bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice

Helicobacter infection causes a chronic superficial gastritis that in some cases progresses via atrophic gastritis to adenocarcinoma. Proapoptotic bak has been shown to regulate radiation-induced apoptosis in the stomach and colon and also susceptibility to colorectal carcinogenesis in vivo. Therefore we investigated the gastric mucosal pathology following H. felis infection in bak-null mice at 6 or 48 wk postinfection. Primary gastric gland culture from bak-null mice was also used to assess the effects of bak deletion on IFN-γ-, TNF-α-, or IL-1β-induced apoptosis. bak-null gastric corpus glands were longer, had increased epithelial Ki-67 expression, and contained fewer parietal and enteroendocrine cells compared with the wild type (wt). In wt mice, bak was expressed at the luminal surface of gastric corpus glands, and this increased 2 wk post-H. felis infection. Apoptotic cell numbers were decreased in bak-null corpus 6 and 48 wk following infection and in primary gland cultures following cytokine administration. Increased gastric epithelial Ki-67 labeling index was observed in C57BL/6 mice after H. felis infection, whereas no such increase was detected in bak-null mice. More severe gastric atrophy was observed in bak-null compared with C57BL/6 mice 6 and 48 wk postinfection, and 76% of bak-null compared with 25% of C57BL/6 mice showed evidence of gastric dysplasia following long-term infection. Collectively, bak therefore regulates gastric epithelial cell apoptosis, proliferation, differentiation, mucosal thickness, and susceptibility to gastric atrophy and dysplasia following H. felis infection

Is climate change causing the range contraction of Cape Rock-jumpers (\u3ci\u3eChaetops frenatus\u3c/i\u3e)?

Species distribution models often suggest strong links between climate and species\u27 distribution boundaries and project large distribution shifts in response to climate change. However, attributing distribution shifts to climate change requires more than correlative models. One idea is to examine correlates of the processes that cause distribution shifts, namely colonization and local extinction, by using dynamic occupancy models. The Cape Rock-jumper (Chaetops frenatus) has disappeared over most of its distribution where temperatures are the highest. We used dynamic occupancy models to analyse Cape Rock-jumper distribution with respect to climate (mean temperature and precipitation over the warmest annual quarter), vegetation (proportion of natural vegetation, fynbos) and land-use type (protected areas). Detection/non-detection data were collected over two phases of the Southern African Bird Atlas Project (SABAP): 1987–1991 (SABAP1) and 2008–2014 (SABAP2). The model described the contraction of the Cape Rock-jumper\u27s distribution between SABAP1 and SABAP2 well. Occupancy probability during SABAP1 increased with the proportion of fynbos and protected area per grid cell, and decreased with increases in mean temperature and precipitation over the warmest annual quarter. Mean extinction probability increased with mean temperature and precipitation over the warmest annual quarter, although the associated confidence intervals were wide. Nonetheless, our results showed a clear correlation between climate and the distribution boundaries of the Cape Rock-jumper, and in particular, the species\u27 aversion for higher temperatures. The data were less conclusive on whether the observed range contraction was linked to climate change or not. Examining the processes underlying distribution shifts requires large datasets and should lead to a better understanding of the drivers of these shifts

Oral iron exacerbates colitis and influences the intestinal microbiome

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS

Vaccination against COVID-19 reduced the mortality risk of COVID-positive hip fracture patients to baseline levels:the nationwide data-linked IMPACT Protect study

SummaryThis nationwide study used data-linked records to assess the effect of COVID-19 vaccination among hip fracture patients. Vaccination was associated with a lower risk of contracting COVID-19 and, among COVID-positive patients, it reduced the mortality risk to that of COVID-negative patients. This provides essential data for future communicable disease outbreaks.PurposeCOVID-19 confers a three-fold increased mortality risk among hip fracture patients. The aims were to investigate whether vaccination was associated with: i) lower mortality risk, and ii) lower likelihood of contracting COVID-19 within 30 days of fracture.MethodsThis nationwide cohort study included all patients aged &gt; 50 years that sustained a hip fracture in Scotland between 01/03/20–31/12/21. Data from the Scottish Hip Fracture Audit were collected and included: demographics, injury and management variables, discharge destination, and 30-day mortality status. These variables were linked to government-managed population level records of COVID-19 vaccination and laboratory testing.ResultsThere were 13,345 patients with a median age of 82.0 years (IQR 74.0–88.0), and 9329/13345 (69.9%) were female. Of 3022/13345 (22.6%) patients diagnosed with COVID-19, 606/13345 (4.5%) were COVID-positive within 30 days of fracture. Multivariable logistic regression demonstrated that vaccinated patients were less likely to be COVID-positive (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.34–0.48, p &lt; 0.001) than unvaccinated patients. 30-day mortality rate was higher for COVID-positive than COVID-negative patients (15.8% vs 7.9%, p &lt; 0.001). Controlling for confounders (age, sex, comorbidity, deprivation, pre-fracture residence), unvaccinated patients with COVID-19 had a greater mortality risk than COVID-negative patients (OR 2.77, CI 2.12–3.62, p &lt; 0.001), but vaccinated COVID19-positive patients were not at increased risk of death (OR 0.93, CI 0.53–1.60, p = 0.783).ConclusionVaccination was associated with lower COVID-19 infection risk. Vaccinated COVID-positive patients had a similar mortality risk to COVID-negative patients, suggesting a reduced severity of infection. This study demonstrates the efficacy of vaccination in this vulnerable patient group, and presents data that will be valid in the management of future outbreaks

Intestinal Preparation Techniques for Histological Analysis in the Mouse

The murine intestinal tract represents a difficult organ system to study due to its long convoluted tubular structure, narrow diameter, and delicate mucosa which undergoes rapid changes after sampling prior to fixation. These features do not make for easy histological analysis as rapid fixation in situ, or after simple removal without careful dissection, results in poor postfixation tissue handling and limited options for high quality histological sections. Collecting meaningful quantitative data by analysis of this tissue is further complicated by the anatomical changes in structure along its length. This article describes two methods of intestinal sampling at necropsy that allow systematic histological analysis of the entire intestinal tract, either through examination of cross sections (circumferences) by the gut bundling technique or longitudinal sections by the adapted Swiss roll technique, together with basic methods for data collection

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Nitrogen cycle disruption through the application of de-icing salts on upland highways

It is hypothesized that episodic introductions of road salt severely disrupt the soil nitrogen cycle at a range of spatial and temporal scales. A field-scale study has confirmed impacts on the nitrogen cycle in soil, soil solution and river samples. There is evidence that ammonium-N retention on cation exchange sites has been reduced by the presence of sodium ions, and that ammonium-N has been flushed from the exchange sites. Increases in soil pH have been caused in naturally acidic uplands. These have enhanced mineralization of organic-N, especially nitrification, leading to a reduction in the mineralizable-N pool of roadside soils. There is evidence to support the hypothesis that organic matter content has been lowered over decades either through desorption or dispersal processes. Multiple drivers are identified that contribute to the disruption of nitrogen cycling processes, but their relative importance is difficult to quantify unequivocally. The influence of road salt on soil and soil solution declines with distance from the highway, but impacts on water chemistry in a local stream are still strongly evident at some distance from the road

Assessing recombinant vaccinia virus as a delivery system for fertility control vaccines in the brushtail possum (Trichosurus vulpecula)

Duckworth, J., Cross, M., Fleming, S., Scobie, S., Whelan, E., Prada, D., Mercer, A., Cowan, P