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During SARS-CoV-2 infection, eosinopenia may reflect a hyperactive immune response. In this study of hospitalized COVID-19 patients, we aimed to better understand the prognostic value of severe eosinopenia (absolute eosinophil count = 0 G/L) and decipher its underlying mechanisms. We retrospectively analyzed the records of COVID-19 patients hospitalized from March to June 2020 in three university hospitals in Marseille, France. We assessed the association between severe eosinopenia and a composite poor outcome in these patients, including the need for oxygen supplementation at >6 L/min, ICU admission, and in-hospital death. Among the 551 COVID-19 patients included in this study, severe eosinopenia was found in 228 (51%) of them on admission to hospital and was associated with a composite poor outcome using multivariate analysis (OR = 2.58; CI95 [1.77–3.75]; p < 0.0001). We found a significant association between the presence of severe eosinopenia on admission and the elevation in C-reactive protein, ferritin, IP-10, and suPAR. The histological findings in a series of 37 autopsies from patients who died from severe COVID-19 and presented with severe eosinopenia showed no pulmonary eosinophil trapping. Severe eosinopenia can be a reliable biomarker associated with a composite poor outcome in hospitalized COVID-19 adult patients. It may reflect the magnitude of immune hyperactivation during severe-to-critical COVID-19.

Changes in gene regulation underlie much of phenotypic evolution.sup.1. However, our understanding of the potential for regulatory evolution is biased, because most evidence comes from either natural variation or limited experimental perturbations.sup.2. Using an automated robotics pipeline, we surveyed an unbiased mutation library for a developmental enhancer in Drosophila melanogaster. We found that almost all mutations altered gene expression and that parameters of gene expression--levels, location, and state--were convolved. The widespread pleiotropic effects of most mutations may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse Drosophila larvae revealed apparent biases in the phenotypes influenced by the enhancer. Developmental enhancers may encode a higher density of regulatory information than has been appreciated previously, imposing constraints on regulatory evolution. A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution., Author(s): Timothy Fuqua [sup.1] [sup.2] , Jeff Jordan [sup.3] , Maria Elize van Breugel [sup.1] , Aliaksandr Halavatyi [sup.1] , Christian Tischer [sup.1] , Peter Polidoro [sup.3] , Namiko Abe [...]

Enhanced-efficiency phosphate fertilisers may play an important role in phosphorus (P) availability in tropical soils by increasing their concentration in solution and enhancing the diffusive flux of P (DFP). This work evaluated the DFP in soil influenced by polymer-coated phosphate fertilisers and organophosphates (enhanced-efficiency phosphate fertilisers) applied to soil, at two matric potentials. The experiment was conducted using a 4 * 2 * 4 + 2 factorial design in which four phosphate fertilisers (conventional monoammonium phosphate (MAP), polymer-coated monoammonium phosphate (POL), pelletised monoammonium phosphate with filter cake (FC) and granulated monoammonium phosphate with swine compost (SC)), two soil water contents corresponding to two matric potentials (-10 and -50 kPa), four anion exchange resin insertion distances (0.5, 1.0, 1.5 and 2.0 cm from the phosphate fertiliser granules) and two control treatments (matric potential of -10 and -50 kPa without fertiliser) were studied across four replicates. Enhanced-efficiency phosphate fertilisers increased the release of P into the soil solution. The values of DFP (nmol [m.sup.-2] 15 [days.sup.-1]) for MAP were in the range of 0. 18-48.69, for POL were 0.19-32.20, for FC were 0.17-19.74 and for SC were 0.17-18.50. For -10 and -50 kPa matric potentials, the values ranged within 0.18-43.07 and 0.17-48.69 nmol [m.sup.-2] 15 [days.sup.-1] respectively. In relation to the distances 0.5, 1.0, 1.5 and 2.0 cm, DFP (nmol [m.sup.-2] 15 [days.sup.-1]) ranged within 17.56-48.69, 0.42-11.39, 0.22-0.57 and 0.17-0.22 respectively. The decrease in the soil water matric potential decreased DFP in the short term for fertilisers with coating technologies compared to MAP. This result indicates that coating technologies hold promise for maintaining DFP over time. Additional keywords: anion exchange resin, diffusion, fertiliser technology, monoammonium phosphate. Received 28 August 2019, accepted 18 December 2019, published online 30 January 2020, Introduction The low phosphorus (P) availability in soils is one of the most limiting factors for crop productivity in tropical regions (DeLonge el al. 2013). When oxidic mineralogy predominates, these [...]

Objetivo: avaliar a carga de trabalho de enfermagem em uma unidade de internação neonatal e correlacionar com características clínicas dos pacientes. Método: estudo descritivo e transversal, com o Nursing Activities Score em uma unidade neonatal de hospital público de ensino. Foram incluídos pacientes hospitalizados por no mínimo 24 horas, no período de 60 dias. Os dados foram analisados segundo estatística descritiva e inferencial. Resultados: a amostra foi composta por 115 pacientes, com total de 1944 medidas. A média do Nursing Activities Score foi de 73%, obtendo-se média de 74% em leitos de cuidados intensivos e 64% em cuidados semi-intensivos. Conclusão: identificou-se uma alta carga de trabalho, com média de 17,5 horas de assistência a cada recém-nascido nas 24 horas, o que pode ter impacto na segurança da assistência. Peso de nascimento e idade gestacional podem representar incremento à carga de trabalho dos profissionais. ABSTRACT Objective: to evaluate the nursing workload at a neonatal unit and to correlate it to patient clinical characteristics. Method: this descriptive, cross-sectional study applied the Nursing Activities Score to assess nursing workload at a neonatal unit of a public teaching hospital. Patients included were those hospitalized for at least 24 hours over 60-day period. Data were analyzed using descriptive and inferential statistics. Results: the sample comprised 115 patients, yielding a total of 1944 measurements. The average Nursing Activities Score at the unit was 73%, an average of 74% for intensive care beds and 64% for semi-intensive ones. Conclusion: high workload was identified at the unit, averaging 17.5 hours of care every 24 hours for each newborn, which can impact the safety of care. Birth weight and gestational age may entail increased workload for nursing staff. RESUMEN Objetivo: evaluar la carga de trabajo de enfermería en una unidad de hospitalización neonatal y relacionarla con las características clínicas de los pacientes. Método: se trata de un estudio descriptivo y transversal, utilizando el Nursing Activities Score en una unidad neonatal, en un hospital universitario público. Se incluyeron pacientes hospitalizados durante al menos 24 horas, dentro del período de 60 días. Se analizaron los datos según estadística descriptiva e inferencial. Resultados: la muestra se compuso de 115 pacientes, totalizando 1944 mediciones. El puntaje promedio del Nursing Activities Score fue del 73%, siendo el promedio para la unidad de cuidados intensivos del 74% y para los cuidados semi intensivos del 64%. Conclusión: se identificó una alta carga de trabajo en la unidad, con un promedio de 17.5 horas de atención a cada neonato en 24 horas, lo que puede impactar la seguridad de la atención. El peso al nacer y la edad gestacional pueden representar un aumento en la carga de trabajo de los profesionales.

Objective: to compare the workload at a neonatal unit, according to Nursing Activities Score, and the dimensioning of nursing staff. Methods: cross-sectional study at a teaching unit with 30 beds. Data collection took place from October 6 to December 6, 2017, and data were analyzed according to descriptive statistics. Results: the sample of 115 neonates, totaling 1944 measurements. The average workload score was 73%. The unit has 107 nursing professionals, while should has 137. The proportion of registered nurses was lower than recommended (34%), whereas the proportion of nursing technicians was higher than recommended (66%). Conclusion: there was an imbalance between workload and number of professionals in nursing staff. Tools as Nursing Activities Score should be applied for supporting the staff dimensioning, since workload can impact the health outcomes and patient safety.

Background: The family of synthetic peptide angiopeps, and particularly angiopep-2 (ANG-2) demonstrated the ability preclinically and clinically to shuttle active molecules across the blood–brain barrier (BBB) and selectively toward brain tumor cells. The literature has also proved that the transport occurs through a specific receptor-mediated transcytosis of the peptide by LRP-1 receptors present both on BBB and tumor cell membranes. However, contradictory results about exploiting this promising mechanism to engineer complex delivery systems, such as nanoparticles, are being obtained. Methodology: For this reason, we applied a molecular docking (MD)-based strategy to investigate the molecular interaction of ANG-2 and the LRP-1 ligand-binding moieties (CR56 and CR17), clarifying the impact of peptide conjugation on its transport mechanism. Results: MD results proved that ANG-2/LRP-1 binding involves the majority of ANG-2 residues, is characterized by high binding energies, and that it is site-specific for CR56 where the binding to 929ASP recalls a transcytosis mechanism, resembling the binding of the receptor to the receptor-associated protein. On the other hand, ANG-2 binding to CR17 is less site-specific but, as proved for apolipoprotein internalization in physiological conditions, it involves the ANG-2 lysin residue. Conclusions: Overall, our results proved that ANG-2 energetic interaction with the LRP-1 receptor is not hindered if specific residues of the peptide are chemically crosslinked to simple or complex engineered delivery systems.

Resumo Este trabalho investiga como a saúde de pessoas lésbicas, gays, bissexuais, travestis, transexuais e intersexuais (LGBTI) tem sido afetada no contexto da pandemia da covid-19, por meio da percepção de ativistas da sociedade civil organizada, no Estado do Rio Grande do Sul (RS), Brasil. Realizou-se uma análise qualitativa, que reporta dados preliminares de um estudo maior sobre a Política Nacional de Saúde LGBTI. O levantamento foi feito entre maio e julho de 2020, com a aplicação de entrevistas realizadas online. O enfoque se deu sobre as percepções, as experiências individuais e coletivas de ativistas sobre a temática da saúde LGBTI, em meio ao atravessamento da pandemia da covid-19. Constataram-se efeitos sobre a mobilização comunitária; o acesso aos serviços de saúde; a saúde mental; e as situações de violência e proteção social. Conclui-se que as intervenções coletivas de pessoas LGBTI são fundamentais em contextos de crise sanitária e dão suporte à garantia do direito à saúde e preservação de políticas públicas a esta população.

Abstract: This study aimed to estimate household pesticide exposure in adult individuals in the Metropolitan Region of Rio de Janeiro, Brazil, and to verify the accessibility of these products in local and online businesses. The data were collected by an online questionnaire (1,015 responses) and a shelf survey in physical and online stores. Among the responses analyzed, 87.5% used pesticides in the previous year, most of which against mosquitoes (64.7%). The most common application method was aerosol spray (38.1%), and the most frequent places of use were bedrooms (29.7%) and living rooms (22.1%). About 30% of respondents reported invasion of pests, and the most common pests were ants (79.1%) and cockroaches (40.4%). Service area (71.6%) and kitchen (17.5%) were the most common storage locations. Approximately 91% of those who lived with children aged under 18 used pesticides. The use of chemical group of pyrethroids prevailed (81.6%), and 90.8% of the reportedly used products are class II [55.7% (highly toxic)] or class III [35.1% (medium toxic)]. The most significant amount of purchased products was in the pest category, followed by mosquitoes. More variety of products were available in online stores than in physical stores. The high exposure of the population to pesticides at household is a public health issue and confirms the need for studies that better assess the risks and consequences of chronic and low-dose exposure to these substances. It is essential to inform the population about the uncertainties and potential risks of indiscriminate use so that they can choose whether to use pesticides in their households.

This study aimed to investigate the antiproteinuric and hyperkalemic mechanisms activated by dual renin-angiotensin system (RAS) blockade in renovascular hypertensive rats (2-kidney 1-clip model [2K-1C]). Six weeks after clipping the left renal artery or sham operation (2K), rats were treated with losartan, enalapril, or both drugs for two weeks. We found that 2K-1C rats displayed higher tail-cuff blood pressure (BP), increased non-clipped kidney Ang II concentration, and more pronounced urinary albumin excretion than 2K. BP was decreased by the treatment with either enalapril or losartan, and the combination of both drugs promoted an additional antihypertensive effect in 2K-1C rats. Renal Ang II content and albuminuria were reduced by either enalapril or losartan in monotherapy and restored to control levels by dual RAS blockade. Albuminuria in 2K-1C rats was accompanied by downregulation of the glomerular slit protein podocin, reduction of the endocytic receptors megalin and cubilin, and a marked decrease in the expression of the ClC-5 chloride channel, compared to 2K animals. Treatment with losartan and enalapril in monotherapy or combination increased the expression of podocin, cubilin, and ClC-5. However, only the combined therapy normalized podocin, cubilin, and ClC-5 protein abundance in the non-clipped kidney of 2K-1C rats. Renovascular hypertensive 2K-1C rats had a lower concentration of plasma potassium compared to 2K rats. Single RAS blockade normalized potassium plasma concentration, whereas 2K-1C rats treated with dual RAS blockade exhibited hyperkalemia. Hypokalemia in 2K-1C rats was accompanied by an increase in the cleaved activated forms of α-ENaC and γ-ENaC and the expression of β-ENaC. Combined RAS blockade but not monotherapy significantly reduced the expression of these ENaC subunits in 2K-1C rats. Indeed, double RAS blockade reduced the abundance of cleaved-α-ENaC to levels lower than those of 2K rats. Collectively, these results demonstrate that the antiproteinuric effect of dual RAS blockade in 2K-1C rats is associated with the restored abundance of podocin and cubilin, and ClC-5. Moreover, double RAS blockade-induced hyperkalemia may be due, at least partially, to an exaggerated downregulation of cleaved α-ENaC in the non-clipped kidney of renovascular hypertensive rats.

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.

We prove surface and volume mean value formulas for classical solutions to uniformly elliptic equations in divergence form with Hölder continuous coefficients. The kernels appearing in the integrals are supported on the level and superlevel sets of the fundamental solution relative the adjoint differential operator. We then extend the aforementioned formulas to some subelliptic operators on Carnot groups. In this case we rely on the theory of finite perimeter sets on stratified Lie groups. [ABSTRACT FROM AUTHOR]

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a ‘meet-in-the-middle’ approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

Abstract Background Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date. Methods We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis ( 10 years). The false discovery rate (q value) was used to account for multiple testing. Results The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98). Conclusions Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk.

Abstract Background Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. Methods Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. Results We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p

Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.