Hodgeomar7845

Multipotent porcine mesenchymal stem cells (pMSC) are invaluable for research and therapeutic use in regenerative medicine. Media used for derivation and expansion of pMSC may play an important role for the selection of MSC subpopulation at an early stage and thereby, the specific basal medium may also affect differentiation potential of these cells. The present study was undertaken to evaluate the effects of αMEM, aDMEM, M199, αMEM/M199, aDMEM/M199 and αMEM/aDMEM media on (1) porcine bone marrow MSC derivation; (2) expression of number of osteogenic markers (ALP, COL1A1, SPP1 and BGLAP) at 5th and 10th passage in pMSC before differentiation; and (3) differentiation of pMSC (at 5th passage) to osteogenic lineage. Morphological changes and matrix formation in osteogenic cells were evaluated by microscopic examination. Calcium deposits in osteocytes were confirmed by Alizarin Red S staining. Based on expression of different markers, it was evident that selection of bone marrow pMSC subpopulations was independent of basal media used. However, the differentiation of those pMSCs, specifically to osteogenic lineage, was dependent on the medium used for expansion of pMSC at the pre-differentiation stage. We demonstrated here that the pMSC grown in combined αMEM/aDMEM (11) medium expressed number of osteogenic markers and these pMSC underwent osteogenic differentiation most efficiently, in comparison to porcine mesenchymal stem cells grown in other media. In conclusion, osteogenic differentiation potential of pMSC maintained in αMEM/aDMEM medium was observed significantly higher compared to cells cultivated in other media and therefore, the combined medium αMEM/aDMEM (11) may preferentially be used for expansion of pMSC, if needed for osteogenic differentiation.The Rab11 apical recycling endosome pathway is a well-established regulator of polarity and lumen formation; however, Rab11-vesicular trafficking also directs a diverse array of other cellular processes, raising the question of how Rab11 vesicles achieve specificity in space, time and content of cargo delivery. In part, this specificity is achieved through effector proteins, yet the role of Rab11 effector proteins in vivo remains vague. Here, we use CRISPR/Cas9 gene editing to study the role of the Rab11 effector Fip5 during zebrafish intestinal development. Zebrafish contain two paralogous genes, fip5a and fip5b, that are orthologs of human FIP5 We find that fip5a- and fip5b-mutant fish show phenotypes characteristic of microvillus inclusion disease, including microvilli defects and lysosomal accumulation. Single and double mutant analyses suggest that fip5a and fip5b function in parallel and regulate trafficking pathways required for assembly of keratin at the terminal web. Remarkably, in some genetic backgrounds, the absence of Fip5 triggers protein upregulation of a closely related family member, Fip1. This compensation mechanism occurs both during zebrafish intestinal development and in tissue culture models of lumenogenesis. In conclusion, our data implicate the Rab11 effectors Fip5 and Fip1 in a trafficking pathway required for apical microvilli formation.Throughout their lives, squids are both predators and prey for a multitude of animals, many of which are at the top of ocean food webs, making them an integral component of the trophic structure of marine ecosystems. The escape jet, which is produced by the rapid expulsion of water from the mantle cavity through a funnel, is central to a cephalopod's ability to avoid predation throughout its life. Although squid undergo morphological and behavioral changes and experience remarkably different Reynolds number regimes throughout their development, little is known about the dynamics and propulsive efficiency of escape jets throughout ontogeny. We examine the hydrodynamics and kinematics of escape jets in squid throughout ontogeny using 2D/3D velocimetry and high-speed videography. All life stages of squid produced two escape jet patterns (1) 'escape jet I' characterized by short rapid pulses resulting in vortex ring formation and (2) 'escape jet II' characterized by long high-volume jets, often with a leading-edge vortex ring. Paralarvae exhibited higher propulsive efficiency than adult squid during escape jet ejection, and propulsive efficiency was higher for escape jet I than escape jet II in juveniles and adults. These results indicate that although squid undergo major ecological transitions and morphology changes from paralarvae to adults, all life stages demonstrate flexibility in escape jet responses and produce escape jets of surprisingly high propulsive efficiency.This article has an associated First Person interview with the first author of the paper.The genomic relationship matrix plays a key role in the analysis of genetic diversity, genomic prediction, and genome-wide association studies. The epistatic genomic relationship matrix is a natural generalization of the classic genomic relationship matrix in the sense that it implicitly models the epistatic effects among all markers. Calculating the exact form of the epistatic relationship matrix requires high computational load, and is hence not feasible when the number of markers is large, or when high-degree of epistasis is in consideration. Currently, many studies use the Hadamard product of the classic genomic relationship matrix as an approximation. However, the quality of the approximation is difficult to investigate in the strict mathematical sense. In this study, we derived iterative formulas for the precise form of the epistatic genomic relationship matrix for arbitrary degree of epistasis including both additive and dominance interactions. The key to our theoretical results is the observation of an interesting link between the elements in the genomic relationship matrix and symmetric polynomials, which motivated the application of the corresponding mathematical theory. Based on the iterative formulas, efficient recursive algorithms were implemented. Compared with the approximation by the Hadamard product, our algorithms provided a complete solution to the problem of calculating the exact epistatic genomic relationship matrix. As an application, we showed that our new algorithms easily relieved the computational burden in a previous study on the approximation behavior of two limit models.

Diabetic retinopathy (DR) is the leading cause of blindness among the working population in the USA. Current therapies, including anti-vascular endothelial growth factor treatments, cannot completely reverse the visual defects induced by DR. MicroRNA-150 (miR-150) is a regulator that suppresses inflammation and pathological angiogenesis. In patients with diabetes, miR-150 is downregulated. As chronic inflammation is a major contributor to the pathogenesis of DR, whether diabetes-associated decrease of miR-150 is merely associated with the disease progression or decreased miR-150 causes retinal inflammation and pathological angiogenesis is still unknown.

We used high-fat diet (HFD)-induced type 2 diabetes (T2D) in wild type (WT) and miR-150 knockout (miR-150

) mice for this study and compared retinal function and microvasculature morphology.

We found that WT mice fed with an HFD for only 1 month had a significant decrease of miR-150 in the blood and retina, and retinal light sensitivity also decreased. The miR-150

mice on the HFD developed diabetes similar to that of the WT. At 7-8 months old, miR-150

mice under normal diet had increased degeneration of retinal capillaries compared with WT mice, indicating that miR-150 is important in maintaining the structural integrity of retinal microvasculature. Deletion of miR-150 worsened HFD-induced retinal dysfunction as early as 1 month after the diet regimen, and it exacerbated HFD-induced T2DR by further increasing retinal inflammation and microvascular degeneration.

These data suggest that decreased miR-150 caused by obesity or diabetic insults is not merely correlated to the disease progression, but it contributes to the retinal dysfunction and inflammation, as well as the development of DR.

These data suggest that decreased miR-150 caused by obesity or diabetic insults is not merely correlated to the disease progression, but it contributes to the retinal dysfunction and inflammation, as well as the development of DR.

Both diabetes mellitus and being female significantly increase the risk of being diagnosed with major depressive disorder (MDD). The diagnosis of MDD, combined with diabetes mellitus, can be detrimental in terms of mortality and morbidity. We aimed at investigating the impact of diabetes mellitus on the gender gap in MDD over the course of a human lifetime.

In a cross-sectional study over the course of 17 years, medical claims data of the general Austrian population (n=8 996 916) between 1997 and 2014 was analyzed. Of these, 123 232 patients with diabetes mellitus were extracted and compared with non-diabetic controls.

In a cohort of 123 232 patients with diabetes mellitus and 1 933 218 controls (52% females, 48% males), women with diabetes had 2.55 times increased ORs to be diagnosed with MDD compared with women without diabetes (95% CI 2.48 to 2.62, p<0.001) between the age of 30 and 69 years. The effect of diabetes mellitus on the prevalence of MDD was significantly smaller in men (OR=1.85, 95% CI 1.80 to 1.91, p<0.001). Between 0 and 30 years and after age 70 years, the gender gap of MDD was not different between patients with and without diabetes mellitus. The peak of the gender gap in MDD in patients with diabetes mellitus was around the age of 40-49 years. A sensitivity analysis identified overweight, obesity and alcohol dependence as the most potent influencing factors of the widening of the gender gap among patients with diabetes mellitus.

Diabetes mellitus is a stronger risk factor for MDD in women than in men, with the greatest width of the gender gap between 40 and 49 years. High-risk patients for MDD, such as overweight female patients with diabetes, should be more carefully assessed and monitored.

Diabetes mellitus is a stronger risk factor for MDD in women than in men, with the greatest width of the gender gap between 40 and 49 years. High-risk patients for MDD, such as overweight female patients with diabetes, should be more carefully assessed and monitored.

Gestational diabetes (GD) is associated with impaired insulin sensitivity in newborns. Adiponectin and retinol-binding protein 4 (RBP-4) are involved in regulating insulin sensitivity. Females are more likely to develop diabetes at young ages than males. We tested the hypothesis that GD may affect RBP-4 and adiponectin levels in early life, and there may be sex-dimorphic associations.

In a nested case-control study of 153 matched pairs of neonates of mothers with GD and euglycemic pregnancies in the Shanghai Birth Cohort, we evaluated cord plasma leptin, high molecular weight (HMW) and total adiponectin and RBP-4 concentrations.

Comparing GD versus euglycemic pregnancies adjusted for maternal and neonatal characteristics in female newborns, cord plasma total adiponectin (mean±SD 30.8±14.3 vs 37.1±16.1 µg/mL, p=0.048) and HMW adiponectin (14.6±7.7 vs 19.3±8.3 µg/mL, p=0.004) concentrations were lower, while RBP-4 concentrations were higher (21.7±5.4 vs 20.0±4.8 µg/mL, p=0.007). In contrast, there were nobsence (RBP-4) of sex dimorphism in some insulin sensitivity regulation-relevant adipokines in early life.

Despite being proposed 4 years ago, there has been no independent validation study of the Rome IV criteria for IBS. We assessed their performance for the diagnosis of IBS in secondary care and compared them with the previous iteration, the Rome III criteria.

We collected complete symptom data from consecutive adult patients with suspected IBS referred to a single UK clinic. All subjects underwent relatively standardised workup, with assessors blinded to symptom status. The reference standard used to confirm IBS was the presence of lower abdominal pain or discomfort in association with altered stool form or frequency, in a patient with no evidence of organic gastrointestinal disease after investigation. Sensitivity, specificity and positive and negative likelihood ratios (LRs), with 95% CIs, were calculated for each of the diagnostic criteria.

The level of agreement between the Rome IV and Rome III criteria was good (kappa=0.65). Compared with the reference standard, sensitivity and specificity of the Ro IBS in this single centre secondary care study, although the clinical relevance of this is uncertain.Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.

The latest evidence in the incidence of central retinal artery occlusion (CRAO) is needed to support the development of novel treatments as orphan drugs. However, up-to-date information on the incidence of CRAO in the ageing or aged population is limited. We aimed to investigate the nationwide epidemiological and clinical characteristics of CRAO in Japan, using nationwide health insurance claims data.

We analysed a total of 16 069 762 claims data in the sampling dataset of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which is the nationwide health insurance claims database of 127 million whole Japanese individuals. CRAO was identified using the International Classification of Diseases 10th edition diagnostic code H34.1. The crude incidence rates and age-standardised incidence rates of CRAO, according to the standard age-structure population of the WHO, were calculated.

The crude incidence rate of CRAO in Japan was 5.84 (95% CI, 5.71 to 5.97) per 100 000 person-years. With respect to the sex-related incidence, the rate was higher 1.40 times in men than in women (6.85 (95% CI, 6.65 to 7.06) vs 4.88 (95% CI, 4.71 to 5.05), p<0.001). The age-standardised incidence rate was 2.53 (95% CI, 2.29 to 2.76) per 100 000 person-years.

The crude incidence rate of CRAO was higher in Japan than in other countries, as reported previously, reflecting the Japanese population structure as a super-aged society. These findings can be helpful for the development of appropriate healthcare policies to address the increasing incidence of CRAO with the ageing population.

The crude incidence rate of CRAO was higher in Japan than in other countries, as reported previously, reflecting the Japanese population structure as a super-aged society. These findings can be helpful for the development of appropriate healthcare policies to address the increasing incidence of CRAO with the ageing population.

We assessed changes in secondhand smoke (SHS) exposure in workplaces and public venues in Poland over a 9-year period following the adoption of a smoke-free policy in Poland in 2010.

Six waves of cross-sectional surveys were carried out between 2009 and 2019.

A nationally representative sample of adult Polish residents (age 15 years and older) was surveyed.Survey respondents self-reported SHS exposure in the workplace and 12 different public venues. Data were analysed separately for samples consisting of (1) all respondents and (2) non-smokers only.SHS exposure was defined based on self-report, which may invoke error such as demand bias or recall bias and study protocol do not include participation of paediatric populations that are key limitations of this study.

Within a year of adopting the smoke-free policy in 2010, the proportion of non-smokers exposed to SHS in Polish workplaces decreased by more than half (from 19.2% in 2009 to 9.5% in 2011). Over 10 years, a substantial reduction in SHS exposure was observed in all public venues. The highest decrease in SHS exposure was observed in transport services (decreased from 45.7% to 11.7% among all respondents and from 44.2% to 11.7% among non-smokers) and in bars/pubs (SHS exposure decreased from 45.0% to 7.0% among all respondents and from 39.4% to 7.0% among non-smokers).

This study demonstrates the substantial success of a national smoke-free law. Nevertheless, smoke-free laws must continue to be refined in terms of their legal boundaries as well as implementation strategies to eliminate disparities in SHS exposure in certain types of venues.

This study demonstrates the substantial success of a national smoke-free law. Nevertheless, smoke-free laws must continue to be refined in terms of their legal boundaries as well as implementation strategies to eliminate disparities in SHS exposure in certain types of venues.

A number of studies have shown that the airborne transmission route could spread some viruses over a distance of 2 meters from an infected person. An epidemic model based only on respiratory droplets and close contact could not fully explain the regional differences in the spread of COVID-19 in Italy. On March 16th 2020, we presented a position paper proposing a research hypothesis concerning the association between higher mortality rates due to COVID-19 observed in Northern Italy and average concentrations of PM

exceeding a daily limit of 50 µg/m

.

To monitor the spreading of COVID-19 in Italy from February 24th to March 13th (the date of the Italian lockdown), official daily data for PM

levels were collected from all Italian provinces between February 9th and February 29th, taking into account the maximum lag period (14 days) between the infection and diagnosis. In addition to the number of exceedances of the daily limit value of PM

, we also considered population data and daily travelling informaon of daily PM10 exceedances and the initial spreading of COVID-19 in the 110 Italian provinces.

To provide useful information for policy-makers and clinicians by analysing the medical service use-divided into Western medicine (WM) and Korean medicine (KM)-of patients with ankle sprains in South Korea between 2015 and 2017.

Cross-sectional, retrospective, observational study.

Tertiary hospitals, WM hospitals, WM clinics, KM hospitals, KM clinics and others in South Korea.

We analysed claim data and patient information from the 2015 to 2017 Health Insurance Review and Assessment National Patient Sample (HIRA-NPS) dataset, including 151 415 patients diagnosed with a 'dislocation, sprain and strain of joints and ligaments at ankle and foot level' (10th revision of the International Statistical Classification of Diseases code S93) who used medical services at least once in 3 years between January 2015 and December 2017 in South Korea.

Cost of medical care, number of consultations, type of institution visited, types of treatment.

There were 160 200 consultations and 53 044 patients in 2015, 149 95hted as a possible cause of increased costs.

To investigate the association between early life famine exposure and cognitive function in adults.

Historical cohort study SETTING North Wollo Zone, Northeast Ethiopia.

We recruited 1047 adult men and women aged 30-38 years who had history of early life exposure to Ethiopian great famine. Based on self-reported age and birth date, participants were categorised into famine exposed in early life (prenatal/postnatal) and non-exposed groups.

The primary outcome measure of this study was cognitive function in adults after early life exposure to famine. Cognitive function was measured using Montreal Cognitive Assessment-basic. Associations between exposure and outcome variables were examined by linear regression analysis models.

Adjusted for covariates, early life exposure to famine showed 1.29 (β=-1.29; 95% CI -2.16 to -0.52) points lower cognitive function score compared with non-exposed. Based on subanalysis for timing of famine exposure, postnatal exposure to famine resulted in 2.26 (β=-2.26; 95% CI function may indicate the relative importance of learning and experience during early childhood for optimal brain development after birth. Further studies are needed to elucidate the potential mechanism behind this association.

To investigate associations of job demands and resources with patient-related burnout among physicians.

Multicentre observational study.

Fifty medical departments at 14 (academic and non-academic) hospitals in the Netherlands.

Four hundred sixty-five physicians (71.6% response rate), comprising 385 (82.8%) medical specialists and 80 (17.2%) residents.

Job demands (workload and bureaucratic demands), job resources (participation in decision making, development opportunities, leader's inspiration, relationships with colleagues and patients)-measured with the validated Questionnaire of Experience and Evaluation of Work and Physician Worklife Survey-and patient-related burnout, measured using the validated Copenhagen Burnout Inventory.

Patient-related burnout was positively associated with workload (b=0.36; 95% CI, 0.25 to 0.48; p<0.001) and negatively associated with development opportunities (b=-0.18; 95% CI, -0.27 to -0.08; p<0.001) and relationships with patients (b=-0.12; 95% CI, -0.22 to -refore, positive physician-patient relationships may be supported to reduce the likelihood of physicians' patient-related burnout. However, the specific support needed to effectively reduce patient-related burnout may vary per healthcare context and thus requires intensified research across healthcare systems and settings.

In stroke survivors, atrial fibrillation (AF) is typically evaluated solely by short-term ECG monitoring in the stroke unit. Prolonged continuous ECG monitoring or insertable cardiac monitors require substantial resources. Chest and thumb ECG could provide an alternative means of AF detection, which in turn could allow prompt anticoagulation to prevent recurrent stroke. The objective of this study was to assess the yield of newly diagnosed AF during 28 days of chest and thumb ECG monitoring two times per day in cryptogenic stroke.

This study, Transient ECG Assessment in Stroke Evaluation, included patients who had a stroke from Region Gävleborg, Sweden, between 2017 and 2019. Patients with a recent ischaemic stroke without documented AF (or other reasons for anticoagulation) before or during ECG evaluation in the stroke unit were evaluated using the Coala Heart Monitor connected to a smartphone application for remote monitoring.

The prespecified number of 100 patients (mean age 67.6±10.8 years; 60% men) was analysed. In nine patients (9%, number needed to screen 11) AF but no other significant atrial arrhythmias (>30 s) was diagnosed. The mean CHA

DS

-VASc score was similar among patients with AF and no AF (4.9±1.1 vs 4.3±1.3; p=0.224) and patients with AF were older (74.3±9.0 vs 66.9±10.8; p=0.049). Patients performed on average 90.1%±15.0% of scheduled transmissions.

In evaluation of cryptogenic stroke, 9% of patients had AF detected using chest and thumb ECG two times per day during 1 month. In many stroke survivors, this is a feasible approach and they will be potentially protected from recurrent stroke by anticoagulation treatment.

NCT03301662.

NCT03301662.

National Spanish studies show that prevalence of cervical human papillomavirus (HPV) infection in the female population is increasingly frequent, with an overall estimate of 14% in women aged 18-65 years. The objective of this study is to know the prevalence and distribution of HPV types in the female population of the Canary Islands prior to the introduction of HPV vaccines and to investigate the associated clinical and sociodemographic factors.

Based on the Primary Health Care database, a sample of adult women (aged 18-65 years) of Gran Canaria (GC) and Tenerife (TF) stratified into nine age groups was carried out between 2002 and 2007. Women were contacted by postal letter and telephone call and were visited in their primary care centre. A clinical-epidemiological survey was completed and cervical samples were taken for cytological study and HPV detection. HPV prevalence and its 95% CI were estimated, and multivariate analyses were performed using logistic regression to identify factors associated withhe determinants of infection are consistent with those of other populations.

There are large inequities in the lung cancer burden for the Indigenous Māori population of New Zealand. We model the potential lifetime health gains, equity impacts and cost-effectiveness of a national low-dose CT (LDCT) screening programme for lung cancer in smokers aged 55-74 years with a 30 pack-year history, and for formers smokers who have quit within the last 15 years.

A Markov macrosimulation model estimated health benefits (health-adjusted life-years (HALYs)), costs and cost-effectiveness of biennial LDCT screening. Input parameters came from literature and NZ-linked health datasets.

New Zealand.

Population aged 55-74 years in 2011.

Biennial LDCT screening for lung cancer compared with usual care.

Incremental cost-effectiveness ratios were calculated using the average difference in costs and HALYs between the screened and the unscreened populations. Equity analyses included substituting non-Māori values for Māori values of background morbidity, mortality and stage-specific survival. Changnnial LDCT lung cancer screening programme in New Zealand is likely to be cost-effective, will improve total population health and reduce health inequities for Māori. Attention must be paid to addressing ethnic inequities in stage-specific lung cancer survival.

Family physicians or general practitioners play central roles in many countries' primary care systems, but family medicine (FM) remains relatively unestablished in Japan. Previous studies in Japan have examined the general population's understanding of FM as a medical specialty, but none have explored this topic using actual FM clinic patients. Here, we describe a protocol to explore the perceptions of FM among long-term patients of one of Japan's oldest FM clinics.

The study will be conducted at the Motowanishi Family Clinic in Hokkaido, Japan, using patients who have attended the clinic for over 10 years. The analysis will adopt a two-phase explanatory sequential mixed methods design. During phase I, quantitative data from participants' medical records will be collected and reviewed, and patients' perceptions of FM will be assessed through a questionnaire. The correlations between participants' knowledge that the clinic specialises in FM and various characteristics will be examined. In phase II, qualitannual academic meeting and submitted for publication in relevant journals. The findings will also be provided to the patients via the clinic's internal newsletter.

To evaluate the incidence of osteoporotic hip fracture in the Macarena Health Area (Seville).

This was a prospective observational study that collected all osteoporotic hip fractures that occurred between March 2013 and February 2014 at the Clinical Unit of Traumatology and Orthopaedics. All cases collected during the first 6 months of the study were followed for 1 year after the occurrence of the event.

We evaluated the incidence of osteoporotic hip fractures in the Macarena Health Area (Seville) from 1 March 2013 to 28 February 2014, and we compared the incidence with that in 2 previous studies carried out with the same methodology in 1994 and 2006. Furthermore, we calculated the morbidity and degree of disability 1 year after the fracture occurred and determined mortality and the associated factors.

The overall incidence was 228 per 100 000 individuals/year (95% CI 204.5 to 251.6), and the incidence was higher in women than in men. In women, the incidence rate decreased in all age groups over time, while in men, the incidence rate increased. The mortality rate 1 year after the episode was 27.2%. The factors associated with overall mortality were a body mass index below 25 kg/m

, renal failure and low plasma proteins.

Our results show a high incidence of osteoporotic hip fracture that is increasing in men, and in men it is associated with a higher mortality than in women. There is room to improve the modifiable factors associated with mortality and the available rehabilitation interventions to reduce the disability associated with these fractures.

Our results show a high incidence of osteoporotic hip fracture that is increasing in men, and in men it is associated with a higher mortality than in women. There is room to improve the modifiable factors associated with mortality and the available rehabilitation interventions to reduce the disability associated with these fractures.

Left bundle branch area pacing (LBBaP) has been accepted as a physiological pacing method that can yield narrow paced QRS waves. For patients with failed biventricular pacing (Bi-V), LBBaP is another feasible option. However, no randomised controlled study has evaluated the efficacy and safety of LBBaP in heart failure patients with left bundle branch block (LBBB). Therefore, we aimed to conduct this type of randomised controlled trial.

This study is a single-centre, randomised controlled non-inferiority trial. This study will be conducted at the cardiac centre of Beijing Anzhen Hospital. From January 2020 to December 2022, 180 heart failure patients with reduced left ventricular ejection fraction (LVEF ≤35%) and LBBB undergoing Bi-V implantation will be consecutively enrolled in this study. Participants will be randomised at a 11 ratio into an experimental group (LBBaP) and a control group (Bi-V). The primary outcome is LVEF. The secondary outcomes are NT-proBNP, duration of the QRS complex, end systolic volume, end diastolic volume, the 6-minute walking test and quality of life (SF-36 scale), all causes of mortality, cardiovascular death, rehospitalisation rate of heart failure, other rehospitalisation rates, major complication rates, procedure costs and hospitalised dates.

This study has been approved by the Beijing Anzhen Hospital Medical Ethics Committee (No. ks201932). The results of this study will be presented at domestic and international conferences. We hypothesise that LBBaP is non-inferior compared with Bi-V for treating patients with heart failure and LBBB. This trial will provide evidence-based recommendations for electrophysiologists.

Chinese Clinical Trial Registry (ChiCTR2000028726).

Chinese Clinical Trial Registry (ChiCTR2000028726).

To compare the effectiveness of three-dimensional printed (3DP), virtual reality (VR) and conventional normal physical (NP) models in clinical education regarding the morphology of craniovertebral junction (CVJ) deformities.

Prospective, multicentre, randomised controlled study.

Three teaching hospitals in China.

One hundred and fifty-three participants in their first year of a 3-year medical residency programme.

All participants were randomised to one of the three groups to learn the morphology of CVJ deformities using 3DP, VR or NP models.

The objective outcomes were evaluated using three-level objective testing. In the first-level test, the participants were required to identify 15 anatomical landmarks on radiographs without CVJ deformities. In the second-level test, all participants were asked to identify the same 15 landmarks on radiographs showing classic CVJ deformities. In the third-level test, the participants were required to describe the key features of three classic cases of CVJ deformctive results show that the 3DP model is more effective teaching instrument than the NP model for learning the pathomorphology of CVJ deformities. The VR model also showed great efficacy, second to 3DP model, in improving participants' understanding of CVJ deformities.

The objective of this study was to address the knowledge gap regarding antibiotic use in Medecins Sans Frontiéres (MSF) projects located in Africa by exploring antibiotic prescription and consumption habits and their drivers at different healthcare levels.

This study used an exploratory study design through thematic analysis of semistructured, in-depth interviews, focus group discussions (FGDs) and field observations in order to understand the main drivers influencing current antibiotics prescription habits and consumption habits of patients in different geographical settings.

The study took place in MSF centres and towns across four countries Guinea-Bissau, Central African Republic (CAR), Democratic Republic of Congo (DRC) and Sudan.

384 respondents participated in the study, which includes project staff, prescribers, community members, patients, among other groups.

Treatment protocols were physically present in all countries except DRC, but compliance to protocols varied across contexts. A failingates widespread use of antibiotics based on unclear assumptions, which are often influenced by patient demands. There needs to be a broader focus on the balance between access and excess, especially in such fragile contexts where access to healthcare is a real challenge.

To explore and reflect on the current anticoagulation therapy offered to patients with atrial fibrillation (AF), potential challenges and the future vision for oral anticoagulants for patients with AF and healthcare professionals in Ireland.

A multistakeholder focus group using a World Café approach.

Nine participants from academic, clinical and health backgrounds attended the focus group together with a facilitator.

Enhanced patient empowerment; more effective use of technology and developing system-based medical care pathways would provide improved supports for AF management. The challenges in providing these include cost and access issues, the doctor-patient relationship and the provision of education. While consensus for developing evidence-based pathways to maximise efficiency and effectiveness of AF treatment was evident, it would require a shared vision between stakeholders of integrated care. The benefits of embracing technological advances for clinicians and patients were evident; however, clsignificant operationalisation issues and barriers to effective treatment/management persist. The reflections reported in this study are a catalyst for future discussion and research.

In this manuscript, we describe broad trends in postoperative mortality in New Zealand (a country with universal healthcare) for acute and elective/waiting list procedures conducted between 2005 and 2017.

We use high-quality national-level hospitalisation data to compare the risk of postoperative mortality between demographic subgroups after adjusting for key patient-level confounders and mediators. We also present temporal trends and consider how rates in postoperative death following acute and elective/waiting list procedures have changed over this time period.

A total of 1 836 683 unique patients accounted for 3 117 374 admissions in which a procedure was performed under general anaesthetic over the study period. We observed an overall 30-day mortality rate of 0.5 per 100 procedures and a 90-day mortality rate of 0.9 per 100. For acute procedures, we observed a 30-day mortality rate of 1.6 per 100, compared with 0.2 per 100 for elective/waiting list procedures. In terms of procedure specialty, respirn System) was also associated with an increased risk of postoperative death. Encouragingly, it appears that risk of postoperative mortality has declined over the past decade, possibly reflecting improvements in perioperative quality of care; however, this decline did not occur equally across procedure specialties.

Cognitive impairment is known to have a significant impact on the quality of life of individuals and their caregivers, yet it is often underdiagnosed. The objective of this study is to assess the extent of cognitive impairment among elders visiting primary healthcare (PHC) practice settings, to explore associated risk factors and discuss current care challenges for PHC providers.

A cross-sectional study was conducted between March 2013 and May 2014.

Fourteen PHC units located in rural and urban areas of the Heraklion district in Crete, Greece.

Consecutive visitors aged at least 60 years attending selected PHC practices.

The Mini-Mental State Examination (MMSE) was used to indicate cognitive status. Associations of low MMSE scores (≤23/24, adjusted for education level) with 12 socio-demographic factors, comorbidities and lifestyle factors were assessed.

A total of 3140 PHC patients met inclusion criteria (43.2% male; mean age 73.7±7.8 years). The average MMSE score was 26.0±3.8; 26.7±3.5 in male and 25.4±3.9 in female participants (p<0.0001). Low MMSE scores were detected in 20.2% of participants; 25.9% for females vs 12.8% for males; p<0.0001. Female gender (adjusted OR (AOR)=2.72; 95% CI 2.31 to 3.47), age (AOR=1.11; 95% CI 1.10 to 1.13), having received only primary or no formal education (AOR=2.87; 95% CI 2.26 to 3.65), alcohol intake (AOR=1.19; 95% CI 1.03 to 1.37), reporting one or more sleep complaints (AOR 1.63; 95% CI 1.14 to 2.32), dyslipidaemia (AOR=0.80; 95% CI 0.65 to 0.98) and history of depression (AOR=1.90; 95% CI 1.43 to 2.52) were associated with low MMSE scores.

This study identified a relatively high prevalence of low MMSE scores among persons attending PHC practices in a southern European community setting and associations with several known risk factors.

This study identified a relatively high prevalence of low MMSE scores among persons attending PHC practices in a southern European community setting and associations with several known risk factors.

We explored Japanese physicians' work-related stressors and identified those unique to this population, as well as clarified the influence of cultural and medical system diversity on these stressors to determine the content of future stress-reducing interventions for hospital physicians in Japan.

We conducted a semistructured, face-to-face interview-based qualitative study between August and October 2017. The collected data were analysed using the grounded theory approach.

Hospitals around the Tokyo metropolitan area, Japan.

Sixteen hospital physicians (mean age (SD)=33.9 (4.2) years; 11 men, 5 women). Seven worked in internal medicine and nine in surgery.

We found unique stressors related to the Japanese medical system and culture, such as continuous all-day work after night shifts, and a hierarchical organisational system called

. The results also indicated that Japanese physicians shared several stressors with Western physicians, such as sleep deprivation, high pressure and the limits of medicine.

Our study clarifies some sources of work-related stressors among hospital physicians in Japan. While the key components of Western interventions might be useful in a Japanese context, the original evidence obtained from this study highlights the necessity of initiating interventions addressing the unique stressors of Japanese physicians. To reduce physicians' stress and enhance their well-being, psychological interventions for hospital physicians must be introduced in Japan.

Our study clarifies some sources of work-related stressors among hospital physicians in Japan. While the key components of Western interventions might be useful in a Japanese context, the original evidence obtained from this study highlights the necessity of initiating interventions addressing the unique stressors of Japanese physicians. To reduce physicians' stress and enhance their well-being, psychological interventions for hospital physicians must be introduced in Japan.

The study analysed medical malpractice claims to assess patient safety in hospitals. The information derived from malpractice claims reflects potential risks and could help lead to reducing medical errors and improving patient safety.

We analysed 4380 medical malpractice claims from 351 grade-A tertiary hospitals in China for 2008-2017. We examined the characteristics of medical errors and patient safety, including the types of medical errors, proportionate liabilities and payments for medical malpractice in different clinical specialties.

We assessed claim characteristics, payment amounts and liability.

Our data analysis demonstrated that 72.5% of the claims involved medical errors, with average payments of US$31 430. The hospital's errors in medical malpractice resulted in 41.4% average liability in patient injury payments. Most medical malpractice cases occurred in Shanghai (817 claims, 18.7%) and Beijing (468 claims, 10.7%). The highest risks for medical error and malpractice claims were related trates to general Chinese hospitals. 36Different specialties had different risk characteristics regarding medical errors, payments and proportionate liabilities. Orthopaedics had the highest number of malpractices claims and higher proportionate liability but lower death rates.

Despite the national effort to integrate the Prevention of Mother-to-Child Transmission (PMTCT) programme into antenatal care clinics in Indonesia, the rate of mother-to-child HIV transmission remains high. This national study was conducted to describe PMTCT programme performance and to identify health facility characteristics associated with this performance in order to inform programme planning and policy development.

A retrospective cross-sectional study in December 2017.

All health facilities providing PMTCT programmes in Indonesia.

All health facilities registering at least one woman in antenatal care in 2017.

PMTCT data extraction from the national reporting system on HIV/AIDS and government reports.

Women retention in the PMTCT programme for at least 3 months and associated health facility characteristics.

A total of 373 health facilities registering 6502 HIV-positive women in antenatal care were included in the analysis. One-third of women (2099) never started antiretroviral treatment. O HIV programme is a high priority.

We observed low retention of HIV-positive pregnant women in the PMTCT programme in Indonesia in 2017. Additional efforts are needed to improve women's retention in the PMTCT programme. Retention could be increased through the delivery of PMTCT programmes by replicating strategies implemented at hospital types A and B located in concentrated HIV epidemic areas where an HIV programme is a high priority.

Craniosynostosis is typically diagnosed and surgically corrected within the first year of life. The diagnosis and surgical correction of the condition can be a very stressful experience for families. Despite this, there is little research exploring the impact that craniosynostosis has on families, especially in the period immediately following diagnosis and correction. In this study, the authors aimed to qualitatively examine the psychosocial experience of families with a child diagnosed with craniosynostosis.

Qualitative study.

Tertiary care paediatric health centre.

Mothers of children newly diagnosed with single-suture, non-syndromic craniosynostosis.

Semistructured interviews regarding parental experience with the initial diagnosis, their decision on corrective surgery for their child, the operative experience, the impact of craniosynostosis on the family and the challenges they encountered throughout their journey.

Thematic analysis, a type of qualitative analysis that provides an in-depth ac other families moving forward.

Overall, the diagnosis of craniosynostosis has a profound impact on families, leading them to face many struggles throughout their journey. A better understanding of these experiences will help to inform future practice, with a hope to improve this experience for other families moving forward.Collectively, the retrotrapezoid nucleus (RTN) and adjacent C1 neurons regulate breathing, circulation and the state of vigilance, but previous methods to manipulate the activity of these neurons have been insufficiently selective to parse out their relative roles. We hypothesize that RTN and C1 neurons regulate distinct aspects of breathing (e.g., frequency, amplitude, active expiration, sighing) and differ in their ability to produce arousal from sleep. Here we use optogenetics and a combination of viral vectors in adult male and female Th-Cre rats to transduce selectively RTN (Phox2b+/Nmb+) or C1 neurons (Phox2b+/Th+) with Channelrhodopsin-2. RTN photostimulation modestly increased the probability of arousal. RTN stimulation robustly increased breathing frequency and amplitude; it also triggered strong active expiration but not sighs. Consistent with these responses, RTN innervates the entire pontomedullary respiratory network, including expiratory premotor neurons in the caudal ventral respiratory group, e of technical limitations (anesthesia, nonselective neuronal actuators). Using optogenetics in unanesthetized rats, we found that selective stimulation of either RTN or C1 neurons activates breathing. However, only RTN triggers active expiration, presumably because RTN, unlike C1, has direct excitatory projections to abdominal premotor neurons. The arousal potential of the C1 neurons is far greater than that of the RTN, however, consistent with C1's projections to brainstem wake-promoting structures. In short, C1 neurons orchestrate cardiorespiratory and arousal responses to somatic stresses, whereas RTN selectively controls lung ventilation and arterial Pco2 stability.Emerging evidence supports roles for secreted extracellular matrix proteins in boosting synaptogenesis, synaptic transmission, and synaptic plasticity. SPARCL1 (also known as Hevin), a secreted non-neuronal protein, was reported to increase synaptogenesis by simultaneously binding to presynaptic neurexin-1α and to postsynaptic neuroligin-1B, thereby catalyzing formation of trans-synaptic neurexin/neuroligin complexes. However, neurexins and neuroligins do not themselves mediate synaptogenesis, raising the question of how SPARCL1 enhances synapse formation by binding to these molecules. Moreover, it remained unclear whether SPARCL1 acts on all synapses containing neurexins and neuroligins or only on a subset of synapses, and whether it enhances synaptic transmission in addition to boosting synaptogenesis or induces silent synapses. To explore these questions, we examined the synaptic effects of SPARCL1 and their dependence on neurexins and neuroligins. Using mixed neuronal and glial cultures from neonatal mousther SPARCL1 acts on all or on only a subset of synapses, induces functional or largely inactive synapses, and generates synapses by bridging presynaptic neurexins and postsynaptic neuroligins. Here, we report that SPARCL1 selectively induces excitatory synapses, increases their efficacy, and enhances their NMDAR content. Moreover, using rigorous genetic manipulations, we show that SPARCL1 does not require neurexins and neuroligins for its activity. Thus, SPARCL1 selectively boosts excitatory synaptogenesis and synaptic transmission by a novel mechanism that is independent of neurexins and neuroligins.Alzheimer's disease (AD) is the leading cause of late-onset dementia, and there exists an unmet medical need for effective treatments for AD. The accumulation of neurotoxic amyloid-β (Aβ) plaques contributes to the pathophysiology of AD. EPHX2 encoding soluble epoxide hydrolase (sEH)-a key enzyme for epoxyeicosatrienoic acid (EET) signaling that is mainly expressed in lysosomes of astrocytes in the adult brain-is cosited at a locus associated with AD, but it is unclear whether and how it contributes to the pathophysiology of AD. In this report, we show that the pharmacologic inhibition of sEH with 1-trifluoromethoxyphenyl- 3-(1-propionylpiperidin-4-yl) urea (TPPU) or the genetic deletion of Ephx2 reduces Aβ deposition in the brains of both male and female familial Alzheimer's disease (5×FAD) model mice. The inhibition of sEH with TPPU or the genetic deletion of Ephx2 alleviated cognitive deficits and prevented astrocyte reactivation in the brains of 6-month-old male 5×FAD mice. 14,15-EET levels in the brains iting sEH or increasing 14,15-epoxyeicosatrienoic acid (EET) enhanced lysosomal biogenesis and amyloid-β (Aβ) clearance in cultured adult astrocytes. Moreover, the infusion of 14,15-EET into the hippocampus of 5×FAD mice not only prevented the aggregation of Aβ, but also reversed the deposition of Aβ. Thus, 14,15-EET plays a key role in the pathophysiology of AD and therapeutic strategies that target this pathway may be an effective treatment.Myelin Protein Zero (MPZ/P0) is the most abundant glycoprotein of peripheral nerve myelin. P0 is synthesized by myelinating Schwann cells, processed in the endoplasmic reticulum (ER) and delivered to myelin via the secretory pathway. The mutant P0S63del (deletion of serine 63 in the extracellular domain of P0), that causes Charcot-Marie-Tooth type 1B (CMT1B) neuropathy in humans and a similar demyelinating neuropathy in transgenic mice, is instead retained the ER where it activates an unfolded protein response. Under ER-stress conditions, protein kinase R-like endoplasmic reticulum kinase (PERK) phosphorylates eukaryotic initiation factor 2α (eIF2α) to attenuate global translation, thus reducing the misfolded protein overload in the ER. Genetic and pharmacological inactivation of Gadd34 (damage-inducible protein 34), a subunit of the PP1 phosphatase complex that promotes the dephosphorylation of eIF2α, prolonged eIF2α phosphorylation and improved motor, neurophysiological, and morphologic deficits in S63del mlar domain of P0) mouse model of Charcot-Marie-Tooth type 1B (CMT1B), the genetic and pharmacological inhibition of Gadd34 (damage-inducible protein 34) prolonged eukaryotic initiation factor 2α (eIF2α) phosphorylation, leading to a proteostatic rebalance that significantly ameliorated the neuropathy. Yet, ablation of protein kinase R-like endoplasmic reticulum kinase (PERK) also ameliorated the S63del neuropathy, despite reduced levels of eIF2α phosphorylation (P-eIF2α). In this study, we provide genetic evidence that eIF2α phosphorylation has a protective role in CMT1B Schwann cells by limiting ERK/c-Jun hyperactivation. Our data support the targeting of the P-eIF2α/Gadd34 complex as a therapeutic avenue in CMT1B and also suggest that PERK may hamper myelination via mechanisms outside its role in the unfolded protein response.