Retrospective study of the morbidity associated with Erythema Nodosum Leprosum in Brazilian leprosy patients

Introduction: Leprosy patients may develop immune-mediated inflammatory reactions, which are the main cause of nerve function impairment and disability. Among them, Erythema Nodosum Leprosum (ENL) is a potentially life-threatening systemic condition. There are few data on ENL-associated morbidity and mortality, and the need of hospitalisation due to its complications. Material and methods: We conducted a retrospective cohort study including patients diagnosed at the Souza Araújo Outpatient Clinic, Rio de Janeiro. All patients had a first ENL episode at the clinic or were admitted to the Evandro Chagas Hospital, between 2005–2010. In 2014, we obtained the required data from the patients’ files to describe ENL morbidity and mortality, including treatment-related adverse events. Results: A total of 112 patients (72% male, median age at diagnosis 35 years, 83% had lepromatous leprosy) developed ENL, among the 676 patients diagnosed with leprosy during the study period. Most of the episodes were chronic and severe. Patients were treated with thalidomide and corticosteroids. Half of the patients receiving corticosteroids had adverse events. 14 patients were hospitalised, ten due to ENL complications. Six patients died, four during the ENL episode. None of these deaths could be considered directly caused by ENL or its treatment.Conclusion: In the group of patients studied, although a high morbidity due to the reaction itself and to the adverse effects of its prolonged treatment was observed, mortality due to ENL was not registered. Prospective studies are required in order to recognise leprosy complications, such as ENL, as consequential causes of death

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051

Prospective Follow-up of Adolescents with and at Risk for Depression::Protocol and Methods of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) Longitudinal Assessments

Objective: To present the protocol and methods for the prospective longitudinal assessments — including clinical and digital phenotyping approaches — of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) study, which comprises Brazilian adolescents stratified at baseline by risk of developing depression or presence of depression. Method: Of 7,720 screened adolescents aged 14-16, we recruited 150 participants (75 boys, 75 girls) based on a composite risk score: 50 with low risk for developing depression (LR), 50 with high risk for developing depression (HR), and 50 with an active untreated major depressive episode (MDD). Three annual follow-up assessments were conducted, involving clinical measures (parent and adolescent-reported questionnaires and psychiatrist assessments), active and passive data sensing via smartphones, and neurobiological measures (neuroimaging and biological material samples). Retention rates were 96% (Wave 1), 94% (Wave 2), and 88% (Wave 3), with no significant differences by sex or group (p &gt; 0.05). Participants highlighted their familiarity with the research team and assessment process as a motivator for sustained engagement.Discussion: This protocol relied on novel aspects, such as the use of a WhatsApp bot, which is particularly pertinent for low-to-middle-income countries, and the collection of information from diverse sources in a longitudinal design, encompassing clinical data, self-reports, parental reports, GPS data, and ecological momentary assessments. The study engaged adolescents over an extensive period and demonstrated the feasibility of conducting a prospective follow-up study with a risk-enriched cohort of adolescents in a middle-income country, integrating mobile technology with traditional methodologies to enhance longitudinal data collection. <br/

Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia

<p>Abstract</p> <p>Background</p> <p>The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis.</p> <p>Methods</p> <p>To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic.</p> <p>Results</p> <p>In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5).</p> <p>Conclusion</p> <p>This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.</p

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Sociopolitical consequences of COVID-19 in the Americas, Europe, and Asia: A multilevel, multicountry investigation of risk perceptions and support for antidemocratic practices

Although different social crises may eventually favor undemocratic and authoritarian forms of governance, at some point, such antidemocratic practices require the support of a significant part of the population to be implemented. The present research investigates how and whether the COVID-19 pandemic might have favoured greater support for antidemocratic governmental practices, on the premise of regaining control and security. Using data from 17 countries (N = 4364) and national-level indicators (i.e., real number of contagions and deaths, and sociopolitical indicators), we test how the risk of contagion and death from COVID-19, along with personal orientations (i.e., social dominance orientation [SDO], right-wing authoritarianism [RWA], and perceived anomie) motivate authoritarian and antidemocratic practices. Results from multilevel models indicate that risk perception and perceptions of political instability predict a wish for stronger leadership, agreement with martial law, and support for a controlling government especially when SDO and RWA are high, while more egalitarian and less conservative people agree less with these authoritarian measures in spite of the levels of risk perception. We discuss the implications for these findings for future research on similar but also dissimilar external events (natural disasters, war, or terror incidents) and the consequences for societies with higher authoritarian tendencies.Fil: Pizarro, José J.. Universidad Católica del Norte; Chile. Universidad del País Vasco; EspañaFil: Cakal, Huseyin. Keele University; Reino UnidoFil: Méndez, Lander. Universidad del País Vasco; EspañaFil: Zumeta, Larraitz N.. Universidad del País Vasco; EspañaFil: Gracia-Leiva, Marcela. Universidad del País Vasco; EspañaFil: Basabe, Nekane. Universidad del País Vasco; EspañaFil: Navarro-Carrillo, Ginés. Universidad de Jaén; EspañaFil: Cazan, Ana Maria. Transilvania University of Brasov; RumaniaFil: Keshavarzi, Saeed. Independent Researcher; IránFil: López López, Wilson. Pontificia Universidad Javeriana; ColombiaFil: Yahiiaiev, Illia. Taras Shevchenko National University of Kyiv; UcraniaFil: Alzugaray Ponce, Carolina. Universidad Santo Tomas; ChileFil: Villagrán, Loreto. Universidad de Concepción; ChileFil: Moyano Díaz, Emilio. Universidad de Talca; ChileFil: Petrović, Nebojša. University of Belgrade; SerbiaFil: Mathias, Anderson. Universidad Autonoma de Coahuila; MéxicoFil: Techio, Elza M.. Universidade Federal da Bahia; BrasilFil: Wlodarczyk, Anna. Universidad Católica del Norte; ChileFil: Alfaro-Beracoechea, Laura. Universidad de Guadalajara; MéxicoFil: Ibarra, Manuel L.. Universidad Nacional Autónoma de México; MéxicoFil: Michael, Andreas. University of Cyprus; ChipreFil: Mhaskar, Sumeet. O.p. Jindal Global University; IndiaFil: Martínez Zelaya, Gonzalo. Universidad Viña del Mar; ChileFil: Bilbao, Marian. Universidad Alberto Hurtado; ChileFil: Delfino, Gisela Isabel. Universidad Pontificia Comillas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carvalho, Catarina L.. Universidad de Porto; PortugalFil: Pinto, Isabel R.. Universidad de Porto; PortugalFil: Mohsin, Falak Zehra. Karachi School Of Business And Leadership; PakistánFil: Espinosa, Agustín. Pontificia Universidad Católica de Perú; PerúFil: Cueto, Rosa María. Pontificia Universidad Católica de Perú; PerúFil: Cavalli, Stefano. Scuola Universitaria Professionale Della Svizzera Italiana; ItaliaFil: da Costa, Silvia. Universidad de Zaragoza; EspañaFil: Amutio, Alberto. Universidad Andrés Bello; Chile. Universidad del País Vasco; EspañaFil: Alonso Arbiol, Itziar. Universidad del País Vasco; EspañaFil: Páez, Darío. Universidad Andrés Bello; Chil

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal: results from the IMAgiNE EURO study

Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.info:eu-repo/semantics/publishedVersio