Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study / Relação dos níveis de hemoglobina com desfechos em transplante renal de doador falecido: um estudo de coorte retrospectivo

ABSTRACT Introduction: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor. Methods: This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors' and kidney transplant patients' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years. Results: We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause. Conclusion: An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.

RESUMO Introdução: A anemia é frequente em pacientes submetidos à terapia substitutiva para insuficiência renal. A anemia nos períodos pré e pós-transplante pode estar relacionada aos desfechos do transplante renal. Portanto, o presente estudo buscou avaliar a relação entre anemia, função retardada do enxerto (FRE), disfunção crônica do enxerto renal (DCE) e óbito por qualquer causa após transplante renal de doador falecido. Métodos: Este foi um estudo retrospectivo com 206 pacientes transplantados renais de doadores falecidos. Analisamos dados demográficos de doadores falecidos e pacientes transplantados renais. Além disso, comparamos parâmetros bioquímicos, status de anemia e medicamentos entre os grupos FRE e não-FRE. Posteriormente, realizamos uma análise multivariada. Também avaliamos desfechos, como DCE em um ano e óbito em dez anos. Resultados: Observamos menor frequência de concentração de hemoglobina (Hb) pré-transplante, mas maior frequência de creatinina sérica do doador e transfusão de hemácias no período de uma semana após o transplante no grupo FRE. Além disso, houve associação independente entre a concentração de Hb antes do transplante e a FRE [OR 0,252; IC 95%: 0,159-0,401; p < 0,001]. Houve também associação entre a concentração de Hb após seis meses de transplante renal e ambos, DCE [OR 0,798; IC95%: 0,687-0,926; p = 0,003] e óbito por qualquer causa. Conclusão: Encontrou-se uma associação entre anemia pré-transplante e FRE e entre anemia seis meses após o transplante e ambos, DCE e óbito por qualquer causa. Assim, a anemia antes ou após o transplante afeta os desfechos de pacientes que foram submetidos a transplante renal de doador falecido.

Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study.

INTRODUCTION: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor. METHODS: This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors' and kidney transplant patients' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years. RESULTS: We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause. CONCLUSION: An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.

Toxicological effects of hydroxychloroquine sulfate and chloroquine diphosphate substances on the early-life stages of fish in the COVID-19 pandemic context.

Hydroxychloroquine sulfate (HCQ) and chloroquine diphosphate (CQ) have been used at increased rates to treat COVID-19 but can constitute a potential environmental risk. The objective was to evaluate the toxicity of sublethal concentrations of HCQ and CQ in zebrafish embryos/larvae. The 50% lethal concentrations (LC50) of HCQ and CQ at 96 h post-fertilization (hpf) were calculated by testing various concentrations on 2,160 embryos. The LC50 obtained were 560 and 800 µM for HCQ and CQ, respectively. Next, the embryotoxicity assay was performed, where 1,200 embryos were subjected to sublethal concentrations of HCQ and CQ. The hatching and heart rates were recorded. After euthanasia, photomicrographs of all larvae were taken to measure the total length, pericardial and yolk sac areas. The embryos exposed to sublethal concentrations of HCQ and CQ showed delayed hatching at 72 hpf, as well as an increase in the heart rate, larger pericardial and yolk sac areas, and body malformations at 96 hpf. The findings show that HCQ and CQ are toxic to fish in the early development phases. Understanding the mechanisms of toxicity will help extrapolate the effects of 4-aminoquinoline derivatives when they reach the aquatic environment in the context of the COVID-19 pandemic.

Physical conditioning in children and adolescents with cerebral palsy: Systematic review and meta-analysis.

INTRODUCTION: Cerebral palsy (CP) can be described as a group of permanent non-progressive disorders that occur in the developing fetal or infant brain. Studies have shown that children and adolescents with CP have low cardiorespiratory fitness and higher energy expenditure during daily activities when compared to typical children. Therefore, interventions focused on the physical conditioning of this population could be critical. OBJECTIVE: To evaluate the effect of physical conditioning training on distance walked and maximum oxygen consumption (VO2 max) in individuals with CP, through a systematic review. METHOD: Two independent researchers performed systematic searches in the PUBMED, SciELO, PEDro, ERIC, and Cochrane databases using the search terms "physical fitness", "aerobic training" or "endurance" combined with "cerebral palsy". INCLUSION CRITERIA: (1) population (children and adolescents with CP between 5 and 18 years old); (2) type of study (experimental studies); (3) type of intervention (physical conditioning protocols); (4) outcome (distance walked in the 6 min walking test - 6MWT, and VO2 max). RESULTS: 386 studies were identified and 5 articles were considered eligible. After physical conditioning training, there was an increase of 46.34 m (p = 0.07) and 5.93. ml. kg-1. min -1 (p < 0.001) in the 6MWT and VO2 max, respectively. CONCLUSION: Physical conditioning training appears to be clinically beneficial to the cardiorespiratory fitness of children and adolescents with CP.

Hematological ratios in coronavirus disease 2019 patients with and without invasive mechanical ventilation.

Patients with the most severe form of coronavirus disease 2019 (COVID-19) often require invasive ventilation. Determining the best moment to intubate a COVID-19 patient is complex decision and can result in important consequences for the patient. Therefore, markers that could aid in clinical decision-making such as hematological indices are highly useful. These markers are easy to calculate, do not generate extra costs for the laboratory, and are readily implemented in routine practice. Thus, this study aimed to investigate differences in the ratios calculated from the hemogram between patients with and without the need for invasive mechanical ventilation (IMV) and a control group. This was an observational retrospective analysis of 212 patients with COVID-19 that were hospitalized between April 1, 2020 and March 31, 2021 who were stratified as IMV (n = 129) or did not require invasive mechanical ventilation (NIMV) (n = 83). A control group of 198 healthy individuals was also included. From the first hemogram of each patient performed after admission, the neutrophil-to-lymphocyte ratio (NLR), the derived NLR (d-NLR), the lymphocyte-to-monocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-platelet ratio (NPR), and the systemic immune-inflammation index (SII) were calculated. All hematological ratios exhibited significant differences between the control group and COVID-19 patients. NLR, d-NLR, SII, and NPR were higher in the IMV group than they were in the NIMV group. The hematological indices addressed in this study demonstrated high potential for use as auxiliaries in clinical decision-making regarding the need for IMV.

Hatchery tanks induce intense reduction in microbiota diversity associated with gills and guts of two endemic species of the São Francisco River.

The São Francisco River (SFR), one of the main Brazilian rivers, has suffered cumulative anthropogenic impacts, leading to ever-decreasing fish stocks and environmental, economic, and social consequences. Rhinelepis aspera and Prochilodus argenteus are medium-sized, bottom-feeding, and rheophilic fishes from the SFR that suffer from these actions. Both species are targeted for spawning and restocking operations due to their relevance in artisanal fisheries, commercial activities, and conservation concerns. Using high-throughput sequencing of the 16S rRNA gene, we characterized the microbiome present in the gills and guts of these species recruited from an impacted SFR region and hatchery tanks (HT). Our results showed that bacterial diversity from the gill and gut at the genera level in both fish species from HT is 87% smaller than in species from the SFR. Furthermore, only 15 and 29% of bacterial genera are shared between gills and guts in R. aspera and P. argenteus from SFR, respectively, showing an intimate relationship between functional differences in organs. In both species from SFR, pathogenic, xenobiont-degrading, and cyanotoxin-producer bacterial genera were found, indicating the critical pollution scenario in which the river finds itself. This study allowed us to conclude that the conditions imposed on fish in the HT act as important modulators of microbial diversity in the analyzed tissues. It also raises questions regarding the effects of these conditions on hatchery spawn fish and their suitability for restocking activities, aggravated by the narrow genetic diversity associated with such freshwater systems.

Ultrasonographic evaluation of cecal appendix diameter in pediatric population.

OBJECTIVE: To stratify ultrasound samples in a pediatric population undergoing evaluation for acute appendicitis to examine the variability in cecal appendix diameter, in different age groups, and to determine whether there is a prevalent value for each age group. METHODS: A retrospective cross-sectional study with 196 children aged 0 to 15 years. Data were extracted from reports of ultrasound examinations carried out between 2008 and 2015. Children with sonographic diagnosis of appendicitis or other signs of periappendiceal inflammation were excluded. RESULTS: The evaluation of the anteroposterior measurement of the cecal appendix revealed a mean diameter of 4.14mm (standard deviation: 0.93mm; 95%CI: 3.86-4.14). Cecal appendix diameter did not differ significant between age groups. CONCLUSION: Evaluation of the anteroposterior diameter of the cecal appendix in centimeters in a sample of 196 children aged 0 to15 years revealed a mean diameter of 4.14mm (standard deviation, 0.93mm. There were no significant differences in cecal appendix diameter following stratification by age. Results indicate a single value can be adopted for mean cecal appendix diameter in pediatric populations.

Ultrasonographic evaluation of cecal appendix diameter in pediatric population

ABSTRACT Objective To stratify ultrasound samples in a pediatric population undergoing evaluation for acute appendicitis to examine the variability in cecal appendix diameter, in different age groups, and to determine whether there is a prevalent value for each age group. Methods A retrospective cross-sectional study with 196 children aged 0 to 15 years. Data were extracted from reports of ultrasound examinations carried out between 2008 and 2015. Children with sonographic diagnosis of appendicitis or other signs of periappendiceal inflammation were excluded. Results The evaluation of the anteroposterior measurement of the cecal appendix revealed a mean diameter of 4.14mm (standard deviation: 0.93mm; 95%CI: 3.86-4.14). Cecal appendix diameter did not differ significant between age groups. Conclusion Evaluation of the anteroposterior diameter of the cecal appendix in centimeters in a sample of 196 children aged 0 to15 years revealed a mean diameter of 4.14mm (standard deviation, 0.93mm. There were no significant differences in cecal appendix diameter following stratification by age. Results indicate a single value can be adopted for mean cecal appendix diameter in pediatric populations.

SARS-CoV-2 Omicron spike mediated immune escape, infectivity and cell-cell fusion

The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that Omicron BA.1 has higher affinity for ACE2 compared to Delta, and confers very significant evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralising antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralisation. Importantly, antiviral drugs remdesevir and molnupiravir retain efficacy against Omicron BA.1. We found that in human nasal epithelial 3D cultures replication was similar for both Omicron and Delta. However, in lower airway organoids, Calu-3 lung cells and gut adenocarcinoma cell lines live Omicron virus demonstrated significantly lower replication in comparison to Delta. We noted that despite presence of mutations predicted to favour spike S1/S2 cleavage, the spike protein is less efficiently cleaved in live Omicron virions compared to Delta virions. We mapped the replication differences between the variants to entry efficiency using spike pseudotyped virus (PV) entry assays. The defect for Omicron PV in specific cell types correlated with higher cellular RNA expression of TMPRSS2, and accordingly knock down of TMPRSS2 impacted Delta entry to a greater extent as compared to Omicron. Furthermore, drug inhibitors targeting specific entry pathways demonstrated that the Omicron spike inefficiently utilises the cellular protease TMPRSS2 that mediates cell entry via plasma membrane fusion. Instead, we demonstrate that Omicron spike has greater dependency on cell entry via the endocytic pathway requiring the activity of endosomal cathepsins to cleave spike. Consistent with suboptimal S1/S2 cleavage and inability to utilise TMPRSS2, syncytium formation by the Omicron spike was dramatically impaired compared to the Delta spike. Overall, Omicron appears to have gained significant evasion from neutralising antibodies whilst maintaining sensitivity to antiviral drugs targeting the polymerase. Omicron has shifted cellular tropism away from TMPRSS2 expressing cells that are enriched in cells found in the lower respiratory and GI tracts, with implications for altered pathogenesis.

Royal Sun Culinary-Medicinal Mushroom Agaricus brasiliensis (Agaricomycetes) as a Functional Food in Gestational Diabetes Mellitus Before and After Fetus Implantation.

Through preclinical tests, this study evaluated the effects of Agaricus brasiliensis consumption in rats with streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) and considered its potential as a functional food. The perinatal period was evaluated considering the daily exposure to A. brasiliensis before and after GDM induction (Abb and Aba, respectively). Nutritional characterization of A. brasiliensis was performed (centesimal composition, ß-glucans, phenolic compounds, and antioxidant activity). Concerning maternal reproductive development, the parameters assessed were maternal weight, oral glucose tolerance, hemogram, biochemical markers, redox status in blood, biochemical markers in amniotic fluid, and reproductive performance. Moreover, embryofetal development was evaluated. A. brasiliensis reduced hyperglycemia before STZ induction and maintained levels similar to the GDM group after STZ induction. A. brasiliensis also reduced alanine aminotransferase, aspartate aminotransferase, triglyceride, and cholesterol levels and increased high-density lipoprotein levels. The mushroom also presented antioxidant activity, improving parameters of oxidative stress. Furthermore, it protected the conceptus from actions promoted by STZ concerning external abnormalities. Thus, daily intake of A. brasiliensis in GDM suggests its potential as a functional food because the nutritional characterization of this mushroom indicated important antioxidant activity, improving lipid and glycemic functions and preventing oxidative damage from STZ.

Natural deep eutectic solvent (NADES): A strategy to improve the bioavailability of blueberry phenolic compounds in a ready-to-use extract.

This study investigated whether a ready-to-use extract obtained using a natural deep eutectic solvent (NADES) affects the pharmacokinetic profile of blueberry phenolic compounds compared to organic solvent (SORG)-extracted compounds. SORG extract was administered as an aqueous solution after solvent removal. Wistar rats received a single dose of crude extract of blueberry obtained using NADES (CE-NADES) or SORG (CE-SORG), followed by LC-DAD-MS/MS analysis of blood and cecal feces. Non-compartmental pharmacokinetic analysis revealed that CE-NADES increased the bioavailability of anthocyanins by 140% compared to CE-SORG. CE-NADES increased the stability of phenolic compounds during in vitro digestion by delaying gastric chyme neutralization. These results suggest that besides being an eco-friendly solvent for the extraction of phytochemicals, choline chloride:glycerol:citric acid-based NADES can be used as a ready-to-use vehicle for increasing oral absorption of bioactive compounds such as anthocyanins.

SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD), in particular to the clinically approved bamlavinimab and imdevimab monoclonal antibodies. B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems as compared to B.1.1.7, associated with B.1.617.2 spike being in a predominantly cleaved state compared to B.1.1.7. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed substantially reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart.

Our study aimed to investigate the effects of the new cardiotonic steroid BD-15 (γ-benzylidene derivatives) in the behavioral parameters, oxidative stress and the Na, K-ATPase activity in the hippocampus, prefrontal cortex and heart from rats to verify the safety and possible utilization in brain disorders. For this study, groups of male Wistar rats were used after intraperitoneal injection of 20, 100 and 200 µg/Kg with BD-15. The groups were treated for three consecutive days and the control group received 0.9% saline. BD-15 did not alter behavior of rats treated with different doses. An increase in the specific α2,3-Na, K-ATPase activity was observed for all doses of BD-15 tested in the hippocampus. However, in the prefrontal cortex, only the dose of 100 µg/Kg increased the activity of all Na, K-ATPase isoforms. BD-15 did not cause alteration in the lipid peroxidation levels in the hippocampus, but in the prefrontal cortex, a decrease of lipid peroxidation (~ 25%) was observed. In the hippocampus, GSH levels increased with all doses tested, while in the prefrontal cortex no changes were found. Subsequently, when the effect of BD-15 on cardiac tissue was analyzed, no changes were observed in the tested parameters. BD-15 at a dosage of 100 µg/Kg proved to be promising because it is considered therapeutic for brain disorders, since it increases the activity of the α3-Na, K-ATPase in the hippocampus and prefrontal cortex, as well as decreasing the oxidative stress in these brain regions. In addition, this drug did not cause changes in the tissues of the heart and kidneys, preferentially demonstrating specificity for the brain.

Analysis of the occurrence of microplastics in beach sand on the Brazilian coast.

The occurrence of microplastics in coastal areas is a growing concern due to the increase in plastic waste pollution in recent decades. This study had as objective to evaluate the occurrence of microplastics in Brazilian beach sand, using a simple and fast methodology. In addition, possible microplastics were classified according to color, shape and chemical composition. The study was conducted on six beaches on the Brazilian coast: Pecado Beach (RJ), Castanheiras Beach (ES), Regência Beach (ES), Imbassaí Beach (BA), Viral Beach (SE) and Ponta dos Mangues Beach (SE). The methodology was adapted from international protocols, with section demarcation (100 m), where samples were collected from the superficial layer of the beach sand in ten quadrants (50 cm × 50 cm). The laboratory extraction procedure consisted of the density separation technique in two stages: the first used sodium chloride solution and the second used zinc chloride solution. For the visual inspection and screening procedures, a stereoscopic microscope was used. A total of 166 items of microplastics were collected on the six beaches on the Brazilian coast under study. The largest quantity of possible microplastics was recorded on the beaches of Viral (SE) and Ponta dos Mangues (SE) with 30.4 items/m2 and 17.4 items/m2, respectively. Regarding colour, white items were predominant (49.3%), and among particle types, fragments represented 85.1%. In addition, some microplastic particles were sent for FT-IR analysis, one of which was identified as being polyethylene. This study contributes to the knowledge of the presence of microplastics in different locations, and to supporting decision makers regarding coastal management.

Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination

Two dose mRNA vaccination provides excellent protection against SARS-CoV-2. However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared to younger participants following first dose. The adjusted odds ratio for inadequate neutralisation activity against the B.1.1.7, P.1 and B.1.351 variant in the older versus younger age group was 4.3 (95% CI 2.0-9.3, p<0.001), 6.7 (95% CI 1.7-26.3, p=0.008) and 1.7 (95% CI 0.5-5.7, p=0.41). Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B-memory cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T-cell IFN{gamma} and IL-2 responses fell with increasing age, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating.

Impact of SARS-CoV-2 B.1.1.7 Spike variant on neutralisation potency of sera from individuals vaccinated with Pfizer vaccine BNT162b2

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.

Intervenção da terapia ocupacional em instituições de longa permanência para idosos a partir da percepção de terapeutas ocupacionais / Occupational therapy interventions in long-stay Institutions for the elderly throughout occupational therapists perceptions

Introdução: A Instituição de Longa Permanência para Idosos (ILPI) é um serviço sociossanitário previsto nas políticas públicas de gerontologia. A atuação da Terapia Ocupacional (TO) neste campo ainda é pouco explorada na literatura. Objetivo: Conhecer e caracterizar a atuação dos TOs em ILPI. Métodos: Estudo qualitativo, exploratório e descritivo. Empregou-se a técnica bola-de-neve para localização e acesso aos 10 TOs com experiência em ILPI na cidade de São Paulo. Esses foram entrevistados no mês de agosto de 2022. Os resultados foram tratados à luz da análise temática por categorias prévias, correspondentes às questões contidas no roteiro semiestruturado de entrevistas, elaborado pelas pesquisadoras. Resultados:As ações do TO caracterizavam-se pela/o(s): acolhimento do sofrimento nos processos de institucionalização e das vivências relacionadas ao luto; prescrição de equipamentos de tecnologia assistiva; intervenções ambientais e ações com cuidadores formais e familiares. As ações objetivavam: a manutenção/resgate da autonomia, funcionalidade e atividades significativas; melhora das habilidades físico-sensório-cognitivas e favorecer as trocas relacionais. Identificou-se pouca compreensão das equipes e chefias sobre a atuação do TO. Conclusão: Os resultados obtidos contribuem para a visibilidade do trabalho da TO neste serviço

Introduction: The Long Stay Institution for the Elderly (LSIE) is a socio-sanitary service foreseen in the public policies of gerontology. The performance of Occupational Therapy (OT) in this field is still little explored in the literature. Objective:To know and characterize the role of Occupational Therapist in LSIE. Methods: Qualitative, exploratory and descriptive study. The snowball technique was used to locate and access the 10 Occupational Therapists with experience in an LSIE in the city of São Paulo. These were treated in August 2022. The results were treated in the light of thematic analysis by previous categories, corresponding to the questions contained in the semi-structured interview script, prepared by the researchers. Results: The actions of the OT were characterized by: embracement of suffering in the institutionalization processes and experiences related to mourning; prescription of assistive technology equipment; environmental interventions and actions with formal and family caregivers. The actions aimed at: maintaining/rescuing autonomy, functionality and meaningful activities; improvement of physical-sensory-cognitive skills and favoring relational exchanges. Little understanding of the teams and managers about the performance of the OT was identified. Conclusion: The results obtained contribute to the visibility of the OT work in this service

Primary culture macrophages from fish as potential experimental model in toxicity studies with multiwalled carbon nanotubes

Multiwalled carbon nanotube (MWCNT) has been broadly used in several sectors of society. This material when exposed to the environment might reach the aquatic animals and cause toxic effects. Here, it was evaluated the MWCNTs toxicity in melanomacrophages primary culture that was submitted to 1 µ gm L-1 MWCNTs for 24 hours. After exposition to MWCNT, 48 and 59% liver and spleen melanomacrophages were healthy, respectively. The control group presented 85% viability. Phagocytosis activity of melanomacrophages was observed by presence of black inclusions in cytoplasm. The findings indicate MWCNT was cytotoxic to melanomacrophages, where its release and effect into aquatic environment must be more studied. Finally, the melanomacrophages present large potential as experimental model for evaluation of carbon-based nanomaterial toxicity.

Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion ΔH69/V70

SARS-CoV-2 amino acid replacements in the receptor binding domain (RBD) occur relatively frequently and some have a consequence for immune recognition. Here we report recurrent emergence and significant onward transmission of a six-nucleotide out of frame deletion in the S gene, which results in loss of two amino acids: H69 and V70. We report that in human infections {Delta}H69/V70 often co-occurs with the receptor binding motif amino acid replacements N501Y, N439K and Y453F, and in the latter two cases has followed the RBD mutation. One of the {Delta}H69/V70+ N501Y lineages, now known as B.1.1.7, has undergone rapid expansion and includes eight S gene mutations: RBD (N501Y and A570D), S1 ({Delta}H69/V70 and {Delta}144) and S2 (P681H, T716I, S982A and D1118H). In vitro, we show that {Delta}H69/V70 does not reduce serum neutralisation across multiple convalescent sera. However, {Delta}H69/V70 increases infectivity and is associated with increased incorporation of cleaved spike into virions. {Delta}H69/V70 is able to compensate for small infectivity defects induced by RBD mutations N501Y, N439K and Y453F. In addition, replacement of H69 and V70 residues in the B.1.1.7 spike reduces its infectivity and spike mediated cell-cell fusion. Based on our data {Delta}H69/V70 likely acts as a permissive mutation that allows acquisition of otherwise deleterious immune escape mutations. Enhanced surveillance for the {Delta}H69/V70 deletion with and without RBD mutations should be considered as a global priority not only as a marker for the B.1.1.7 variant, but potentially also for other emerging variants of concern. Vaccines designed to target the deleted spike protein could mitigate against its emergence as increased selective forces from immunity and vaccines increase globally. HighlightsO_LI{Delta}H69/V70 is present in at least 28 SARS-CoV-2 lineages C_LIO_LI{Delta}H69/V70 does not confer escape from convalescent sera C_LIO_LI{Delta}H69/V70 increases spike infectivity and compensates for RBD mutations C_LIO_LI{Delta}H69/V70 is associated with greater spike cleavage C_LIO_LIB.1.1.7 requires {Delta}H69/V70 for optimal spike cleavage and infectivity C_LI