The Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans.

Background: A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. Methods: Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. Result: Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. Conclusion: Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

iEnhancer-DCSA: identifying enhancers via dual-scale convolution and spatial attention.

BACKGROUND: Due to the dynamic nature of enhancers, identifying enhancers and their strength are major bioinformatics challenges. With the development of deep learning, several models have facilitated enhancers detection in recent years. However, existing studies either neglect different length motifs information or treat the features at all spatial locations equally. How to effectively use multi-scale motifs information while ignoring irrelevant information is a question worthy of serious consideration. In this paper, we propose an accurate and stable predictor iEnhancer-DCSA, mainly composed of dual-scale fusion and spatial attention, automatically extracting features of different length motifs and selectively focusing on the important features. RESULTS: Our experimental results demonstrate that iEnhancer-DCSA is remarkably superior to existing state-of-the-art methods on the test dataset. Especially, the accuracy and MCC of enhancer identification are improved by 3.45% and 9.41%, respectively. Meanwhile, the accuracy and MCC of enhancer classification are improved by 7.65% and 18.1%, respectively. Furthermore, we conduct ablation studies to demonstrate the effectiveness of dual-scale fusion and spatial attention. CONCLUSIONS: iEnhancer-DCSA will be a valuable computational tool in identifying and classifying enhancers, especially for those not included in the training dataset.

A case of a common bile duct stone containing a metallic clip appearing after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is currently the standard procedure for the treatment of benign gallbladder diseases. Although the ligature clip may fall off and shift after surgery, relevant reports are rare. We describe the formation of common bile duct stone in an elderly female in which a metal clip displaced into the common bile duct 6 years after LC.

Extracorporeal membrane oxygenation for thyroid surgery in patients with severe tracheal stenosis.

Venovenous extracorporeal membrane oxygenation is effective for maintaining gas exchange in patients with respiratory failure or severe tracheal stenosis. Perioperative anesthetic management of severe airway obstruction can be associated with ventilation or intubation difficulties. Consequently, venovenous extracorporeal membrane oxygenation could be an option for treating such patients to avoid potential risks. However, only a limited number of similar cases have been reported. Therefore, we have summarized two cases to provide theoretical and practical references for treating patients with respiratory failure or severe tracheal stenosis using extracorporeal membrane oxygenation.

Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-ß2/Smad3 signaling.

Pathological scars mainly refer to hypertrophic scars and keloids, and have a high incidence. Moreover, these scars seriously affect the patient's appearance and are associated with significant pain. The present study aimed to investigate the inhibitory effect of microRNA (miR)­29a from human adipose­derived mesenchymal stem cells (hADSCs) exosomes on scar formation. Firstly, the expression of miR­29a in thermal skin tissues of mice and human hypertrophic scar fibroblasts (HSFBs) was detected via reverse transcription­quantitative PCR. Exosomes derived from miR­29a­modified hADSCs were extracted and the influence of miR­29a­modified hADSCs­exo on the proliferation and function of HSFBs was determined. Lastly, the effect of miR­29a­modified hADSCs­exo on scar formation was determined using a thermal mouse model. The results demonstrated that miR­29a was downregulated in scar tissues after scalding and in HSFBs. After treating HSFBs with miR­29a­modified hADSC exosomes, miR­29a­overexpressing hADSC exosomes inhibited the proliferation and migration of HSFBs. Moreover, it was found that TGF­ß2 was the target of miR­29a, and that hADSC exosome­derived miR­29a inhibited the fibrosis of HSFBs and scar hyperplasia after scalding in mice by targeting the TGF­ß2/Smad3 signaling pathway. In summary, the current data indicated that miR­29a­modified hADSC exosome therapy can decrease scar formation by inhibiting the TGF­ß2/Smad3 signaling pathway via its derived exogenous miR­29a, and this may be useful for the future treatment of pathological scars by providing a potential molecular basis.

Enhancement of transdermal delivery of artemisinin using microemulsion vehicle based on ionic liquid and lidocaine ibuprofen.

A microemulsion system based on ionic liquid (IL) and deep eutectic compound was proposed to improve the transdermal delivery of artemisinin. Deep eutectic lidocaine ibuprofen (Lid·Ibu) was selected as the oil phase, and the imidazolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEmim]Cl), was incorporated into the aqueous phase as a transdermal enhancer. The ingredients for the microemulsion in this study were selected, and their ratios were optimized. The optimal microemulsion carrier was composed of 45 wt% of water phase, 45 wt% surfactant phase (containing Tween-80, Span-20, and ethanol (co-surfactant) with the weight ratio of 1:1:1), and 10 wt% Lid·Ibu as the oil phase with artemisinin loading of 1.0 wt% (all the ratios were based on the total weight of microemulsion). Physical properties of this microemulsion, including particle size (41.95 ± 0.85 nm), viscosity (26.65 ± 0.13 mPa·s) and density (1.02 g/cm3), were measured. In-vitro transdermal assay showed a remarkable enhancement of artemisinin transport through the skin, with the permeation flux being 3-fold of the value for isopropyl myristate system in 6 h. The impact of IL-based microemulsion (ILME) on stratum corneum (SC) was investigated by DSC, ATR-FTIR and AFM, which unveiled that the ILME possesses the ability of reducing the SC barrier by disrupting the regular arrangement of keratin, resulting in enhancement of transdermal delivery of artemisinin. This current work suggested that the microemulsion proposed here had an excellent capability to promote the transdermal delivery of artemisinin, which might also be a promising vehicle for the skin delivery of other hydrophobic natural drugs.

Highly active Ce, Y, La-modified Cu/SiO2 catalysts for hydrogenation of methyl acetate to ethanol.

Rare earth element (Ce, Y, and La) modified Cu/SiO2 catalysts via hydrolysis precipitation and impregnation method were fabricated for the vapor-phase hydrogenation of methyl acetate to ethanol. LaO x showed the most pronounced promotion in the catalytic tests. After detailed characterizations, via N2 adsorption-desorption, XRD, N2O chemisorption, FTIR, H2-TPR, H2-TPD, TEM, XPS, and TG/DTA, we found that the addition of promoter LaO x can decrease the particle size while in turn, it can increase the dispersion of copper species. The strong interactions between copper and lanthanum atoms alter the surface chemical states of the copper species. This results in the generation of more Cu+ species and high S Cu + values, which are responsible for the excellent activity and stability during hydrogenation. In addition, the content of additive LaO x and reaction conditions (reaction temperature and LHSV) were optimized. Then, the long-term stability performance was evaluated over the selected catalyst in contrast with Cu/SiO2.

Chest circumference and sitting height among children and adolescents from Lhasa, tibet compared to other high altitude populations.

OBJECTIVES: The adaptation of human beings to a high altitude environment during growth has been reported in several populations but is less known for Tibetans. The objective of this study was to investigate similarities and differences of Tibetans in patterns and characteristics of physical growth and development in comparison to other high altitude populations. METHODS: We measured the stature, weight, chest circumference and sitting height of 2,813 healthy children and adolescents aged 6- to 21-year-old living at 3,658-4,500 m in Tibet, China, and compared them with published data from other high altitude populations. Eligible participants must have been born and raised in Tibet, and both their parents' families have to be Tibetan for at least the past three generations. RESULTS: The physical growth and development of children and adolescents in Tibet and the Andes followed similar patterns, such as delayed growth, short stature and sitting height, and large chest dimensions. Relative to stature, Tibetan sitting heights are similar to Andeans, but chest circumferences are smaller. CONCLUSIONS: Findings from this study reinforce the conclusion that Tibetan and Andean populations have adapted differently to high altitude hypoxia. The physical features of each population may result from unique adaptation to hypoxia, as well as socio-ecological factors, such as poor nutrition.

Protein functional properties prediction in sparsely-label PPI networks through regularized non-negative matrix factorization.

BACKGROUND: Predicting functional properties of proteins in protein-protein interaction (PPI) networks presents a challenging problem and has important implication in computational biology. Collective classification (CC) that utilizes both attribute features and relational information to jointly classify related proteins in PPI networks has been shown to be a powerful computational method for this problem setting. Enabling CC usually increases accuracy when given a fully-labeled PPI network with a large amount of labeled data. However, such labels can be difficult to obtain in many real-world PPI networks in which there are usually only a limited number of labeled proteins and there are a large amount of unlabeled proteins. In this case, most of the unlabeled proteins may not connected to the labeled ones, the supervision knowledge cannot be obtained effectively from local network connections. As a consequence, learning a CC model in sparsely-labeled PPI networks can lead to poor performance. RESULTS: We investigate a latent graph approach for finding an integration latent graph by exploiting various latent linkages and judiciously integrate the investigated linkages to link (separate) the proteins with similar (different) functions. We develop a regularized non-negative matrix factorization (RNMF) algorithm for CC to make protein functional properties prediction by utilizing various data sources that are available in this problem setting, including attribute features, latent graph, and unlabeled data information. In RNMF, a label matrix factorization term and a network regularization term are incorporated into the non-negative matrix factorization (NMF) objective function to seek a matrix factorization that respects the network structure and label information for classification prediction. CONCLUSION: Experimental results on KDD Cup tasks predicting the localization and functions of proteins to yeast genes demonstrate the effectiveness of the proposed RNMF method for predicting the protein properties. In the comparison, we find that the performance of the new method is better than those of the other compared CC algorithms especially in paucity of labeled proteins.

Risk of suicidal behavior with antidepressants in bipolar and unipolar disorders.

OBJECTIVE: To examine the risk of suicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar II, and unipolar major depressive disorders. DESIGN: A 27-year longitudinal (1981-2008) observational study of mood disorders (Research Diagnostic Criteria diagnoses based on Schedule for Affective Disorders and Schizophrenia and review of medical records) was used to evaluate antidepressants and risk for suicidal behavior. Mixed-effects logistic regression models examined propensity for antidepressant exposure. Mixed-effects survival models that were matched on the propensity score examined exposure status as a risk factor for time until suicidal behavior. SETTING: Five US academic medical centers. RESULTS: Analyses of 206 participants with bipolar I disorder revealed 2,010 exposure intervals (980 exposed to antidepressants; 1,030 unexposed); 139 participants with bipolar II disorder had 1,407 exposure intervals (694 exposed; 713 unexposed); and 361 participants with unipolar depressive disorder had 2,745 exposure intervals (1,328 exposed; 1,417 unexposed). Propensity score analyses confirmed that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-effects survival analyses, those with bipolar I disorder had a significant reduction in risk of suicidal behavior by 54% (HR = 0.46; 95% CI, 0.31-0.69; t = -3.74; P < .001) during periods of antidepressant exposure compared to propensity-matched unexposed intervals. Similarly, the risk was reduced by 35% (HR = 0.65; 95% CI, 0.43-0.99; t = -2.01; P = .045) in bipolar II disorder. By contrast, there was no evidence of an increased or decreased risk with antidepressant exposure in unipolar disorder. CONCLUSIONS: Based on observational data adjusted for propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior.

Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU*.

OBJECTIVE: To determine validity and reliability of the Cornell Assessment of Pediatric Delirium, a rapid observational screening tool. DESIGN: Double-blinded assessments were performed with the Cornell Assessment of Pediatric Delirium completed by nursing staff in the PICU. These ratings were compared with an assessment by consultation liaison child psychiatrist using the Diagnostic and Statistical Manual IV criteria as the "gold standard" for diagnosis of delirium. An initial series of duplicate Cornell Assessment of Pediatric Delirium assessments were performed in blinded fashion to assess interrater reliability. Nurses recorded the time required to complete the Cornell Assessment of Pediatric Delirium screen. SETTING: Twenty-bed general PICU in a major urban academic medical center over a 10-week period, March-May 2012. PATIENTS: One hundred eleven patients stratified over ages ranging from 0 to 21 years and across developmental levels. INTERVENTION: Two hundred forty-eight paired assessments completed. MEASUREMENTS AND MAIN RESULTS: The Cornell Assessment of Pediatric Delirium had an overall sensitivity of 94.1% (95% CI, 83.8-98.8%) and specificity of 79.2% (95% CI, 73.5-84.9%). Overall Cronbach's α of 0.90 was observed, with a range of 0.87-0.90 for each of the eight items, indicating good internal consistency. A scoring cut point of 9 demonstrated good interrater reliability of the Cornell Assessment of Pediatric Delirium when comparing results of the screen between nurses (overall κ = 0.94; item range κ = 0.68-0.78). In patients without significant developmental delay, sensitivity was 92.0% (95% CI, 85.7-98.3%) and specificity was 86.5% (95% CI, 75.4-97.6%). In developmentally delayed children, the Cornell Assessment of Pediatric Delirium showed decreased specificity of 51.2% (95% CI, 24.7-77.8%) but sensitivity remained high at 96.2% (95% CI, 86.5-100%). The Cornell Assessment of Pediatric Delirium takes less than 2 minutes to complete. CONCLUSIONS: With an overall prevalence rate of 20.6% in our study population, delirium is a common problem in pediatric critical care. The Cornell Assessment of Pediatric Delirium is a valid, rapid, observational nursing screen that is urgently needed for the detection of delirium in PICU settings.

Knockdown of FAK inhibits the invasion and metastasis of Tca­8113 cells in vitro.

Tongue cancer originating on the surface of the tongue is most commonly squamous cell carcinoma, which has a higher invasive ability and a lower survival rate compared with other forms of tongue cancer. Notably, tongue squamous cell carcinomas metastasize into lymph nodes at early stages. Focal adhesion kinase (FAK) is an important protein tyrosine kinase involved in invasion and metastasis of cancer cells. In the present study, the role of FAK in the invasion and metastasis of tongue cancer was evaluated and the underlying mechanisms involved in this process were explored. FAK knockdown was performed using shRNA in the tongue cancer cell line, Tca­8113, and the invasion and metastasis potentials were analyzed using wound healing and transwell assays, respectively. Cytoskeletal arrangement was detected by fluorescence using TRITC­conjugated phalloidin staining. The activity of matrix metalloproteinase (MMP)­2 and ­9 was examined by gelatin zymography. Paxillin distribution was observed by immunofluorescence. The levels of E­cadherin, N­cadherin, MMP­2 and ­9, and c­Jun N­terminal kinase (JNK) was detected by western blot analysis. Wound healing and transwell assays demonstrated that FAK knockdown inhibited the invasion and metastasis of Tca­8113 cells. Further analysis revealed that FAK knockdown caused the rearrangement of the cytoskeleton and decreased the activity of MMP­2 and ­9. Immunofluorescence analysis revealed that downregulation of FAK induced the relocalization of paxillin. Paxillin accumulated as dots and patches at the cell membrane in control cells. By contrast, in FAK knockdown cells, paxillin was distributed homogeneously in the cytoplasm. Western blot analysis revealed that FAK knockdown inhibited epithelial-mesenchymal transition (EMT) and decreased levels of MMP­2 and ­9, and p­JNK. Knockdown of FAK inhibits the invasion and metastasis of Tca­8113 by decreasing MMP­2 and ­9 activities and led to the rearrangement of the cytoskeleton and inhibited the EMT.