Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice.

Background: Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the in vivo efficacy and mechanism of disulfiram's antiatherosclerotic activity is yet to be explored.

Methods And Results: We used human/mouse macrophages, endothelial cells, and smooth muscle cells and a hyperlipidemic mouse model of atherosclerosis to determine disulfiram antiatherosclerotic efficacy and mechanism.

Differential physiological and production responses of C3 and C4 crops to climate factor interactions.

This study examined the effect of the interactions of key factors associated with predicted climate change (increased temperature, and drought) and elevated CO concentration on C3 and C4 crop representatives, barley and sorghum. The effect of two levels of atmospheric CO concentration (400 and 800 ppm), three levels of temperature regime (21/7, 26/12 and 33/19°C) and two regimes of water availability (simulation of drought by gradual reduction of irrigation and well-watered control) in all combinations was investigated in a pot experiment within growth chambers for barley variety Bojos and sorghum variety Ruby. Due to differences in photosynthetic metabolism in C3 barley and C4 sorghum, leading to different responses to elevated CO concentration, we hypothesized mitigation of the negative drought impact in barley under elevated CO concentration and, conversely, improved performance of sorghum at high temperatures.

Decreased FAM13B Expression Increases Atrial Fibrillation Susceptibility by Regulating Sodium Current and Calcium Handling.

A specific genetic variant associated with atrial fibrillation risk, rs17171731, was identified as a regulatory variant responsible for controlling expression. The atrial fibrillation risk allele decreases expression, whose knockdown alters the expression of many genes in stem cell-derived cardiomyocytes, including , and led to pro-arrhythmogenic changes in the late sodium current and Ca cycling. knockout mice had increased P-wave and QT interval duration and were more susceptible to pacing-induced arrhythmias vs control mice.

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice.

Pyroptosis executor Gasdermin (GsdmD) promotes atherosclerosis in mice and humans. Disulfiram (DSF) was recently shown to potently inhibit GsdmD, but the in-vivo efficacy and mechanism of DSF's anti-atherosclerotic activity is yet to be explored. We used human/mouse macrophages and a hyperlipidemic mouse model of atherosclerosis to determine DSF anti-atherosclerotic efficacy and mechanism.

Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study.

Background: Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis.

Impavido attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.

Impavido (Miltefosine) is an FDA-approved drug for treating leishmaniasis and primary amebic meningoencephalitis. We have shown previously that Miltefosine increased cholesterol release and dampened Nlrp3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages, and attenuated Nlrp3 inflammasome assembly in mice.

Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice.

The activities of the NLRP3 and AIM2 inflammasomes and Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard lung cancer progression. Using a metastatic Lewis lung carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD) mice form significantly fewer cancer foci in lungs, exhibit markedly decreased lung cancer metastasis, and show a significant ∼50% increase in median survival rate. The cleaved forms of GsdmD and IL-1β were detected in lung tumor tissue, indicating inflammasome activity in lung tumor microenvironment (TME).

Climate change alters impacts of extreme climate events on a tropical perennial tree crop.

Anthropogenic climate change causes more frequent and intense fluctuations in the El Niño Southern Oscillation (ENSO). Understanding the effects of ENSO on agricultural systems is crucial for predicting and ameliorating impacts on lives and livelihoods, particularly in perennial tree crops, which may show both instantaneous and delayed responses. Using cocoa production in Ghana as a model system, we analyse the impact of ENSO on annual production and climate over the last 70 years.

Single and interactive effects of variables associated with climate change on wheat metabolome.

One of the key challenges linked with future food and nutritional security is to evaluate the interactive effect of climate variables on plants' growth, fitness, and yield parameters. These interactions may lead to unique shifts in the morphological, physiological, gene expression, or metabolite accumulation patterns, leading to an adaptation response that is specific to future climate scenarios. To understand such changes, we exposed spring wheat to 7 regimes (3 single and 4 combined climate treatments) composed of elevated temperature, the enhanced concentration of CO, and progressive drought stress corresponding to the predicted climate of the year 2100.

The association between nurses' physical activity counselling and patients' perceptions of care quality in a primary care facility in Ghana.

Many countries including Ghana and Australia have adopted physical activity (PA) counselling in healthcare as a public health improvement strategy. Even so, more evidence is needed to improve clinical PA counselling among clinicians, including nurses. This study examined the association between nurses' physical activity counselling (NPAC) and patients' perceptions of care quality.

The dissertation journey during the COVID-19 pandemic: Crisis or opportunity?

Despite dissertation's significance in enhancing the quality of scholarly outputs in tourism and hospitality fields, insufficient research investigates the challenges and disruptions students experience amidst a public health crisis. This study aims to fill the research gaps and integrate attribution and self-efficacy theories to understand how the COVID-19 pandemic influences students' decision-making and behaviours during the dissertation writing process. Qualitative exploration with 15 graduate students was conducted.

Oxidant resistant human apolipoprotein A-I functions similarly to the unmodified human isoform in delaying atherosclerosis progression and promoting atherosclerosis regression in hyperlipidemic mice.

Background: Transgenic overexpression of apolipoprotein A-I (apoA1) has been shown to delay atherosclerosis lesion progression and promote lesion regression in mouse models; however, apoA1 is subject to oxidation by myeloperoxidase (MPO) and loss of function. The activity of oxidant resistant human apoA1 was compared to unmodified human apoA1 in mouse models of atherosclerosis progression and regression.

Methods And Results: Human apoA1 and the MPO oxidant resistant 4WF isoform transgenic mice were bred to LDL receptor deficient (LDLr KO) mice and fed a western-type diet.

Fine Mapping of the Mouse Locus Yields Three Atherosclerosis Modifying Sub-Regions.

A mouse strain intercross between AKR/J and DBA/2J mice identified three replicated atherosclerosis quantitative trait loci (QTLs). Our objective was to fine map mouse atherosclerosis modifier genes within a genomic region known to affect lesion development in apoE-deficient () mice. We dissected the QTL on the distal end of chromosome 2 by breeding a panel of congenic strains and measuring aortic root lesion area in 16-week-old male and female mice fed regular laboratory diets.

Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis.

Activation of inflammasomes, such as Nlrp3 and AIM2, can exacerbate atherosclerosis in mice and humans. Gasdermin D (GsdmD) serves as a final executor of inflammasome activity, by generating membrane pores for the release of mature Interleukin-1beta (IL-1β). Inflammation dampens reverse cholesterol transport (RCT) and promotes atherogenesis, while anti-IL-1β antibodies were shown to reduce cardiovascular disease in humans.

Soat1 mediates the mouse strain effects on cholesterol loading-induced endoplasmic reticulum stress and CHOP expression in macrophages.

We previously demonstrated that AKR vs. DBA/2 mouse bone marrow derived macrophages have higher levels of free cholesterol and lower levels of esterified cholesterol after cholesterol loading, and that AKR, but not DBA/2, macrophages induced C/EBP homologous protein (CHOP) expression after cholesterol loading. We earlier determined that the free and esterified cholesterol level effect is due to a truncation in the sterol O-acyltransferase 1 (Soat1) gene, encoding acetyl-coenzyme A acetyltransferase 1 (ACAT1).

The Influence of Physicians' Physical Activity Prescription on Indicators of Health Service Quality.

Introduction: Many researchers are of the opinion that the incorporation of physical activity prescription (PAP) into healthcare is a move that can add value to healthcare, but there are others who think this move would rather disrupt clinical practice. This study, therefore, examined the influence of physicians' PAP (PPAP) on healthcare quality indicators.

Methods: The study adopted a correlational approach and was performed at a primary care facility.

Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice.

High-density lipoprotein (HDL) metabolism is facilitated in part by scavenger receptor class B, type 1 (SR-B1) that mediates HDL uptake into cells. Higher levels of HDL have been associated with protection in other diseases, however, its role in prostate cancer is not definitive. SR-B1 is up-regulated in prostate cancer tissue, suggesting a possible role of this receptor in tumor progression.

Serological evidence of infection in slaughtered sheep and goats at Kumasi Abattoir, Ghana.

Q fever, caused by , is an important zoonosis worldwide. Q fever is documented in many parts of the world; however, information on the disease in Ghana is scanty. This study was therefore conducted to provide evidence of exposure of sheep and goats slaughtered at the Kumasi Abattoir to .