Non-insidious Large Joint Manifestation of Severe Cachectic Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which constitutional symptoms typically occur before joint swelling becomes a true clinical phenomenon. Weight loss, although common, is generally mild in nature and occurs after long standing inflammation. While large joints do become inflamed, RA has a much stronger predilection for the small joints. Our case is a rarity in the fact that there was initial large joint swelling without long standing inflammation. Additionally, the weight loss was cachectic in nature and extreme. Furthermore, while extra-articular manifestations do commonly occur, spontaneous pneumothorax is certainly atypical. The content of this manuscript serves to enlighten hospitalist physicians and residents, as to the odd way in which a case like this may present

Individual, occupational, and workplace correlates of occupational health and safety vulnerability in a sample of Canadian workers

Objective: To describe OH&amp;S vulnerability across a diverse sample of Canadian workers.Methods: A survey was administered to 1,835 workers employed more than 15 hrs/week in workplaces with at least five employees. Adjusted logistic models were fitted for three specific and one overall measure of workplace vulnerability developed based on hazard exposure and access to protective OH&amp;S policies and procedures, awareness of employment rights and responsibilities, and workplace empowerment.Results: More than one third of the sample experienced some OH&amp;S vulnerability. The type and magnitude of vulnerability varied by labor market sub-group. Younger workers and those in smaller workplaces experienced signficantly higher odds of multiple types of vulnerability. Temporary workers reported elevated odds of overall, awareness- and empowerment-related vulnerability, while respondents born outside of Canada had significantly higher odds of awareness vulnerability.Conclusion: Knowing how labor market sub-groups experience different types of vulnerability can inform better-tailored primary prevention interventions.<br /

ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice

Background & Aims We investigated whether ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) is involved in development of hepatocellular carcinoma (HCC). Methods We analyzed clinical and gene expression data from The Cancer Genome Atlas. Albumin-Cre (HepWT) mice and mice with hepatocyte-specific disruption of Abl1 (HepAbl–/– mice) were given hydrodynamic injections of plasmids encoding the Sleeping Beauty transposase and transposons with the MET gene and a catenin β1 gene with an N-terminal truncation, which induces development of liver tumors. Some mice were then gavaged with the ABL1 inhibitor nilotinib or vehicle (control) daily for 4 weeks. We knocked down ABL1 with short hairpin RNAs in Hep3B and Huh7 HCC cells and analyzed their proliferation and growth as xenograft tumors in mice. We performed RNA sequencing and gene set enrichment analysis of tumors. We knocked down or overexpressed NOTCH1 and MYC in HCC cells and analyzed proliferation. We measured levels of phosphorylated ABL1, MYC, and NOTCH1 by immunohistochemical analysis of an HCC tissue microarray. Results HCC tissues had higher levels of ABL1 than non-tumor liver tissues, which correlated with shorter survival times of patients. HepWT mice with the MET and catenin β1 transposons developed liver tumors and survived a median 64 days; HepAbl–/– mice with these transposons developed tumors that were 50% smaller and survived a median 81 days. Knockdown of ABL1 in human HCC cells reduced proliferation, growth as xenograft tumors in mice, and expression of MYC, which reduced expression of NOTCH1. Knockdown of NOTCH1 or MYC in HCC cells significantly reduced cell growth. NOTCH1 or MYC overexpression in human HCC cells promoted proliferation and rescued the phenotype caused by ABL1 knockdown. The level of phosphorylated (activated) ABL1 correlated with levels of MYC and NOTCH1 in human HCC specimens. Nilotinib decreased expression of MYC and NOTCH1 in HCC cell lines, reduced the growth of xenograft tumors in mice, and slowed growth of liver tumors in mice with MET and catenin β1 transposons, reducing tumor levels of MYC and NOTCH1. Conclusions HCC samples have increased levels of ABL1 compared with nontumor liver tissues, and increased levels of ABL1 correlate with shorter survival times of patients. Loss or inhibition of ABL1 reduces proliferation of HCC cells and slows growth of liver tumors in mice. Inhibitors of ABL1 might be used for treatment of HCC

Single or double headed capsules for the investigation of suspected small bowel bleeding: Are two heads better than one

BackgroundCapsule endoscopy is now the accepted first line investigation for suspected small bowel (SB) bleeding. Recent evidence suggests the diagnostic yield for SB pathology may be higher for tailored double headed (DH) SB capsules. Whether other forms of bidirectional capsules offer a similar advantage is less clear.AimTo compare the efficacy of single headed versus bidirectional capsules in detecting pathology in patients with suspected small bowel bleeding.MethodsA single centre prospective comparison study was conducted over an 8 month period in a tertiary care hospital. Patients referred with overt or suspected SB bleeding were assigned to either SB3 Medtronic SB capsule (SH) during the initial four months or PillCam Colon 2 Medtronic capsule (DH) during the subsequent four months. Studies were analysed by trained Capsule Endoscopists and approved by our institutions capsule review board. Findings were compared between SH and DH capsules using a chi2 or t-test as appropriate. A p value of &lt;0.05 was considered significant.Results201 subjects were included, mean age 61.8 years, 90 (45%) male. Majority referred with occult bleeding, 153 (76%). DH and SH capsule used in 100 and 101 cases, respectively. 90% (n=181) capsules were complete and overall diagnostic yield was 57% (n=114). Diagnostic yield was similar between both groups - DH 53% (n=53), SH 60% (n=61). Positive finding in overt bleeding; SH 85% (n=22) versus DH 50% (n=11), p&lt;0.02. SH capsules more frequently detected SB inflammation, 27 (27%) versus 9 (9%), p&lt;0.002. More patients had another diagnosis in the DH (19) than the SH (9), p&lt;0.04, the majority were type 1a vascular lesions, “red spots” or diminutive colonic polyps.ConclusionSingle head and double head capsules perform similary in terms of diagnostic yield overall. This supports the continued use of standard small bowel capsules for investigation of the small bowel

Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study Cohort: Does Race or Ethnicity Moderate Findings?

Background During the COVID-19 pandemic in the United States, mental health among youth has been negatively affected. Youth with a history of adverse childhood experiences (ACEs), as well as youth from minoritized racial-ethnic backgrounds, may be especially vulnerable to experiencing COVID-19–related distress. The aims of this study are to examine whether exposure to pre-pandemic ACEs predicts mental health during the COVID-19 pandemic in youth and whether racial-ethnic background moderates these effects. Methods From May to August 2020, 7983 youths (mean age, 12.5 years; range, 10.6–14.6 years) in the Adolescent Brain Cognitive Development (ABCD) Study completed at least one of three online surveys measuring the impact of the pandemic on their mental health. Data were evaluated in relation to youths\u27 pre-pandemic mental health and ACEs. Results Pre-pandemic ACE history significantly predicted poorer mental health across all outcomes and greater COVID-19–related stress and impact of fears on well-being. Youths reported improved mental health during the pandemic (from May to August 2020). While reporting similar levels of mental health, youths from minoritized racial-ethnic backgrounds had elevated COVID-19–related worry, stress, and impact on well-being. Race and ethnicity generally did not moderate ACE effects. Older youths, girls, and those with greater pre-pandemic internalizing symptoms also reported greater mental health symptoms. Conclusions Youths who experienced greater childhood adversity reported greater negative affect and COVID-19–related distress during the pandemic. Although they reported generally better mood, Asian American, Black, and multiracial youths reported greater COVID-19–related distress and experienced COVID-19–related discrimination compared with non-Hispanic White youths, highlighting potential health disparities

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Probing the Links between Political Economy and Non-Traditional Security: Themes, Approaches, and Instruments

This is a pre-print of an article published in International Politics. The definitive publisher-authenticated version of: Hameiri, Shahar, and Lee Jones. "Probing the links between political economy and non-traditional security: Themes, approaches and instruments." International Politics (2015), is available online at: http://dx.doi.org/10.1057/ip.2015.1In recent decades, the security agenda for states and international organisations has expanded dramatically to include a range of ‘non-traditional’, transnational security issues. It is often suggested that globalisation has been a key driver for the emergence or intensification of these problems, but, surprisingly, little sustained scholarly effort has been made to examine the link between responses to the new security agenda and the changing political economy. This curious neglect largely reflects the mutual blind-spots of the sub-disciplines of International Security Studies and International Political Economy, coupled with the dominance of approaches that tend to neglect economic factors. This special issue, which this article introduces, aims to overcome this significant gap. In particular, it focuses on three key themes: the broad relationship between security and the political economy; what is being secured in the name of security, and how this has changed; and how things are being secured – what modes of governance have emerged to manage security problems. In all of these areas, the contributions point to the crucial role of the state in translating shifting state-economy relations to new security definitions and practices

Expression of Genes Encoding Multi-Transmembrane Proteins in Specific Primate Taste Cell Populations

BACKGROUND: Using fungiform (FG) and circumvallate (CV) taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive), sour cells (PKD2L1-positive), as well as other taste cell populations. Transmembrane protein 44 (TMEM44), a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1), a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1), a calcium-binding transmembrane protein; and anoctamin 7 (ANO7), a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B), a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins expressed in primate taste buds provides new insights into the processes of taste cell development, signal transduction, and information coding. Discrete taste cell populations exhibit highly specific gene expression patterns, supporting a model whereby each mature taste receptor cell is responsible for sensing, transmitting, and coding a specific taste quality

Comparing regional organizations in global multilateral institutions:ASEAN, the EU and the UN

Structural change brought about by the end of the Cold War and accelerated globalisation have transformed the global environment. A global governance complex is emerging, characterised by an ever-greater functional and regulatory role for multilateral organisations such as the United Nations (UN) and its associated agencies. The evolving global governance framework has created opportunities for regional organisations to participate as actors within the UN (and other multilateral institutions). This article compares the European Union (EU) and Association of Southeast Asian Nations (ASEAN) as actors within the UN network. It begins by extrapolating framework conditions for the emergence of EU and ASEAN actorness from the literature. The core argument of this article is that EU and ASEAN actorness is evolving in two succinct stages: Changes in the global environment create opportunities for the participation of regional organisations in global governance institutions, exposing representation and cohesion problems at the regional level. In response, ASEAN and the EU have initiated processes of institutional adaptation