Scinax cruentommus (Anura: Hylidae) in the upper Rio Negro drainage, Amazonas state, Brazil, with the redescription of its advertisement call

Scinax cruentommus (Anura: Hylidae) na bacia do alto Rio Negro, Amazonas, Brasil, com a redescrição do seu canto de anúncio. Nós apresentamos o primeiro registro de Scinax cruentommus no alto Rio Negro, Amazonas, Brasil. Nós também redescrevemos o seu canto de anúncio e fazemos comparações acústicas com os dados disponíveis para outras espécies do Clado de Scinax ruber da bacia amazônica. Com a obtenção de novos dados para S. cruentommus, os parâmetros acústicos suplementaram a sua diagnose congenérica em relação às outras espécies amazônicas do Clado de S. ruber além das características propostas em sua descrição original.Scinax cruentommus (Anura: Hylidae) in the upper Rio Negro drainage, Amazonas state, Brazil, with the redescription of its advertisement call. We provide the first record for Scinax cruentommus from the upper Rio Negro, Amazonas state, Brazil. We also redescribe its advertisement call and make acoustic comparisons with available data for other species of the Scinax ruber Clade in the Amazon Basin. With the assessment of further data on S. cruentommus, the acoustic traits have supplemented its congeneric diagnosis in comparison with the other Amazonian species of the S. ruber Clade besides the features proposed in its original description

Portuguese recommendations for the use of biological and targeted synthetic diseasemodifying antirheumatic drugs in patients with rheumatoid arthritis – 2020 update

Objective: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). Methods: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. Results: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. Conclusion: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.info:eu-repo/semantics/publishedVersio

Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis - 2015 update

OBJECTIVE: To update recommendationsforthe treatment of psoriatic arthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 16 recommendations included in this document were discussed and updated. The level of agreement among Portuguese Rheumatologists was assessed using an online survey. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with psoriatic arthritis (PsA). Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area oftherapeutic intervention.Asmore evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

After the epidemic: Zika virus projections for Latin America and the Caribbean

Background: Zika is one of the most challenging emergent vector-borne diseases, yet its future public health impact remains unclear. Zika was of little public health concern until recent reports of its association with congenital syndromes. By 3 August 2017 ~217,000 Zika cases and ~3,400 cases of associated congenital syndrome were reported in Latin America and the Caribbean. Some modelling exercises suggest that Zika virus infection could become endemic in agreement with recent declarations from the The World Health Organisation. Methodology/Principal findings: We produced high-resolution spatially-explicit projections of Zika cases, associated congenital syndromes and monetary costs for Latin America and the Caribbean now that the epidemic phase of the disease appears to be over. In contrast to previous studies which have adopted a modelling approach to map Zika potential, we project case numbers using a statistical approach based upon reported dengue case data as a Zika surrogate. Our results indicate that ~12.3 (0.7–162.3) million Zika cases could be expected across Latin America and the Caribbean every year, leading to ~64.4 (0.2–5159.3) thousand cases of Guillain-Barré syndrome and ~4.7 (0.0–116.3) thousand cases of microcephaly. The economic burden of these neurological sequelae are estimated to be USD ~2.3 (USD 0–159.3) billion per annum. Conclusions/Significance: Zika is likely to have significant public health consequences across Latin America and the Caribbean in years to come. Our projections inform regional and federal health authorities, offering an opportunity to adapt to this public health challenge

Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy

INTRODUCTION: Hereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study. METHODS: The phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed. RESULTS: At month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: –21.0; p = 1.84 × 10–10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I–II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10–7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10–7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10–15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10–15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo. CONCLUSION: Vutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p