Exploring experiences of proculturation in international students during the COVID-19 pandemic.

This study intends to find what are the experiences of international students semiotically adapting to unfamiliar signs in the United Kingdom before and during the COVID-19 pandemic. Semi-structured interviews were conducted with six international university students to learn about their experiences of adapting to a new country. Data were analysed using thematic analysis. Two themes were classified as dialogical self in interpersonal adaptation and linguistic elements of semiotic adaptation, each with two subthemes. Participants' experiences of merging self-constructs seem reflective of proculturation theory. The researchers termed 'language bridges' to refer to social representations dependent on language-specific signs. Some of the participants' self-constructs relied on signs not provided by the environment during the COVID-19 pandemic. Overall, proculturation offers insight into the complex psychological and social processes of adapting to unfamiliar signs.

Baryon Acoustic Oscillations from Integrated Neutral Gas Observations: an instrument to observe the 21cm hydrogen line in the redshift range 0.13 < z < 0.45 - status update.

BINGO (BAO from Integrated Neutral Gas Observations) is a unique radio telescope designed to map the intensity of neutral hydrogen distribution at cosmological distances, making the first detection of Baryon Acoustic Oscillations (BAO) in the frequency band 980 MHz - 1260 MHz, corresponding to a redshift range 0.127 < z < 0.449. BAO is one of the most powerful probes of cosmological parameters and BINGO was designed to detect the BAO signal to a level that makes it possible to put new constraints on the equation of state of dark energy. The telescope will be built in Paraíba, Brazil and consists of two \thicksim 40m mirrors, a feedhorn array of 50 horns, and no moving parts, working as a drift-scan instrument. It will cover a 15 ^{\circ} ∘ declination strip centered at \sim \delta ∼ δ =-15 ^{\circ} ∘ , mapping \sim ∼ 5400 square degrees in the sky. The BINGO consortium is led by University of São Paulo with co-leadership at National Institute for Space Research and Campina Grande Federal University (Brazil). Telescope subsystems have already been fabricated and tested, and the dish and structure fabrication are expected to start in late 2020, as well as the road and terrain preparation.

Human γδ thymocytes are functionally immature and differentiate into cytotoxic type 1 effector T cells upon IL-2/IL-15 signaling.

Cytotoxicity and IFN-γ production by human γδ T cells underlie their potent antitumor functions. However, it remains unclear where and how human γδ T cells acquire these key effector properties. Given the recent disclosure of a major contribution of the thymus to murine γδ T cell functional differentiation, in this study we have analyzed a series of human pediatric thymuses. We found that ex vivo-isolated γδ thymocytes produced negligible IFN-γ and lacked cytolytic activity against leukemia cells. However, these properties were selectively acquired upon stimulation with IL-2 or IL-15, but not IL-4 or IL-7. Unexpectedly, TCR activation was dispensable for these stages of functional differentiation. The effects of IL-2/IL-15 depended on MAPK/ERK signaling and induced de novo expression of the transcription factors T-bet and eomesodermin, as well as the cytolytic enzyme perforin, required for the cytotoxic type 1 program. These findings have implications for the manipulation of γδ T cells in cancer immunotherapy.

Engagement of NKp30 on Vδ1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication.

Natural cytotoxicity receptors (NCRs) were originally identified as specific natural killer cell activating receptors that, on binding to their endogenous ligands, trigger the killing of tumor cell targets. We recently described the differentiation of a novel subset of NCR(+) Vδ1 T cells characterized by a remarkably high cytolytic potential against cancer cells. Here we demonstrate that the engagement of NKp30, one of the NCRs expressed de novo on Vδ1 T cells after stimulation, triggers the production of high levels of CCL3/MIP-1α, CCL4/ MIP-1ß, and CCL5/RANTES but not of CXCL12/SDF-1. In turn, this NKp30-induced secretion of cc-chemokines is able to significantly suppress the replication of a CCR5 tropic strain of HIV-1 in CD4(+)/CCR5(+) infected PM1 cell lines. This experimental evidence disclosing an unanticipated antiviral function of NCR(+) Vδ1 T cells opens new avenues for understanding the pathogenic role and for manipulating the function of γδ T cells in HIV-1 infection.

Development of a Unified Specimen for Adhesive Characterization-Part 2: Experimental Study on the Mode I (mDCB) and II (ELS) Fracture Components.

Adhesive bonding has been increasingly employed in multiple industrial applications. This has led to a large industrial demand for faster, simpler, and cheaper characterization methods that allow engineers to predict the mechanical behavior of an adhesive with numerical models. Currently, these characterization processes feature a wide variety of distinct standards, specimen configurations, and testing procedures and require deep knowhow of complex data-reduction schemes. By suggesting the creation of a new and integrated experimental tool for adhesive characterization, it becomes possible to address this problem in a faster and unified manner. In this work, following a previous numerical study, the mode I and II components of fracture-toughness characterization were validated experimentally in two different configurations, Balanced and Unbalanced. For mode I, it was demonstrated that both configurations presented similar numerical and experimental R-curves. The relative error against standard tests was lower than ±5% for the Balanced specimen; the Unbalanced system showed higher variations, which were predicted by the numerical results. Under mode II, the Balanced specimen displayed plastic deformation due to high deflections. On the contrary, the Unbalanced specimen did not show this effect and presented a relative error of approximately ±2%. Nonetheless, it was proven that this approach to obtain such data by using a single unified specimen is still feasible but needs further development to obtain with similar precision of standard tests. In the end, a conceptual change is proposed to solve the current mode II issues.

Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells.

The success of cancer immunotherapy depends on productive tumor cell recognition by killer lymphocytes. γδ T cells are a population of innate-like lymphocytes endowed with strong, MHC-unrestricted cytotoxicity against tumor cells. This notwithstanding, we recently showed that a large proportion of human hematologic tumors is resistant to γδ peripheral blood lymphocytes (PBLs) activated with specific agonists to the highly prevalent Vγ9Vδ2 TCR. Although this probably constitutes an important limitation to current γδ T cell-mediated immunotherapy strategies, we describe here the differentiation of a novel subset of Vδ2(-) Vδ1(+) PBLs expressing natural cytotoxicity receptors (NCRs) that directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells. We show that Vδ1(+) T cells can be selectively induced to express NKp30, NKp44 and NKp46, through a process that requires functional phosphatidylinositol 3-kinase (PI-3K)/AKT signaling on stimulation with γ(c) cytokines and TCR agonists. The stable expression of NCRs is associated with high levels of granzyme B and enhanced cytotoxicity against lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition. Thus, NKp30(+) Vδ1(+) T cells constitute a novel, inducible and specialized killer lymphocyte population with high potential for immunotherapy of human cancer.

Development of a Unified Specimen for Adhesive Characterisation-Part 1: Numerical Study on the Mode I (mDCB) and II (ELS) Fracture Components.

Adhesives are increasingly being employed in industrial applications as a replacement for traditional mechanical joining methods, since they enable improvements in the strength-to-weight ratio and lower the cost of the overall structures. This has led to a need for adhesive mechanical characterisation techniques that can provide the data needed to build advanced numerical models, allowing structural designers to expedite the adhesive selection process and grant precise optimisation of bonded connection performance. However, mechanically mapping the behaviour of an adhesive involves numerous different standards resulting in a complex network of various specimens, testing procedures and data reduction methods that concern techniques which are exceedingly complex, time-consuming, and expensive. As such, and to address this problem, a novel fully integrated experimental characterisation tool is being developed to significantly reduce all the issues associated with adhesive characterisation. In this work, a numerical optimisation of the unified specimen's fracture toughness components, comprising the combined mode I (modified double cantilever beam) and II (end-loaded split) test, was performed. This was achieved by computing the desired behaviour as a function of the apparatus' and specimens' geometries, through several dimensional parameters, and by testing different adhesives, widening the range of applications of this tool. In the end, a custom data reduction scheme was deduced and set of design guidelines was defined.

Extended Finite Element Method (XFEM) Model for the Damage Mechanisms Present in Joints Bonded Using Adhesives Doped with Inorganic Fillers.

The use of adhesive bonding in diverse industries such as the automotive and aerospace sectors has grown considerably. In structural construction, adhesive joints provide a unique combination of low structural weight, high strength and stiffness, combined with a relatively simple and easily automated manufacturing method, characteristics that are ideal for the development of modern and highly efficient vehicles. In these applications, ensuring that the failure mode of a bonded joint is cohesive rather than adhesive is important since this failure mode is more controlled and easier to model and to predict. This work presents a numerical technique that enables the precise prediction of the bonded joint's behavior regarding not only its failure mode, but also the joint's strength, when inorganic fillers are added to the adhesive. To that end, hollow glass particles were introduced into an epoxy adhesive in different amounts, and a numerical study was carried out to simulate their influence on single lap joint specimens. The numerical results were compared against experimental ones, not only in terms of joint strength, but also their failure pattern. The neat adhesive, which showed 9% and 20% variations in terms of failure load and displacement, respectively. However, looking at the doped configurations, these presented smaller variations of about 2% and 10% for each respective variable. In all cases, by adding glass beads, crack initiation tended to change from adhesive to cohesive but with lower strength and ductility, correctly modeling the general experimental behavior as intended.

The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity.

On the path to successful immunotherapy of hematopoietic tumors, gammadelta T cells offer great promise because of their human leukocyte antigen (HLA)-unrestricted targeting of a wide variety of leukemias/lymphomas. However, the molecular mechanisms underlying lymphoma recognition by gammadelta T cells remain unclear. Here we show that the expression levels of UL16-binding protein 1 (ULBP1) determine lymphoma susceptibility to gammadelta T cell-mediated cytolysis. Consistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vgamma9(+) T cells, significantly inhibits lymphoma cell killing. Specific loss-of-function studies demonstrate that the role of ULBP1 is nonredundant, highlighting a thus far unique physiologic relevance for tumor recognition by gammadelta T cells. Importantly, we observed a very wide spectrum of ULBP1 expression levels in primary biopsies obtained from lymphoma and leukemia patients. We suggest this will impact on the responsiveness to gammadelta T cell-based immunotherapy, and therefore propose ULBP1 to be used as a leukemia/lymphoma biomarker in upcoming clinical trials.

Characterization of the Effect of Hollow Glass Beads on the Mechanical Properties of Structural Adhesives.

Adhesives are extensively used in the automotive and aeronautical industries as they enable the creation of durable and light weight joints, with exceptional strength to weight ratios. The constant search for the means of adapting the mechanical performance of adhesives to each application has led to the use of several types of fillers to change their properties. Following a study on the effect of inorganic fillers, i.e., hollow glass beads, in the failure mechanisms of single lap joint's (SLJ), this work focuses on the response of the strength and fracture properties of structural adhesives to this filler. To this end, their tensile strength and mode I fracture properties were thoroughly analyzed by performing bulk tensile and double-cantilever beam (DCB) tests, at a quasi-static speed. The specimens were manufactured by adding different %v/v of filler to two epoxy-based crash resistant adhesives. Both adhesives have shown a negligible effect on the tensile strength, a decrease in strain at failure and critical energy release rate in mode I, as well as an increase of the Young's modulus, for higher % in volume of hollow glass beads. These phenomena were further analyzed recurring to scanning electron microscopy, and the concept of rule of mixtures.

Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia.

BACKGROUND: Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent Vδ1+γδ T cells, represent a promising allogeneic platform. METHODS: Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. RESULTS: CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo, even on tumor rechallenge. CONCLUSIONS: Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML.

Inhibition of murine gammadelta lymphocyte expansion and effector function by regulatory alphabeta T cells is cell-contact-dependent and sensitive to GITR modulation.

Gammadelta T cells are highly cytolytic lymphocytes that produce large amounts of pro-inflammatory cytokines during immune responses to multiple pathogens. Furthermore, their ability to kill tumor cells has fueled the development of gammadelta-T-cell-based cancer therapies. Thus, the regulation of gammadelta-T-cell activity is of great biological and clinical relevance. Here, we show that murine CD4+CD25+ alphabeta T cells, the vast majority of which express the Treg marker, Foxp3, abolish key effector functions of gammadelta T cells, namely the production of the pro-inflammatory cytokines, IFN-gamma and IL-17, cytotoxicity, and lymphocyte proliferation in vitro and in vivo. We further show that suppression is dependent on cellular contact between Treg and gammadelta T cells, results in the induction of an anergic state in gammadelta lymphocytes, and can be partially reversed by manipulating glucocorticoid-induced TNF receptor-related protein (GITR) signals. Our data collectively dissect a novel mechanism by which the expansion and pro-inflammatory functions of gammadelta T cells are regulated.

Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood gammadelta T cells.

BACKGROUND: Vgamma9Vdelta2 T lymphocytes are regarded as promising mediators of cancer immunotherapy due to their capacity to eliminate multiple experimental tumors, particularly within those of hematopoietic origin. However, Vgamma9Vdelta2 T-cell based lymphoma clinical trials have suffered from the lack of biomarkers that can be used as prognostic of therapeutic success. DESIGN AND METHODS: We have conducted a comprehensive study of gene expression in acute lymphoblastic leukemias and non-Hodgkin's lymphomas, aimed at identifying markers of susceptibility versus resistance to Vgamma9Vdelta2 T cell-mediated cytotoxicity. We employed cDNA microarrays and quantitative real-time PCR to screen 20 leukemia and lymphoma cell lines, and 23 primary hematopoietic tumor samples. These data were analyzed using state-of-the-art bioinformatics, and gene expression patterns were correlated with susceptibility to Vgamma9Vdelta2 T cell mediated cytolysis in vitro. RESULTS: We identified a panel of 10 genes encoding cell surface proteins that were statistically differentially expressed between "gammadelta-susceptible" and "gammadelta-resistant" hematopoietic tumors. Within this panel, 3 genes (ULBP1, TFR2 and IFITM1) were associated with increased susceptibility to Vgamma9Vdelta2 T-cell cytotoxicity, whereas the other 7 (CLEC2D, NRP2, SELL, PKD2, KCNK12, ITGA6 and SLAMF1) were enriched in resistant tumors. Furthermore, some of these candidates displayed a striking variance of expression among primary follicular lymphomas and T-cell acute lymphoblastic leukemias. CONCLUSIONS: Our results suggest that hematopoietic tumors display a highly variable repertoire of surface proteins that can impact on Vgamma9Vdelta2 cell-mediated immunotargeting. The prognostic value of the proposed markers can now be evaluated in upcoming Vgamma9Vdelta2 T cell-based lymphoma/leukemia clinical trials.

Broad Cytotoxic Targeting of Acute Myeloid Leukemia by Polyclonal Delta One T Cells.

Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1+ T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of "Delta One T" (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy. Unlike chemotherapy, DOT-cell targeting did not select for outgrowth of specific AML lineages, suggesting a broad recognition domain, an outcome that was consistent with the polyclonality of the DOT-cell T-cell receptor (TCR) repertoire. However, AML reactivity was only slightly impaired upon Vδ1+ TCR antibody blockade, whereas it was strongly dependent on expression of the NKp30 ligand, B7-H6. In contrast, DOT cells did not show reactivity against normal leukocytes, including CD33+ or CD123+ myeloid cells. Adoptive transfer of DOT cells in vivo reduced AML load in the blood and target organs of multiple human AML xenograft models and significantly prolonged host survival without detectable toxicity, thus providing proof-of-concept for DOT-cell application in AML treatment.

Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of Human Vγ9Vδ2 T Cells.

Vγ9Vδ2 T cells, the main subset of γδ T lymphocytes in human peripheral blood, are endowed with antitumor functions such as cytotoxicity and IFNγ production. These functions are triggered upon T-cell receptor-dependent activation by non-peptidic prenyl pyrophosphates ("phosphoantigens") that are selective agonists of Vγ9Vδ2 T cells, and which have been evaluated in clinical studies. Because phosphoantigens have shown interindividual variation in Vγ9Vδ2 T-cell activities, we asked whether metabolic resources, namely lipids such as cholesterol, could affect phosphoantigen-mediated Vγ9Vδ2 T-cell activation and function. We show here that Vγ9Vδ2 T cells express the LDL receptor upon activation and take up LDL cholesterol. Resulting changes, such as decreased mitochondrial mass and reduced ATP production, correlate with downregulation of Vγ9Vδ2 T-cell activation and functionality. In particular, the expression of IFNγ, NKG2D, and DNAM-1 were reduced upon LDL cholesterol treatment of phosphoantigen-expanded Vγ9Vδ2 T cells. As a result, their capacity to target breast cancer cells was compromised both in vitro and in an in vivo xenograft mouse model. Thus, this study describes the role of LDL cholesterol as an inhibitor of the antitumor functions of phosphoantigen-activated Vγ9Vδ2 T cells. Our observations have implications for therapeutic applications dependent on Vγ9Vδ2 T cells. Cancer Immunol Res; 6(4); 448-57. ©2018 AACR.

Prevalence of clinically validated primary causes of end-stage renal disease (ESRD) in a State Capital in Northeastern Brazil.

INTRODUCTION: Knowledge of validated primary causes of end-stage renal disease (ESRD) is extremely relevant in the realm of public health. The literature lacks validated studies on the primary causes of ESRD. OBJECTIVE: The aim of this study was to estimate the prevalence of the causes of ESRD in a State Capital in Northeastern Brazil. METHODS: This cross-sectional study was based on the analysis of medical records of patients on hemodialysis at five specialized centers in Fortaleza, CE, Brazil. Deaths and patients referred to other centers outside Fortaleza were excluded from the study. The data of 830 patients were initially collected, but 818 remained enrolled after the exclusion criteria were applied, the equivalent to 48% of the patents on dialysis in the city. RESULTS: 61.1% of the patients were males. Twenty-two percent of all enrolled individuals were aged 60-69 years. Patient mean age was 55.7 ± 16 years. The most common validated cause of ESRD was unknown (35.3%), followed by diabetes mellitus (26.4%), adult polycystic kidney disease (6.2%), graft failure (6.2%), obstructive uropathy (5.7%), and primary glomerulonephritis (5.3%). Before validation, primary hypertension was the most frequent cause of chronic kidney disease (22.9%), decreased to 3.8% after validation. CONCLUSION: The data contradicted national studies reporting primary hypertension as the main cause of chronic kidney disease (CKD). A high rate of unknown causes and categorization bias were observed mainly in relation to primary hypertension as a cause of CKD, which affects the overall prevalence of causes of ESRD in patients on dialysis.

Desafios da sífilis congénita na atenção primária à saúde em Alagoas, Brasil, 2009-2018 / Desafíos de la sífilis congénita en la atención primaria de salud en Alagoas, Brasil, 2009-2018 / Challenges of congenital syphilis in primary health care in Alagoas, Brazil, 2009-2018

Resumo Introdução: A sífilis é um agravo sexual causado pela bactéria Treponema pallidum, podendo causar defeitos congênitos quando há transmissão vertical da grávida infectada para seu concepto. No Brasil e no estado de Alagoas, caracteriza-se como problema de saúde pública a ser controlado, principalmente na Atenção Primária à Saúde que conta com a Estratégia Saúde da Família para o diagnóstico e o tratamento da sífilis na gestação, prevenindo os casos congênitos. Objetivo: Analisar as correlações entre a cobertura da Estratégia Saúde da Família e os indicadores da Sífilis Congênita no estado de Alagoas, Brasil, entre 2009 e 2018. Método: Trata-se de um estudo transversal retrospectivo com dados secundários do Ministério da Saúde sobre os indicadores de Sífilis Congênita e cobertura da Estratégia Saúde da Família em Alagoas. Utilizou-se o software Statistical Package for the Social Sciences -versão 25 e as correlações foram consideradas significantes com p-valor < 0,05. Resultados: Entre 2009-2018, notificou-se 3.407 casos de Sífilis Congênita em Alagoas e 73,6% das gestantes realizam o pré-natal. Contudo, observou-se que o momento do diagnóstico da sífilis materna não ocorreu durante o pré-natal; o tratamento materno não foi realizado ou realizado de forma inadequada; e apenas 9% das parcerias sexuais das gestantes foram tratadas. Conclusão: Em Alagoas, existem lacunas para o diagnóstico oportuno e o tratamento efetivo da sífilis na gestação, mesmo com a disponibilidade de insumos e protocolos assistenciais.

Resumen Introducción: La sífilis es un delito sexual causado por la bacteria Treponema pallidum, que puede causar defectos de nacimiento cuando hay transmisión vertical de la mujer embarazada infectada a su hijo. En Brasil y en el estado de Alagoas, es un problema de salud pública que debe ser controlado, especialmente en la Atención Primaria de Salud que se apoya en la Estrategia de Salud de la Familia para el diagnóstico y tratamiento de la sífilis en el embarazo, previniendo así los casos congénitos. Objetivo: Analizar las correlaciones entre la cobertura de la Estrategia de Salud de la Familia y los indicadores de Sífilis Congénita en el estado de Alagoas, Brasil, entre 2009 y 2018. Método: Se trata de un estudio transversal retrospectivo con datos secundarios del Ministerio de Salud sobre los indicadores de Sífilis Congénita y la cobertura de la Estrategia de Salud de la Familia en Alagoas. Se utilizó el software Statistical Package for the Social Sciences - versión 25 y las correlaciones se consideraron significativas con un valor p < 0,05. Resultados: Entre 2009-2018 se notificaron 3.407 casos de Sífilis Congénita en Alagoas y el 73,6% de las embarazadas realizaron control prenatal. Sin embargo, se observó que el momento del diagnóstico de la sífilis materna no se produjo durante la atención prenatal; el tratamiento materno no se realizó o se realizó de forma inadecuada; y sólo el 9% de las parejas sexuales de las embarazadas recibieron tratamiento. Conclusión: En Alagoas, existen lagunas para el diagnóstico oportuno y el tratamiento eficaz de la sífilis en el embarazo, incluso con la disponibilidad de insumos y protocolos de atención.

Análise dos níveis de escolaridade nos casos de sífilis na gestação e sífilis congênita, no Brasil, 2010-2019

Objetivo: Analisar a relação da escolaridade em casos de sífilis na gestação e congênita no Brasil. Métodos: Estudo observacional analítico retrospectivo, utilizando dados secundários do Sistema de Informação de Agravos de Notificação, coletados entre os meses de março e abril de 2021, referente ao período de 2010-2019, tabulados em planilhas do programa Microsoft Excel 2016. No tratamento estatístico, utilizou-se o software Join Point, analisando as tendências em Variações percentuais anuais (Annual Percentage Change) e em Variação percentual anual média (Average Annual Percentage Change). Resultados: No período analisado, as tendências de sífilis na gestação, em mulheres com escolaridade ? 8 anos, apresentou em âmbito nacional e regiões Norte e Nordeste, comportamento significativamente crescentes a partir do Fundamental completo. As regiões Centro-Oeste, Sudeste e Sul apresentaram tendência significativamente crescente nas categorias de escolaridade Médio incompleto e completo, Superior incompleto e completo. Quanto à análise acerca sífilis congênita, há tendências significativamente crescentes nas mães com de 8 anos ou mais de estudo formal no Brasil e nas regiões Nordeste, Centro-oeste, Sudeste e Sul. Acerca da sífilis congênita na região Norte análise estatística aponta às tendências crescentes das categorias de escolaridade Fundamental completo, Médio incompleto e completo, enquanto as categorias Superior incompleto e completo apresentam tendências estacionárias. Conclusões: Tradicionalmente, os casos de sífilis na gestação e sífilis congênita estão associados a baixa escolaridade. Entretanto, o aumento médio da escolaridade da população brasileira e a incidência elevadas dos casos, apontam para a necessidade a reorganização das estratégias de prevenção e controle dessa IST.

Epidemiological and clinical profile and trend analysis of hospitalizations for fall-related injuries among older adults, Alagoas (Brazil), 2008­2019 / Perfil epidemiológico e clínico e tendência temporal de internações por quedas em idosos, Alagoas (Brasil), 2008­2019

Objective: To analyze the epidemiological and clinical profile and the time trend of hospitalizations for fall-related injuries among older people (aged 60 years or older) in Alagoas between 2008 and 2019. Methods: This is a time series study with data collected from the Hospital Information System of the Unified National Health System (SIHSUS) referring to hospitalizations for fallrelated injuries among older adults in Alagoas (Brazil) between 2008 and 2019. Hospitalization and lethality rates, average annual percent change (AAPC), and annual percent change (APC) were calculated; time trends were analyzed using a Joinpoint Regression Model according to sex, skin color, age range, and causes. A 95% confidence interval (95%CI) was adopted. A p-value<0.01 was adopted for defining statistical significance. Results: In Alagoas, 14 817 cases of hospitalizations due to fall-related injuries were reported among older people in the analyzed period. The highest incidence rate was observed in 2016 (48.39/10 000 inhabitants). There were 517 deaths, and the mean lethality rate was 3.4%. A higher proportion of cases was seen in men (66.36%; n=9832), those aged 80 years or older(34.59%; n=5125), and with Brown skin (54.70%; n=8106). The incidence coefficient varied, showing an upward trend with time (APC: 4.1; 95%CI 0.2­8.2; p<0.01). Conclusion: The study showed a higher incidence in individuals aged 80 years or older, men, and found an upward trend in hospitalizations. We suggest the'

Objetivo: Analisar o perfil epidemiológico e clínico e a tendência temporal das internações por quedas em idosos de 60 anos ou mais, ocorridas em Alagoas, no período de 2008­2019. Metodologia: Realizou-se um estudo de séries temporais com dados coletados no Sistema de Informações Hospitalares do Sistema Único de Saúde, referentes a internações por quedas em idosos de 60 anos ou mais em Alagoas (Brasil), entre 2008 e 2019. Foram calculadas as taxas de incidência de internação e letalidade, a variação percentual anual média (AAPC) e a variação anual percentual (APC). A tendência foi analisada pelo modelo de regressão por pontos de inflexão (joinpoint regression model) segundo sexo, cor, faixa etária e categoria de causas. Adotou-se intervalo de confiança de 95% (IC95%) e, para análise do nível de significância estatística, valor de p < 0,01. Resultados: Foram notificados 14.817 casos de internações por quedas em idosos de 60 anos ou mais no período analisado, em Alagoas. A maior taxa de incidência ocorreu em 2016 (48,39/10 mil habitantes). Ocorreram 517 óbitos, e a taxa média de letalidade foi de 3,4%. Verificou-se maior proporção de casos no sexo masculino (66,36%; n = 9.832), na faixa etária de 80 anos (34,59%; n = 5.125) e na cor parda (54,70%; n = 8.106). Houve variação do coeficiente de incidência, o qual apresentou comportamento temporal crescente (APC: 4,1; IC95% de 0,2 a 8,2; p < 0,01). Conclusão: O estudo mostrou maior incidência na faixa etária de 80 anos ou mais no período analisado, maior frequência no sexo masculino e tendência crescente de internações. Sugere-se otimizar a assistência hospitalar e incentivar programas de prevenção de quedas em idosos.

Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept.

PURPOSE: The Vδ1+ subset of γδ T lymphocytes is a promising candidate for cancer immunotherapy, but the lack of suitable expansion/differentiation methods has precluded therapeutic application. We set out to develop and test (preclinically) a Vδ1+ T-cell-based protocol that is good manufacturing practice compatible and devoid of feeder cells for prompt clinical translation. EXPERIMENTAL DESIGN: We tested multiple combinations of clinical-grade agonist antibodies and cytokines for their capacity to expand and differentiate (more than 2-3 weeks) Vδ1+ T cells from the peripheral blood of healthy donors and patients with chronic lymphocytic leukemia (CLL). We characterized the phenotype and functional potential of the final cellular product, termed Delta One T (DOT) cells, in vitro and in vivo (xenograft models of CLL). RESULTS: We describe a very robust two-step protocol for the selective expansion (up to 2,000-fold in large clinical-grade cell culture bags) and differentiation of cytotoxic Vδ1+ (DOT) cells. These expressed the natural cytotoxicity receptors, NKp30 and NKp44, which synergized with the T-cell receptor to mediate leukemia cell targeting in vitro When transferred in vivo, DOT cells infiltrated tumors and peripheral organs, and persisted until the end of the analysis without showing signs of loss of function; indeed, DOT cells proliferated and produced abundant IFNγ and TNFα, but importantly no IL17, in vivo Critically, DOT cells were capable of inhibiting tumor growth and preventing dissemination in xenograft models of CLL. CONCLUSIONS: We provide a clinical-grade method and the preclinical proof of principle for application of a new cellular product, DOT cells, in adoptive immunotherapy of CLL. Clin Cancer Res; 22(23); 5795-804. ©2016 AACR.