, these extracts have the potential for use in the preparation of toothpaste and other drugs related to various oral diseases. | 25,241,105 | [
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Assessment of cardiorespiratory and neuromotor fitness in children with developmental coordination disorder. | The decreased participation in physical activity by children with probable developmental coordination disorder (pDCD) has raised concerns about their aerobic fitness and lung function levels. The purpose of the present study was to examine assessment of cardiorespiratory and neuromotor fitness, using laboratory-based tests during an incremental treadmill protocol in healthy children with and without pDCD. Twenty sex children ages 6-9 years took part in this study. Motor coordination was assessed using the Movement Assessment Battery for Children (MABC). All participants performed a cardiopulmonary exercise test (CPET) on a cycle ergometer. Pulmonary function was assessed by spirometric measurements (forced vital capacity: FVC, forced expiratory volume in 1s: FEV1) and walking distance (6MWD) was assessed using the 6-min walking test. The children with pDCD had lower VO2max than children without pDCD (p < 0.01). Moreover, FVC and FEV1 were significantly higher in children without pDCD than in children with the disorder (p < 0.05, p < 0.01 respectively). Likewise, children with pDCD had poorer performance on the 6MWD than children without pDCD (p < 0.01). A significant correlation between the absolute value for FEV1 and 6MWD (r = 0.637, p < 0.05) in pDCD group was observed. We found a significant correlation between VO2max and MABC score (r = -0.612, p < .001) and between VO2max and 6MWD (r = 0.502, p < .001) for all children. Moreover, a significant correlation between VO2max and FEV1 (r = 0.668, p < .05) was found in children with pDCD. Overall, the reduced aerobic capacity of DCD was associated with decreased of lung function, as well as an alteration of peripheral muscle responses. | 25,241,114 | [
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SAHA-based novel HDAC inhibitor design by core hopping method. | The catalytic activity of the histone deacetylase (HDAC) is directly relevant to the pathogenesis of cancer, and HDAC inhibitors represented a promising strategy for cancer therapy. SAHA (suberoanilide hydroxamic acid), an effective HDAC inhibitor, is an anti-cancer agent against T-cell lymphoma. However, SAHA has adverse effects such as poor pharmacokinetic properties and severe toxicities in clinical use. In order to identify better HDAC inhibitors, a compound database was established by core hopping of SAHA, which was then docked into HDAC-8 (PDB ID: 1T69) active site to select a number of candidates with higher docking score and better interaction with catalytic zinc ion. Further ADMET prediction was done to give ten compounds. Molecular dynamics simulation of the representative compound 101 was performed to study the stability of HDAC8-inhibitor system. This work provided an approach to design novel high-efficiency HDAC inhibitors with better ADMET properties. | 25,241,128 | [
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SDS-PAGE and IR spectroscopy to evaluate modifications in the viral protein profile induced by a cationic porphyrinic photosensitizer. | Reactive oxygen species can be responsible for microbial photodynamic inactivation due to its toxic effects, which include severe damage to proteins, lipids and nucleic acids. In this study, the photo-oxidative modifications of the proteins of a non-enveloped T4-like bacteriophage, induced by the cationic porphyrin 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide were evaluated. Two methods were used: sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and infrared spectroscopy. SDS-PAGE analysis showed that the phage protein profile was considerably altered after photodynamic treatment. Seven protein bands putatively corresponding to capsid and tail tube proteins were attenuated and two other were enhanced. Infrared spectroscopy confirmed the time-dependent alteration on the phage protein profile detected by SDS-PAGE, indicative of a response to oxidative damage. Infrared analysis showed to be a promising and rapid screening approach for the analysis of the modifications induced on viral proteins by photosensitization. In fact, one single infrared spectrum can highlight the changes induced to all viral molecular structures, overcoming the delays and complex protocols of the conventional methods, in a much simple and cost effective way. | 25,241,141 | [
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Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration. | We developed an intra-articular (IA) drug delivery system to treat osteoarthritis (OA) that consisted of kartogenin conjugated chitosan (CHI-KGN). Kartogenin, which promotes the selective differentiation of mesenchymal stem cells (MSCs) into chondrocytes, was conjugated with low-molecular-weight chitosan (LMWCS) and medium-molecular-weight chitosan (MMWCS) by covalent coupling of kartogenin to each chitosan using an ethyl(dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) catalyst. Nanoparticles (NPs, 150 ± 39 nm) or microparticles (MPs, 1.8 ± 0.54 μm) were fabricated from kartogenin conjugated-LMWCS and -MMWCS, respectively, by an ionic gelation using tripolyphosphate (TPP). The in vitro release profiles of kartogenin from the particles showed sustained release for 7 weeks. When the effects of the CHI-KGN NPs or CHI-KGN MPs were evaluated on the in vitro chondrogenic differentiation of human bone marrow MSCs (hBMMSCs), the CHI-KGN NPs and CHI-KGN MPs induced higher expression of chondrogenic markers from cultured hBMMSCs than unconjugated kartogenin. In particular, hBMMSCs treated with CHI-KGN NPs exhibited more distinct chondrogenic properties in the long-term pellet cultures than those treated with CHI-KGN MPs. The in vivo therapeutic effects of CHI-KGN NPs or CHI-KGN MPs were investigated using a surgically-induced OA model in rats. The CHI-KGN MPs showed longer retention time in the knee joint than the CHI-KGN NPs after IA injection in OA rats. The rats treated with CHI-KGN NPs or CHI-KGN MPs by IA injection showed much less degenerative changes than untreated control or rats treated with unconjugated kartogenin. In conclusion, CHI-KGN NPs or CHI-KGN MPs can be useful polymer-drug conjugates as an IA drug delivery system to treat OA. | 25,241,157 | [
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Gpn1 and Gpn3 associate tightly and their protein levels are mutually dependent in mammalian cells. | Gpn1 and Gpn3 are GTPases individually required for nuclear targeting of RNA polymerase II. Here we show that whereas Gpn3-EYFP distributed between the cytoplasm and cell nucleus, it was mainly cytoplasmic when coexpressed with Gpn1-Flag. Gpn3-Flag retained Gpn1-EYFP in the cytoplasm. However, Gpn3-EYFP/Gpn1-Flag nucleocytoplasmic shuttling was revealed after inhibiting nuclear export with leptomycin B. All Gpn3-EYFP coimmunoprecipitated with Gpn1-Flag, and all Gpn1-EYFP with Gpn3-Flag. Importantly, most endogenous Gpn1 and Gpn3 also associate. Gpn1-Gpn3 interaction was essential to maintain steady-state protein levels of both GTPases. We propose that most Gpn1 and Gpn3 associate, are mobilized, and function as a protein complex. | 25,241,168 | [
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Weighted diagnostic criteria for developmental dysplasia of the hip. | To establish clinical diagnostic criteria for developmental dysplasia of the hip (DDH) that model the practices of expert clinicians. Of 23 clinical criteria for the diagnosis of DDH, ranked in order of diagnostic importance by international consensus, the 7 most highly ranked were placed in all possible combinations to create unique case vignettes. Twenty-six experts rated 52 vignettes for the presence of DDH. We modeled the data to determine which of the 7 criteria were associated with a clinician's opinion that the vignette represented DDH. From the resulting regression coefficients, for each vignette we calculated a probability of DDH. An independent panel rated the same vignettes using a visual analog scale response. We correlated the visual analog scale ratings with probabilities derived from the model. Our model identified 4 of 7 criteria as predictive of DDH (P < .001): Ortolani/Barlow test (β = 3.26), limited abduction (β = 1.48), leg length discrepancy (β = 0.74), and first-degree family history of DDH (β = 1.39). There was substantial correlation between the probability of DDH predicted by the model and that derived from an independent expert panel (r = 0.73; P < .001). Weighted clinical criteria for inferring the likelihood of DDH produced consistent results in the judgment of 2 separate groups of experts. Using these weights, nonexperts could establish the probability of DDH in a manner approaching the practice of clinical experts. | 25,241,185 | [
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Deployment-related depression screening, 2001-2008: comparing clinical versus research surveys. | Potential adverse mental health effects of deployment, including depression, are an ongoing concern. Although a previous study assessed under-reporting of depression on post-deployment health assessments compared to anonymous surveys, those results were not examined at the individual level to identify demographic or military factors that may be associated with unwillingness to report depression symptoms. To compare self-reported depression symptoms on post-deployment health assessments with responses to the same depression questions on a research survey. This cross-sectional study analyzed depression screening responses from 2001 to 2008 from participants of the Millennium Cohort Study, a longitudinal military cohort study, who completed a post-deployment health assessment within 30 days of a research survey. Kappa statistics and percent positive and negative agreement were calculated. Demographic and military characteristics associated with discordant screening results were examined. Initial analyses were performed in 2011, with additional analyses in 2013. Moderate agreement (κ=0.464) was observed between paired survey responses. A higher proportion of active duty members, the unmarried, and new accessions into military service endorsed depression symptoms on the research survey but not the military-linked survey. In stratified analyses, agreement was higher in Reserve/National Guard members than active duty (κ=0.561 vs 0.409). New active duty accessions showed lower agreement (κ=0.388), as did unmarried active duty participants (κ=0.304). Deployment health surveys are important tools for identifying returning service members experiencing depression symptoms. However, these findings suggest that ongoing stigma and barriers to appropriate follow-up mental health care remain to be addressed in the military setting. | 25,241,198 | [
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Monopolar electromyographic signals recorded by a current amplifier in air and under water without insulation. | It was recently proposed that one could use signal current instead of voltage to collect surface electromyography (EMG). With EMG-current, the electrodes remain at the ground potential, thereby eliminating lateral currents. The purpose of this study was to determine whether EMG-currents can be recorded in Tap and Salt water, as well as in air, without electrically shielding the electrodes. It was hypothesized that signals would display consistent information between experimental conditions regarding muscle responses to changes in contraction effort. EMG-currents were recorded from the flexor digitorum muscles as participant's squeezed a pre-inflated blood pressure cuff bladder in each experimental condition at standardized efforts. EMG-current measurements performed underwater showed no loss of signal amplitude when compared to measurements made in air, although some differences in amplitude and spectral components were observed between conditions. However, signal amplitudes and frequencies displayed consistent behavior across contraction effort levels, irrespective of the experimental condition. This new method demonstrates that information regarding muscle activity is comparable between wet and dry conditions when using EMG-current. Considering the difficulties imposed by the need to waterproof traditional bipolar EMG electrodes when underwater, this new methodology is tremendously promising for assessments of muscular function in aquatic environments. | 25,241,214 | [
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Breast cancer during follow-up and progression - A population based cohort on new cancers and changed biology. | Emerging data indicate an important role for biopsies of clinically/radiologically defined breast cancer 'recurrences'. The present study investigates tumour related events (relapses, other malignancies, benign conditions) after a primary breast cancer diagnosis. The cohort includes 2102 women, representing all patients, with primary invasive breast cancer during 2000-2011 in the county of Värmland, Sweden. A comparative analysis of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation (Ki67) between the primary tumour and the relapse was performed and related to outcome. With a mean follow-up time of 4.8 years, 1060 out of 2102 patients have had a biopsy taken after the initial breast cancer diagnosis demonstrating 177 recurrences, 93 other malignancies (colorectal, lung, skin), 40 cancer in situ (skin, breast) and 857 benign lesions. Approximately 70% (177 out of 245) of all cases of relapsed breast cancer underwent a biopsy during this time period. For patients with recurrences, ER (n=127), PR (n=101), HER2 (n=73) and Ki67 (n=55) status in both primary tumour and the corresponding relapse were determined. The discordance of receptor status was 14.2%, 39.6%, 9.6% and 36.3%, respectively. Loss of ER or PR in the relapse resulted in a significant increased risk of death (hazard ratio (HR) 3.62; 95% confidence interval (CI), 1.65-7.94) and (HR 2.34; 95% CI, 1.01-5.47) compared with patients with stable ER or PR positive tumours. The proportion of patients losing ER was bigger in the group treated with endocrine therapy alone or in combination with chemotherapy, 16.7% and 13.3%, respectively, compared with the group treated with chemotherapy alone or that which received no treatment 4.3% and 7.7%, respectively. Discordance of biomarkers between the primary tumour and the corresponding relapse was seen in 10-40% of the patients, adjuvant therapies seem to drive clonal selections. Patients with tumours losing ER or PR during progression have worse survival compared with patients with retained receptor expression. | 25,241,230 | [
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Regulation of the transbilayer movement of diacylglycerol in the plasma membrane. | This mini-review presents recent advances in the regulation of the membrane transbilayer movement (or flip-flop) of diacylglycerol (DAG), a key intermediate in lipid metabolism and a second messenger in lipid-mediated signaling. Despite progresses in lipid biophysics and imaging, little is known about the DAG dynamics across the two leaflets of the plasma membrane in living cells. Previous model membrane studies with DAG analogs demonstrated their fast flip-flop suggesting that DAG is evenly distributed between the two leaflets of the plasma membrane. However, recent molecular dynamics simulations indicate that DAG transbilayer movement depends on the lipid environment surrounding the lipid, i.e. DAG flips more slowly across a more ordered "lipid raft-like" bilayer (enriched in sphingomyelin/cholesterol) than across a more fluid bilayer (composed of unsaturated glycerophospholipids). Furthermore using the yellow fluorescent protein-tagged C1AB domain from protein kinase C-γ (EYFP-C1AB) that selectively binds DAG, we recently proved that the sphingomyelin (SM) content in the plasma membrane outer leaflet regulates DAG transbilayer movement in Madin-Darby canine kidney cells treated with bacterial phosphatidylcholine-specific phospholipase C. The dose-dependent inhibition of DAG flip-flop by SM could be reproduced in model membranes using fluorescent short chain DAG analog. Regulation of DAG transbilayer movement by the outer leaflet SM content is expected to modify the downstream recruitment of C1-domain containing effectors, thus bringing new insights on the role of DAG dynamics in cell pathophysiology. | 25,241,257 | [
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Prevalence of Escherichia coli sequence type 131 and its H30 subclone among E. coli isolates in a French hospital. | The prevalence of Escherichia coli sequence type 131 (ST131) and its subclone H30 was assessed among a collection of 490 E. coli isolated in 2013 in a French university hospital. The prevalence of ST131 was 4% among bloodstream isolates (regardless of antimicrobial resistance) and 17.2% among extended-spectrum β-lactamase (ESBL)-producing isolates. Although a much lower prevalence of ST131 was found among bloodstream E. coli isolates compared with other countries, a large predominance of H30 subclone within ST131 was confirmed. It was also confirmed that, among ESBL-producing E. coli, ST131 isolates were more frequently resistant to amoxicillin/clavulanic acid, ceftazidime, fluoroquinolones and aminoglycosides than non-ST131 isolates. | 25,241,262 | [
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Histone deacetylase inhibition enhances the lymphomacidal activity of the anti-CD22 monoclonal antibody HB22.7. | HB22.7, an anti-CD22 monoclonal antibody has shown consistent preclinical activity against non-Hodgkin lymphoma (NHL). Histone deacetylase inhibitors (HDACi) have demonstrated efficacy in lymphoma and can modulate cell surface receptor expression. To augment the lymphomacidal activity of HB22.7 we examined the combination of AR42 (an HDACi) and HB22.7 in vitro and in vivo. The combination resulted in 10-fold increased potency in 6 NHL cell lines when compared to either drug alone. Both drugs reduced tumor progression in xenografts, but the combination was significantly more efficacious and resulted in regression of established tumors, without toxicity. AR42 inhibited HB22.7-mediated CD22 internalization, suggesting that increased efficacy could be due to higher availability of CD22. Overall, the synergistic effects of HB22.7 and AR42 on in vitro cytotoxicity and in vivo anti-tumor activity make this combination an attractive option for further pre-clinical and clinical evaluation. | 25,241,275 | [
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Hole-pin joining structure with fiber-round-hole distribution of lobster cuticle and biomimetic study. | Observations of the cuticle of the Boston Spiny Lobster using scanning electron microscope (SEM) show that it is a natural biocomposite consisting of chitin fibers and sclerotic-protein matrix with hierarchical and helicoidal structure. The SEM images also indicate that there is a hole-pin joining structure in the cuticle. In this joining structure, the chitin fibers in the neighborhood of the joining holes continuously round the holes to form a fiber-round-hole distribution. The maximum pullout force of the fibers in the fiber-round-hole distribution, which is closely related to the fracture toughness of the cuticle, is investigated and compared with that of the fibers in non-fiber-round-hole distribution based on their representative models. It is revealed that the maximum pullout force of the fibers in the fiber-round-hole distribution is significantly larger than that of the fibers in the non-fiber-round-hole distribution, and that a larger diameter of the hole results in a larger difference in the maximum pullout forces of the fibers between the two kinds of the fiber distributions. Inspired by the fiber-round-hole distribution found in the cuticle, composite specimens with the fiber-round-hole distribution were fabricated with a special mold and process to mirror the fiber-round-hole distribution. The fracture toughness of the biomimetic composite specimens is tested and compared with that of the conventional composite specimens with the non-fiber-round-hole distribution. It is demonstrated that the fracture toughness of the biomimetic composite specimens with the fiber-round-hole distribution is significantly larger than that of the conventional composite specimens with the non-fiber-round-hole distribution. | 25,241,280 | [
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Processing and mechanical behavior of lamellar structured degradable magnesium-hydroxyapatite implants. | Multilayered (laminated) composites exhibit tunable mechanical behavior compared to bulk materials due to the presence of more interfaces and therefore magnesium based composites are gaining wide popularity as biodegradable materials targeted for temporary implant applications. The objective of the present work is to fabricate magnesium based lamellar metal matrix composites (MMCs) for degradable implant applications. Nano-hydroxyapatite (HA) powder was selected as the secondary phase and lamellar structured magnesium-nano-hydroxyapatite (Mg-HA) composites of 8, 10 and 15wt% HA were fabricated by ball milling and spark plasma sintering. It was found that HA particles were coated on the Mg flakes after 20h of ball milling carried out using tungsten carbide (WC) as the milling media. Spark plasma sintering of the milled powders resulted in the formation of lamellar structure of Mg with the presence of HA and magnesium oxide (MgO) at the inter-lamellar sites of the composites. Phase analysis of the milled powder by an X-ray diffraction (XRD) method confirms the presence of HA and MgO along with Mg after sintering. Corrosion behavior of the composites investigated by potentiodynamic polarization tests shows a reduction in the inter-lamellar corrosion with increase in HA content and the best corrosion resistance is found for the Mg-10% HA composite. This composite also exhibits maximum Vickers hardness. Young׳s modulus and fracture toughness measured by nano-indentation method were higher for the Mg-8% HA composite. The results thus suggest that lamellar structured Mg composites with 8% and 10% HA show promise for temporary degradable orthopedic implant applications because of their improved corrosion resistance and superior mechanical properties. | 25,241,282 | [
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Endoluminal release of ureteral ligature after hysterectomy. | Iatrogenic ureteral injury is a well-recognized complication of abdominal total hysterectomy. We report a case of a 57-year-old female who underwent abdominal total hysterectomy for a uterine myoma and experienced severe right flank pain postoperatively. The imaging study displayed an obstruction of the right distal ureter. Under ureteroscopy, an extraluminal ligature was released with a holmium:yttrium-aluminum-garnet laser. The stenotic segment was immediately relieved. Two months later, the intravenous urogram illustrated patency of the distal ureter with regression of right hydronephrosis. There was no recurrent hydronephrosis during 1 year of follow-up. | 25,241,286 | [
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Critical limb ischemia and the diseased popliteal artery. | The unique anatomical location and particular biomechanical factors affecting the popliteal artery provide a challenge to determine the proper endovascular, surgical, or combined intervention for patients with critical limb ischemia who often require prompt management in the presence of severe lifestyle-limiting symptoms or of the risk of limb loss or both. Herein, we provide an overview and practical guide for endovascular management of popliteal artery disease in the setting of critical limb ischemia. | 25,241,317 | [
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Tibiopedal access for lower extremity arterial intervention: when to use and how to perform. | Tibiopedal artery access is being used with increasing frequency as an alternative access to facilitate procedural success in lower extremity arterial intervention. This technique is usually employed in the setting of critical limb ischemia and tibial artery intervention, but it may offer potential practical advantages for popliteal artery and even superficial femoral artery intervention in unique situations. As in all cases of lower extremity arterial intervention, consideration of access is important not only for initial approach to any obstructing lesion but also for exit strategy. The dorsalis pedis artery and posterior tibial artery can be readily accessed if necessary owing to their relatively superficial position in the foot or the ankle, yet their normal diameter and the presence of significant calcification (a common finding in patients with tibial occlusive disease and critical limb ischemia) can pose difficulties as well. In addition, the peroneal artery in the lower leg can be accessed percutaneously; however, its size and depth may present additional challenges. Meticulous attention to detail is paramount in avoiding complications in what may be the only distal vessel supplying the foot. This article describes common techniques in using tibiopedal artery access as a means of alternative access for successful infrainguinal intervention. | 25,241,320 | [
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Optimal use of atherectomy in critical limb ischemia. | Critical limb ischemia (CLI) is the most severe and debilitating form of peripheral arterial disease and is associated with high rates of limb loss and cardiovascular mortality. The unique physical environment of tibial occlusive disease underlying most CLI cases limits treatment options and long-term durability, with resulting frequent rates of persistent obstruction, restenosis, and reintervention. Atherectomy represents a potential strategy to improve acute and late results when treating patients with CLI. Available atherectomy devices each have specific performance characteristics, evidentiary rationale, and limitations that mandate a clear understanding of the optimal albeit evolving use of this category of interventional tools. | 25,241,322 | [
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Outpatient follow-up for critical limb ischemia. | Outpatient follow-Up for critical limb ischemia offers the clinician the opportunity to monitor the patient for risk factor modification and wound healing. Routine surveillance following intervention will improve long-term patency. | 25,241,323 | [
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Development of the Lémann index to assess digestive tract damage in patients with Crohn's disease. | There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD). We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods. Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall. In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment. | 25,241,327 | [
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Peripheral mechanisms in appetite regulation. | Peripheral mechanisms in appetite regulation include the motor functions of the stomach, such as the rate of emptying and accommodation, which convey symptoms of satiation to the brain. The rich repertoire of peripherally released peptides and hormones provides feedback from the arrival of nutrients in different regions of the gut from where they are released to exert effects on satiation, or regulate metabolism through their incretin effects. Ultimately, these peripheral factors provide input to the highly organized hypothalamic circuitry and vagal complex of nuclei to determine cessation of energy intake during meal ingestion, and the return of appetite and hunger after fasting. Understanding these mechanisms is key to the physiological control of feeding and the derangements that occur in obesity and their restoration with treatment (as shown by the effects of bariatric surgery). | 25,241,326 | [
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Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis. | To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice. We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (<65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test. Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P<0.01) compared to the younger patient group (<65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P<0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups. In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results. | 25,241,333 | [
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Unplanned or unwanted? A randomized study of national estimates of pregnancy intentions. | To evaluate the effect of question wording on national estimates of pregnancy intentions. Data drawn from a national probability survey. The FECOND study in France in 2010. Five thousand two hundred and seventy-two women and 3,373 men who reported 11,603 pregnancies. Participants randomly assigned to answer 1 of 2 questions on whether they had planned or wanted each of their pregnancies. Generalized estimated equation regression models used to test for differences in pregnancy intentions by question wording. The use of different wording yielded a 6% point difference in estimates: 33.5% pregnancies were "unplanned," and 27.4% were "unwanted." The addition of information on reasons for not using contraception at the time of conception lead to significant recoding, which resulted in a significant reduction in the wording effect: 23.7% (95% CI 22.4-25.0) of pregnancies were unplanned, and 21.2% (95% CI 19.9-22.5) were unwanted. Results from the multivariate analysis confirm the greater chance of reporting an unplanned as compared with an unwanted pregnancy (relative risk 1.25 [95% CI 1.17-1.33]), even after recoding (relative risk 1.15 [95% CI 1.06-1.24]). This study shows the strong effect of question wording on estimates of pregnancy intentions. The results also support the value of adding information on reasons for nonuse of contraception when assessing pregnancy intentions. | 25,241,373 | [
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Relationship between rate of infection and markers of inflammation/immunity in Holy Birman cats with feline coronavirus. | The aim of this study was to assess whether Holy Birman cats (HB) have a peculiar immune profile and a higher rate of infection by feline coronaviruses (FCoV). Leucocyte and lymphocyte subsets, antibody titers, α1-acid glycoprotein (AGP), globulin fractions, IL-4, IL-12 and IFN-γ in blood and fecal FCoV excretion were determined in HB (n = 75) and in cats from other breeds (n = 94). Significantly higher CD4/CD8 ratio, IFN-γ concentration and IL12/IL4 ratio and significantly lower IL-4 concentration and proportion of shedders were found in HB than in other breeds. No other differences were found. In conclusion, this study did not provide evidence of peculiar immune profiles in HB, except for a prevalent Th1 profile, that may explain why in our caseload the rate of shedders was lower in HB than in other breeds. | 25,241,387 | [
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0.02480959,
0.4354378,
0.1926234,
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... |
The relationship of obesity and weight gain to childhood teasing. | This article examines the relationship between weight gain and childhood teasing in children. Anthropometric data and self-reported teasing experiences were collected on a sample of second and third graders at a local elementary school in a disadvantaged suburban community. The study model uses bio-ecological development theory in which child development is understood in context: the child's physical characteristics influence the social environment, which interact and influence the behaviors that result in physical development and characteristics such as weight gain. Results suggest that teasing influences BMI change and that the relationship is more complex than simply stating that obese children are teased. | 25,241,400 | [
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Understanding and managing myeloma. | Multiple myeloma cannot be cured and treatment can be complex. This article outlines the pathophysiology of the condition, together with the diagnostic process and the available treatment options. | 25,241,434 | [
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How to boost a low-morale medical practice team: twenty-five strategies. | Low morale can decrease productivity and cooperation among medical practice employees, and increase work errors, absenteeism, and turnover. That is why practice managers must be mindful of their employees' morale and develop a toolkit of strategies that they can use to assess and boost waning morale. This article suggests 25 practical and affordable strategies medical practice managers can use to increase their staffs' morale. It explores the high cost of low morale, including five invisible costs that are often overlooked but that nonetheless drain practice resources. Furthermore, this article suggests 25 warning signs of low morale and suggests 10 causes of low morale in the workplace. It also provides practice managers with a quick 10-question quiz to administer to their employees to help them assess employee morale. Finally, this article describes five easy and affordable games practice managers can play with their employees to build camaraderie and teamwork and to increase staff morale. | 25,241,449 | [
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Maximizing collections from patient services billing. | The field of medical billing and collections continues to evolve along with current developments in U.S. healthcare reform. Although there has been a significant shift of payment responsibility from third-party payers to patients, many practices are not equipped to handle this change. As patients' financial obligations increase, the physician's ability to collect from patients will become increasingly important. Inability to collect bills receivable can adversely affect the revenue cycle of the practice. Solutions include improvement of the point-of-service collection processes, properly trained office staff, written financial policies, and the use of technology to facilitate online payments. Patients should fully understand their financial responsibilities and options available to them for payment of services rendered. | 25,241,445 | [
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[Regulating effect of anodonta glucan HBP-A on chondrocytes through Wnt pathway]. | To investigate regulation function of anodonta glucan HBP-A on chondrocytes through Wnt pathway in vitro. Rat chondrocytes were cultured and differentiated induced with IL-1beta (10 ng/ml) in vitro. Chondrocytes were divided into five groups:IL-13 group,IL-1beta + IWP-2 (5 microM,Wnt pathway inhibitor) group, IL-1beta + HBP-A (0.3 mg/ml) group and IL-1beta + IWP-2 + HBP-A group. Wnt-3a, beta-catenin (24 h,48 h,72 h) and MMP-13(72 h) genes expression were detected by Rt-PCR, while beta-catenin, MMP-13, Sox-9 and coll-II (48 h) protein expression were measured by Western-blot. After induction of IL-1beta, gene expression of Wnt-3a, beta-catenin and MMP-13 were increased,so were the protein expression of beta-catenin and MMP-13. In contrast,protein expression of Sox-9 and Coll-II were declined. Following addition of HBP-A, Wnt-3a, beta-catenin and MMP-13 were shown as induction of IL-1beta, but protein expression of Sox-9 and Coll-II were upgraded. Combining HBP-A with IWP-2 led to the lowest level in Wnt-3a, beta-catenin gene and beta-catenin protein expression and highest expression of Sox-9 protein. HBP-A could not only delay the differentiation of chondrocytes through downgrading the signal expression of Wnt/beta-catenin,but also adjust the expression of Wnt-3a, beta-catenin and Sox-9 when combinated with the Wnt inhibitor. | 25,241,462 | [
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[Extorsion traction and pushing manipulation with fingers for the treatment of anterior shoulder dislocation in elderly]. | To investigate a manipulating therapy for treatment of anterior shoulder dislocation in elderly. From October 2011 to June 2012,27 elderly patients with anterior shoulder dislocation were treated by extorsion traction and pushing manipulation with fingers, including 7 males and 20 females aged from 65 to 86 years old with an average of 77. The course of disease ranged from 1 h to 1 d. The shoulder manifested square deformity, Dugus signs showed positive, and X-ray displayed anterior shoulder dislocation. Dugus fixation was applied for and removed external fixation at 3 weeks after operation and carried out shoulder functional exercise. Functional evaluation standard on shoulder joint injuries was used for evaluate clinical outcomes. All patients were gained reduction for the first time, and followed up at 3 months after operation, no dislocation occurred. According to functional evaluation standard on shoulder joint injuries, 22 cases got an excellent result,2 cases good,and 1 case moderate. Extorsion traction and pushing manipulating therapy for treatment of anterior shoulder dislocation in elderly, which has advantages of simple, convenient, less painful, and can avoid iatrogenic injury, is feasible to widespread. | 25,241,476 | [
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Pastoral counseling in the 21st century: the centrality of community. | In this article, I argue that the notion of ecclesia or faith community is a central, existential anthropological premise that can shape how we understand facets of pastoral counseling such as diagnosis, process, and aims. Implicit here is the idea that the distinctiveness of pastoral counseling lies not simply in accountability and authority vis-à-vis community, but in its use of a communitarian anthropology to understand the importance of community for psychosocial development, resiliency, and healing. I argue further that in the 21st century the centrality of the notion of community is, and will continue to be, critical, because of political and economic forces that undermine community, giving rise to psychosocial alienation, depression, etc. | 25,241,493 | [
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Pedagogical progeniture or tactical translation? George Fordyce's additions and modifications to William Cullen's philosophical chemistry--Part I. | This article contributes to a growing body of research on the dissemination, dispersion or diffusion of scientific knowledge via pedagogical networks. By examining students' handwritten lecture notes, I compare the eighteenth-century chemistry lectures given by William Cullen (1710-1790) at Glasgow and Edinburgh Universities with those of his one-time student George Fordyce (1736-1802), in London, at first privately and then as part of the medical education of physicians at St. Thomas's Hospital. Part I examines the broad structure of Cullen's and Fordyce's courses, comparing both course content and pedagogical approaches to ask how far knowledge flowed directly 'downstream,' and the extent to which it was transformed, translated or transmuted in the process of transmission. Part II (forthcoming) will approach the affinity theories of Cullen and Fordyce in greater depth, revealing the dynamics of knowledge transfer. The results shed light on the transmission of knowledge and skills between master and student, and reflect on whether Fordyce can be better described as Cullen's pedagogical progeny, or less straightforwardly as a tactical translator. | 25,241,503 | [
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Does fluoride gel/foam application time affect enamel demineralization? | The American Dental Association Council on Scientific Affairs recommends a four-minute application of professionally applied topical fluoride, based on clinical evidence for caries reduction. However, some product manufacturers imply that a one-minute application is sufficient. The purpose of this laboratory study was to ascertain if a one-minute application of acidulated phosphate fluoride (APF) is equivalent to a four-minute application for reduction of enamel demineralization. We measured baseline hardness of polished bovine enamel before treatment with APF gel or foam for one or four minutes (N = 10). A control group received no fluoride treatment. The teeth were then immersed in pooled human saliva for 30 minutes, rinsed, and subjected to lactic acid gel to simulate the initial stage of dental caries. After three hours, the hardness was measured and the difference in hardness was determined as an indication of demineralization. We found that enamel hardness was significantly reduced after exposure to lactic acid gel. The reduction was significantly less in all APF-treatment groups compared to the control. However, there was no significant difference between a tooth exposed to APF gel or foam for 1 minute or for 4 minutes (ANOVA/Student-Newman-Keuls, significance level 0.05). In conclusion, APF gel and foam reduced enamel demineralization regardless of a one- or four-minute application time. | 25,241,499 | [
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[Minimally invasive treatment of tibial plateau fracture under arthroscopy monitoring]. | Twenty six patients with fracture of tibial plateau was under arthroscopy assisted reduction, the joint surface of bone graft, and USES the steel plate fixation treatment. Average surgery time was 65 min (70-120 min), average fracture healing time was 15 weeks (12-17 weeks), joint surface anatomical reattachment rate was 92.9%. Using break knee function criteria evaluation of curative effect: 18 cases great 6 cases wed, 2 cases ok, fine rate was 92.3%. No infection, deep venous thrombosis and small leg fascia chamber syndrome and other complications. Conclusion is that treatment of tibial plateau fractures under arthroscope has advantages of small trauma, check intuitively and reset accurately, functional recovery of patients are satisfied, the treatment has certain clinical application value. | 25,241,526 | [
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... |
[Piezosurgery for surgically assisted rapid maxillary expansion under local anesthesia]. | This study evaluates piezosurgery for surgically assisted rapid maxillary expansion (SARME) under local anesthesia. SARME was performed on adults with maxillary transverse deficiency under local anesthesia with a piezosurgical device. Fourteen patients (six males and eight females) underwent lateral maxillary osteotomies, midpalatal osteotomies, and bilateral pterygomaxillary disjunction. The feelings of patients during the operation were determined through questionnaires. All patients underwent SARME in the out-patient operating room. The surgical procedures were completed under local anesthesia. All patients exhibited satisfactory tolerance. Ultrasonic bone-cutting surgery was recently introduced as a feasible alternative to the conventional tools of cranio-maxillofacial surgery for its technical characteristics of precision and safety. The device used was unique in that cutting action occurred when the tool was employed on mineralized tissues, but stoped on soft tissues. The results of the questionnaires showed that eight (57.14%) patients felt a mild sensation of ultrasonic vibration, tweleve (85.7 1%) felt mild tolerable pain and tooth soreness during surgery, and eleven (78.57%) felt little fear and hardly heard the ultrasonic sound. Preoperative and postoperative six months later measurements showed an evident effect of expansion. Piezosurgery enabled patients to undergo all the steps of SARME under local anesthesia, but more cases and longer follow-up are needed to verif ' the results. | 25,241,535 | [
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[Clinical application of primary tumor contralateral facial artery musculocutaneous flap to reconstruct oral and maxillofacial defects]. | This study aims to explore the method that uses primary tumor contralateral facial artery musculocutaneous (FAMM) flap to reconstruct defects of the tongue and floor of mouth. Six cases were selected for the use of primary tumor contralateral FAMM flap to reconstruct tongue and floor of mouth defects after tumor resection. The FAMM flap of the six cases had a long pedicle that could reach the contralateral tongue and floor of mouth. All flaps were intact until post-operation. All patients experienced post-operation complications, such as temporary facial tension and limited mouth opening, which improved after 3 months. Half a year later, the flaps still did not show signs of shrinking. Features of the primary tumor contralateral FAMM flap include the tissue-like material provided for reconstructing tongue or floor of mouth defects, easy acquisition, and high survival rate with minimal donor site morbidity. As such, it is an ideal material for repairing tongue and floor of mouth defects. | 25,241,536 | [
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Treatment outcome of tuberculosis patients in a clinic of Bangalore. | A total of 112 cases (New = 101, previously treated = 11) were diagnosed as suffering from tuberculosis (TB) at a private clinic in Bangalore city. The clinic identified TB suspects, established diagnosis of TB, administered direct observation of treatment (DOT), maintained treatment cards and undertook defaulter retrieval actions as and when required. The Revised National Tuberculosis Control Programme (RNTCP) provided support in terms of sputum microscopy supply of patient-wise drug boxes and registration of patients. Ninety six (95.1%) of new cases and 10 (90.9%) of previously treated cases had successful treatment outcome. Most patients completed treatment within the prescribed period. No TB deaths were reported during the period of treatment. | 25,241,566 | [
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Injection site abscess due to Mycobacterium tuberculosis following DPT vaccination. | Injection site abscesses are not so uncommon and usually bacterial in origin. Very occasionally, these are due to mycobacteria, particularly rapidly growing non-tuberculous mycobacteria. Mycobacterium tuberculosis is rarely implicated as a cause of injection site abscess as documented in this report following DPT vaccination. Various possible mechanisms for such an unusual event are also briefly explored. | 25,241,575 | [
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In vivo redox effects of Aspidosperma quebracho-blanco Schltdl., Lantana grisebachii Stuck and Ilex paraguariensis A. St.-Hil. on blood, thymus and spleen of mice. | Argentinian native plants Aspidosperma quebracho-blanco, Lantana grisebachii and Ilex paraguariensis are known to have antiinflammatory and antioxidant properties. We demonstrated it in vivo by the redox changes in murine hemolymphatic tissues after infusive extract intake of these plants as revealed in organic trophism, tissue phenolics, hydroperoxides, superoxide, nitrites and gamma-glutamyltranspeptidase in thymus, blood and spleen. A. quebracho-blanco reduced hydroperoxidation in blood and spleen of both sexes, with gamma-glutamyltranspeptidase negativization in lymphatic organs and thymic nitrosative up-regulation. Males have shown increased phenolic content in blood after treatment. L. grisebachii and I. paraguariensis treatment exhibited incomplete antioxidation and oxidative induction in the studied tissues. Different results according to sex were found in redox response to phenolics and their kinetics, with males showing antioxidant effects, whereas females showed oxidative susceptibility. A. quebracho-blanco exhibited protection of murine tissues against oxidation in both sexes and modulation of their trophism, supporting its therapeutic uses in inflammatory diseases. Also, gender had significant influence in phenolic biodistribution and redox response. | 25,241,588 | [
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Mass propagation of Cymbidium giganteum Wall. ex Lindl. using in vitro seedlings. | In vitro seedlings were used as explants for protocorm like bodies (PLBs) production which in turn were used for regeneration purpose. PLBs were induced from the base of seedlings (1.0-1.5 cm in size) in MS + BAP (8.88 microM). After 90 days of inoculation, PLBs production rate started declining and most of the PLBs turned into plantlets. Preculture of seedlings in 1.0 microM thidiazuron (TDZ) for 7 days and transfer to BAP supplemented medium resulted in production of 16 PLBs per seedling within 90 days of culture. Increase of TDZ concentration to 2.5 microM and preculture time 15 days, resulted in induction of highest number of PLBs (19 PLBs per seedling) in the basal medium. The results emphasized the importance of thidiazuron (TDZ) concentration and preculture time for PLBs proliferation from the base of seedlings. The PLBs thus produced were used for regeneration studies. Irrespective of single, segmented or clumps of PLBs, the regeneration response was 100% in 2,4-D (4.52 microM) and KN (4.64 microM) but when KN was replaced by BAP (8.88 microM), response was observed only in clumps of PLBs, whereas in single and segmented ones it was 99 and 97%, respectively. Regenerants developed stout root system in half strength M medium supplemented with 2.84 microM of IAA and transferred to greenhouse with 90% survival. The present study holds tremendous potential as the mother plant is not destroyed and PLBs are produced as a continuous system. | 25,241,591 | [
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In vitro regeneration in olive (Olea europaea L.) cv, 'Frontio' from nodal segments. | An efficient and reproducible protocol for plantlet regeneration from nodal segments of Olive cv 'Frontio' has been developed. Media and explants browning due to exudation of phenolics from the explants were controlled by fortification of the medium with 100 mg/L ascorbic acid. Best establishment of olive explants was observed on half-strength MS salts fortified with 2.0 mg/L 6-benzylaminopurine (BAP), which resulted in 56.2% of bud break and 93.7% survival whereas, a combination of full strength MS medium with 1.0 mg/L each of 3-indole-butyric-acid (IBA) and kinetin was found to be the best for shoot multiplication, in terms of number of shoots (3.6 shoots/explant) and shoot length (2.2 cm). The in vitro shoots were rooted on half-strength MS medium fortified with 0.2 mg/L IBA and 0.2 mg/L alpha-naphthalene acetic acid (NAA) with 1.5 g/L activated charcoal, which supported optimum rooting (60%), with an average of 2-3 roots/shoot, about 2.4 cm length were produced on four weeks of culture. | 25,241,592 | [
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The impact of an integrated care service on service users: the service users' perspective. | The purpose of this paper is to examine the effects of an integration programme on service users from users' own perspective. Multi-method approach was used. Both quantitative and qualitative data collection and analysis were employed to uncover and examine service users' views of the impact of the integration programme. An improvement in the physical functioning of one in three occupational equipment users; a rise in the level of satisfaction of 85 per cent of occupational health and 82 per cent of physiotherapy users; older people with complex problems and high-level needs were able to be helped to live at home; and waiting times for both assessment and for services within two weeks and four weeks were below the national achievement and ministerial targets. The impact of the integration programme on users was complex. Positive outcomes were achieved for some user groups and individuals but not for others. A lack of change outcomes in social care, and service users' low level of satisfaction with social care services appears to be associated with the impact of agency work and the predominant aim in social work of achieving maintenance and prevention outcomes. This paper contributes to knowledge on what and how the total integration in Cambridgeshire has benefited users. | 25,241,596 | [
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0.2339136... |
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