Search

Abstract Global fits explore different parameter regions of a given model and apply constraints obtained at many energy scales. This makes it challenging to perform global fits of simplified models, which may not be valid at high energies. In this study, we derive a unitarity bound for a simplified vector dark matter model with an s-channel vector mediator and apply it to global fits of this model with GAMBIT in order to correctly interpret missing energy searches at the LHC. Two parameter space regions emerge as consistent with all experimental constraints, corresponding to different annihilation modes of the dark matter. We show that although these models are subject to strong validity constraints, they are currently most strongly constrained by measurements less sensitive to the high-energy behaviour of the theory. Understanding when these models cannot be consistently studied will become increasingly relevant as they are applied to LHC Run 3 data.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6–9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Abstract Using the GAMBIT global fitting framework, we constrain the MSSM with an eV-scale gravitino as the lightest supersymmetric particle, and the six electroweakinos (neutralinos and charginos) as the only other light new states. We combine 15 ATLAS and 12 CMS searches at 13 TeV, along with a large collection of ATLAS and CMS measurements of Standard Model signatures. This model, which we refer to as the $${{\tilde{G}}}$$ G ~ -EWMSSM, exhibits quite varied collider phenomenology due to its many permitted electroweakino production processes and decay modes. Characteristic $${{\tilde{G}}}$$ G ~ -EWMSSM signal events have two or more Standard Model bosons and missing energy due to the escaping gravitinos. While much of the $${{\tilde{G}}}$$ G ~ -EWMSSM parameter space is excluded, we find several viable parameter regions that predict phenomenologically rich scenarios with multiple neutralinos and charginos within the kinematic reach of the LHC during Run 3, or the High Luminosity LHC. In particular, we identify scenarios with Higgsino-dominated electroweakinos as light as 140 GeV that are consistent with our combined set of collider searches and measurements. The full set of $${{\tilde{G}}}$$ G ~ -EWMSSM parameter samples and GAMBIT input files generated for this work is available via Zenodo.

Background: B-cell receptor-associated protein 31 (BCAP31) has protective effects against alveolar epithelial type II cells (AECII) damage by inhibiting mitochondrial injury in acute lung injury (ALI) induced by lipopolysaccharide (LPS), whereas the precise mechanism is still unclear. It is known that PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy can remove damaged mitochondria selectively, which may be involved in BCAP31 protection against mitochondrial injury. Methods: In the current study, ALI mice models were established by using surfactant protein C (Sftpc)-BCAP31 transgenic mice (BCAP31TG mice) and AECII-specific BCAP31 knockout mice (BCAP31CKO mice) treated with LPS. Results: BCAP31 expression in lung tissue and AECII were inhibited in ALI mice. Under LPS challenge, lower level of BCAP31 was found to correlate positively with pathological injury of the lung, respiratory dysfunction, mortality rates, inflammation response, and AECII damage. Further study showed that down-regulation of BCAP31 induced decreased phosphorylation of PINK1 via reduced binding to PINK1, thereby restraining PINK1/Parkin-mediated mitophagy. Down-regulation of mitophagy promoted mitochondrial injury, as shown by the increase in mitochondrial permeability transition pore opening rate, together with enhanced mitochondrial reactive oxygen species (mROS), which were accompanied by increased cellular apoptosis and reactive oxygen species (ROS). The increased cellular ROS contributed to the inflammatory response via activation of nuclear factor κB (NF-κB). In contrast, BCAP31 overexpression promoted phosphorylation of PINK1 and PINK1/Parkin-mediated mitophagy, thus blocking the mROS/ROS/NF-κB pathway, favoring a protective condition that ultimately led to the inhibition of AECII apoptosis and inflammatory response in LPS-induced ALI. Conclusion: Ultimately, BCAP31 alleviated ALI by activating PINK1/Parkin-mediated mitophagy and blocking the mROS/ROS/NF-κB pathway in AECII.

A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein–Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.

Aim: The aim is to profile patients with undiagnosed type 2 diabetes (T2D) mellitus in urban communities in South Trinidad, 2019–2020. Settings and Design: This cross-sectional study took place in grocery stores and malls in urban communities, in South Trinidad, from November 2019 to January 2020. Subjects and Methods: Adults between the ages of 40–60, body mass index ≥23 kg/m2; undiagnosed with T2D, and who gave informed consent were enrolled in the study, through convenience sampling (n = 86). The main outcome measures were glycemic states that were assessed using glycated hemoglobin clinical cut points of 0.85 and 19.77% of males with a waist:hip ratio >0.9. Alcohol consumption was linked to higher glycemic states (P = 0.045). However, no statistically significant correlations were found between all other risk factors assessed and glycemic states. Conclusion: There were no statistically significant associations for risk factors, except for alcohol consumption, among glycemic states.

Abstract Background Hypersensitivity pneumonitis (HP) is a common type among all the interstitial lung diseases, and transbronchial lung cryobiopsy is an alternative diagnostic technique for interstitial lung diseases. In this study, we describe the clinical and pathological features of fibrotic hypersensitivity pneumonitis diagnosed with transbronchial lung cryobiopsy (TBLC). Methods A total of 46 diffused parenchyma lung disease (DPLD) patients received TBLC were included in this study. Medical records including medical history spirometry examinations, 6‐min walk test (6MWT) results, high resolution computed tomographic (HRCT) scans, BAL, and histopathology were collected. Results of HRCT and histopathology were compared and classified, especially. Results Sixteen patients were diagnosed with fibrotic HP, the mean age of whom was 56.3 ± 12.1 years, and 62.5% of them were male. Three of the 16 patients had been misdiagnosed as tuberculosis and received antituberculosis medications, five patients had been diagnosed as unclassifiable pulmonary fibrosis, and five patients had been diagnosed as idiopathic pulmonary fibrosis (IPF). Thirteen (81.3%) patients had a normal lymphocyte count in BAL. The pathological features of usual interstitial pneumonia (UIP) were detected in 11 (68.8%) of the cases, poor defined granulomatous was detected in nine (56.3%) of the cases, and bronchiolocentric fibrosis was detected in two (12.5%) of the 16 cases. Conclusions Fibrotic hypersensitivity pneumonitis should be included in differential diagnosis of pulmonary fibrosis. Pathological characteristics of fibrotic hypersensitivity pneumonitis could be demonstrated from cryobiopsy lung tissue. TBLC is recommended as an alternative diagnostic technique, which may improve the specificity of hypersensitivity pneumonia detection, and UIP is the most frequent pathological finding.

Low socioeconomic status (SES) is associated with greater morbidity and increased healthcare resource utilization (HRU) in IBD. We examined whether a financial assistance program (FAP) to improve healthcare access affected outcomes and HRU in a cohort of indigent IBD patients requiring biologics. IBD patients (>18 years) receiving care at a ‘safety-net’ hospital who initiated biologics as outpatients between 1 January 2010 and 1 January 2019 were included. Patients were divided by FAP status. Patients without FAP had Medicare, Medicaid, or commercial insurance. Primary outcomes were steroid-free clinical remission at 6 and 12 months. Secondary outcomes were surgery, hospitalization, and ED utilization. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Decision tree analysis (DTA) was also performed. We included 204 patients with 258 new biologic prescriptions. FAP patients had less complex Crohn’s disease (50.7% vs. 70%, p = 0.033) than non-FAP patients. FAP records indicated fewer prior surgeries (19.6% vs. 38.4% p = 0.003). There were no statistically significant differences in remission rates, disease duration, or days between prescription and receipt of biologics. In multivariable logistic regression, adjusting for baseline demographics and disease severity variables, FAP patients were less likely to undergo surgery (OR: 0.28, 95% CI [0.08–0.91], p = 0.034). DTA suggests that imaging utilization may shed light on surgical differences. We found FAP enrollment was associated with fewer surgeries in a cohort of indigent IBD patients requiring biologics. Further studies are needed to identify interventions to address healthcare disparities in IBD.

Abstract We introduce the GAMBIT Universal Model Machine (GUM), a tool for automatically generating code for the global fitting software framework GAMBIT, based on Lagrangian-level inputs. GUM accepts models written symbolically in FeynRules and SARAH formats, and can use either tool along with MadGraph and CalcHEP to generate GAMBIT model, collider, dark matter, decay and spectrum code, as well as GAMBIT interfaces to corresponding versions of SPheno, micrOMEGAs, Pythia and Vevacious (C ). In this paper we describe the features, methods, usage, pathways, assumptions and current limitations of GUM. We also give a fully worked example, consisting of the addition of a Majorana fermion simplified dark matter model with a scalar mediator to GAMBIT via GUM, and carry out a corresponding fit.

Abstract We assess the status of a wide class of WIMP dark matter (DM) models in light of the latest experimental results using the global fitting framework GAMBIT. We perform a global analysis of effective field theory (EFT) operators describing the interactions between a gauge-singlet Dirac fermion and the Standard Model quarks, the gluons and the photon. In this bottom-up approach, we simultaneously vary the coefficients of 14 such operators up to dimension 7, along with the DM mass, the scale of new physics and several nuisance parameters. Our likelihood functions include the latest data from Planck, direct and indirect detection experiments, and the LHC. For DM masses below 100 GeV, we find that it is impossible to satisfy all constraints simultaneously while maintaining EFT validity at LHC energies. For new physics scales around 1 TeV, our results are influenced by several small excesses in the LHC data and depend on the prescription that we adopt to ensure EFT validity. Furthermore, we find large regions of viable parameter space where the EFT is valid and the relic density can be reproduced, implying that WIMPs can still account for the DM of the universe while being consistent with the latest data.

Abstract Absent in melanoma 2 (AIM2) is a novel member of interferon (IFN)‐inducible PYHIN proteins. In innate immune cells, AIM2 servers as a cytoplasmic double‐stranded DNA sensor, playing a crucial role in the initiation of the innate immune response as a component of the inflammasome. AIM2 expression is increased in patients with systemic lupus erythematosus (SLE), psoriasis, and primary Sjogren's syndrome, indicating that AIM2 might be involved in the pathogenesis of autoimmune diseases. Meanwhile, AIM2 also plays an antitumorigenesis role in an inflammasome independent‐manner. In melanoma, AIM2 is initially identified as a tumor suppressor factor. However, AIM2 is also found to contribute to lung tumorigenesis via the inflammasome‐dependent release of interleukin 1β and regulation of mitochondrial dynamics. Additionally, AIM2 reciprocally dampening the cGAS‐STING pathway causes immunosuppression of macrophages and evasion of antitumor immunity during antibody treatment. To summarize the complicated effect and role of AIM2 in autoimmune diseases and cancers, herein, we provide an overview of the emerging research progress on the function and regulatory pathway of AIM2 in innate and adaptive immune cells, as well as tumor cells, and discuss its pathogenic role in autoimmune diseases, such as SLE, psoriasis, primary Sjogren's syndrome, and cancers, such as melanomas, non‐small‐cell lung cancer, colon cancer, hepatocellular carcinoma, renal carcinoma, and so on, hopefully providing potential therapeutic and diagnostic strategies for clinical use.

The incidence of allergic disorders has been increasing over the past few decades, especially in industrialized countries. Allergies can affect people of any age. The pathogenesis of allergic diseases is complex and involves genetic, epigenetic, and environmental factors, and the response to medication is very variable. For some patients, avoidance is the sole effective therapy, and only when the triggers are identifiable. In recent years, the intestinal microbiota has emerged as a significant contributor to the development of allergic diseases. However, the precise mechanisms related to the effects of the microbiome on the pathogenesis of allergic diseases are unknown. This review summarizes the recent association between allergic disorders and intestinal bacterial dysbiosis, describes the function of gut microbes in allergic disease development from both preclinical and clinical studies, discusses the factors that influence gut microbial diversity and advanced techniques used in microbial analysis. Ultimately, more studies are required to define the host-microbial relationship relevant to allergic disorders and amenable to new therapeutic interventions.

Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system. Clinical presentation of this disease can range from mild manifestations including skin hyperextensibility and joint hypermobility, to more severe complications such as vascular and organ rupture. While there may be accompanying inflammation in some of the subtypes of EDS, the pathogenic mechanisms have not been clearly defined. Thorough evaluation incorporates clinical examination, family history, laboratory testing, and imaging. In recent years, studies have identified multiple gene variants involved in the pathogenesis of specific EDS subtypes as well as elaborate clinical diagnostic criteria and classification models used to differentiate overlapping conditions. The differential diagnosis of EDS includes hypermobility spectrum disorders, Marfan syndrome, Loey-Dietz syndrome, Cutis laxa syndromes, autosomal dominant polycystic kidney disease, osteogenesis Imperfecta Type 1, fibromyalgia, depression, and chronic fatigue syndrome. Surgical treatment is reserved for complications, or emergencies involving vascular or orthopedic injury because of the risk of poor wound healing. Management techniques each have their own consequences and benefits, which will also be discussed in this review article. Patients affected by this spectrum of disorders are impacted both phenotypically and psychosocially, diminishing their quality of life.

Complex regional pain syndrome (CRPS) purports to explain extremity pain accompanied by a variety of subjective complaints, including sensitivity to touch, fatigue, burning sensations, allodynia and signs consistent with voluntary immobilization, including skin changes, edema and trophic changes. By its own definition, CRPS pain is disproportionate to any inciting event or underlying pathology, which means that the syndrome describes non-anatomic and exaggerated symptoms. Although CRPS was coined in the early 1990s, physicians have described unexplained exaggerated pain for centuries. Before a small group of researchers assigned this historical phenomenon with the name CRPS, other physicians in various subspecialties investigated the existence of a common pathophysiologic mechanism but found none. The literature was searched for evidence of a reproducible pathologic mechanism for CRPS. Although some have suggested that CRPS is an autoimmune disease, there is a paucity of evidence to support this. While cytokines such as IL-1β, IL-6 and TNF-α have been detected during the early phases of CRPS, this cannot lead to the conclusion that CRPS is an autoimmune disease, nor that it is an autoinflammatory disorder. Moreover, intravenous immunoglobulin has showed inconsistent results in the treatment of CRPS. On the other hand, CRPS has been found to meet at least three out of four criteria of malingering, which was previously a DSM-IV diagnosis; and its diagnostic criteria are virtually identical to current DSM-5 Functional Neurological Disorder (“FND”), and proposed ICD-11 classification, which includes FND as a distinct neurological diagnosis apart from any psychiatric condition. Unfortunately, the creation of CPRS is not merely misguided brand marketing. It has serious social and health issues. At least in part, the existence of CRPS has led to the labeling of many patients with a diagnosis that allows the inappropriate use of invasive surgery, addictive opioids, and ketamine. The CRPS hypothesis also ignores the nature and purpose of pain, as a symptom of some organic or psychological process. Physicians have long encountered patients who voice symptoms that cannot be biologically explained. Terminology historically used to describe this phenomenon have been medically unexplained symptoms (“MUS”), hysterical, somatic, non-organic, psychogenic, conversion disorder, or dissociative symptoms. The more recent trend describes disorders where there is a functional, rather than structural cause of the symptoms, as “functional disorders.” Physicians report high success treating functional neurological symptoms with reassurance, physiotherapy, and cognitive behavior therapy measured in terms of functional improvement. The CRPS label, however, neither leads to functional improvement in these patients nor resolution of symptoms. Under principles of evidence-based medicine, the CRPS label should be abandoned and the syndrome should simply be considered a subset of FNDs, specifically Functional Pain Disorder; and treated appropriately.

Bullous skin diseases are a group of dermatoses characterized by blisters and bullae in the skin and mucous membranes. The etiology and pathogenesis of bullous skin diseases are not completely clear. The most common are pemphigus and bullous pemphigoid (BP). Autoantibodies play critical roles in their pathogenesis. Abnormalities in the adhesion between keratinocytes in patients with pemphigus leads to acantholysis and formation of intra-epidermal blisters. Anti-desmoglein autoantibodies are present both in the circulation and skin lesions of patients with pemphigus. The deficient adhesion of keratinocytes to the basement membrane in BP patients gives rise to subepidermal blisters. Autoantibodies against the components of hemidesmosome can be detected in BP patients. Many novel therapeutics based on knowledge of the pathogenesis have emerged in recent years. Keywords: Tolerance, Autoimmune skin diseases, Bullous pemphigoid, Autoantibody, Immunosuppression

Polymyositis (PM) and dermatomyositis (DM) are different disease subtypes of idiopathic inflammatory myopathies (IIMs). The main clinical features of PM and DM include progressive symmetric, predominantly proximal muscle weakness. Laboratory findings include elevated creatine kinase (CK), autoantibodies in serum, and inflammatory infiltrates in muscle biopsy. Dermatomyositis can also involve a characteristic skin rash. Both polymyositis and dermatomyositis can present with extramuscular involvement. The causative factor is agnogenic activation of immune system, leading to immunologic attacks on muscle fibers and endomysial capillaries. The treatment of choice is immunosuppression. PM and DM can be distinguished from other IIMs and myopathies by thorough history, physical examinations and laboratory evaluation and adherence to specific and up-to-date diagnosis criteria and classification standards. Treatment is based on correct diagnosis of these conditions. Keywords: Idiopathic inflammatory myopathy, Polymyositis, Dermatomyositis, Diagnosis criteria, Treatment

Abstract Background Homocysteine has been long considered a risk factor for atherosclerosis. However, cardiovascular events cannot be reduced through homocysteine lowering by B vitamin supplements. Although several association studies have reported an elevation of serum homocysteine levels in cardiovascular diseases, the relationship of homocysteine with ST-segment elevation myocardial infarction (STEMI) is not well established. Methods We prospectively enrolled STEMI patients who were consecutively admitted to an intensive care unit following coronary intervention in a single medical center in Taiwan. Control subjects were individuals who presented to the outpatient or emergency department with acute chest pain but subsequently revealed patent coronary arteries by coronary arteriography. The association between serum homocysteine levels and STEMI was investigated. A culture system using human coronary artery endothelial cells was also established to examine the toxic effects of homocysteine at the cellular level. Results Patients with chest pain were divided into two groups. The STEMI group included 56 patients who underwent a primary percutaneous coronary intervention. The control group included 17 subjects with patent coronary arteries. There was no difference in serum homocysteine levels (8.4 ± 2.2 vs. 7.6 ± 1.9 μmol/L, p = 0.142). When stratifying STEMI patients by the Killip classification into higher (Killip III-IV) and lower (Killip I-II) grades, CRP (3.3 ± 4.1 vs. 1.4 ± 2.3 mg/L, p = 0.032), peak creatine kinase (3796 ± 2163 vs. 2305 ± 1822 IU/L, p = 0.023), and SYNTAX scores (20.4 ± 11.1 vs. 14.8 ± 7.6, p = 0.033) were significantly higher in the higher grades, while serum homocysteine levels were similar. Homocysteine was not correlated with WBCs, CRP, or the SYNTAX score in STEMI patients. In a culture system, homocysteine at even a supraphysiological level of 100 μmol/L did not reduce the cell viability of human coronary artery endothelial cells. Conclusions Homocysteine was not elevated in STEMI patients regardless of Killip severity, suggesting that homocysteine is a bystander instead of a causative factor of STEMI. Our study therefore supports the current notion that homocysteine-lowering strategies are not essential in preventing cardiovascular disease.

Abstract Systemic lupus erythematosus (SLE) is a chronic relapsing–remitting autoimmune disease with highly heterogeneous phenotypes. Biomarkers with high sensitivity and specificity are useful for early diagnosis as well as monitoring disease activity and long-term complications. Epigenetics potentially provide novel biomarkers in autoimmune diseases. These may include DNA methylation changes in relevant lupus-prone genes or histone modifications and microRNAs to upregulate and downregulate relevant gene expression. The timing and nature of epigenetic modification provide such changes. In lupus, DNA methylation alterations in cytokine genes, such as IFN-related gene and retrovirus gene, have been found to offer biomarkers for lupus diagnosis. Histone modifications such as histone methylation and acetylation lead to transcriptional alterations of several genes such as PTPN22, LRP1B, and TNFSF70. There are varieties of microRNAs applied as lupus biomarkers, including DNMT1-related microRNAs, renal function-associated microRNAs, microRNAs involved in the immune system, and microRNAs for phenotype classification. Thus, we conclude a wide range of promising roles of epigenetic biomarkers aiding in the diagnosing and monitoring of lupus diseases and the risk of organ damage.

Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE.

Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 μg folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.

Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P

The topic of building related illness came into the public's eye as a major health issue in the mid 1970s, when several cases of pneumonia were found to be associated with an infectious agent in Philadelphia. This agent was subsequently found to be a gram-positive bacterium known as Legionella pneumoniae. During the ensuing 30 years, a myriad of symptom constellations, disorders, clinical syndromes and illnesses have been attributed to indoor living or working environments. Over time, there appeared to be no limit to claims of building related illness, and it was “reported” that almost any kind of clinical symptom, real or imaginary, could be blamed on indoor environments. As society became more and more litigious, many of these disorders were erroneously played out in courtrooms rather than medical offices, creating a circus atmosphere surrounding this class of disorders. With the advent of the internet, as well as other advances in telecommunications, these issues eventually became part of a media frenzy, and all truths could be thrown out the window as issues became more and more decided upon by emotions and unfounded beliefs, rather than scientific data and logical thinking.

Small bowel cancer is a rare, gastrointestinal cancer originating from the small intestines. Carcinogenesis in the jejunum, the middle segment of the small intestines, occurs less commonly than in the duodenum and ileum. Despite the increasing incidences globally, the cancer is still poorly understood, which includes lack of pathological understanding and etiological reasoning, as it seems to exhibit both similarities and differences with other types of cancers. A 76-year-old Asian man was presented with abdominal pain, which was later attributed to an adenocarcinoma in the jejunum. Initial immunoreactive staining results found no connections to colorectal cancer. The microsatellite instability test was further examined by immunohistochemistry which revealed them to be wild-type. From our exome-capture sequencing results, mutations of WRN may be important as they represent the only genetic defect in this jejunal cancer. The patient has since undergone surgical resection of his cancer and is currently being treated with chemotherapy. The pathology, genomic markers, and treatments are described along with literature review.