Rock partridge (Alectoris graeca graeca) population density and trends in central Greece

The rock partridge is an emblematic species of the Greek avifauna and one of the most important game species in the country. The present study, which combined long term in–situ counts with distance sampling methodology in central Greece, indicated that the species’ population in Greece is the highest within its European distribution, in contrast to all prior considerations. Inter–annual trends suggested a stable rock partridge population both within hunting areas and wildlife refuges, whereas during summer, the species presented significantly higher densities in altitudes of more than 1,000 m, most probably due to the effect of predation at lower zones. The similarity of population structure between wildlife refuges and hunting zones along with the stable population trends demonstrate that rock partridge harvest in the country is sustainable

Liver disease is a significant risk factor for cardiovascular outcomes – A UK Biobank study

Background & Aims: Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events. Methods: Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c). Results: A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range:1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03–1.26; p = 0.008), AF (1.30; 1.12–1.51; p <0.001); HF (1.30; 1.09–1.56; p = 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02–1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01–1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001). Conclusion: Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat. Impact and implications: Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers

Poor glycaemic control and ectopic fat deposition mediates the increased risk of non-alcoholic steatohepatitis in high-risk populations with type 2 diabetes: Insights from Bayesian-network modelling.

BackgroundAn estimated 55.5% and 37.3% of people globally with type 2 diabetes (T2D) will have concomitant non-alcoholic fatty liver disease (NAFLD) and the more severe fibroinflammatory stage, non-alcoholic steatohepatitis (NASH). NAFLD and NASH prevalence is projected to increase exponentially over the next 20 years. Bayesian Networks (BNs) offer a powerful tool for modelling uncertainty and visualising complex systems to provide important mechanistic insight.MethodsWe applied BN modelling and probabilistic reasoning to explore the probability of NASH in two extensively phenotyped clinical cohorts: 1) 211 participants with T2D pooled from the MODIFY study & UK Biobank (UKBB) online resource; and 2) 135 participants without T2D from the UKBB. MRI-derived measures of visceral (VAT), subcutaneous (SAT), skeletal muscle (SMI), liver fat (MRI-PDFF), liver fibroinflammatory change (liver cT1) and pancreatic fat (MRI-PDFF) were combined with plasma biomarkers for network construction. NASH was defined according to liver PDFF >5.6% and liver cT1 >800ms. Conditional probability queries were performed to estimate the probability of NASH after fixing the value of specific network variables.ResultsIn the T2D cohort we observed a stepwise increase in the probability of NASH with each obesity classification (normal weight: 13%, overweight: 23%, obese: 36%, severe obesity: 62%). In the T2D and non-T2D cohorts, elevated (vs. normal) VAT conferred a 20% and 1% increase in the probability of NASH, respectively, while elevated SAT caused a 7% increase in NASH risk within the T2D cohort only. In those with T2D, reducing HbA1c from the 'high' to 'low' value reduced the probability of NASH by 22%.ConclusionUsing BNs and probabilistic reasoning to study the probability of NASH, we highlighted the relative contribution of obesity, ectopic fat (VAT and liver) and glycaemic status to increased NASH risk, namely in people with T2D. Such modelling can provide insights into the efficacy and magnitude of public health and pharmacological interventions to reduce the societal burden of NASH

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

BACKGROUND: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID. OBJECTIVES: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection. METHODS: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls. RESULTS: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months. CONCLUSION: CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID. TRIAL REGISTRATION NUMBER: NCT04369807

Homologous and heterologous re-challenge with Salmonella Typhi and Salmonella Paratyphi A in a randomised controlled human infection model

Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior exposure is thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever. Empirical data to support this hypothesis are limited, and there are few studies describing the occurrence of heterologous-protection between these closely related serovars. We performed a challenge-re-challenge study using a controlled human infection model (CHIM) to investigate the extent of infection-derived immunity to Salmonella Typhi or Paratyphi A infection. We recruited healthy volunteers into two groups: naïve volunteers with no prior exposure to Salmonella Typhi/Paratyphi A and volunteers previously-exposed to Salmonella Typhi or Paratyphi A in earlier CHIM studies. Within each group, participants were randomised 1:1 to oral challenge with either Salmonella Typhi (104 CFU) or Paratyphi A (103 CFU). The primary objective was to compare the attack rate between naïve and previously challenged individuals, defined as the proportion of participants per group meeting the diagnostic criteria of temperature of ≥38°C persisting for ≥12 hours and/or S. Typhi/Paratyphi bacteraemia up to day 14 post challenge. The attack-rate in participants who underwent homologous re-challenge with Salmonella Typhi was reduced compared with challenged naïve controls, although this reduction was not statistically significant (12/27[44%] vs. 12/19[63%]; Relative risk 0.70; 95% CI 0.41–1.21; p = 0.24). Homologous re-challenge with Salmonella Paratyphi A also resulted in a lower attack-rate than was seen in challenged naïve controls (3/12[25%] vs. 10/18[56%]; RR0.45; 95% CI 0.16–1.30; p = 0.14). Evidence of protection was supported by a post hoc analysis in which previous exposure was associated with an approximately 36% and 57% reduced risk of typhoid or paratyphoid disease respectively on re-challenge. Individuals who did not develop enteric fever on primary exposure were significantly more likely to be protected on re-challenge, compared with individuals who developed disease on primary exposure. Heterologous re-challenge with Salmonella Typhi or Salmonella Paratyphi A was not associated with a reduced attack rate following challenge. Within the context of the model, prior exposure was not associated with reduced disease severity, altered microbiological profile or boosting of humoral immune responses. We conclude that prior Salmonella Typhi and Paratyphi A exposure may confer partial but incomplete protection against subsequent infection, but with a comparable clinical and microbiological phenotype. There is no demonstrable cross-protection between these serovars, consistent with the co-circulation of Salmonella Typhi and Paratyphi A. Collectively, these data are consistent with surveillance and modelling studies that indicate multiple infections can occur in high transmission settings, supporting the need for vaccines to reduce the burden of disease in childhood and achieve disease control. Trial registration NCT02192008; clinicaltrials.gov

Greater ectopic fat deposition and liver fibroinflammation, and lower skeletal muscle mass in people with type 2 diabetes

ObjectiveType 2 diabetes (T2D) is associated with significant end-organ damage and ectopic fat accumulation. Multiparametric magnetic resonance imaging (MRI) can provide a rapid, noninvasive assessment of multiorgan and body composition. The primary objective of this study was to investigate differences in visceral adiposity, ectopic fat accumulation, body composition, and relevant biomarkers between people with and without T2D.MethodsParticipant demographics, routine biochemistry, and multiparametric MRI scans of the liver, pancreas, visceral and subcutaneous adipose tissue, and skeletal muscle were analyzed from 266 participants (131 with T2D and 135 without T2D) who were matched for age, gender, and BMI. Wilcoxon and χ2 tests were performed to calculate differences between groups.ResultsParticipants with T2D had significantly elevated liver fat (7.4% vs. 5.3%, p = 0.011) and fibroinflammation (as assessed by corrected T1 [cT1]; 730 milliseconds vs. 709 milliseconds, p = 0.019), despite there being no differences in liver biochemistry, serum aspartate aminotransferase (p = 0.35), or alanine transaminase concentration (p = 0.11). Significantly lower measures of skeletal muscle index (45.2 cm2 /m2 vs. 50.6 cm2 /m2 , p = 0.003) and high-density lipoprotein cholesterol (1.1 mmol/L vs. 1.3 mmol/L, p ConclusionsMultiparametric MRI revealed significantly elevated liver fat and fibroinflammation in participants with T2D, despite normal liver biochemistry. This study corroborates findings of significantly lower measures of skeletal muscle and high-density lipoprotein cholesterol in participants with T2D versus those without T2D

Two-enzyme systems for glycolipid and polyglycerolphosphate lipoteichoic acid synthesis in Listeria monocytogenes

Lipoteichoic acid (LTA) is an important cell wall polymer in Gram-positive bacteria and often consists a polyglycerolphosphate backbone chain that is linked to the membrane by a glycolipid. In Listeria monocytogenes this glycolipid is Gal-Glc-DAG or Gal-Ptd-6Glc-DAG. Using a bioinformatics approach, we have identified L. monocytogenes genes predicted to be involved in glycolipid (lmo2555 and lmo2554) and LTA backbone (lmo0644 and lmo0927) synthesis. LTA and glycolipid analysis of wild-type and mutant strains confirmed the function of Lmo2555 and Lmo2554 as glycosyltransferases required for the formation of Glc-DAG and Gal-Glc-DAG. Deletion of a third gene, lmo2553, located in the same operon resulted in the production of LTA with an altered structure. lmo0927 and lmo0644 encode proteins with high similarity to the staphylococcal LTA synthase LtaS, which is responsible for polyglycerolphosphate backbone synthesis. We show that both proteins are involved in LTA synthesis. Our data support a model whereby Lmo0644 acts as an LTA primase LtaP and transfers the initial glycerolphosphate onto the glycolipid anchor, and Lmo0927 functions as LTA synthase LtaS, which extends the glycerolphosphate backbone chain. Inactivation of LtaS leads to severe growth and cell division defects, underscoring the pivotal role of LTA in this Gram-positive pathogen

Bayesian networks and imaging-derived phenotypes highlight the role of fat deposition in COVID-19 hospitalisation risk

Objective: Obesity is a significant risk factor for adverse outcomes following coronavirus infection (COVID-19). However, BMI fails to capture differences in the body fat distribution, the critical driver of metabolic health. Conventional statistical methodologies lack functionality to investigate the causality between fat distribution and disease outcomes.Methods: We applied Bayesian network (BN) modelling to explore the mechanistic link between body fat deposition and hospitalisation risk in 459 participants with COVID-19 (395 non-hospitalised and 64 hospitalised). MRI-derived measures of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat were included. Conditional probability queries were performed to estimate the probability of hospitalisation after fixing the value of specific network variables.Results: The probability of hospitalisation was 18% higher in people living with obesity than those with normal weight, with elevated VAT being the primary determinant of obesity-related risk. Across all BMI categories, elevated VAT and liver fat (&gt;10%) were associated with a 39% mean increase in the probability of hospitalisation. Among those with normal weight, reducing liver fat content from &gt;10% to &lt;5% reduced hospitalisation risk by 29%.Conclusion: Body fat distribution is a critical determinant of COVID-19 hospitalisation risk. BN modelling and probabilistic inferences assist our understanding of the mechanistic associations between imaging-derived phenotypes and COVID-19 hospitalisation risk

Cellular Architecture Mediates DivIVA Ultrastructure and Regulates Min Activity in Bacillus subtilis

The assembly of the cell division machinery at midcell is a critical step of cytokinesis. Many rod-shaped bacteria position septa using nucleoid occlusion, which prevents division over the chromosome, and the Min system, which prevents division near the poles. Here we examined the in vivo assembly of the Bacillus subtilis MinCD targeting proteins DivIVA, a peripheral membrane protein that preferentially localizes to negatively curved membranes and resembles eukaryotic tropomyosins, and MinJ, which recruits MinCD to DivIVA. We used structured illumination microscopy to demonstrate that both DivIVA and MinJ localize as double rings that flank the septum and first appear early in septal biosynthesis. The subsequent recruitment of MinCD to these double rings would separate the Min proteins from their target, FtsZ, spatially regulating Min activity and allowing continued cell division. Curvature-based localization would also provide temporal regulation, since DivIVA and the Min proteins would localize to midcell after the onset of division. We use time-lapse microscopy and fluorescence recovery after photobleaching to demonstrate that DivIVA rings are highly stable and are constructed from newly synthesized DivIVA molecules. After cell division, DivIVA rings appear to collapse into patches at the rounded cell poles of separated cells, with little or no incorporation of newly synthesized subunits. Thus, changes in cell architecture mediate both the initial recruitment of DivIVA to sites of cell division and the subsequent collapse of these rings into patches (or rings of smaller diameter), while curvature-based localization of DivIVA spatially and temporally regulates Min activity