Early-life glucocorticoids accelerate lymphocyte count senescence in roe deer.

Immunosenescence corresponds to the progressive decline of immune functions with increasing age. Although it is critical to understand what modulates such a decline, the ecological and physiological drivers of immunosenescence remain poorly understood in the wild. Among them, the level of glucocorticoids (GCs) during early life are good candidates to modulate immunosenescence patterns because these hormones can have long-term consequences on individual physiology. Indeed, GCs act as regulators of energy allocation to ensure allostasis, are part of the stress response triggered by unpredictable events and have immunosuppressive effects when chronically elevated. We used longitudinal data collected over two decades in two populations of roe deer (Capreolus capreolus) to test whether higher baseline GC levels measured within the first year of life were associated with a more pronounced immunosenescence and parasite susceptibility. We first assessed immunosenescence trajectories in these populations facing contrasting environmental conditions. Then, we found that juvenile GC levels can modulate lymphocyte trajectory. Lymphocyte depletion was accelerated late in life when GCs were elevated early in life. Although the exact mechanism remains to be elucidated, it could involve a role of GCs on thymic characteristics. In addition, elevated GC levels in juveniles were associated with a higher abundance of lung parasites during adulthood for individuals born during bad years, suggesting short-term negative effects of GCs on juvenile immunity, having in turn long-lasting consequences on adult parasite load, depending on juvenile environmental conditions. These findings offer promising research directions in assessing the carry-over consequences of GCs on life-history traits in the wild.

Health Disparities in Pediatric Epilepsy: Methods and Lessons Learned.

Epilepsy affects 1% of youth and is associated with neurocognitive and psychosocial comorbidities, increased risk of mortality, and poor health-related outcomes. Health disparities in children and youth with epilepsy (CYE) have been understudied. A Special Interest Group (SIG) within the Pediatric Epilepsy Research Consortium is conducting a scoping review to systematically assess the literature and highlight the gaps in access to clinical care and management of pediatric epilepsy. The methodology for this review is presented. In conducting a peer-reviewed assessment of the scope of health disparities in pediatric epilepsy, we learned that developing the methodology for and conducting a comprehensive scoping review with multiple contributors resulted in a time-intensive process. While there is an evidence to suggest that health disparities do exist in CYE, very few studies have focused on these disparities. Disparity results are often not included in key elements of articles, lending them to be underemphasized and underrecognized. Preliminary conclusions inform several important research considerations.

Out-of-Hospital COVID-19 Deaths: Consequences for Quality of Medical Care and Accuracy of Cause of Death Coding.

Objectives. To examine age and temporal trends in the proportion of COVID-19 deaths occurring out of hospital or in the emergency department and the proportion of all noninjury deaths assigned ill-defined causes in 2020. Methods. We analyzed newly released (March 2021) provisional COVID-19 death tabulations for the entire United States. Results. Children (younger than 18 years) were most likely (30.5%) and elders aged 64 to 74 years were least likely (10.4%) to die out of hospital or in the emergency department. In parallel, among all noninjury deaths, younger people had the highest proportions coded to symptoms, signs, and ill-defined conditions, and percentage symptoms, signs, and ill-defined conditions increased from 2019 to 2020 in all age-race/ethnicity groups. The majority of young COVID-19 decedents were racial/ethnic minorities. Conclusions. The high proportions of all noninjury deaths among children, adolescents, and young adults that were coded to ill-defined causes in 2020 suggest that some COVID-19 deaths were missed because of systemic failures in timely access to medical care for vulnerable young people. Public Health Implications. Increasing both availability of and access to the best hospital care for young people severely ill with COVID-19 will save lives and improve case fatality rates.

How service users and carers understand, perceive, rephrase, and communicate about "depressive episode" and "schizophrenia" diagnoses: an international participatory research.

BACKGROUND: For ICD-11, the WHO emphasized the clinical utility of communication and the need to involve service users and carers in the revision process. AIMS: The objective was to assess whether medical vocabulary was accessible, which kinds of feelings it activated, whether and how users and carers would like to rephrase terms, and whether they used diagnosis to talk about mental health experiences. METHOD: An innovative protocol focused on two diagnoses (depressive episode and schizophrenia) was implemented in 15 different countries. The same issues were discussed with users and carers: understanding, feelings, rephrasing, and communication. RESULTS: Most participants reported understanding the diagnoses, but associated them with negative feelings. While the negativity of "depressive episode" mostly came from the concept itself, that of "schizophrenia" was largely based on its social impact and stigmatization associated with "mental illness". When rephrasing "depressive episode", a majority kept the root "depress*", and suppressed the temporal dimension or renamed it. Almost no one suggested a reformulation based on "schizophrenia". Finally, when communicating, no one used the phrase "depressive episode". Some participants used words based on "depress", but no one mentioned "episode". Very few used "schizophrenia". CONCLUSION: Data revealed a gap between concepts and emotional and cognitive experiences. Both professional and experiential language and knowledge have to be considered as complementary. Consequently, the ICD should be co-constructed by professionals, service users, and carers. It should take the emotional component of language, and the diversity of linguistic and cultural contexts, into account.

Ethnic differences in risk factors for adverse birth outcomes between Pakistani, Bangladeshi, and White British mothers.

AIM: Reducing poor maternal and infant outcomes in pregnancy is the aim of maternity care. Adverse health behaviours lead to increased risk and can adversely mediate birth outcomes. This study examines whether risk factors are similar, different, or clustered according to maternal ethnicity. DESIGN: Retrospective analysis of routinely collected data (2008-2013). METHODS: We analysed data routinely collected data from a local University Hospital Ciconia Maternity information System (CMiS), for White British, Pakistani, and Bangladeshi women (N = 15,211) using cross-tabulations, ANCOVA, adjusted standardized residuals (ASR), and Pearson's chi-squared statistics. RESULTS: The results demonstrate distinct clusters of risk factors between White British, Pakistani, and Bangladeshi mothers. Additionally, Pakistani mothers had the highest number of statistically significant risk factors, according to maternal ethnicity, showing that 49% of women in this cohort that were diagnosed with diabetes were Pakistani, 21.5% of White British women smoked and results showed that Bangladeshi mothers delivered the lightest weight infants (adjusted mean: 3,055.4 g). CONCLUSIONS: This study showed differences in the risk factors between White British, Pakistani, and Bangladeshi mothers. The identified risk factors were clustered by maternal ethnicity. IMPACT: Identification of these risk factor clusters can help policymakers and clinicians direct resources and may help reduce ethnic variation found in these populations that might be attributed to adverse health behaviours and increased risk factors.

Understanding the consumption of folic acid during preconception, among Pakistani, Bangladeshi and white British mothers in Luton, UK: a qualitative study.

BACKGROUND: To review the similarities and differences in Pakistani, Bangladeshi and White British mothers health beliefs (attitudes, knowledge and perceptions) and health behaviour regarding their consumption of folic acid pre-conception, to reduce the risk of neural tube defects. METHODS: Our study used a descriptive qualitative research approach, implementing face-to-face focus group discussions with Pakistani, Bangladeshi or White British mothers (normal birth outcomes and mothers with poor birth outcomes) and semi-structured interviews or focus groups with service providers using semi-structured topic guides. This method is well suited for under researched areas where in-depth information is sought. There were three sample groups: 1. Pakistani, Bangladeshi and White British mothers with normal birth outcomes (delivery after 37 weeks of gestation, in the preceding 6 to 24 months, weighing 2500 g and living within a specified postcode area in Luton, UK). 2. Pakistani Bangladeshi and white British bereaved mothers who had suffered a perinatal mortality (preceding 6 to 24 months, residing within a specificied postcode area). 3. Healthcare professionals working on the local maternity care pathway (i.e. services providing preconception, antenatal, antepartum and postpartum care). Transcribed discussions were analysed using the Framework Analysis approach. RESULTS: The majority of mothers in this sample did not understand the benefits or optimal time to take folic acid pre-conception. Conversely, healthcare professionals believed the majority of women did consume folic acid, prior to conception. CONCLUSIONS: There is a need to increase public health awareness of the optimal time and subsequent benefits for taking folic acid, to prevent neural tube defects.

A comparison of antenatal classifications of 'overweight' and 'obesity' prevalence between white British, Indian, Pakistani and Bangladeshi pregnant women in England; analysis of retrospective data.

BACKGROUND: Maternal obesity increases women's risk of poor birth outcomes, and statistics show that Pakistani and Bangladeshi women (who are born or settled) in the UK experience higher rates of perinatal mortality and congenital anomalies than white British or white Other women. This study compares the prevalence of maternal obesity in Indian, Pakistani, Bangladeshi and white British women using standard and Asian-specific BMI metrics. METHOD: Retrospective cross-sectional analysis using routinely recorded secondary data in Ciconia Maternity information System (CMiS), between 2008 and 2013. Mothers (n = 15,205) whose ethnicity was recorded as white British, Bangladeshi, Pakistani or Indian. Adjusted standardised residuals and Pearson Chi-square. MAIN OUTCOME MEASURES: Percentage of mothers stratified by ethnicity (Indian, Pakistani, Bangladeshi and white British) who are classified as overweight or obese using standard and revised World Health Organisation BMI thresholds. RESULTS: Compared to standard BMI thresholds, using the revised BMI threshold resulted in a higher prevalence of obesity: 22.8% of Indian and 24.3% of Bangladeshi and 32.3% of Pakistani women. Pearson Chi-square confirmed that significantly more Pakistani women were classified as 'obese' compared with white British, Indian or Bangladeshi women (χ 2  = 499,88 df = 9, p < 0.001). CONCLUSIONS: There are differences in the prevalence of obese and overweight women stratified by maternal ethnicity of white British, Indian, Pakistani and Bangladeshi. Using revised anthropometric measures in Indian, Pakistani and Bangladeshi women has clinical implications for identifying risks associated with obesity and increased complications in pregnancy.

Activity of Norspermidine on Bacterial Biofilms of Multidrug-Resistant Clinical Isolates Associated with Persistent Extremity Wound Infections.

Biofilm formation is a major virulence factor for numerous pathogenic bacteria and is cited as a central event in the pathogenesis of chronic human infections, which is in large part due to excessive extracellular matrix secretion and metabolic changes that occur within the biofilm rendering them highly tolerant to antimicrobial treatments. Polyamines, including norspermidine, play central roles in bacterial biofilm development, but have also recently been shown to inhibit biofilm formation in select strains of various pathogenic bacteria. The aim of this study was to evaluate in vitro the biofilm dispersive and inhibitory activities of norspermidine against multidrug-resistant clinical isolates of Acinetobacter baumannii(n = 4), Klebsiella pneumoniae (n = 3), Pseudomonas aeruginosa (n = 5) and Staphylococcus aureus (n = 4) associated with chronic extremity wound infections using the semi-quantitative 96-well plate method and confocal laser microscopy. In addition to the antibiofilm activity, biocompatibility of norspermidine was also evaluated by measuring toxicity in vitro to human cell lines and whole porcine tissue explants using MTT viability assay and histological analysis. Norspermidine (5-20 mM) had variable dispersive and inhibitory activity on biofilms which was dependent on both the strain and species. Of the clinical bacterial species evaluated herein, A. baumannii isolates were the most sensitive to the effect of norspermidine, which was in part due to the inhibitory effects of norspermidine on bacterial motility and expression of genes involved in the production of homoserine lactones and quorum sensing molecules both essential for biofilm formation. Importantly, exposure of cell lines and whole tissues to norspermidine for prolonged periods of time (≥24 h) was observed to reduce viability and alter tissue histology in a time and concentration dependent manner, with 20 mM exposure having the greatest negative effects on both tissues and individual cell lines. Collectively our findings demonstrate that, similar to other polyamines, norspermidine displays both inhibitory and dispersive activities on biofilms of clinical multidrug-resistant bacterial isolates, in particular for strains of A. baumannii. Additionally our findings suggest that direct application may be considered on tissues, albeit for limited exposure times.

Specific antenatal interventions for Black, Asian and Minority Ethnic (BAME) pregnant women at high risk of poor birth outcomes in the United Kingdom: a scoping review.

BACKGROUND: Disparity exists in maternal and infant birth outcomes of Black and Minority Ethnic (BAME) women giving birth in the United Kingdom (UK) compared to the majority. There is therefore a need to reconsider existing maternity service provision to ensure culturally competent services. The purpose of this scoping review was to ascertain what specific maternity interventions have been implemented in the UK for BAME women (2004-2014) so that increased awareness of the need and scope of specific maternity interventions for BAME women can be identified. METHODS: A scoping review was conducted in order to determine the evidence base. It was determined that no prior systematic reviews had been conducted and it was apparent that literature in this field was sparse. Scoping review is an ideal method when literature is likely to be heterogeneous and the research field relatively unexplored. A keyword strategy was used implementing population (P), intervention (I), comparison (C) and outcomes (O). RESULTS: An initial 2188 papers were identified. Following screening and review, only 5 heterogeneous papers remained suitable and were included. The included interventions employed sample sizes of N = 160-1441, examined a range of different outcome measures and were delivered across different parts of the UK with high numbers of BAME residents. CONCLUSIONS: There is a lack of rigorous research interventions and practice interventions which are currently documented, of specific maternity interventions which are aimed to address culturally competent maternity services and the sharing of best practice addressing the increased risks of BAME women delivering in the UK.

All-cancers mortality rates approaching diseases of the heart mortality rates as leading cause of death in Texas.

OBJECTIVES: Diseases of the heart and malignant neoplasms (all-cancers) are the leading causes of death in the United States. The gap between the two has been closing in recent years. To assess the gap status in Texas and to establish a baseline to support evaluation efforts for the Cancer Prevention Research Institute of Texas, mortality data from 2006 to 2009 were analyzed. METHODS: Immediate cause of death data in Texas for the years 2006-2009 were analyzed and rates developed by sex, race/ethnicity, and four metropolitan counties. RESULTS: Overall, for the years 2006-2009, the age-adjusted mortality rates (AARs) among Texas residents for both diseases of the heart and all-cancers decreased; however, during this time frame, there was greater improvement in diseases of the heart AARs as compared with all-cancers AARs. For the four large metropolitan counties of Bexar, Dallas, Harris, and Travis, data were analyzed by sex and race/ethnicity, and 11 of the 12 largest percent mortality rate decreases were for diseases of the heart. CONCLUSIONS: Age-adjusted mortality rates among Texas residents from diseases of the heart are showing improvement as compared with the rates for all-cancers.

Biological carbon capture from biogas streams: Insights into Cupriavidus necator autotrophic growth and transcriptional profile.

Recycling carbon-rich wastes into high-value platform chemicals through biological processes provides a sustainable alternative to petrochemicals. Cupriavidus necator, known for converting carbon dioxide (CO2) into polyhydroxyalkanoates (PHA) was studied for the first time using biogas streams as the sole carbon source. The bacterium efficiently consumed biogenic CO2 from raw biogas with methane at high concentrations (50%) proving non-toxic. Continuous addition of H2 and O2 enabled growth trends comparable to glucose-based heterotrophic growth. Transcriptomic analysis revealed CO2-adaptated cultures exhibited upregulation of hydrogenases and Calvin cycle enzymes, as well as genes related to electron transport, nutrient uptake, and glyoxylate cycle. Non-adapted samples displayed activation of stress response mechanisms, suggesting potential lags in large-scale processes. These findings showcase the setting of growth parameters for a pioneering biological biogas upgrading strategy, emphasizing the importance of inoculum adaptation for autotrophic growth and providing potential targets for genetic engineering to push PHA yields in future applications.

Cupriavidus necator as a platform for polyhydroxyalkanoate production: An overview of strains, metabolism, and modeling approaches.

Cupriavidus necator is a bacterium with a high phenotypic diversity and versatile metabolic capabilities. It has been extensively studied as a model hydrogen oxidizer, as well as a producer of polyhydroxyalkanoates (PHA), plastic-like biopolymers with a high potential to substitute petroleum-based materials. Thanks to its adaptability to diverse metabolic lifestyles and to the ability to accumulate large amounts of PHA, C. necator is employed in many biotechnological processes, with particular focus on PHA production from waste carbon sources. The large availability of genomic information has enabled a characterization of C. necator's metabolism, leading to the establishment of metabolic models which are used to devise and optimize culture conditions and genetic engineering approaches. In this work, the characteristics of available C. necator strains and genomes are reviewed, underlining how a thorough comprehension of the genetic variability of C. necator is lacking and it could be instrumental for wider application of this microorganism. The metabolic paradigms of C. necator and how they are connected to PHA production and accumulation are described, also recapitulating the variety of carbon substrates used for PHA accumulation, highlighting the most promising strategies to increase the yield. Finally, the review describes and critically analyzes currently available genome-scale metabolic models and reduced metabolic network applications commonly employed in the optimization of PHA production. Overall, it appears that the capacity of C. necator of performing CO2 bioconversion to PHA is still underexplored, both in biotechnological applications and in metabolic modeling. However, the accurate characterization of this organism and the efforts in using it for gas fermentation can help tackle this challenging perspective in the future.

Unraveling prevalence of homoacetogenesis and methanogenesis pathways due to inhibitors addition.

Three inhibitors targeting different microorganisms, both from Archaea and Bacteria domains, were evaluated for their effect on CO2 biomethanation: sodium ionophore III (ETH2120), carbon monoxide (CO), and sodium 2-bromoethanesulfonate (BES). This study examines how these compounds affect the anaerobic digestion microbiome in a biogas upgrading process. While archaea were observed in all experiments, methane was produced only when adding ETH2120 or CO, not when adding BES, suggesting archaea were in an inactivated state. Methane was produced mainly via methylotrophic methanogenesis from methylamines. Acetate was produced at all conditions, but a slight reduction on acetate production (along with an enhancement on CH4 production) was observed when applying 20 kPa of CO. Effects on CO2 biomethanation were difficult to observe since the inoculum used was from a real biogas upgrading reactor, being this a complex environmental sample. Nevertheless, it must be mentioned that all compounds had effects on the microbial community composition.

Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice.

Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lacI transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline.

Paxillin and phospholipase D interact to regulate actin-based processes in Dictyostelium discoideum.

The actin cytoskeleton forms a membrane-associated network whose proper regulation is essential for numerous processes, including cell differentiation, proliferation, adhesion, chemotaxis, endocytosis, exocytosis, and multicellular development. In this report, we show that in Dictyostelium discoideum, paxillin (PaxB) and phospholipase D (PldB) colocalize and coimmunoprecipitate, suggesting that they interact physically. Additionally, the phenotypes observed during development, cell sorting, and several actin-required processes, including cyclic AMP (cAMP) chemotaxis, cell-substrate adhesion, actin polymerization, phagocytosis, and exocytosis, reveal a genetic interaction between paxB and pldB, suggesting a functional interaction between their gene products. Taken together, our data point to PldB being a required binding partner of PaxB during processes involving actin reorganization.

Joint Effects of Socioeconomic Position, Race/Ethnicity, and Gender on COVID-19 Mortality among Working-Age Adults in the United States.

Substantial racial/ethnic and gender disparities in COVID-19 mortality have been previously documented. However, few studies have investigated the impact of individual socioeconomic position (SEP) on these disparities. Objectives: To determine the joint effects of SEP, race/ethnicity, and gender on the burden of COVID-19 mortality. A secondary objective was to determine whether differences in opportunities for remote work were correlated with COVID-19 death rates for sociodemographic groups. Design: Annual mortality study which used a special government tabulation of 2020 COVID-19-related deaths stratified by decedents' SEP (measured by educational attainment), gender, and race/ethnicity. Setting: United States in 2020. Participants: COVID-19 decedents aged 25 to 64 years old (n = 69,001). Exposures: Socioeconomic position (low, intermediate, and high), race/ethnicity (Hispanic, Black, Asian, Indigenous, multiracial, and non-Hispanic white), and gender (women and men). Detailed census data on occupations held by adults in 2020 in each of the 36 sociodemographic groups studied were used to quantify the possibility of remote work for each group. Main Outcomes and Measures: Age-adjusted COVID-19 death rates for 36 sociodemographic groups. Disparities were quantified by relative risks and 95% confidence intervals. High-SEP adults were the (low-risk) referent group for all relative risk calculations. Results: A higher proportion of Hispanics, Blacks, and Indigenous people were in a low SEP in 2020, compared with whites. COVID-19 mortality was five times higher for low vs. high-SEP adults (72.2 vs. 14.6 deaths per 100,000, RR = 4.94, 95% CI 4.82-5.05). The joint detriments of low SEP, Hispanic ethnicity, and male gender resulted in a COVID-19 death rate which was over 27 times higher (178.0 vs. 6.5 deaths/100,000, RR = 27.4, 95% CI 25.9-28.9) for low-SEP Hispanic men vs. high-SEP white women. In regression modeling, percent of the labor force in never remote jobs explained 72% of the variance in COVID-19 death rates. Conclusions and Relevance: SARS-CoV-2 infection control efforts should prioritize low-SEP adults (i.e., the working class), particularly the majority with "never remote" jobs characterized by inflexible and unsafe working conditions (i.e., blue collar, service, and retail sales workers).

Global sensitivity and uncertainty analysis of a microalgae model for wastewater treatment.

The results of a global sensitivity and uncertainty analysis of a microalgae model applied to a Membrane Photobioreactor (MPBR) pilot plant were assessed. The main goals of this study were: (I) to identify the sensitivity factors of the model through the Morris screening method, i.e. the most influential factors; (II) to calibrate the influential factors online or offline; and (III) to assess the model's uncertainty. Four experimental periods were evaluated, which encompassed a wide range of environmental and operational conditions. Eleven influential factors (e.g. maximum specific growth rate, light intensity and maximum temperature) were identified in the model from a set of 34 kinetic parameters (input factors). These influential factors were preferably calibrated offline and alternatively online. Offline/online calibration provided a unique set of model factor values that were used to match the model results with experimental data for the four experimental periods. A dynamic optimization of these influential factors was conducted, resulting in an enhanced set of values for each period. Model uncertainty was assessed using the uncertainty bands and three uncertainty indices: p-factor, r-factor and ARIL. Uncertainty was dependent on both the number of influential factors identified in each period and the model output analyzed (i.e. biomass, ammonium and phosphate concentration). The uncertainty results revealed a need to apply offline calibration methods to improve model performance.