Inflammation is Associated With Subclinical Atherosclerosis

Cardiovascular disease increases with age and menopause. Atherosclerosis directly contributes to cardiovascular disease and subclinical markers of atherosclerosis are noninvasive methods that help to detect early vascular changes. Thus, risk factors associated with markers of subclinical atherosclerosis may be targeted for interventions in individuals at high risk of developing cardiovascular disease. C-Reactive Protein (CRP), a marker of inflammation, has been found to be associated with cardiovascular events in a large number of populations. However, studies examining the association between CRP and markers of subclinical atherosclerosis have been limited. The cross-sectional association between CRP and central arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), was tested in a biracial (Caucasian and Black) cohort of 154 women transitioning through menopause within the Study of Women's Health Across the Nation (mean age 50.8 ± 2.6; 44.2% Black). After adjustment for age, systolic blood pressure, ethnicity, study site, waist circumference, diastolic blood pressure, and physical activity, the mean pulse wave velocity increased with increasing CRP tertiles (758.5 cm/s, 784.5 cm/s, 861.7 cm/s; p for trend = .01). Furthermore, the association was stronger in women later in their transition compared to women earlier in their transition (p for interaction = .02). The cross-sectional association between CRP and systemic arterial stiffness, assessed by brachial artery distensibility, was tested in 1069 women of the same cohort (mean age 53.6 ± 2.6 years). After adjustment for confounders, the mean distensibility decreased with increasing tertiles of CRP (p for trend = .001). This pattern was similar in women of different ethnic groups and stages of the menopausal transition. The association between CRP and three year incident peripheral arterial disease (PAD), assessed by the ankle-brachial index (ABI), was tested in a biracial (Caucasian and Black) cohort of 1918 older adults within the Health, Aging, Body, and Composition Study (mean age 73.6±2.9; 40.3% Black). Participants in the top tertile of CRP had an increased odds of developing PAD compared to those in the bottom tertile (OR=1.87, 95% CI= 1.22 to 2.88). Given the high prevalence of cardiovascular disease, finding risk factors associated with early vascular changes in high risk populations is of public health importance

Regulation of Monocyte-Macrophage Responses in Cirrhosis—Role of Innate Immune Programming and Checkpoint Receptors

Many aspects of the innate immune system have been studied in cirrhosis, and abnormalities have been described supporting both a pro-inflammatory and anti-inflammatory phenotype of myeloid cells. However, the findings of these studies vary by stage of disease and methodology. The recent description of the syndrome of acute-on-chronic liver failure (ACLF) has refined our understanding of the natural history of cirrhosis. In this context, we review the regulatory mechanisms at play that contribute to the immune abnormalities described in advanced liver disease. Specifically, we review the evidence for epigenetic mechanisms regulating monocyte phenotype, and the role of checkpoint receptors on regulating innate and adaptive immune cell function

Vaccination in liver diseases and liver Transplantation: Recommendations, implications and opportunities in the post-covid era

The interest in vaccination efficacy and toxicity has surged following the Covid-19 pandemic. Immune responses to several vaccines have been shown to be suboptimal in patients with chronic liver disease (CLD) or post-liver transplant (LT), as a consequence of cirrhosis-associated immune dysfunction (CAID) or post-LT immunosuppression respectively. Accordingly, vaccine-preventable infections may be more common or severe than in the general population. The Covid-19 pandemic has greatly accelerated research and development into vaccination technology and platforms, which will have spillover benefits for liver patients. The aims of this review are: (i) to discuss the impact of vaccine-preventable infections on CLD and post-LT patients, (ii) to appraise current evidence supporting vaccination strategies, and (iii) to provide some insight into recent developments relevant for liver patients

Association of thirty-year alcohol consumption typologies and fatty liver: Findings from a large population cohort study.

OBJECTIVE: To evaluate the longitudinal relationship between repeated measures of alcohol consumption and risk of developing fatty liver. PATIENTS AND METHODS: This study includes 5407 men and women from a British population-based cohort, the Whitehall II study of civil servants, who self-reported alcohol consumption by questionnaire over approximately 30 years (1985-1989 through to 2012-2013). Drinking typologies during midlife were linked to measures of fatty liver (the fatty liver index, FLI) when participants were in older age (age range 60-84 years) and adjusted for age, socio-economic position, ethnicity, and smoking. RESULTS: Those who consistently drank heavily had two-fold higher odds of increased FLI compared to stable low-risk moderate drinkers after adjustment for covariates (men: OR = 2.04, 95%CI = 1.53-2.74; women: OR = 2.24, 95%CI = 1.08-4.55). Former drinkers also had an increased FLI compared to low-risk drinkers (men: OR = 2.09, 95%CI = 1.55-2.85; women: OR = 1.68, 95%CI = 1.08-2.67). There were non-significant differences in FLI between non-drinkers and stable low-risk drinkers. Among women, there was no increased risk for current heavy drinkers in cross sectional analyses. CONCLUSION: Drinking habits among adults during midlife affect the development of fatty liver, and sustained heavy drinking is associated with an increased FLI compared to stable low-risk drinkers. After the exclusion of former drinkers, there was no difference between non-drinkers and low-risk drinkers, which does not support a protective effect on fatty liver from low-risk drinking. Cross-sectional analyses among women did not find an increased risk of heavy drinking compared to low-risk drinkers, thus highlighting the need to take a longitudinal approach.AB, DON and SB were supported by grants from the European Research Council (ERC-StG-2012- 309337_AlcoholLifecourse, PI: Britton, http://www.ucl.ac.uk/alcohol-lifecourse) and UK Medical Research Council/Alcohol Research UK (MR/M006638/1). The UK Medical Research Council (MR/K013351/1; G0902037), British Heart Foundation (RG/13/2/30098), and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II Study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Suspected Intestinal Tuberculosis Might Be Crohn's Disease

In this case report we provide evidence that supports a link between mycobacteria and Crohn's disease. The patient in question, KG, presented on three separate occasions over a ten years period with features suggestive of intestinal tuberculosis. He was treated successfully on each occasion with antimycobacterial drugs. When he presented a fourth time with the same symptoms, he was diagnosed with Crohn's disease based on findings from endoscopy, histology and CT. Subsequently he was treated with a course of steroids and made a full recovery. This case adds weight to the theory that mycobateria has an aetiological role in Crohn's disease

Leading Large N Modification of QCD_2 on a Cylinder by Dynamical Fermions

We consider 2-dimensional QCD on a cylinder, where space is a circle. We find the ground state of the system in case of massless quarks in a $1/N$ expansion. We find that coupling to fermions nontrivially modifies the large $N$ saddle point of the gauge theory due to the phenomenon of `decompactification' of eigenvalues of the gauge field. We calculate the vacuum energy and the vacuum expectation value of the Wilson loop operator both of which show a nontrivial dependence on the number of quarks flavours at the leading order in $1/N$.Comment: 24 pages, TIFR-TH-94/3

A permeability assay for mouse intestinal organoids

Here, we describe an assay for intestinal permeability in mouse intestinal organoids, although this may also be adapted for other species. Propidium iodide (PI) does not penetrate intact biological membranes and thus cannot enter the lumen of intact organoids. Passage of PI within the lumen can be induced by tight junction disruption or epithelial cell death. This technique measures PI-stained extruded dead cells within the organoid lumen to analyze the effect of insults, toxins, or treatments on intestinal organoid permeability

Towards a synthesis of C<SUB>3</SUB>-tribenzohemifullerene, a C<SUB>42</SUB>H<SUB>18</SUB> fragment of [60]fullerene

A short, simple synthesis of C3-trinaphthotriphenylene 6, C42H24, from readily available precursors involving threefold Wittig reactions and threefold oxidative photocyclizations is reported; flash vacuum pyrolysis of 6 in the quest for C3-tribenzohemifullerene 5, C42H18, has so far led only to the formation of monobridged product 12, C42H22

SARS-CoV-2 infection and liver involvement

The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless, the mechanism of liver injury in SARS-CoV-2 infection remains largely unknown. This review aims to provide an overview of the mechanisms by which SARS-CoV-2 induces liver injury, and the impact of COVID-19 on cirrhosis, alcohol-related liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, hepatitis B and C virus infection, liver-transplant recipients and patients with hepatocellular carcinoma. Finally, emerging data on vaccination in liver diseases is discussed, to help inform public health policy