Direct whole-genome sequencing of HIV-1 for clinical drug-resistance analysis and public health surveillance.

BACKGROUND: Human Immunodeficiency virus type 1 (HIV-1) remains a significant global health threat partly due to its ability to develop resistance to anti-retroviral therapies. HIV-1 genotype and drug resistance analysis of the polymerase (pol) sequence is a mainstay of its clinical and public health management. However, as new treatments and resistances evolve, analysis methods must change accordingly. In this study, we outline the development and implementation of a direct whole-genome sequencing approach (dWGS) using probe-capture target-enrichment for HIV-1 genotype and drug resistance analysis. METHODS: We implemented dWGS and performed parallel pol Sanger sequencing for clinical samples, followed by comparative genotype and drug-resistance analysis. These HIV-1 WGS sequences were also utilised for a novel partitioned phylogenetic analysis. RESULTS: Optimised nucleic acid extraction and DNAse I treatment significantly increased HIV-1 whole-genome coverage and depth, and improved recovery of high-quality genomes from low viral load clinical samples, enabling routine sequencing of viral loads as low as 1000 copies/mL. Overall, dWGS was robust, accurate and more sensitive for detecting low-frequency variants at drug-resistance sites compared to Sanger sequencing. Analysis of multiple sequence regions improved phylogenetic reconstruction for recombinant HIV-1 sequences compared to analysis of pol sequence alone. CONCLUSIONS: These findings demonstrate dWGS enhances HIV-1 drug-resistance analysis by quantitative variant detection and improves reconstruction of HIV-1 phylogenies compared to traditional pol sequencing. This work supports that HIV-1 dWGS is a viable option to replace Sanger sequencing for clinical and public health applications.

An integrated agroforestry-bioenergy system for enhanced energy and food security in rural sub-Saharan Africa.

Most people in rural sub-Saharan Africa lack access to electricity and rely on traditional, inefficient, and polluting cooking solutions that have adverse impacts on both human health and the environment. Here, we propose a novel integrated agroforestry-bioenergy system that combines sustainable biomass production in sequential agroforestry systems with biomass-based cleaner cooking solutions and rural electricity production in small-scale combined heat and power plants and estimate the biophysical system outcomes. Despite conservative assumptions, we demonstrate that on-farm biomass production can cover the household's fuelwood demand for cooking and still generate a surplus of woody biomass for electricity production via gasification. Agroforestry and biochar soil amendments should increase agricultural productivity and food security. In addition to enhanced energy security, the proposed system should also contribute to improving cooking conditions and health, enhancing soil fertility and food security, climate change mitigation, gender equality, and rural poverty reduction.

Microglia in Health and Diseases: Integrative Hubs of the Central Nervous System (CNS).

Microglia are usually referred to as "the innate immune cells of the brain," "the resident macrophages of the central nervous system" (CNS), or "CNS parenchymal macrophages." These labels allude to their inherent immune function, related to their macrophage lineage. However, beyond their classic innate immune responses, microglia also play physiological roles crucial for proper brain development and maintenance of adult brain homeostasis. Microglia sense both external and local stimuli through a variety of surface receptors. Thus, they might serve as integrative hubs at the interface between the external environment and the CNS, able to decode, filter, and buffer cues from outside, with the aim of preserving and maintaining brain homeostasis. In this perspective, we will cast a critical look at how these multiple microglial functions are acquired and coordinated, and we will speculate on their impact on human brain physiology and pathology.

Superior Pedicle Inverted T-reduction Mammaplasty with Short Horizontal Scar.

Background: Superior pedicle breast reduction is a very popular technique among plastic surgeons. This technique has had many variations looking for fewer complications and better long-lasting results. The aim of this article is to present a novel technique of breast reduction, making variations in the design of the periareolar incision, using a superior pedicle with a constant vertical incision of 5 cm and a shortened horizontal incision. Methods: The superior pedicle inverted T-mammoplasty with a shortened horizontal scar technique was performed in 1200 patients who underwent surgery between 2010 and 2023; follow-up examination was carried out for an average of 1 year (3 months to 3 years). A patient satisfaction survey was conducted. Results: Patient satisfaction rate was 99%. There were no cases of total necrosis of the areola-nipple complex, 2.7% of the patients presented partial necrosis of the areola-nipple complex, 1.4% of the patients presented local infection, 1.7% presented dehiscence at some point of the vertical or horizontal suture, 4% of the patients presented a widened scar, 8% of the patients presented alteration in the sensibility of the areola-nipple complex, and 0.6% of the patients presented hematoma. With this technique, a rise of the areola-nipple complex of up to 22cm was achieved. Conclusions: The superior pedicle inverted T-mammaplasty with shortened horizontal scar technique showed a lower number of surgical complications compared with other techniques previously used for breast reduction, even when applied in gigantomasty. It provides lasting results and a high rate of patient satisfaction.

Clearance of ß-amyloid and synapses by the optogenetic depolarization of microglia is complement selective.

Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo. Membrane depolarization rapidly changes microglia morphology and leads to enhanced phagocytosis. We found that the optogenetic stimulation of microglia can efficiently promote ß-amyloid (Aß) clearance in the brain parenchyma, but it can also enhance synapse elimination. Importantly, the inhibition of C1q selectively prevents synapse loss induced by microglia depolarization but does not affect Aß clearance. Our data reveal independent microglia-mediated phagocytosis pathways toward Aß and synapses. Our results also shed light on a synergistic strategy of depolarizing microglia and inhibiting complement functions for the clearance of Aß while sparing synapses.

The genomic epidemiology of Neisseria meningitidis carriage from a randomised controlled trial of 4CMenB vaccination in an asymptomatic adolescent population.

Background: Oropharyngeal carriage of Neisseria meningitidis is frequent during adolescence, representing a major source of invasive meningococcal disease. This study examined the impact of a serogroup B vaccination (Bexsero, GSK 4CMenB) programme on adolescent N. meningitidis carriage using genomic data. Methods: A total 34,489 oropharyngeal samples were collected as part of a state-wide cluster randomised-controlled trial in South Australia during 2017 and 2018 (NCT03089086). Samples were screened for the presence of N. meningitidis DNA by porA PCR prior to culture. Whole genome sequencing was performed on all 1772 N. meningitidis culture isolates and their genomes were analysed. Findings: Unencapsulated meningococci were predominant at baseline (36.3% of isolates), followed by MenB (31.0%), and MenY (20.5%). Most MenB were ST-6058 from hyperinvasive cc41/44, or ST-32 and ST-2870 from cc32. For MenY, ST-23 and ST-1655 from cc23 were prevalent. Meningococcal carriage was mostly unchanged due to the vaccination programme; however, a significant reduction in ST-53 capsule-null meningococci prevalence was observed in 2018 compared to 2017 (OR = 0.52; 95% CI: 0.30-0.87, p = 0.0106). This effect was larger in the vaccinated compared to the control group (OR = 0.37; 95% CI: 0.12-0.98, p = 0.0368). Interpretation: While deployment of the 4CMenB vaccination did not alter the carriage of hyperinvasive MenB in the vaccinated population, it altered the carriage of other N. meningitidis sequence types following the vaccination program. Our findings suggest 4CMenB vaccination is unlikely to reduce transmission of hyperinvasive N. meningitidis strains and therefore ongoing targeted vaccination is likely a more effective public health intervention. Funding: This work was funded by GlaxoSmithKline Biologicals SA.

Chromium in the Diet of Dairy Calves: Benefits for Growth Performance, Feed Efficiency, Digestibility, and Health.

Chromium (Cr) is a mineral that helps animals subjected to stressful conditions. The suckling period is characterized by several stressful episodes, particularly during the first hours after birth and at weaning. There is little consumption of concentrate by calves in the first weeks of life; consequently, consuming any supplement added to feed would be negligible. Thus, the hypothesis was that the calves would take it in earlier if Cr were consumed in a milk replacer instead. Therefore, our study aimed to determine whether including organic Cr in calf feed (via milk replacer or concentrate) during the suckling phase would improve calf health and growth performance. Twenty-four male Holstein calves with an average age of 8 ± 4 days and 39.8 ± 6.9 kg average body weight were used. Calves were randomly divided into three groups: (a) Chromium-Milk (CR-M), receiving 4 mg Cr/animal/day via milk replacer during the 60 experimental days of suckling (n = 8); (b) Chromium-Concentrate (CR-C), receiving 4 mg Cr/animal/day via concentrate (n = 8); (c) Control (C), animals that did not receive Chromium (n = 8). The experiment lasted 75 days, divided into two well-defined stages: suckling (1-60 days) and weaning (61-75 days). Body weight weekly, daily feed intake, and blood samples taken every two weeks during the experiment were evaluated. At the end of the experiment, the apparent digestibility evaluation was carried out, with the results of weight and consumption carried out, and a feed efficiency analysis was carried out. It was observed that the inclusion of organic Cr (regardless of whether it was milk or concentrate) increased body weight gain (kg) for the CR-C group: 41.8 kg, CR-M: 40.4 kg compared to the C: 34.2 kg (p = 0.01). The protein digestibility was higher in the CR-M group (52%, p = 0.05). Cr consumption increased Cr concentrations in the serum of the calves and was higher in the first week in the animals in the CR-M group. This did not happen for the C group; however, with higher concentrate consumption, Cr concentrations increased and remained high until the end of the experiment. Glucose concentrations were higher in the groups that consumed Cr. Total protein concentrations were higher in the CR-M and CR-C groups than in group C. Immunoglobulin A concentrations were higher in groups CR-C and CR-M than in group C (days 40 and 60). In conclusion, the adding Cr to calf feed improves their health, indirectly favors growth performance, and increases protein digestibility.

High variability in Factor IX one-stage assay in samples spiked with nonacog beta pegol among different pairs of reagent/detection system.

INTRODUCTION: Haemophilia B (HB) is an X-linked hereditary bleeding disorder characterized by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates modified to extend their half-life have been developed, called extended half-life factors (EHL: extended half-life). Nonacog beta pegol (N9-GP) is a glycopegylated recombinant human FIX molecule that has a half-life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. To diagnose and monitor the treatment of haemophiliac patients, FIX activity is determined with the one-stage clotting assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9-PG with 10 different activated partial thromboplastin time (APTT) reagents on three platforms, in samples spiked in vitro with N9-GP, at four different concentration levels. METHODS: It was measured the recovery of N9-GP with 10 different APTT reagents (polyphenol, ellagic acid, silice dioxide, colloidal silica as APTT activator on three platforms, in sample spiked in vitro with N9-GP. RESULTS: The results show heterogeneity in the activity of N9-GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific calibrator of each coagulometer. A recovery percentage between 87% and 108% was obtained only with polyphenol and ellagic acid as activator in the three platforms evaluated. The other reagents studied overestimate or underestimate, with no clear profile. When a calibration curve was performed with a calibrator prepared from the N9-GP vial, all APTT reagents met the established recovery requirement. CONCLUSION: APTT reagents with polyphenol or ellagic acid as activator would be the only ones appropriate when using the commercially available OSA with specific calibrator to monitor patients treated with N9-GP.

Quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes.

Background: Novel therapies in metastatic cancers have contributed to improvements in survival outcomes, yet real-world data suggest that improvements may be mainly driven by those patient groups who already had the highest survival outcomes. This study aimed to develop and apply a framework for quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes based on published aggregate data. Methods: Nine (N = 9) novel therapies for metastatic breast cancer (mBC), metastatic colorectal cancer (mCRC), and metastatic non-small cell lung cancer (mNSCLC) were identified, 3 for each cancer type. Individual patient data (IPD) for overall survival (OS) and progression-free survival (PFS) were replicated from published Kaplan-Meier (KM) curves. For each cancer type, data were pooled for the novel therapies and comparators separately and weighted based on sample size to ensure equal contribution of each therapy in the analyses. Parametric (mixture) distributions were fitted to the weighted data to model and extrapolate survival. The inequality in survival was defined by the absolute difference between groups with the highest and lowest survival for 2 stratifications: one for which survival was stratified into 2 groups and one using 5 groups. Additionally, a linear regression model was fitted to survival estimates for the 5 groups, with the regression coefficient or slope considered as the inequality gradient (IG). The impact of the pooled novel therapies was subsequently defined as the change in survival inequality relative to the pooled comparator therapies. A probabilistic analysis was performed to quantify parameter uncertainty. Results: The analyses found that novel therapies were associated with significant increases in inequalities in survival outcomes relative to their comparators, except in terms of OS for mNSCLC. For mBC, the inequalities in OS increased by 13.9 (95% CI: 1.4; 26.6) months, or 25.0%, if OS was stratified in 5 groups. The IG for mBC increased by 3.2 (0.3; 6.1) months, or 24.7%. For mCRC, inequalities increased by 6.7 (3.0; 10.5) months, or 40.4%, for stratification based on 5 groups; the IG increased by 1.6 (0.7; 2.4) months, or 40.2%. For mNSCLC, inequalities decreased by 14.9 (-84.5; 19.0) months, or 12.2%, for the 5-group stratification; the IG decreased by 2.0 (-16.1; 5.1) months, or 5.5%. Results for the stratification based on 2 groups demonstrated significant increases in OS inequality for all cancer types. In terms of PFS, the increases in survival inequalities were larger in a relative sense compared with OS. For mBC, PFS inequalities increased by 8.7 (5.9; 11.6) months, or 71.7%, for stratification based on 5 groups; the IG increased by 2.0 (1.3; 2.6) months, or 67.6%. For mCRC, PFS inequalities increased by 5.4 (4.2; 6.6) months, or 147.6%, for the same stratification. The IG increased by 1.3 (1.1; 1.6) months, or 172.7%. For mNSCLC, inequalities increased by 18.2 (12.5; 24.4) months, or 93.8%, for the 5-group stratification; the IG increased by 4.0 (2.8; 5.4) months, or 88.1%. Results from the stratification based on 2 groups were similar. Conclusion: Novel therapies for mBC, mCRC, and mNSCLC are generally associated with significant increases in survival inequalities relative to their comparators in randomized controlled trials, though inequalities in OS for mNSCLC decreased nonsignificantly when stratified based on 5 groups. Although further research using real-world IPD is warranted to assess how, for example, social determinants of health affect the impact of therapies on health inequalities among patient groups, the proposed framework can provide important insights in the absence of such data.

Visceral adipose tissue reference data computed for GE HealthCare DXA from the National Health and Nutrition Examination Survey data set.

OBJECTIVE: The National Health and Nutrition Examination Survey (NHANES) characterizes body composition representative of the US population using dual-energy x-ray absorptiometry (DXA) scans. These population-level trends of abdominal subcutaneous and visceral adipose tissue (SAT and VAT) are useful for identifying measures associated with increased disease risk. Recently, VAT and SAT data collected by Hologic DXA in NHANES were published online; however, there are known differences in the absolute calibration of DXA systems by make. The purpose of this study was to create reference tables suitable for calculating z scores and percentile values for GE HealthCare (GEHC) DXA systems. METHODS: DXA scans were acquired on participants aged 8 to 59 years using Hologic systems. DXA measures were converted to GEHC and described using the least median squares curve fitting method in pediatrics (aged <20 years) and adults (aged 20-59 years). RESULTS: A total of 11,972 adults and 7298 pediatrics were included for this analysis. Adult and pediatric curves were generated by sex and by ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian, Other) and were derived as a function of age. CONCLUSIONS: These results show the ability to generate VAT and SAT reference data for GEHC systems using Hologic DXA data representative of the US youth and adult population.

Characterisation of Cooked Cheese Flavour: Non-Volatile Components.

This work examined the role of selected non-volatile compounds in cooked cheese flavour, both as tastants and as precursors of aroma generation in the Maillard reaction. The effect of cooking on the concentration of selected non-volatile compounds (organic acids, sugars, amino acids, γ-glutamyl dipeptides, and diketopiperazines) in six cheeses (mature Cheddar, mozzarella, Parmesan, and mild Cheddar (low, medium, and high fat)) was determined. Sugars, amino acids, and γ-glutamyl dipeptides were extracted and analysed by LC, whereas diketopiperazines were extracted by solid-phase extraction and analysed by GC-MS. Sugars, amino acids, and γ-glutamyl dipeptides decreased in concentration during cooking, whereas diketopiperazines and some organic acids increased in concentration. Diketopiperazines were above the taste threshold in some cooked cheeses and below the threshold in uncooked cheeses. The role of fat content in cooked cheese flavour is discussed. Furthermore, γ-glutamyl dipeptide concentration increased during 24 months of ageing in low, medium, and high-fat Cheddars, with similar levels of γ-glutamyl dipeptide detected in aged low and high-fat Cheddars. This work will give valuable insight for the dairy industry to inform the development of cheeses, especially low-fat variants, for use in cooked foods.

A COVID-19 isolation facility for people experiencing homelessness in Berlin, Germany: a retrospective patient record study.

Introduction: People experiencing homelessness (PEH) are disproportionately affected by the COVID-19 pandemic. For many PEH it is impossible to isolate due to the lack of permanent housing. Therefore, an isolation facility for SARS-CoV-2 positive PEH was opened in Berlin, Germany, in May 2020, offering medical care, opioid and alcohol substitution therapy and social services. This study aimed to assess the needs of the admitted patients and requirements of the facility. Materials and methods: This was a retrospective patient record study carried out in the isolation facility for PEH in Berlin, from December 2020 to June 2021. We extracted demographic and clinical data including observed psychological distress from records of all PEH tested positive for SARS-CoV-2 by RT-PCR. Data on duration and completion of isolation and the use of the facilities' services were analyzed. The association of patients' characteristics with the completion of isolation was assessed by Student's t-test or Fisher's exact test. Results: A total of 139 patients were included in the study (89% male, mean age 45 years, 41% with comorbidities, 41% non-German speakers). 81% of patients were symptomatic (median duration 5 days, range 1-26). The median length of stay at the facility was 14 days (range 2-41). Among the patients, 80% had non-COVID-19 related medical conditions, 46% required alcohol substitution and 17% opioid substitution therapy. Three patients were hospitalized due to low oxygen saturation. No deaths occurred. Psychological distress was observed in 20%, and social support services were used by 65% of PEH. The majority (82%) completed the required isolation period according to the health authority's order. We did not observe a statistically significant association between completion of the isolation period and sociodemographic characteristics. Conclusion: The specialized facility allowed PEH a high compliance with completion of the isolation period. Medical care, opioid and alcohol substitution, psychological care, language mediation and social support are essential components to address the specific needs of PEH. Besides contributing to infection prevention and control, isolation facilities may allow better access to medical care for SARS-CoV-2 infected PEH with possibly positive effects on the disease course.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work.

This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

Addition of chromium propionate in dog food: metabolic, immunological, and oxidative effects.

Chromium is a trace element essential in metabolising carbohydrates, lipids, and proteins and is involved in other biological functions. Therefore, this study determined whether chromium propionate supplementation in dogs improves haematologic, metabolic, immune/inflammatory, and antioxidant biomarkers. A commercial product (Labex® Chromium) containing 0.4% chromium was used at 500 g/ton of food, which provided an additional calculated amount of 2 mg of chromium per kg of food. We used ten beagles divided into two treatments: the chromium group (supplemented with 0.380 mg of chromium/dog/day; T-CHR) and the control group comprised dogs fed a basal diet (no chromium supplementation). The experiment included two periods of 28 days, with an interval of 15 days, i.e. the dogs in the control group in the first period were in the chromium group in the second period (all dogs underwent all treatments in a crossover design). Dogs supplemented with chromium had higher serum mineral levels on days 14 and 28 (P ≤ 0.001). The group in the chromium group showed significantly higher numbers of total leukocytes and lymphocytes and concentrations of total protein, globulin, thio-proteins, and catalase activity in blood than the control group. Serum urea concentrations and TBARS (lipid peroxidation) were lower (P ≤ 0.05) in the chromium group. Tendencies towards lower concentrations of reactive oxygen species were observed on day 28 in the T-CHR group (P = 0.10). Chromium supplementation increased the concentration of cytokines in serum (tumour necrosis factor-alpha [TNF-α], IFN-γ, and IL-10) and C-reactive protein (P ≤ 0.05). Dogs in the chromium group had higher gamma globulin concentrations than controls (P ≤ 0.001). These findings suggest that supplementation with chromium propionate (2 mg/kg) in food positivity modulates metabolic, antioxidant, and immune indicators in dogs.

Hair mercury is associated with dyslipidemia and cardiovascular risk: An anthropometric, biochemical and genetic cross-sectional study of Amazonian vulnerable populations.

This cross-sectional study evaluated the association between human exposure to mercury and cardiovascular risk using lipid profile (including apolipoproteins) and genetic analysis of Amazonian riverine population. Anthropometric data (gender, age, height, weight, blood pressure, and neck and waist circumferences) of the participants were recorded. Total mercury and methylmercury (MeHg) content were quantified in hair by ICP-MS and GC-pyro-AFS system. Polymorphisms rs662799, rs693, rs429358 and rs7412 (of genes of apolipoproteins A-V, B, and E at positions 112 and 158, respectively) were genotyped by real-time PCR. The population presented a dyslipidemia profile significantly correlated with high mercury levels. The apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) index was also positively correlated with mercury, supporting a possible causal relationship. Allelic distributions were similar to those described in other populations, suggesting that genetic susceptibility may not have a significant role in the lipid alterations found in this work. This study demonstrated for the first time: i) the relationship between mercury exposure and cardiovascular risk-related apolipoproteins in humans, ii) the ApoB levels and the ApoB/ApoA-I index as the risk factors more strongly associated to the mercury-related dyslipidemia in humans, and iii) the prevalence of high/moderate risk of acute myocardial infarction in the vulnerable and chronically exposed-populations of the Amazon, in addition to the genotypic profile of the three most frequent polymorphisms in apolipoproteins of relevance for cardiovascular risk. This early detection of lipid alterations is essential to prevent the development of cardiovascular diseases (CVD), especially in chronically exposed populations such as those found in the Amazon. Therefore, in addition to provide data for the Minamata Convention implementation, our work is in line with the efforts joined by all members of the World Health Organization committed to reducing premature deaths originating from non-communicable diseases by 25% in 2025, including CVD.

Access to a dementia-friendly garden on behavioural and psychological symptoms of dementia, falls and psychotropic medication use in residents of an aged care home in Melbourne, Australia.

OBJECTIVE: Residents of care homes need access to outdoors. This may improve behavioural and psychological symptoms of dementia (BPSD) and quality of life in residents living with dementia. Barriers including lack of accessibility and increased falls risk, which may be mitigated using dementia-friendly design. This prospective cohort study followed a group of residents in the first 6 months after the opening of a new dementia-friendly garden. METHOD: Nineteen residents participated. The Neuropsychiatric Inventory - Nursing Home Version (NPI-NH) and psychotropic medication use were collected at baseline, 3 and 6 months. The facility's falls rate during this time and feedback from staff and residents' next of kin were collected. RESULTS: Total NPI-NH scores decreased, though not significantly. Feedback was positive overall; the falls rate decreased. Usage of the garden was low. CONCLUSIONS: Despite its limitations, this pilot study adds to the literature about the importance of access to the outdoors for people who are experiencing BPSD. Staff remain concerned about falls risk despite the dementia-friendly design, and many residents do not access outdoors frequently. Further education may help to remove barriers to encouraging residents to access the outdoors.

Mosquito Fauna in the Mangroves of Yucatan, Mexico, and Identification of Alphavirus RNA.

The surveillance of arboviruses in mangrove mosquitoes is a neglected topic in Mexico. The Yucatan State is part of a peninsula and, therefore, is rich in mangroves along its coast. The purpose of the study was to identify alphavirus in the mosquito fauna of mangroves. Mosquitoes were captured in mangrove settings in seven communities in Yucatan between June 2019 and August 2021. From 1900 to 2200 h and from 0500 to 0800 h, mosquitoes were captured with a backpack-mounted aspirator. In total, 3,167 female mosquitoes of five genera and nine species were captured. Aedes taeniorhynchus and Anopheles crucians were the most abundant mosquitoes collected. Mosquitoes were sorted into 210 pools and tested by reverse transcription-polymerase chain reaction for alphavirus ribonucleic acid (RNA). Alphavirus RNA was found in Ae. taeniorhynchus, An. pseudopunctipennis, and An. crucians collected in the Celestun Mangrove. The community is part of the Ria Celestun Biosphere Reserve, and the presence arbovirus-infected mosquitoes could pose a health risk to residents and visitors alike in the area.

Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.

The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, ß and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ-/- mice; their "rescue" by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNß or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work / Enfermedades no transmisibles en la Región de las Américas: revisión del programa de trabajo de la Organización Panamericana de la Salud tras 25 años de actividades / Doenças não transmissíveis nas Américas: uma revisão do programa de trabalho de 25 anos da Organização Pan-Americana da Saúde

ABSTRACT This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

RESUMEN En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

RESUMO Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

A genome-informed higher rank classification of the biotechnologically important fungal subphylum Saccharomycotina.

The subphylum Saccharomycotina is a lineage in the fungal phylum Ascomycota that exhibits levels of genomic diversity similar to those of plants and animals. The Saccharomycotina consist of more than 1 200 known species currently divided into 16 families, one order, and one class. Species in this subphylum are ecologically and metabolically diverse and include important opportunistic human pathogens, as well as species important in biotechnological applications. Many traits of biotechnological interest are found in closely related species and often restricted to single phylogenetic clades. However, the biotechnological potential of most yeast species remains unexplored. Although the subphylum Saccharomycotina has much higher rates of genome sequence evolution than its sister subphylum, Pezizomycotina, it contains only one class compared to the 16 classes in Pezizomycotina. The third subphylum of Ascomycota, the Taphrinomycotina, consists of six classes and has approximately 10 times fewer species than the Saccharomycotina. These data indicate that the current classification of all these yeasts into a single class and a single order is an underappreciation of their diversity. Our previous genome-scale phylogenetic analyses showed that the Saccharomycotina contains 12 major and robustly supported phylogenetic clades; seven of these are current families (Lipomycetaceae, Trigonopsidaceae, Alloascoideaceae, Pichiaceae, Phaffomycetaceae, Saccharomycodaceae, and Saccharomycetaceae), one comprises two current families (Dipodascaceae and Trichomonascaceae), one represents the genus Sporopachydermia, and three represent lineages that differ in their translation of the CUG codon (CUG-Ala, CUG-Ser1, and CUG-Ser2). Using these analyses in combination with relative evolutionary divergence and genome content analyses, we propose an updated classification for the Saccharomycotina, including seven classes and 12 orders that can be diagnosed by genome content. This updated classification is consistent with the high levels of genomic diversity within this subphylum and is necessary to make the higher rank classification of the Saccharomycotina more comparable to that of other fungi, as well as to communicate efficiently on lineages that are not yet formally named. Taxonomic novelties: New classes: Alloascoideomycetes M. Groenew., Hittinger, Opulente & A. Rokas, Dipodascomycetes M. Groenew., Hittinger, Opulente & A. Rokas, Lipomycetes M. Groenew., Hittinger, Opulente, A. Rokas, Pichiomycetes M. Groenew., Hittinger, Opulente & A. Rokas, Sporopachydermiomycetes M. Groenew., Hittinger, Opulente & A. Rokas, Trigonopsidomycetes M. Groenew., Hittinger, Opulente & A. Rokas. New orders: Alloascoideomycetes: Alloascoideales M. Groenew., Hittinger, Opulente & A. Rokas; Dipodascomycetes: Dipodascales M. Groenew., Hittinger, Opulente & A. Rokas; Lipomycetes: Lipomycetales M. Groenew., Hittinger, Opulente & A. Rokas; Pichiomycetes: Alaninales M. Groenew., Hittinger, Opulente & A. Rokas, Pichiales M. Groenew., Hittinger, Opulente & A. Rokas, Serinales M. Groenew., Hittinger, Opulente & A. Rokas; Saccharomycetes: Phaffomycetales M. Groenew., Hittinger, Opulente & A. Rokas, Saccharomycodales M. Groenew., Hittinger, Opulente & A. Rokas; Sporopachydermiomycetes: Sporopachydermiales M. Groenew., Hittinger, Opulente & A. Rokas; Trigonopsidomycetes: Trigonopsidales M. Groenew., Hittinger, Opulente & A. Rokas. New families: Alaninales: Pachysolenaceae M. Groenew., Hittinger, Opulente & A. Rokas; Pichiales: Pichiaceae M. Groenew., Hittinger, Opulente & A. Rokas; Sporopachydermiales: Sporopachydermiaceae M. Groenew., Hittinger, Opulente & A. Rokas. Citation: Groenewald M, Hittinger CT, Bensch K, Opulente DA, Shen X-X, Li Y, Liu C, LaBella AL, Zhou X, Limtong S, Jindamorakot S, Gonçalves P, Robert V, Wolfe KH, Rosa CA, Boekhout T, Cadez N, Péter G, Sampaio JP, Lachance M-A, Yurkov AM, Daniel H-M, Takashima M, Boundy-Mills K, Libkind D, Aoki K, Sugita T, Rokas A (2023). A genome-informed higher rank classification of the biotechnologically important fungal subphylum Saccharomycotina. Studies in Mycology 105: 1-22. doi: 10.3114/sim.2023.105.01 This study is dedicated to the memory of Cletus P. Kurtzman (1938-2017), a pioneer of yeast taxonomy.