Blalocksherrill9813

Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP

-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).

The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs.

ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway.

The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

In contrast to childhood obesity, studies involving thin children are much fewer, especially in developed countries. Furthermore, most reports do not address the impact of childhood thinness on height velocity. This study investigated the prevalence of thinness and its effect on height velocity in schoolchildren in the United Arab Emirates (UAE). Weight and height were measured in 29,410 schoolchildren (50.5% females), as part of the health assessment (academic year 2014-2015). The body mass index (BMI) was classified as normal, thinness, overweight, or obese using cutoffs established by the International Obesity Task Force (IOTF), World Health Organization, and Centers for Disease Control.

The median age was 10.2years (range, 3-19). Using the IOTF scale, one-quarter of the children aged 4-6years and one-third of the children aged 7-9years were thin (BMI ≤ 18.5kg/m

). Thinness was less prevalent (8-10%) in adolescents. Group peak height velocity was delayed 1-3years in thin children and was higher in children with excess body fat. In conclusion thinness was the highest (25-33%) in children aged 4-9years of age and their peak height velocity was delayed 1-3years when compared to the other children.

The median age was 10.2 years (range, 3-19). Using the IOTF scale, one-quarter of the children aged 4-6 years and one-third of the children aged 7-9 years were thin (BMI ≤ 18.5 kg/m2). Thinness was less prevalent (8-10%) in adolescents. Group peak height velocity was delayed 1-3 years in thin children and was higher in children with excess body fat. In conclusion thinness was the highest (25-33%) in children aged 4-9 years of age and their peak height velocity was delayed 1-3 years when compared to the other children.

The aim of the study was the assessment of the early impact of the selected kinesiotaping technique on the static stability of the knee joint in patients with ACL rupture on the basis of stabilographic parameters.

Sixty-two patients with a complete ACL rupture (32 patients in experimental group and 30patients in placebo group) took part in the randomized single-blind, placebo-controlled trial.The ligament technique of KT was taken into consideration. Application of a KT tape only onthe injured knee was to stabilize the knee joint. Experimental group had application of KT onthe injured knee and the placebo group had a KT placebo application (with no tension on KT).Intervention and stabilographic test in both groups was the same. Research tools included measurements of static stabilographic parameters on stabilometricplatform CQStab2P®. Outcome measures were assessed before intervention and after KTapplication. The analysis included evaluation of outcome variables - total path length, (SP),statokinesiogram ation number ACTRN12616001407482 .

This study was registered retrospectively in the Australian New Zealand Clinical Trials Registry (ANZCTR). Registration number ACTRN12616001407482 .

Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice.

Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ

) test (p < 0·05 was considered as unstable).

Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) ry management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited.

The study was registered with Clinical trials.gov Identifier NCT04534569.

The study was registered with Clinical trials.gov Identifier NCT04534569.

Sjögren's syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved.

Eighty percent confluent stem cells were replenished with serum-free Dulbecco's modified Eagle's medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were cat-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups.

These results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen.

These results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen.

Medical societies and funding agencies strongly recommend that patients be included as partners in research publications and grant applications. Although this "top-down" approach is certainly efficient at forcing this new and desirable type of collaboration, our past experience demonstrated that it often results in an ambiguous relationship as not yet well integrated into the cultures of either patients' or the researchers'. The question our group raised from this observation was "How to generate a cultural shift toward a fruitful and long-lasting collaboration between patients and researchers? A "bottom-up" approach was key to our stakeholders. The overall objective was to build a trusting and bidirectional-ecosystem between patients and researchers. The specific objectives were to document 1) the steps that led to the development of the first patient-partner strategic committee within a research center in the Province of Québec; 2) the committee's achievements after 3 years.

Eighteen volunteer members, nvironment of science.

We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting.

Our analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams.

Overall, 40% of the patients received a molecular diag-scale national collaboration.

Clinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.

Theileria orientalis is a tick-borne hemoparasite that causes anemia, ill thrift, and death in cattle globally. The Ikeda strain of T. orientalis is more virulent than other strains, leading to severe clinical signs and death of up to 5% of affected animals. Within the Asia-Pacific region, where it affects 25% of Australian cattle, T. orientalis Ikeda has a significant economic impact on the cattle industry. In 2017, T. orientalis Ikeda was detected in a cattle herd in Albermarle County, Virginia, United States. Months earlier, the U.S. was alerted to the invasion of the Asian longhorned tick, Haemaphysalis longicornis, throughout the eastern U.S. Abundant H. longicornis ticks were identified on cattle in the T. orientalis-affected herd in VA, and a subset of ticks from the environment were PCR-positive for T. orientalis Ikeda. A strain of T. orientalis from a previous U.S. outbreak was not transmissible by H. longicornis; however, H. longicornis is the primary tick vector of T. orientalis Ikeda in other reVA-U.S.-T. orientalis Ikeda strain. This data provides important information for the U.S. cattle industry regarding the potential spread of this parasite and the necessity of enhanced surveillance and control measures.

Our findings demonstrate that U.S. H. longicornis ticks are competent vectors of the VA-U.S.-T. orientalis Ikeda strain. This data provides important information for the U.S. cattle industry regarding the potential spread of this parasite and the necessity of enhanced surveillance and control measures.

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.

Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.

We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens.

We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levelitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo.

In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.

In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.Our previous study showed the intrinsic ability of descending noradrenergic neurons projecting from the locus coeruleus to the spinal dorsal horn (SDH) to suppress itch-related behaviors. Noradrenaline and α1A-adrenaline receptor (α1A-AR) agonist increase inhibitory synaptic inputs onto SDH interneurons expressing gastrin-releasing peptide receptors, which are essential for itch transmission. However, the contribution of α1A-ARs expressed in SDH inhibitory interneurons to itch-related behavior remains to be determined. In this study, RNAscope in situ hybridization revealed that Adra1a mRNA is expressed in SDH inhibitory interneurons that are positive for Slc32a1 mRNA (known as vesicular GABA transporter). Mice with conditional knock-out of α1A-ARs in inhibitory interneurons (Vgat-Cre;Adra1aflox/flox mice) exhibited an increase in scratching behavior when induced by an intradermal injection of chloroquine, but not compound 48/80, which are known as models of histamine-independent and dependent itch, respectively. Furthermore, knockout of inhibitory neuronal α1A-ARs in the SDH using the CRISPR-Cas9 system also increased the scratching behavior elicited by chloroquine but not compound 48/80. Our findings demonstrated for the first time that α1A-ARs in SDH inhibitory interneurons contribute to the regulation of itch signaling with preference for histamine-independent itch.Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can be used for large-scale dataset comparisons at population resolution on simulated and real data. Using Kssd, we prioritize references for all 1,019,179 bacteria whole genome sequencing (WGS) runs from NCBI Sequence Read Archive and find misidentification or contamination in 6164 of these. Additionally, we analyze WGS and exome runs of samples from the 1000 Genomes Project.

UK FASHIoN was a multicentre randomised controlled trial comparing hip arthroscopic surgery (HA) with personalised hip therapy (PHT, physiotherapist-led conservative care), for patients with hip pain attributed to femoroacetabular impingement (FAI) syndrome. Our aim was to describe the treatment and trial participation experiences of patients, to contextualise the trial results and offer further information to assist treatment decision-making in FAI.

We conducted in-depth semi-structured telephone interviews with a purposive sample of trial participants from each of the trial arms. They were interviewed after they received treatment and completed their first year of trial participation. Thematic analysis and constant comparison analytical approaches were used to identify themes of patient treatment experiences during the trial.

Forty trial participants were interviewed in this qualitative study. Their baseline characteristics were similar to those in the main trial sample. On average, their hip-related inform future FAI patients.

Arthroscopic surgery for hip impingement versus best conventional care ( ISRCTN64081839 ). 28/02/2014.

Arthroscopic surgery for hip impingement versus best conventional care ( ISRCTN64081839 ). 28/02/2014.

Studies indicate high rates of substance use among youth experiencing homelessness (YEH). Further, the social networks of YEH, although multi-dimensional in composition, are largely comprised of other YEH, substance users, and individuals who do not provide the youth with tangible or emotional support. For YEH who have the opportunity to enter a housing program, helping them to reduce their substance use and strengthen their prosocial supportive connections during this critical transition period may increase their stability and reduce their risk of re-entering homelessness. The goal of this study is to pilot test a brief motivational network intervention (MNI), delivered by case managers, to help former YEH who have recently transitioned to a housing program reduce their substance use and strengthen their prosocial supportive connections.

Up to 60 residents of housing programs in the Los Angeles area will be randomized to receive four sessions of usual case manager support or four sessions of case managergap by pilot testing a computer-assisted MNI, delivered using MI techniques, that can help case managers work with recent YEH to reduce substance use and increase permanent supportive connections during the critical transitional period from homelessness to housing. Trial registration ClinicalTrials.gov Identifier NCT04637815. Registered November 10, 2020.

Neurocysticercosis is the most common parasitic infection of the central nervous system, brain being the most frequent site. Intramedullary location of cysticercus is a rarely described entity in literature. Widespread dissemination of cysticercus is also considered a rare occurrence, and only a handful of cases are documented, almost exclusively from tropical nations. Here we present a case of disseminated cysticercosis with rare initial presentation as acute dorsal myelopathy resulting from intramedullary cysticercus.

A 62-year-old male patient from India (Asian) presented with features of dorsal myelopathy as manifested by acute-onset symmetric paraparesis, sensory loss below umbilicus, and double sphincter dysfunction. General physical examination revealed pea-sized nodules in skin and tongue. On spinal cord imaging, it was found that he had intramedullary cysticercus with diffuse perilesional edema. Brain and muscle imaging showed extensive cysticercosis suggestive of dissemination. Histological examination from skin nodule and antibody assay confirmed the diagnosis of cysticercosis. Following steroid administration, our patient showed improvement with observable increase in power of the lower limbs. He was subsequently discharged with antiepileptics, symptomatic therapy, and regular physiotherapy. Antihelminthic agents were initially avoided in view of extensive cysticercosis in brain including crucial areas such as brainstem.

Rare manifestation of a rare but treatable disorder makes it an important reportable observation in the context of tropical medicine.

Rare manifestation of a rare but treatable disorder makes it an important reportable observation in the context of tropical medicine.

The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). However, the specific mechanism of non-SMAD and classical SMAD signaling interactions is still unclear, which needs to be further explored.

In ATDC5 cells, USP15 overexpression and knockout were performed using the transfected lentivirus USP15 and Crispr/Cas9. Western blotting and immunofluorescence staining were used to test p-SMAD2 and cartilage phenotype-related molecular markers. In rat OA models, immunohistochemistry, hematoxylin and eosin (HE)/Safranin-O fast green staining, and histology were used to examine the regulatory activity of USP15 in TGF-β/SMAD2 signaling and the cartilage phenotype. Then, ERK2 overexpression and knockout were performed. The expressions of USP15, p-SMAD2, and the cartilage phenotype were evaluated in vitro and in vivo. To address whether USP15 is required for ERK2 and TGF-β/SMAD2 signaling, we performed rescue experiments.

Taken together, our study revealed positive feedback regulation between USP15 and ERK2, which played a critical role in TGF-β/SMAD2 signaling to inhibit OA progression. Therefore, this specific mechanism can guide the clinical treatment of OA.

There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities.

The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDmulti-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Early postanal growth of preterm infants has many effects on early and late health. However, evidence on growth pattern in Chinese preterm infant population during early life is insufficient. This study aims to describe the growth trajectory, catch-up growth, and risk of overweight of preterm infants during the first 2 years of life in a Chinese community population.

All preterm infants (n = 10,624) received routine childcare in one primary maternal and child healthcare network in 8 years were included. Body weight and length/height at corrected age (CA) 40 weeks, CA 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months were extracted and converted to z-scores based on the World Health Organization (WHO) standards. According to the intrauterine growth status, infants were divided into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) infants. Changes of z-score were used to describe the growth velocity. Generalized estimating equation (uring the first 2 years of life. Catch-up growth is accompanied by risk of overweight as early as CA 3 months. (349 words).

Body weight and length/height of preterm infants are above the WHO standards in the Chinese community population during the first 2 years of life. Catch-up growth is accompanied by risk of overweight as early as CA 3 months. (349 words).

The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.

Hospitalised COVID-19 patients will be randomised (21) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.

Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered aminated; this Letter serves as a summary of the key elements of the full protocol.

Eudract number 2020-002027-10 ClinicalTrials.gov Identifier NCT04475601 , registered June 8, 2020 FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

Powered prosthetic ankles provide battery-powered mechanical push-off, with the aim of reducing the metabolic demands of walking for people with transtibial amputations. The efficacy of powered ankles has been shown in active, high functioning individuals with transtibial amputation, but is less clear in other populations. Additionally, it is unclear how use of apowered prosthesis influences everyday physical activity and mobility.

Individuals with unilateral transtibial amputations participated in a randomized clinical trial comparing their prescribed, unpowered prosthesis and the BiOM powered prosthesis. Participants' metabolic costs and self-selected walking speeds were measured in the laboratory and daily step count, daily steps away from home, and walking speed were measured over two weeks of at-home prosthesis use. Participants also rated their perception of mobility and quality of life and provided free-form feedback. Dependent measures were compared between prostheses and the relationships betweentionally, self-reported preferences did not often correlate with objective measures of function. This highlights the need for future clinical research to include both perception and objective measures to better inform prosthetic prescription.

https//clinicaltrials.gov , #NCT02828982. Registered 12 July 2016, https//clinicaltrials.gov/ct2/show/NCT02828982.

https//clinicaltrials.gov , #NCT02828982. Registered 12 July 2016, https//clinicaltrials.gov/ct2/show/NCT02828982.

HoMEcare aRm rehabiLItatioN (MERLIN) is an unactuated version of the robotic device ArmAssist combined with a telecare platform. Stroke patients are able to train the upper limb function using serious games at home. The aim of this study is to investigate the effect of MERLIN training on the upper limb function of patients with unilateral upper limb paresis in the chronic phase of stroke (> 6months post stroke).

Patients trained task specific serious games for three hours per week during six weeks using an unactuated version of a robotic device. Progress was monitored and game settings were tailored through telerehabilitation. Measurements were performed six weeks pre-intervention (T0), at the start (T1), end (T2) and six weeks post-intervention (T3). Primary outcome was the Wolf Motor Function Test (WMFT). Secondary outcomes were other arm function tests, quality of life, user satisfaction and motivation.

Twelve patients were included, ten completed the training. From start of the intervention to six weeks follow up, WMFT improved significantly with 3.8 points (p = .006), which is also clinically relevant. No significant changes in quality of life were observed. Patients were overall satisfied with the usability of the device. Comfort and the robustness of the system need further improvements.

Patients in the chronic phase of stroke significantly improved their upper limb function with the MERLIN training at home. Trial registration This study is registered at the Netherlands Trial Register (NL7535). Registered 18-02-2019, https//www.trialregister.nl/trial/7535 .

Patients in the chronic phase of stroke significantly improved their upper limb function with the MERLIN training at home. Trial registration This study is registered at the Netherlands Trial Register (NL7535). Registered 18-02-2019, https//www.trialregister.nl/trial/7535 .

Mental well-being and work engagement are both desirable, positive states of mind that help employees to better function in the workplace. While occupational researchers have argued in favor of considering both states concurrently, it is less clear how this might be translated to provide an instrument characterizing the workforce accordingly. The present study describes empirical efforts to operationalize a construct called engaged well-being.

We used employee-level data (n = 13,538) from three waves of the German linked personnel panel (LPP; 2012-2017). Exploratory factor analysis and a combination of hierarchical and non-hierarchical cluster analyses linked with within-sum-of-squares statistics were used to identify distinct profiles describing mental well-being and work engagement concurrently. These profiles were then used as the basis to identify cut-offs to create replicable categories of engaged well-being. Using the longitudinal data from a subgroup providing data across more than one wave, we obser time suggest its potential utility in organizational interventions. Future studies are needed to further explore both the antecedents, correlates, and potential effects of engaged well-being.

Metastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis.

EVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesiz in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.

Biloma, an encapsulated collection of bile outside the biliary tree, supported by a predominantly iatrogenic biliary fistula, and bile likeage are two of the most important surgical complications after liver resection. We, hypothesized to conduct a project aimed to prevent, or reduce, the formation of biloma or biliary fistula applying on the hepatic resection area the cyanoacrylate glue (Glubran2).

We searched in our surgical database all patients underwent liver resection for mCRC from January 2013 to December 2018 and we found a total of 510 patients. 205 patients for Group A (study population included patients in which we have used Glubran2 during surgical procedure) and 113 patients for Group B (control group), were enrolled.

In both Groups no patients died during hospitalization and the 30-day mortality was 0 %. During follow-up in Group A, a biliary fistula was found in 2 patients (1 %) versus 3 patients in the Group B (2,6 %). In patients enrolled in Group A no adverse event were reported relate to the use of Glubran2.

It is possible to affirm that the use of Glubran2 as biliostatic agent after liver resection is useful to prevent bile leakage complication and biloma formation and its use demonstrated to be safe and feasible during liver surgery.

It is possible to affirm that the use of Glubran2 as biliostatic agent after liver resection is useful to prevent bile leakage complication and biloma formation and its use demonstrated to be safe and feasible during liver surgery.

Timely initiation of breastfeeding, also known as early initiation of breastfeeding, is a well-recognized life-saving intervention to reduce neonatal mortality. However, only one quarter of newborns in Uttar Pradesh, India were breastfed in the first hour of life. This paper aims to understand the association of community-based prenatal counselling and postnatal support at place of delivery with early initiation of breastfeeding in Uttar Pradesh, India.

Data from a cross-sectional survey of 9124 eligible women (who had a live birth in 59 days preceding the survey) conducted in 25 districts of Uttar Pradesh, India, in 2018, were used. Simple random sampling was used to randomly select 40 Community Development Blocks (sub district administrative units) in 25 districts. The Primary Sampling Units (PSUs), health service delivery unit for frontline workers, were selected randomly from a linelisting of PSUs in each selected Community Development Block. Bivariate and multivariate logistic regression analyses werl support immediately after birth on improving early initiation of breastfeeding, irrespective of place of delivery, indicates the importance of enhancing coverage of both the interventions through community and facility-based programs in Uttar Pradesh.

A significant association of prenatal counselling and postnatal support immediately after birth on improving early initiation of breastfeeding, irrespective of place of delivery, indicates the importance of enhancing coverage of both the interventions through community and facility-based programs in Uttar Pradesh.

Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression.

The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry.

YAP over-expression enhanced glioma cell autophagy under basal and induced coinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.

Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC.

According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2).

A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008).

Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.Chronic Infection of Hepatitis B virus (HBV) is one risk factor of hepatocellular carcinoma (HCC). Much effort has been made to research the process of HBV-associated HCC, but its molecular mechanisms of carcinogenesis remain vague. Here, weighted gene co-expression network analysis (WGCNA) was employed to explore the co-expressed modules and hub/key genes correlated to HBV-associated HCC. We found that genes of the most significant module related to HBV-associated HCC were enriched in DNA replication, p53 signaling pathway, cell cycle, and HTLV-1 infection associated pathway; these cellular pathways played critical roles in the initiation and development of HCC or viral infections. Furthermore, seven hub/key genes were identified based on the topological network analysis, and their roles in HCC were verified by expression and Kaplan-Meier survival analysis. Protein-protein interaction and KEGG pathway analysis suggested that these key genes may stimulate cellular proliferation to promote the HCC progression. This study provides new perspectives to the knowledge of the key pathways and genes in the carcinogenesis process of HBV-associated HCC, and our findings provided potential therapeutic targets and clues of the carcinogenesis of HBV-associated HCC.

It is widely acknowledged that recruitment to randomised controlled trials (RCTs) is challenging, particularly trials that operate across multiple sites. A research area in need of further high-quality evaluation, including RCTs, is school-based mental health interventions for refugee children and adolescents. However, engaging schools with interventions and associated evaluations can be challenging. This paper explores the application of behavioural insights, i.e. evidence-based understanding of how people behave and make decisions, to RCT recruitment at the school level via email communications. A pilot study of applying behavioural insights to mail outs attempting to recruit schools to a RCT of a trauma-focused group intervention for refugee children and adolescents experiencing symptoms of post-traumatic stress is reported. Rates of school involvement between the behavioural insights approach (n = 31) and a standard outreach approach (n = 65) are compared.

Schools were more likely to give a positive response to the mail out designed using the behavioural insights framework than standard outreach. Accounts of recruitment strategies such as this are valuable additions to the literature on RCT methodology given the potential for recruitment issues to affect trial operations.

Schools were more likely to give a positive response to the mail out designed using the behavioural insights framework than standard outreach. Accounts of recruitment strategies such as this are valuable additions to the literature on RCT methodology given the potential for recruitment issues to affect trial operations.In addition to providing structural support, caveolin-1 (Cav1), a component of lipid rafts, including caveolae, in the plasma membrane, is involved in various cellular mechanisms, including signal transduction. Although pre-synaptic membrane dynamics and trafficking are essential cellular processes during synaptic vesicle exocytosis/synaptic transmission and synaptic vesicle endocytosis/synaptic retrieval, little is known about the involvement of Cav1 in synaptic vesicle dynamics. Here we demonstrate that synaptic vesicle exocytosis is significantly impaired in Cav1-knockdown (Cav1-KD) neurons. Specifically, the size of the synaptic recycled vesicle pool is modestly decreased in Cav1-KD synapses and the kinetics of synaptic vesicle endocytosis are somewhat slowed. Notably, neurons rescued by triple mutants of Cav1 lacking palmitoylation sites mutants show impairments in both synaptic transmission and retrieval. Collectively, our findings implicate Cav1 in activity-driven synaptic vesicle dynamics-both exocytosis and endocytosis-and demonstrate that palmitoylation of Cav1 is important for this activity.

Given a collection of coexpression networks over a set of genes, identifying subnetworks that appear frequently is an important research problem known as mining frequent subgraphs. Maximal frequent subgraphs are a representative set of frequent subgraphs; A frequent subgraph is maximal if it does not have a super-graph that is frequent. In the bioinformatics discipline, methodologies for mining frequent and/or maximal frequent subgraphs can be used to discover interesting network motifs that elucidate complex interactions among genes, reflected through the edges of the frequent subnetworks. Further study of frequent coexpression subnetworks enhances the discovery of biological modules and biological signatures for gene expression and disease classification.

We propose a reverse search algorithm, called RASMA, for mining frequent and maximal frequent subgraphs in a given collection of graphs. A key innovation in RASMA is a connected subgraph enumerator that uses a reverse-search strategy to enumerate connen experiments enables the discovery of functional modules and subnetwork biomarkers. We have proposed a reverse search algorithm for mining maximal frequent subnetworks. Enrichment analysis of the extracted maximal frequent subnetworks reveals that subnetworks that are frequent are highly enriched with known biological ontologies.TMEM132D is a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Defining a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the sole TMEM132 ortholog in C. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations in C. elegans tmem-132 that disrupt interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects in tmem-132 mutants, whereas gain-of-function of TMEM132D in mammalian cells inhibits WRC, leading to decreased abundance of select WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.

Dementia is a progressive neurocognitive disease with a substantial social burden. No apparent breakthroughs in treatment options have emerged so far; thus, disease prevention is essential for at-risk populations. Depression and cerebrovascular disease (CVD) are independent risk factors for dementia, but no studies have examined their interaction effect on dementia risk. This study aimed to identify the association of depression and CVD with the risk of dementia and evaluate whether dementia risk among patients with comorbid depression and CVD is higher than the sum of the individual risk due to each condition.

A population-based cohort study was conducted to analyze the Korean National Health Insurance Service-National Sample Cohort data of all individuals over 50 years of age. Individuals who had not been diagnosed with dementia at baseline were included and followed up from January 1, 2005, to December 31, 2013. A time-varying Cox proportional hazard regression model adjusted for potential confounding e associated with an increased risk of dementia, and their coexistence additively increased dementia risk more than the sum of the individual risks.

In this population-based nationwide cohort with long-term follow-up, depression and CVD were associated with an increased risk of dementia, and their coexistence additively increased dementia risk more than the sum of the individual risks.

No versatile web app exists that allows epidemiologists and managers around the world to comprehensively analyze the impacts of COVID-19 mitigation. The http//covid-webapp.numerusinc.com/ web app presented here fills this gap.

Our web app uses a model that explicitly identifies susceptible, contact, latent, asymptomatic, symptomatic and recovered classes of individuals, and a parallel set of response classes, subject to lower pathogen-contact rates. The user inputs a CSV file of incidence and, if of interest, mortality rate data. A default set of parameters is available that can be overwritten through input or online entry, and a user-selected subset of these can be fitted to the model using maximum-likelihood estimation (MLE). Model fitting and forecasting intervals are specifiable and changes to parameters allow counterfactual and forecasting scenarios. Confidence or credible intervals can be generated using stochastic simulations, based on MLE values, or on an inputted CSV file containing Markov chain al modelling or computer coding expertise with an invaluable tool for assessing the impacts of different outbreak mitigation policies and measures. This includes an ability to generate an epidemic-suppression or curve-flattening index that measures the intensity with which behavioural responses suppress or flatten the epidemic curve in the region under consideration.Saphenous veins used for coronary artery bypass surgery are subjected to considerable vascular trauma when harvested by conventional methods. This vascular damage is responsible, at least in part, for the inferior patency of the saphenous vein when compared with the internal thoracic artery. The performance of saphenous vein grafts is improved when this conduit is harvested atraumatically using the no-touch technique. There is growing evidence that the success of the no-touch technique is due to the preservation of a number of vascular structures including the endothelium, vasa vasorum and perivascular fat. There is conflicting evidence regarding the degree of endothelial damage to the endothelium of conventional versus no-touch saphenous vein grafts. In general, it has been shown that this single layer of cells lining the lumen exhibits considerable damage associated with a combination of vascular trauma and high pressure intraluminal distension. Increased platelet aggregation and thrombus formation at the exposed subendothelial membrane is due to a local reduction of endothelium-derived factors including nitric oxide. In addition, damage to the vasa vasorum of conventionally-harvested veins will reduce transmural blood flow, a condition shown to promote neointimal hyperplasia and atheroma formation. By stripping off the perivascular fat during conventional harvesting, mechanical support of the graft is reduced and the source of adipocyte-derived factors potentially beneficial for graft patency removed. While most agree that endothelial damage to the saphenous vein affects graft patency, the contribution of other tissue-derived factors affected by vascular damage at harvesting need to be considered.

The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region.

We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC.

Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.