Objectives
Although fermented food use is ubiquitous in humans, the ecological and evolutionary factors contributing to its emergence are unclear. Here we investigated the ecological contexts ...surrounding the consumption of fruits in the late stages of fermentation by wild primates to provide insight into its adaptive function. We hypothesized that climate, socioecological traits, and habitat patch size would influence the occurrence of this behavior due to effects on the environmental prevalence of late‐stage fermented foods, the ability of primates to detect them, and potential nutritional benefits.
Materials and methods
We compiled data from field studies lasting at least 9 months to describe the contexts in which primates were observed consuming fruits in the late stages of fermentation. Using generalized linear mixed‐effects models, we assessed the effects of 18 predictor variables on the occurrence of fermented food use in primates.
Results
Late‐stage fermented foods were consumed by a wide taxonomic breadth of primates. However, they generally made up 0.01%–3% of the annual diet and were limited to a subset of fruit species, many of which are reported to have mechanical and chemical defenses against herbivores when not fermented. Additionally, late‐stage fermented food consumption was best predicted by climate and habitat patch size. It was more likely to occur in larger habitat patches with lower annual mean rainfall and higher annual mean maximum temperatures.
Discussion
We posit that primates capitalize on the natural fermentation of some fruits as part of a nutritional strategy to maximize periods of fruit exploitation and/or access a wider range of plant species. We speculate that these factors contributed to the evolutionary emergence of the human propensity for fermented foods.
Wild primates consuming fermented fruits.
Anxiety and depressive disorders are among the most commonly diagnosed psychiatric disorders, yet they remain largely undertreated in the U.S. and Black adults are especially unlikely to seek or ...receive mental health services. Symptom severity has been found to impact treatment-seeking behaviors as have sociocultural factors. Yet no known research has tested whether these factors work synergistically to effect willingness to seek treatment. Further, emerging data point to the importance of transdiagnostic risk factors such as intolerance of uncertainty (IU). IU may be negatively related to seeking treatment given that Black adults may be uncertain whether treatment might benefit them. Thus, the current study examined the relations between symptom severity/IU and willingness to seek treatment for anxiety/depression problems and the impact of key sociocultural variables (i.e., cultural mistrust–interpersonal relations CMI-IR, perceived discrimination PED) on these relations among 161 (85% female) Black undergraduates. Consistent with prediction, symptom severity was positively related to willingness, but unexpectedly, IU was positively related. There was a significant Symptom Severity × CMI-IR interaction such that severity was positively related to willingness among students with lower cultural mistrust, but not higher mistrust. There were also significant IU × PED interaction such that IU was positively related to willingness among students with lower PED, but not higher PED. Results highlight the importance of considering the interplay between symptom severity, transdiagnostic vulnerability factors, and sociocultural variables when striving to identify factors related to treatment seeking behaviors among anxious and/or depressed Black students.
•IVs: symptom severity (SS) and intolerance of uncertainty (IU).•SS is positively related to treatment seeking willingness among Black students.•IU is positively related to treatment seeking willingness.•SS-willingness relation occurs when cultural mistrust low.•IU-willingness relation occurs when perceived discrimination low.
Abstract Description Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic ...cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. Methods A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest. Results Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. Conclusions TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.
Background:
HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence ...vary widely between sources. We aimed to i) extract and summarise existing national HBV prevalence estimates, ii) add a new estimate based on primary care data, and; iii) critique data sources from which estimates were derived.
Methods:
We undertook a narrative review, searching for national estimates of CHB case numbers in the UK (incorporating incidence, prevalence and/or test positivity data) across a range of overlapping sources, including governmental body reports, publications from independent bodies (including medical charities and non-governmental organisations) and articles in peer-reviewed scientific journals. An alternative proxy for population prevalence was obtained via the UK antenatal screening programme which achieves over 95% coverage of pregnant women. We also searched for diagnoses of HBV in the QResearch primary care database based on laboratory tests and standardised coding.
Results:
We identified six CHB case number estimates, of which three reported information concerning population subgroups, including number of infected individuals across age, sex and ethnicity categories. Estimates among sources reporting prevalence varied from 0.27% to 0.73%, congruent with an estimated antenatal CHB prevalence of <0.5%. Our estimate, based on QResearch data, suggests a population prevalence of ~0.05%, reflecting a substantial underestimation based on primary care records.
Discussion
: Estimates varied by sources of error, bias and missingness, data linkage, and “blind spots” in HBV diagnoses testing/registration. The UK HBV burden is likely to be concentrated in vulnerable populations who may not be well represented in existing datasets including those experiencing socioeconomic deprivation and/or homelessness, ethnic minorities and people born in high-prevalence countries. This could lead to under- or over-estimation of population prevalence estimation. Multi-agency collaboration is required to fill evidence gaps.
The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. ...Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
. Cross reactivity of PDE12 inhibitors with other PDEs and
toxicity were measured. In EMCV assays, CO-17 potentiated the effect of IFNα by 3 log
. The compounds were selective for PDE12 when tested against a panel of other PDEs and non-toxic at up to 42 mg kg
in rats
. Thus, we have identified PDE12 inhibitors (CO-17 and CO-63), and established the principle that inhibitors of PDE12 have antiviral properties. Early studies suggest these PDE12 inhibitors are well tolerated at the therapeutic range, and reduce viral load in studies of DENV, HCV, WNV and SARS-CoV-2 in human cells and WNV in a mouse model.
Early combination antiretroviral therapy (cART) reduces the size of the viral reservoir in paediatric and adult HIV infection. Very early-treated children may have higher cure/remission potential.
In ...an observational study of 151 in utero (IU)-infected infants in KwaZulu-Natal, South Africa, whose treatment adhered strictly to national guidelines, 76 infants diagnosed via point-of-care (PoC) testing initiated cART at a median of 26 h (IQR 18–38) and 75 infants diagnosed via standard-of-care (SoC) laboratory-based testing initiated cART at 10 days (IQR 8–13). We analysed mortality, time to suppression of viraemia, and maintenance of aviraemia over the first 2 years of life.
Baseline plasma viral loads were low (median 8000 copies per mL), with 12% of infants having undetectable viraemia pre-cART initiation. However, barely one-third (37%) of children achieved suppression of viraemia by 6 months that was maintained to >12 months. 24% had died or were lost to follow up by 6 months. Infant mortality was 9.3%. The high-frequency virological failure in IU-infected infants was associated not with transmitted or acquired drug-resistant mutations but with cART non-adherence (plasma cART undetectable/subtherapeutic, p<0.0001) and with concurrent maternal cART failure (OR 15.0, 95%CI 5.6–39.6; p<0.0001). High-frequency virological failure was observed in PoC- and SoC-tested groups of children.
The success of early infant testing and cART initiation strategies is severely limited by subsequent cART non-adherence in HIV-infected children. Although there are practical challenges to administering paediatric cART formulations, these are overcome by mothers who themselves are cART-adherent. These findings point to the ongoing obligation to address the unmet needs of the mothers. Eliminating the particular barriers preventing adequate treatment for these vulnerable women and infants need to be prioritised in order to achieve durable suppression of viraemia on cART, let alone HIV cure/remission, in HIV-infected children.
Wellcome Trust, National Institutes of Health.
An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland
in April 2022 and has now been identified in 35 countries
. Several recent studies have suggested an ...association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4
T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10
). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.
We examine mid- to late Holocene centennial-scale climate variability in Ireland using proxy data from peatlands, lakes and a speleothem. A high degree of between-record variability is apparent in ...the proxy data and significant chronological uncertainties are present. However, tephra layers provide a robust tool for correlation and improve the chronological precision of the records. Although we can find no statistically significant coherence in the dataset as a whole, a selection of high-quality peatland water table reconstructions co-vary more than would be expected by chance alone. A locally weighted regression model with bootstrapping can be used to construct a ‘best-estimate’ palaeoclimatic reconstruction from these datasets. Visual comparison and cross-wavelet analysis of peatland water table compilations from Ireland and Northern Britain show that there are some periods of coherence between these records. Some terrestrial palaeoclimatic changes in Ireland appear to coincide with changes in the North Atlantic thermohaline circulation and solar activity. However, these relationships are inconsistent and may be obscured by chronological uncertainties. We conclude by suggesting an agenda for future Holocene climate research in Ireland.
Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and ...the epigenetic age of the airway epithelium and peripheral blood of PLWH.
Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV1/FVC<0.70, and FEV1 decline over 6 years in blood.
The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV1/FVC<LLN was associated with greater GrimAge residuals (Beta=1.74, 95%CI=0.37-3.24, P=0.019). FEV1 decline was inversely correlated with GrimAge residuals in blood (r=−0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV1/FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031).
GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD.
Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.
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