According to the original „hub-and-spoke” model of conceptual representations, the neural network for semantic memory requires a single convergence zone located in the anterior temporal lobes (ATLs). However, a more recent version of this model acknowledges that a graded specialization of the left and right ATLs might emerge as a consequence of their differential connectivity with language and sensory-motor regions. A recent influential paper maintained that both the format of semantic representations (representational account) and their differential connectivity (connectivity account) could contribute to the cognitive consequences of atrophy to the left versus the right ATL atrophy. That paper, however, also raised questions as to whether the distinction between representational and connectivity accounts is a meaningful question. I argue that an important theoretical difference exists between the representational and the connectivity-based models and that investigations, based on this difference, should allow to choose between these alternative accounts.Nurses are often at risk of burnout due to the effects of occupational stress. Implementing mindfulness wellness programming, that is easy to access and incorporate into the workday, can be effective in reducing occupational stress.Cell-division protein kinases (CDKs) are gorgeous examples of targets for the helpful treatment of cancer by using multi-target inhibitors. Specifically, targeting cell-division protein kinase1/cyclin B (CDK1/Cyclin B), cell-division protein kinase 2/cyclin A (CDK2/Cyclin A) and cell-division protein kinase 4/cyclin D1 (CDK4/Cyclin D1) are considered a safe strategy to over the toxicity complications which are emerging from low specificity. In this work, we conducted the double docking and molecular dynamics to explicate the effect of amygdalin upon conformational modifications of selected targets. Moreover, the principal component analysis (PCA) was employed to inspect the effect of amygdalin on the fundamental motions of the each protein as target. Docking results illustrated that the binding free energies of amygdalin (AMY) to CDK1/Cyclin B, CDK 2/Cyclin A and CDK 4/Cyclin D1 were to be -9.41, -9.02 and -10.6 kcal/mol, respectively. The PCA results disclosed that binding of the AMY minimized the fundamental dynamics of CDK1/Cyclin B and CDK2/Cyclin A. The obtained results can give an insight into inhibitory activity of amygdalin that could help in designing of potential inhibitors. In the other word, it can be used AMY to inhibit other mechanisms and/or hallmarks of cancer.Communicated by Ramaswamy H. Sarma.Since 2015, the prevalence of severe hepatitis-hydropericardium syndrome, which is caused by the novel genotype fowl adenovirus serotype 4 (FAdV-4), has increased in China and led to considerable economic losses. The replication cycle of FAdV-4, especially the emerging highly pathogenic novel genotype FAdV-4, remains largely unknown. The adenovirus fibre interacts with the cellular receptor as the initial step in adenovirus (AdV) infection. In our previous studies, the complete genome sequence showed that the fibre patterns of FAdV-4 were distinct from all other AdVs. Here, protein-blockage and antibody-neutralization assays were performed to confirm that the novel FAdV-4 short fibre was critical for binding to susceptible leghorn male hepatocellular (LMH) cells. Subsequently, fibre 1 was used as bait to investigate the receptor on LMH cells via mass spectrometry. The chicken coxsackie and adenovirus receptor (CAR) protein was confirmed as the novel FAdV-4 receptor in competition assays. We further identified the D2 domain of CAR (D2-CAR) as the active domain responsible for binding to the short fibre of the novel FAdV-4. Taken together, these findings demonstrate for the first time that the chicken CAR homolog is a cellular receptor for the novel FAdV-4, which facilitates viral entry by interacting with the viral short fibre through the D2 domain. Collectively, these findings provide an in-depth understanding of the mechanisms of the emerging novel genotype FAdV-4 invasion and pathogenesis.Background Outpatient primary care clerkships are an important part of medical students’ education.Traditional clerkships usually partner a student with a single preceptor in that physician’s clinic. However, it can be quite difficult for the preceptor to balance the educational needs of the students, the expectations of the patients and the organizational demands of the clinic practice.Objective An innovative scheduling model (named „Patients as Teachers” [PAT] clinic) was developed as part of our third-year Family Medicine clerkship. The goal was to increase the students’ opportunities for independence and improve their satisfaction without negatively impacting the flow of the clinic or patient satisfaction.Design The third-year medical students spent part of their clerkship working in the PAT clinic and part of the time working with an individual preceptor in that preceptor’s clinic in the traditional, usual fashion (PAU clinic-precepting as usual). The students completed patient-logs regarding the patients they saw and their level of participation. They also completed a voluntary survey regarding their experiences.Results Students performed more independent interviews (90.3 vs 59.0%) and independent exams (96.2 vs 63.3%) in the PAT clinic than while working with their traditional preceptor (both p less then 0.01). Students were highly satisfied with the experience with 89.5% stating they would recommend it and 87.7% finding the PAT clinic to be an equal or superior experience to the PAU experience.Conclusions Using a combination of time in the PAT clinic and time with a one on one preceptor in the usual fashion was successful in increasing opportunities for student autonomy and achieving a high level of student satisfaction in our third-year Family Medicine clerkship. Additional opportunities for innovative scheduling could be considered for meeting a variety of clerkship and clinic needs.Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. Shanghai reported the first imported case of COVID-19 (Coronavirus Disease 2019) in 20 January 2020. A combinative approach of real-time RT-PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. Real-time RT-PCR and CRISPR-based assay both reported positive. This sample belonged to Betacoronavirus and shared a more than 99% nucleotide (nt) identity with the Wuhan SARS-CoV-2 isolates. We further compared pros and cons of common molecular diagnostics in UP. In this study, we illustrated the importance of combining molecular diagnostics to rule out common pathogens and performed mNGS to obtain unbiased potential pathogen result for the diagnosis of UP.Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models, prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology and MRI. Twelve adult NHPs were divided into an SCI group (n=8, 24 and 48 weeks) and a control group (n=4). An impactor (=4 mm) was driven to compress the left C5 cord at 800 mm/s. The contusion displacement and peak force was 4.08±0.17 mm and 19.8±4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68±0.47 mm and 5.99±0.24 mm2 at 24 weeks-post-injury (WPI), and 5.29±0.17 mm and 5.95±0.24 mm2 at 48 WPI. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced while the staining intensity increased at 24 WPI and 48 WPI compared to the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared to pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the DRG was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.Objective Activation of nicotinic acetylcholine receptors (nAChRs) results in neuroprotection via a poorly understood molecular mechanism. In this study, we aimed to investigate the effect of nAChR stimulation with nicotine on the regulation of microRNA (miRNA) expression and identify the molecular pathway involved in neuroprotection.Methods We conducted miRNA expression profiling using a microarray to identify the miRNAs regulated by nicotine. miR-132-5p expression was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cells were treated with nicotine, a miR-132-5p mimic or its inhibitor, and the cell viability was assessed. CREB, Bcl-2, Bax, cleaved caspase-3, and α-tubulin protein expression levels were determined by Western blotting analysis.Results Using a rodent miRNA microarray, we identified 37 miRNAs regulated by nicotine. The microarray and RT-qPCR results showed 1.67-fold and 1.5-fold increases in miR-132-5p, respectively, upon nicotine treatment. Immunoblotting revealed a >2-fold increase in phosphorylation of CREB with nicotine, peaking at 4 h. Nicotine treatment of cells increased viability from 35% to 54%, and Bcl-2 immunoreactivity increased by 1.4-fold. Overexpression of miR-132-5p increased cell viability from 38% to 70% and increased Bcl-2 expression by 3.9-fold. Inhibition of miR-132-5p decreased cell viability to 25%, whereas no change was observed in Bcl-2. Bax expression remained unchanged following treatment with a miR-132-5p mimic or its inhibitor.Discussion Our results suggest that nAChR activation facilitates cell survival by upregulating miR-132-5p, which upregulates the anti-apoptotic protein Bcl-2. These results present miR-132-5p as a potential novel therapeutic target to achieve neuroprotection via stimulation of nAChRs.Abbreviations CCK-8 Cell counting kit-8; nAChR Nicotinic acetylcholine receptor; NGF Nerve growth factor; WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt].Allosteric changes modulate the enzymatic activity, leading to activation or inhibition of the molecular target. Understanding the induced fit accommodation mechanism of a ligand in its lowest-free energy state and the subsequent conformational changes induced in the protein are important questions for drug design. In the present study, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA) were applied to analyze the glycerol-3-phosphate dehydrogenase of Leishmania mexicana (LmGPDH) conformational changes induced by its cofactor and substrate binding. GPDH is a nicotinamide adenine dinucleotide (NAD)-dependent enzyme, which has been reported as an interesting target for drug discovery and development against leishmaniasis. Despite its relevance for glycolysis and pentose phosphate pathways, the structural flexibility and conformational motions of LmGPDH in complex with NADH and dihydroxyacetone phosphate (DHAP) remain unexplored. Here, we analyzed the conformational dynamics of the enzyme-NADH complex (cofactor), and the enzyme-NADH-DHAP complex (adduct), mapped the hydrogen-bond interactions for the complexes and pointed some structural determinants of the enzyme that emerge from these contacts to NADH and DHAP. Finally, we proposed a consistent mechanism for the conformational changes on the first step of the reversible redox conversion of dihydroxyacetone phosphate to glycerol 3-phosphate, indicating key residues and interactions that could be further explored in drug discovery.Communicated by Ramaswamy H. Sarma.The occurrence of 28 common antibiotics in wild and farmed aquatic products from different species was comprehensively investigated in the present study. The results showed that a larger number of antibiotics could be detected quantitatively in wild samples, while the farmed samples had higher concentrations. Twenty, 17, and 14 target compounds were found in the muscles of wild molluscs, wild fish and farmed fish with total concentrations of 2.02-16.4 ng g-1, 0.51-11.9 ng g-1, and less then LOD – 144 ng g-1, respectively. Quinolones could be frequently detected in all investigated samples with higher concentrations, while sulphonamides were only detected more frequently in wild molluscs. For wild samples, sulfamethoxazole, sulphamethazine, clarithromycin, and ciprofloxacin are the main antibiotics that were detected in molluscs and fish with different residues. However, there was almost no significant residue difference among different wild fish. Compared with other studies in China or overseas, antibiotic residues in the investigated fish were almost always at a relative low level. Monte Carlo simulation showed that the farmed fish posed higher health risks than the wild fish, while the proportion of the consumers with chronic toxic risk (HI) of farmed fish higher than 0.05 (a distinct risk) was only 1.15 %.PURPOSE Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targetsegulating the malignant behaviors of triple-negative breast cancer cells, which suggested miR-331-3p as a potential target for the treatment of triple-negative breast cancer.Background Stroke survivors find it difficult to participate in daily activities, despite their improvement throughout the rehabilitation process. Thus, it has been questioned whether day-rehabilitation services provide adequate preparation for participation and reintegration into the community. Self-management programs can improve survivors’ self-efficacy to manage their condition and participation. Improving Participation After Stroke Self-Management program (IPASS) is an occupational therapy-based group intervention developed in the United States, which has been effective in improving participation outcomes.Objective To evaluate the feasibility and effectiveness of the IPASS adapted for an Israeli population of individuals admitted to a day-rehabilitation center after stroke.Methods A single-center, randomized, assessor-blind study was conducted. Eligible participants were randomized to receive the IPASS (intervention group), in addition to standard individual therapy or standard care only (control group). Feasibility was based on attendance rate and a feedback questionnaire. Effectiveness was evaluated with the Functional Independence Measure (FIM), the Reintegration to Normal Living Index (RNLI) and self-efficacy questionnaires.Results Sixty participants were included, of which 39 completed baseline and post-intervention evaluations. The intervention group improved significantly in the FIM scores (p .05). Moderate effect sizes (≥0.35) were found for the FIM and RNLI, and large effect sizes (≥0.65) for two subcategories in the participation self-efficacy questionnaire.Conclusions The results support the feasibility of the adapted IPASS, and show a trend for positive effects in improving participation and self-efficacy in managing participation in home and community activities, for an Israeli post-stroke population.We previously reported on a mutant lipase KV1 (Mut-LipKV1) from Acinetobacter haemolyticus which optimal pH was raised from 8.0 to 11.0 after triple substitutions of surface aspartic acid (Asp) with lysine (Lys). Herein, this study further examined the Mut-LipKV1 by molecular docking, molecular dynamics (MD) simulations and molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations to explore the structural requirements that participated in the effective binding of tributyrin and its catalytic triad (Ser165, Asp259 and His289) and identify detailed changes that occurred post mutation. Mut-LipKV1 bound favorably with tributyrin (-4.1 kcal/mol) and formed a single hydrogen bond with His289, at pH 9.0. Despite the incongruent docking analysis data, results of MD simulations showed configurations of both the tributyrin-Mut-LipKV1 (RMSD 0.3 nm; RMSF 0.05 - 0.3 nm) and the tributyrin-wildtype lipase KV1 (tributyrin-LipKV1) complexes (RMSD 0.35 nm; RMSF 0.05 - 0.4 nm) being comparably stable at pH 8.0. MM-PBSA analysis indicated that van der Waals interactions made the most contribution during the molecular binding process, with the Mut-LipKV1-tributyrin complex (-44.04 kcal/mol) showing relatively lower binding energy than LipKV1-tributyrin (-43.83 kcal/mol), at pH 12.0. All tributyrin-Mut-LipKV1 complexes displayed improved binding free energies over a broader pH range from 8.0 - 12.0, as compared to LipKV1-tributyrin. Future empirical works are thus, important to validate the improved alkaline-stability of Mut-LipKV1. In a nutshell, our research offered a considerable insight for further improving the alkaline tolerance of lipases.Communicated by Ramaswamy H. Sarma.Pancreatic ductal adenocarcinoma (PDAC) is a pancreatic malignancy suffering from poor prognosis; the worst among all types of cancer. Chemotherapy, which is the standard regime for treatment in most cases, is often rendered useless as drug resistance quickly sets in after prolonged exposure to the drug. The implication of PAX2 transcription factor in regulating several ATP-binding cassette (ABC) transporter proteins that are responsible for the acquisition of drug resistance in PDAC makes it a potential target for treatment purposes. In this study, the 3D structure of PAX2 protein was modeled, and the response of key amino acids to perturbation was identified. Subsequently, kappadione, a vitamin K derivative, was found to bind efficiently to PAX2 with a binding energy of -9.819 kcal/mol. The efficacy of mechanism and mode of binding was studied by docking the protein with DNA in the presence and absence of the drug. The presence of kappadione disrupted DNA binding with key effector resides, preventing the DNA from coming into contact with the binding region essential for protein translation. By occupying the DNA binding region and replacing it with a ligand, the mechanism by which DNA interacts with PAX2 could be manipulated. Inhibition of PAX2-DNA binding using kappadione and other small molecules can prove to be beneficial for combating chemoresistance in PDAC, as proposed through in silico approaches.Communicated by Ramaswamy H. Sarma.The presence or absence of cytogenetic mutations is proposed to be responsible for the pathogenesis of acute myeloid leukaemia (AML). However, the current classification system is inadequate to elucidate the molecular heterogeneity of the disease, and therapy failures frequently occur. Leukaemia stem cells (LSCs) initiate and maintain the clonal hierarchy of AML and exhibit properties of self-renewal remaining recalcitrant to conventional chemotherapy. In this study, we identified a novel long non-coding RNA (lncRNA) MAGI2 antisense RNA 3 (MAGI2-AS3) in AML and investigated its functional role in regulating LSCs self-renewal. LSCs were identified by immunoprofiling of CD34+ CD123+ in AML patients’ marrow. MAGI2-AS3 exhibited a poor expression level in LSCs than the normal human haematopoietic stem cells. Lentivirus-mediated upregulation of MAGI2-AS3 or leucine-rich repeats and Ig-like domains 1 (LRIG1) impaired LSCs self-renewal. MAGI2-AS3-overexpressed LSCs acquired the ability of self-renewal following lentivirus-mediated knockdown of LRIG1. Methylation-dependent inhibition of LRIG1 was evident in LSCs. MAGI2-AS3 was found to induce occupancy of TET2 at the LRIG1 promoter. Lentivirus-mediated downregulation of TET2 could impair MAGI2-AS3-mediated elevation of LRIG1 and neutralize the inhibitory effect of MAGI2-AS3 on LSCs self-renewal. In vivo analysis indicated an elevated overall survival of NOD/SCID mice injected with LSCs in the presence of MAGI2-AS3. Altogether, the key findings support the potential of lncRNA MAGI2-AS3 to serve as a novel candidate for the improvement of AML treatment.Malignant tumors can be targeted by accounting for their metastatic capabilities. Matrix metalloproteinases (MMPs) are the key players in tumor metastasis facilitating through their proteolytic activities of angiogenesis and extracellular matrix components (ECM) degradation. MMP-2 and MMP-9 being the members of a distinguished class of MMPs more commonly known as gelatinases are the prominent enzymes which are involved in different cancer progression stages. Targeting these isoforms specifically has always been a challenging task due to highly similar structural and functional features among the other members of MMPs with well preserve active sites containing catalytic zinc atom that was the only reason that none of the MMP inhibitor has been successfully marketed for the tumor pathology up till now. Therefore, non-competitive inhibitors with different structural attributed are needed to be evaluated at the molecular level for further experiments. The present study deals with the application of molecular dynamics simulation for the investigation of an alternative pathway for the inhibition of MMP-2 and MMP-9 by a sesquiterpene isolated from Polygonum barbatum which demonstrates the characteristics binding to the S1′ subsite of the enzymes followed by in vitro gene expression studies. The simulation results provide information on the possible binding profile producing inhibitory effects imposed by the inhibitor to these enzymes by acquiring different structural and dynamical features. Moreover, thermodynamic quantities based on the computationally intensive thermodynamic integration approach were also obtained in terms of inhibitor binding affinity computed for the inhibitor against MMP-2 and MMP-9 that completely augmented the experimental gene expression study.Communicated by Ramaswamy H. Sarma.Dredging activities can lead to the re-suspension of contaminated sediments, resulting in a potential hazard for the whole ecosystem and also for human health. Six-month active biomonitoring was performed in order to monitor the trends of different classes of both legacy (organochlorine – OCPs – and organophosphate (OPs) compounds and polychlorinated biphenyls – PCBs) and emerging (polybromodiphenyl ethers – PBDE – and per- and polyfluoroalkyl substances – PFASs) organohalogen compounds, as well as polycyclic aromatic hydrocarbons (PAHs), in blue mussel (Mytilus edulis spp.) specimens transplanted at different depths in the Flekkefjord fjord. Such biomonitoring was performed to evaluate the efficacy of sediment restoration activities and to check for the potential environmental risk for the biota and food safety for human seafood. Negligible contamination by OCPs, OPs, PBDEs and PFASs was noted in mussels over the 6-month biomonitoring, while a notable increase in the concentrations of PCBs and PAHs occurred in mussels transplanted at 15 m depth in three sampling sites within the fjord, as a consequence of an undersea landslide which occurred during restoration activities. Levels of PCBs and PAHs suggested a potential risk for mussel predators and also for the human health, as they exceeded the limit set by the European Commission for the consumption of bivalve molluscs. These results confirm the reliability of active biomonitoring to flank dredging activities aimed at ecosystem restoration in order to monitor the trend of contaminants and to estimate the potential risk for the aquatic communities and human health.Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with the burden largely borne by people living in low- and middle-income countries. Adolescents are central to NCD control through the potential to modify risks and alter the trajectory of these diseases across the life-course. However, an absence of epidemiological data has contributed to the relative exclusion of adolescents from policies and responses. This paper documents the design of a study to measure the burden of metabolic syndrome (a key risk for NCDs) and poor mental health (a key outcome) amongst Indonesian adolescents. Using a mixed-method design, we sampled 16-18-year-old adolescents from schools and community-based settings across Jakarta and South Sulawesi. Initial formative qualitative enquiry used focus group discussions to understand how young people conceptualise mental health and body weight (separately); what they perceive as determinants of these NCDs; and what responses to these NCDs should invo a more comprehensive measure of NCD burden, risk and correlates.Background The United Nations 2030 Sustainable Development Goals have reaffirmed the international community’s commitment to maternal, newborn, and child health, with further investments in achieving quality essential service coverage and financial protection for all.Objective Using a modified version of the 1978 Tanahashi model as an analytical framework for measuring and assessing health service coverage, this paper aims to examine the system of care at the community level in Ghana’s Volta Region to highlight the continued reforms needed to achieve Universal Health Coverage.Methods The Tanahashi model evaluates health system coverage through five key measures that reflect different stages along the service provision continuum availability of services; accessibility; initial contact with the health system; continued utilization; and quality coverage. Data from cross-sectional household and health facility surveys were used in this study. Immunization and antenatal care services were selected as tracer interventions to serve as proxies to assess systems bottlenecks.Results Financial access and quality coverage were identified as the biggest bottlenecks for both tracer indicators. Financial accessibility, measured by enrollment in Ghana’s National Health Insurance Scheme was poor with 16.94% presenting valid membership cards. Childhood immunization was high but dropped modestly from 93.8% at initial contact to 76.7% quality coverage. For antenatal care, estimates ranged from 65.9% at initial visit to 25.1% quality coverage.Conclusion Results highlight the difficulty in achieving high levels of quality service coverage and the large variations that exist within services provided at the primary care level. While vertical investments have been prioritized to benefit specific health services, a comprehensive systems approach to primary health care needs to be further strengthened to reach Ghana’s Universal Health Coverage objectives.Fibromyalgia (FM) diagnosis remains a challenge for clinicians due to a lack of objective diagnostic tools. One proposed solution is the use of quantitative ultrasound (US) techniques, such as image texture analysis, which has demonstrated discriminatory capabilities with other chronic pain conditions. From this, we propose the use of image texture variables to construct and compare two machine learning models (support vector machine [SVM] and logistic regression) for differentiating between the trapezius muscle in healthy and FM patients. US videos of the right and left trapezius muscle were acquired from healthy (n = 51) participants and those with FM (n = 57). The videos were converted into 64,800 skeletal muscle regions of interest (ROIs) using MATLAB. The ROIs were filtered by an algorithm using the complex wavelet structural similarity index (CW-SSIM), which removed ROIs that were similar. Thirty-one texture variables were extracted from the ROIs, which were then used in nested cross-validation to construct SVM and elastic net regularized logistic regression models. The generalized performance accuracy of both models was estimated and confirmed with a final validation on a holdout test set. The predicted generalized performance accuracy of the SVM and logistic regression models was computed to be 83.9 ± 2.6% and 65.8 ± 1.7%, respectively. The models achieved accuracies of 84.1%, and 66.0% on the final holdout test set, validating performance estimates. Although both machine learning models differentiate between healthy trapezius muscle and that of patients with FM, only the SVM model demonstrated clinically relevant performance levels.The purpose of this study was to quantify possible differences in sprint mechanical outputs in soccer according to soccer playing standard, position, age and sex. Sprint tests of 674 male and female players were analysed. Theoretical maximal velocity (v0), horizontal force (F0), horizontal power (Pmax), force-velocity slope (SFV), ratio of force (RFmax) and index of force application technique (DRF) were calculated from anthropometric and spatiotemporal data using an inverse dynamic approach applied to the centre-of-mass movement. Players of higher standard exhibited superior F0, v0, Pmax, RFmax and DRF scores (small to large effects) than those of lower standard. Forwards displayed clearly superior values for most outputs, ahead of defenders, midfielders and goalkeepers, respectively. Male >28 y players achieved poorer v0, Pmax and RFmax than 24 y players for the same measures (small). The sex differences in sprint mechanical properties ranged from small to very large. These results provide a holistic picture of the force-velocity-power profile continuum in sprinting soccer players and serve as useful background information for practitioners when diagnosing individual players and prescribing training programmes.Background High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia.Material and methods In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down’s syndrome or other malformations, and type of leukemia.Results Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (1-2 years old; 1.0 (95% CI 0.6, 1.5) for 3-8 years old; 1.0 (95% CI 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI 1.2, 8.8).Conclusion This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.Macroautophagy/autophagy, an evolutionarily conserved eukaryotic bioprocess, plays an important role in the bulk degradation of intracellular macromolecules, organelles, and invading pathogens. PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) functions as a key protein in autophagy initiation and progression. The activity of PIK3C3 is tightly regulated by multiple post-translational modifications, including ubiquitination, however, the regulatory mechanisms underpinning the reversible deubiquitination of PIK3C3 remain poorly understood. Recently, we identified the E3 ubiquitin ligase NEDD4/NEDD4-1 as a positive regulator of autophagy through decreasing the K48-linked ubiquitination of PIK3C3 by recruiting USP13.The disease burden associated with air pollution continues to grow. The World Health Organization (WHO) estimates ≈7 million people worldwide die yearly from exposure to polluted air, half of which-3.3 million-are attributable to cardiovascular disease (CVD), greater than from major modifiable CVD risks including smoking, hypertension, hyperlipidemia, and diabetes mellitus. This serious and growing health threat is attributed to increasing urbanization of the world’s populations with consequent exposure to polluted air. Especially vulnerable are the elderly, patients with pre-existing CVD, and children. The cumulative lifetime burden in children is particularly of concern because their rapidly developing cardiopulmonary systems are more susceptible to damage and they spend more time outdoors and therefore inhale more pollutants. World Health Organization estimates that 93% of the world’s children aged less then 15 years-1.8 billion children-breathe air that puts their health and development at risk. Here, we present growing scientific evidence, including from our own group, that chronic exposure to air pollution early in life is directly linked to development of major CVD risks, including obesity, hypertension, and metabolic disorders. In this review, we surveyed the literature for current knowledge of how pollution exposure early in life adversely impacts cardiovascular phenotypes, and lay the foundation for early intervention and other strategies that can help prevent this damage. We also discuss the need for better guidelines and additional research to validate exposure metrics and interventions that will ultimately help healthcare providers reduce the growing burden of CVD from pollution.Accumulating evidence indicates that lncRNAs can interact with miRNAs to regulate target mRNAs through competitive interactions. However, this mechanism remains largely unexplored in laryngeal squamous cell carcinoma (LSCC). In this study, transcriptome-wide RNA sequencing was performed on 3 pairs of LSCC tissues and adjacent normal tissues to investigate the expression profiles of lncRNAs, miRNAs and mRNAs, with differential expression of 171 lncRNAs, 36 miRNAs and 1709 mRNAs detected. Seven lncRNAs, eight mRNAs and three miRNAs were identified to be dysregulated in patients’ tissues by using qRT-PCR. GO and KEGG pathway enrichment analyses were performed to elucidate the potential functions of these differentially expressed genes in LSCC. Subsequently, a ceRNA (lncRNA-miRNA-mRNA) network including 4631 ceRNA pairs was constructed based on predicted miRNAs shared by lncRNAs and mRNAs. Cis- and transregulatory lncRNAs were analysed by bioinformatics-based methods. Importantly, mRNA-related ceRNA networks (mRCNs) were further obtained based on potential cancer-related coding genes. Coexpression between lncRNAs and downstream mRNAs was used as a criterion for the validation of mRCNs, with the ZNF561-AS1-miR217-WNT5A and SATB1-AS1-miR1299-SAV1/CCNG2/SH3 KBP1/JADE1/HIPK2 ceRNA regulatory interactions determined, followed by experimental validation after siRNA transfection. Moreover, ceRNA activity analysis revealed that different activities of ceRNA modules existing in specific pathological environments may contribute to the tumorigenesis of LSCC. Consistently, both downregulated SATB1-AS1 and ZNF561-AS1 significantly promoted laryngeal cancer cell migration and invasion, indicating their important roles in LSCC via a ceRNA regulatory mechanism. Taken together, the results of this investigation uncovered and systemically characterized a lncRNA-related ceRNA regulatory network that may be valuable for the diagnosis and treatment of LSCC.Objectives To test the feasibility of an evidence-based protocol for procedural sedation in adults at our emergency department, using a mixture of ketamine and propofol (’ketofol’) in a 1 to 4 ratio. We hypothesize that the protocol is safe and effective and can facilitate procedural sedation.Methods During 14 months, adults in need of procedural sedation at our university hospital emergency department were included in a prospective convenience sample study. Patients with important comorbidity were discussed with the anaesthesiology department for feasibility of sedation in the emergency department setting. Outcome measures were procedural success, respiratory and hemodynamic events, vomiting, agitation or hallucinations, recall and physician’s satisfaction.Results Sixty-one patients between 18 and 89 years were included. All but one procedure were successful. Six respiratory events were registered in 6 patients (9.8%). These consisted of airway obstruction alleviated by airway repositioning and without influence on vital signs except for one brief episode of desaturation. Neither hemodynamic events nor vomiting were reported. Five patients (8.2%) experienced pleasant hallucinations and one patient (1.6%) became agitated upon awakening but recovered rapidly without medication. Three patients (4.9%) had recall and physician satisfaction rate was 93.4%.Conclusion A feasibility trial of an implemented protocol for ketofol procedural sedation in adults showed only minor respiratory events, a low incidence of agitation or hallucinations, minimal recall and a high success and physician satisfaction rate. Despite a non-consecutive and limited sample used, ketofol in a 1 to 4 ratio appears safe and effective for use in the emergency department.Staphylococcus aureus is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against S. aureus, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular S. aureus remains unknown. Targeting of intracellular pathogens by macroautophagy/autophagy is recognized as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to S. aureus-infected hosts remains controversial. Here, using larval zebrafish, we showed that the autophagy marker Lc3 rapidly decorates S. aureus following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both cyba/p22phox knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc dimethyl sulfoxide; DPI diphenyleneiodonium; EGFP enhanced green fluorescent protein; GFP green fluorescent protein; hpf hours post-fertilization; hpi hours post-infection; Irf8 interferon regulatory factor 8; LAP LC3-associated phagocytosis; lyz lysozyme; LWT london wild type; Map1lc3/Lc3 microtubule-associated protein 1 light chain 3; NADPH oxidase nicotinamide adenine dinucleotide phosphate oxidase; RFP red fluorescent protein; ROS reactive oxygen species; RT-PCR reverse transcriptase polymerase chain reaction; Sqstm1/p62 sequestosome 1; Tg transgenic; TSA tyramide signal amplification.The study examined the effect of a weight control intervention on BMI, physical activity levels, and psychological variables toward physical activity. Thirty-three middle-aged obese women participated in the 16-week weight control intervention. Results indicated that the participants’ BMI significantly decreased and physical activity levels significantly increased over the intervention. Moreover, exercise self-efficacy and perceived benefits toward physical activity significantly increased, but perceived barriers of physical activity gradually decreased over the intervention. The study suggests that it is important to consider not only physical activity itself, but also the various psychological variables when planning and implementing the weight control program.OBJECTIVES The primary aim of this paper was to produce a model that predicts outcome in the group-phase of the 2015 Rugby World Cup and to determine the relevance and importance of performance indicators (PIs) that are significant in predicting outcome. A secondary aim investigated whether this model accurately predicted match outcome in the knockout-phase of the competition. METHODS Data was the PIs from the 40 group-phase games of the 2015 RWC. Given the binary outcome (win/lose), a random forest classification model was built using the data sets. The outcome of the knockout-phase was predicted using this model and accuracy of prediction of the model from the group-phase. RESULTS The model indicated that thirteen PIs were significant to predicting match outcome in the group-phase and provided accurate prediction of match outcome in the knockout-phase. These PIs were tackle-ratio, clean breaks, average carry, lineouts won, penalties conceded, missed tackles, lineouts won in the opposition 22, defenders beaten, metres carried, kicks from hand, lineout success, penalties in opposition 22 m and scrums won. For the group-phase matches tackle ratio, clean breaks and average carry were accurate standalone predictors of match outcome and respectively predicted 75%, 70% and 73% of match outcomes. The model based on the group-phase predicted correctly 7 from 8 (87.5%) knockout-phase matches. In the knockout-phase clean breaks predicted 7 from 8 outcomes, whilst tackle ratio and average carry predicted 6 from 8 outcomes.Purpose To determine the feasibility of using contrast-enhanced ultrasonography (CEUS) to dynamically examine the scope and development of radiofrequency ablation (RFA) lesions in the canine prostate.Material and methods Ten male canines were divided into two groups of five canines each the 1 week after the RFA group and the 1 month after the RFA group. RFA was performed on one side of the prostate in each canine. For the 1 month after the RFA group, the other side of the prostate underwent RFA prior to euthanasia, and the RFA lesion on this side was included as the immediate RFA group. The RFA lesion volume was measured by CEUS. The evaluation efficacy of CEUS for prostate RFA lesions was determined and compared with the pathological measurements.Results In the immediately after RFA group, 1 week after RFA group, and 1 month after RFA group, the RFA lesion volumes were 0.77 ± 0.34, 1.11 ± 0.61, and 0.19 ± 0.09 cm3, as measured by CEUS; the volumes measured by pathology at the corresponding time points were 0.85 ± 0.28, 0.96 ± 0.31, and 0.20 ± 0.06 cm3, respectively. CEUS accurately assessed the RFA lesions at all the time points, and the measurement results were not significantly different from those of the pathological results (p > .05).Conclusions CEUS reflects the extent of prostate RFA lesions and dynamically shows their changes in blood flow perfusion.The efficacy of family-based treatment (FBT) in outpatient settings has led to efforts to incorporate FBT principles into higher levels of care. The present study examined predictors of improvement in an FBT-based partial hospitalization program/intensive outpatient program (PHP/IOP) as measured by the Eating Disorder Examination-Questionnaire. Participants were 113 patients with anorexia nervosa (AN) or eating disorder not otherwise specified (EDNOS) consecutively participating in an FBT-based PHP/IOP. Multilevel modeling was used to investigate predictors for adolescents and young adults separately. Predictors considered included illness duration, previous hospitalization, hospitalization immediately prior to treatment, previous outpatient therapy, hospitalization during treatment, diagnosis, gaining 4 pounds in 4 weeks, and family status as time-invariant variables. Time-varying variables considered included depression symptoms and mothers’/fathers’ ratings of parental self-efficacy and expressed emotion. For adolescents, depression by time and diagnosis by time interactions were statistically significant. At all levels of depression, adolescent patients with AN demonstrated greater reductions in eating disorder symptoms compared to patients with EDNOS. For young adults, depression and gaining 4 pounds in 4 weeks were significant predictors. The relationships for young adults were curvilinear such that, while lower eating disorder symptoms were found during treatment, these gains were not maintained at follow up.Background Renal impairment and atrial fibrillation (AF) often coexist. However, risk factors associated with renal impairment in AF patients have not been studied in a large population. Accordingly, this study investigated clinical factors associated with renal impairment in AF patients.Methods From January 2012 to December 2016, 2,298 inpatients with non-valvular AF (NVAF) mainly for catheter ablation were enrolled in this cross-sectional study. Data collection included past medical history, echocardiography measurements, current medicine use and biochemical results. The estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal impairment was defined as a history of chronic kidney disease or an eGFR ≤90 ml/min/1.73 m2. Multivariate logistic regression was conducted to evaluate the relationship between the factors screened and eGFR.Results The mean eGFR was 88.6 ± 17.1 ml/min/1.73 m2. The overall prevalence of renal impairment was 47.4%. Multivariate logistic regression showed that factors associated with renal impairment were age (OR 1.12; 95% CI 1.11-1.14), non-paroxysmal AF (OR 1.28; 95% CI 1.04-1.58), use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) (OR 1.58; 95% CI 1.28-1.95), congestive heart failure (OR 1.80; 95% CI 1.05-3.07), left ventricular ejection fraction (LVEF) less then 50% (OR 2.39; 95% CI 1.34-4.28), and prior transient ischemic attack (TIA)/stroke/systematic embolism (SE) (OR 2.69; 95% CI 1.68-4.29).Conclusions Renal dysfunction is highly prevalent in Chinese NVAF patients and is significantly associated with older age, non-paroxysmal AF, use of ACEI/ARB, congestive heart failure, LVEF less then 50% and prior TIA/stroke/SE. Further studies on the mechanisms by which these risk factors affect renal function in NVAF patients need to be conducted.Central venous catheterization of children is often a challenging procedure due to small anatomical structures. Ultrasound guidance has been shown to reduce complications and improve cannulation success as compared with the landmark-based technique. In-plane techniques allow for longitudinal visualization of the vessels and real-time visualization of needle track during its advancement. When in-plane and syringe-free techniques are combined, advancement of the guidewire can also be visualized. We aim to introduce our supraclavicular approach for brachiocephalic vein cannulation in pediatric patients. A syringe-free and in-plane technique is used to cannulate the patients. The subclavian, jugular, and the brachiocephalic veins were visualized by endocavity micro-convex ultrasound probe as a Y shape during the cannulation procedure. We present a case series of successful cannulation by using this technique.Prenylated chalcones are a family of natural chalcones that have been reported to exhibit a high antioxidant activity. In this paper, the density functional calculations are carried out to study, systematically, the antiradical properties of four prenylated natural chalcones namely isobavachalcone (I), xanthohumol (II), desmethylxanthohumol (III) and broussochalcone (IV). The radical scavenging ability of all the possible CH and OH bonds of chalcones I-IV were discussed in detail thermodynamically and kinetically. The results reveal that the CH bonds of the prenyl substituent are the most thermodynamically preferred sites for free radical attack and thus play an important role on the antiradical activity of the investigated chalcones. For the OH bonds, it has been found that the B ring is more preferred for attacking free radicals than the A ring. Kinetic investigations have revealed that the CH bond and the OH bonds of the B ring can trap HO•/HOO• radicals. These results are of great significance in better understanding the chemical mechanism of the radical-scavenging action and open new perspectives for the design of new potent antioxidant agents.Communicated by Ramaswamy H. Sarma.Home care is essential for the continuity of care, but rural communities struggle to procure these services regularly. As rural populations age, these difficulties may be exacerbated. This study examines the challenges and solutions for offering home care in rural areas. Healthcare professionals held focus groups and one-on-one interviews in rural communities, and these interviews were recorded and analyzed using thematic analysis. Changing rural contexts, stakeholder relationships, and sustainable communities were the primary themes. Increasing knowledge, sharing information, and dialogue among stakeholders were also crucial. Collaboration between professions may also create more sustainable home care in rural communities.Herein, we report the synthesis and single crystal X-ray structure of Cu(II)-picolinic acid complex, 1 as a potent topoisomerase I inhibitor. The complex 1 crystallized in the triclinic crystal system with space group P-1. Comparative in vitro binding studies of complex 1 with CT DNA and tRNA were carried out revealing an electrostatic binding mode with higher binding propensity towards tRNA. The intrinsic bonding constant value, Kb was calculated to be 4.36 × 104 and 8.78 × 104 M-1 with CT DNA and tRNA respectively. DNA cleavage activity was carried out with a pBR322 plasmid DNA substrate to ascertain the cleaving ability. Furthermore, Topo-I inhibition assay of complex 1, performed via gel electrophoresis revealed a significant inhibitory effect on the enzyme catalytic activity at a minimum concentration of 15 µM. The DFT studies were carried out to provide better insight in the electronic transitions observed in the absorption spectrum of the complex 1. Molecular docking studies were carried out with DNA, RNA and Topo-I to determine the specific binding preferences at the target site and complement the spectroscopic studies.