High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-ß-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients.

Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-ß-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.

HIV-1 drug resistance and genetic diversity in people with HIV-1 in Cape Verde.

OBJECTIVES: To characterize the genetic diversity and drug resistance profiles of people with HIV-1 failing ART in Cape Verde (CV). DESIGN: Cross-sectional study conducted between January 2019 and December 2021 in 24 health centres on the islands of Santiago and São Vicente. METHODS: The HIV-1 pol gene was sequenced in individuals with a detectable viral load. HIV-1 genetic diversity was determined by phylogenetic analysis. Drug resistance mutation patterns and resistance phenotypes were estimated using the Stanford algorithm. RESULTS: Viral load was detected in 73 of 252 (29%) enrolled participants and sequencing data were produced for 58 (79%) participants. CRF02 AG strains predominated (46.5%), followed by subtype G (22.4%). Most patients (80%) had mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) (67%), nucleoside reverse transcriptase inhibitors (55%), integrase inhibitors (10%) and/or protease inhibitors (7%) used in Cape Verde, a significant increase compared with a study conducted in 2010-2011. The most common mutations were M184V/I (43%), K103N/S (36%) and G190A/S (19%). NNRTI resistance was associated with younger age and exposure to two or more drug regimens. CONCLUSION: The HIV-1 epidemic in Cape Verde is mainly driven by CRF02_AG and subtype G. Resistance to NNRTIs and/or NRTIs is highly prevalent and resistance to LPV/r and DTG is emerging. Our results support the use of DTG-based first-line ART and protease inhibitor-based regimens for patients with virological failure, but emerging resistance to LPV/r and DTG is a concern. Continued monitoring of drug resistance is essential to ensure adequate healthcare for PWH in Cape Verde.

Use of cone-beam tomography and digital subtraction radiography for diagnosis and evaluation of traumatized teeth treated with endodontic surgery and MTA. A case report.

The aim of this paper was to report the diagnosis and evaluation of periradicular bone repair by using computed tomography and digital subtraction radiography in an endodontic surgery case treated with mineral trioxide aggregate (MTA). The patient had local swelling and fistula 7 years after trauma in the upper jaw. Periapical lesion on tooth #12 and root resorption of tooth #11 were detected radiographically. Endodontic therapy and placement of intracanal medication were carried out. After 3 months, with no improvement in the clinical signs and symptoms, computed tomography was performed, showing extensive apical bone resorption on tooth #12 and dental resorption promoting communication of the root canal with the periodontium of tooth #11. The patient was referred to endodontic surgery. After surgery and postoperative periods of 15, 30, 60, 90, and 120 days, standardized radiographs were taken, digitized, and subjected to digital subtraction of the images using Adobe Photoshop CS software. Four years later, a cone-beam computed tomography was performed, showing bone repair and absence of root resorption at tooth #11. In this clinical case, digital subtraction radiography was effective for early detection of new bone formation and evolution of repair.

Efficiency of Amino Acid Utilization in Nellore Cattle Grazing Low-Quality Forage Supplemented with Different Sources of Nitrogen.

This study aimed to evaluate the effects of supplementation with non-protein nitrogen (NPN) or ruminal undegradable protein (RUP) on intake, digestibility, and amino acid (AA) use efficiency of Nellore cattle grazing during the dry season. Eight Nellore steers (12 ± 2 months old) were used in quadruplicate Latin squares (2 × 2). The animals were placed on Urochloa brizantha cv. Xaraés under continuous grazing. The treatments included the following: (1) urea supplementation (NPN) and (2) supplementation of corn gluten meal 60 (CGM, RUP). Animals supplemented with CGM showed higher intakes of dry matter (DM) supplement, total AA, essential AA, and individual AA. The supplementation did not affect the total AA digestibility, total AA flux, and the AA fluxes of microbial origin and RUP from the diet (p > 0.05). The ruminal microorganism origin flux of total AA to the duodenum was 44.5% and 52.7% for animals supplemented with NPN and CGM, respectively. Animals supplemented with CGM showed an increase in blood concentrations of isoleucine (+19.09 µmol/L), cystine (+27.29 µmol/L), and albumin (+0.11 g/dL) (p < 0.05), but this increase was not accompanied by an improvement in N use efficiency of steers (p > 0.05). RUP supplementation via CGM can be an efficient nutritional strategy to enhance the intake and absorption of AA by Nellore cattle grazing low-quality forage during the dry season.

Long-Term and Low-Level Envelope C2V3 Stimulation by Highly Diverse Virus Isolates Leads to Frequent Development of Broad and Elite Antibody Neutralization in HIV-1-Infected Individuals.

A minority of HIV-1-infected patients produce broadly neutralizing antibodies (bNAbs). Identification of viral and host correlates of bNAb production may help develop vaccines. We aimed to characterize the neutralizing response and viral and host-associated factors in Angola, which has one of the oldest, most dynamic, and most diverse HIV-1 epidemics in the world. Three hundred twenty-two HIV-1-infected adults from Angola were included in this retrospective study. Phylogenetic analysis of C2V3C3 env gene sequences was used for virus subtyping. Env-binding antibody reactivity was tested against polypeptides comprising the C2, V3, and C3 regions. Neutralizing-antibody responses were determined against a reference panel of tier 2 Env pseudoviruses in TZM-bl cells; neutralizing epitope specificities were predicted using ClustVis. All subtypes were found, along with untypeable strains and recombinant forms. Notably, 56% of the patients developed cross neutralizing, broadly neutralizing, or elite neutralizing responses. Broad and elite neutralization was associated with longer infection time, subtype C, lower CD4+ T cell counts, higher age, and higher titer of C2V3C3-specific antibodies relative to failure to develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients. V3 and C3 regions were significantly less variable in elite neutralizers than in weak neutralizers and nonneutralizers, suggesting an active role of V3C3-directed bNAbs in controlling HIV-1 replication and diversification. In conclusion, prolonged and low-level envelope V3C3 stimulation by highly diverse and ancestral HIV-1 isolates promotes the frequent elicitation of bNAbs. These results provide important clues for the development of an effective HIV-1 vaccine. IMPORTANCE Studies on neutralization by antibodies and their determinants in HIV-1-infected individuals have mostly been conducted in relatively recent epidemics caused by subtype B and C viruses. Results have suggested that elicitation of broadly neutralizing antibodies (bNAbs) is uncommon. The mechanisms underlying the elicitation of bNAbs are still largely unknown. We performed the first characterization of the plasma neutralizing response in a cohort of HIV-1-infected patients from Angola. Angola is characterized by an old and dynamic epidemic caused by highly diverse HIV-1 variants. Remarkably, more than half of the patients produced bNAbs, mostly targeting the V3-glycan supersite in HIV-1. This was associated with higher age, longer infection time, lower CD4+ T cell counts, subtype C infection, or higher titer of C2V3C3-specific antibodies relative to patients that did not develop bNAbs. These results may help develop the next generation of vaccine candidates for HIV-1.

Uma análise do processo de trabalho dos profissionais da saúde e educação no PSE / An analysis of the work process of health and education professionals in the PSE

RESUMO Estudos trazem contribuições sobre o Programa Saúde na Escola, mas poucos investigam o processo de trabalho dos profissionais, a fim de compreender se existe a conformação de projetos intersetoriais e integrados ou tecnologias como mediadoras nas práticas de trabalho. O presente estudo buscou analisar as práticas dos profissionais em uma Unidade de Saúde da Família, em Salvador-BA. Este estudo de caso, de abordagem qualitativa, envolveu uma Unidade de Saúde e quatro escolas. Os procedimentos para coleta de dados compreenderam entrevistas semiestruturadas, análise documental e observação participante. A construção das categorias de análise ocorreu a partir do referencial teórico do processo de trabalho em saúde de Mendes Gonçalves. Os resultados demonstraram: fragilidades nas relações de parceria entre os agentes; percepção do objeto de trabalho pelos profissionais, predominantemente, como identificação de doenças e saber clínico preponderante em relação ao saber da saúde coletiva. As ações de saúde aproximaram os agentes, mas apresentaram práticas hegemônicas, desarticuladas, setoriais, focadas na doença e executadas, principalmente, por meio de palestras. Não existem projetos integrados e intersetoriais ou tecnologia educacional como recurso auxiliar nas práticas de trabalho. Os produtos, resultantes da participação de todos, trarão contribuições para melhor articulação entre os profissionais que atuam nesses espaços.

ABSTRACT Studies contribute to the School Health Program. However, only some investigate the work process of professionals to understand the possible conformation of intersectoral and integrated projects, or technologies as mediators in work practices. The present study sought to analyze the practices of professionals in a Family Health Unit/Primary Health Care unit in Salvador, Bahia, Brazil. This qualitative case study involved a Primary Health Care unit and four schools. The data collection procedures comprised semi-structured interviews, document analysis, and participant observation. The analysis categories were built from the theoretical framework of the health work process by Mendes Gonçalves. The results showed: weak partnership relationships between agents; professionals' perception of the object of work, predominantly identifying diseases and preponderant clinical knowledge vis-à-vis the knowledge of collective health. Health actions gathered the agents, but they presented hegemonic, disjointed, sectoral practices, focused on the disease, and conducted mainly through lectures. No integrated and intersectoral projects or educational technology as an additional resource in the work practices were observed. The products deriving from the participation of all will improve articulation between the professionals working in these spaces.

Estudo retrospectivo de apreensões de alimentos da 1º Delegacia da Saúde Pública - Departamento de Polícia e Proteção à Cidadania

Os alimentos podem veicular diversos Micro-organismos patogênicos, causando varias afecções e surtos trazendo riscos à saúde pública. Essa contaminação pode ter ocorrência desde o início da produção da matéria-prima até as etapas de transporte, recepção, armazenamento e manipulação dos alimentos. Vencida a etapa de industrialização, os alimentos continuam expostos à contaminação nos centros de distribuição, supermercados, restaurantes, mercearias e na residência do consumidor. Esses alimentos podem estar contaminados por bactérias e suas toxinas, vírus, parasitas, metais pesados e produtos químicos. A ingestão de alimentos contaminados pode causar as Doenças Transmitidas por Alimentos, as quais representam alto risco à saúde da população, e geralmente são causadas por falhas em produção; armazenamento; processamento; manipulação; conservação de alimentos. O presente trabalho trata-se de um estudo retrospectivo, onde foram avaliadas as ocorrências da 10 Delegacia da Saúde Pública, DPPC (Departamento de Polícia e Proteção à Cidadania). O Departamento de Polícia de Proteção à Cidadania (DPPC) é um órgão de execução da Delegacia Geral de Polícia que tem a importante missão de orientar a população sobre seus direitos fundamentais e corrigir eventuais abusos, entre eles o risco à saúde pública através de alimentos impróprios e nocivos.

Food can transmit many pathogenic microorganisms, causing various diseases and outbreaks bringing risks to public health. This contamination may have occurred since the beginning of raw material production until transporting, receiving, storing and handling of food. After the industrialization step, the food continuous exposed to contamination in distribution centers, supermarkets, restaurants, grocery stores and the residence of the consumer. These foods can be contaminated by bacteria and their toxins, viruses, parasites, heavy metals and chemicals. The ingestion of contaminated food can cause the Foodborne Diseases, which represent high risk to public health, and are often causes by failures in production, storage, processing, manipulation and preservation of food. This resource is a retrospective study, evaluating the occurrence of the 1st Precinct of Public Health, DPPC (Department of Police and Protection of Citizenship). The Police Department for the Protection of Citizenship (DPPC) is an executive organ of the General Police Precinct that has the important task of educating the public about their fundamental rights and to correct abuses, including the risk to public health through food unfit and harmful.

Diagnóstico endodôntico: comparação entre aspectos clínicos e histológicos / Endodontic diagnosis: evaluation between clinical and histological findings

Objetivos: Neste estudo, nos propomos a analisar as alterações histológicas de trinta polpas dentárias correlacionando-as com os achadosclínicos para verificar a concordância entre o diagnóstico clínico e histopatológico e contribuir para o conhecimento sobre diagnósticoendodôntico. Métodos: Utilizando-se a metodologia de Oliveira4, as condições pulpares foram classificadas clinicamente como normal, pulpite reversível, pulpite em fase de transição, pulpite irreversível e necrose.Resultados: Foi observada falta de correlação entre os diagnósticos clínicos e histopatológicos nos casos classificados como reversíveis eem fase de transição, os quais histologicamente consistiram de lesões irreversíveis ou alterações degenerativas. Todos os casos classificadosclinicamente como irreversíveis corresponderam aos diagnósticos histopatológicos.Conclusão: Concluiu-se que a correlação entre o diagnóstico clínico e histopatológico da polpa dentária se mostra controversa, ainda quea semiotécnica utilizada tenha sido imprescindível para a orientação sobre a irreversibilidade da lesão pulpar.

Objective: In this study, the aim was to analyze the histologic alterations in thirty dental pulps and correlate them with the clinical findings to verify agreement between the clinical and histopathologic diagnosis and contribute to knowledge about endodontic diagnosis. Methods: Using the methodology of Oliveira4, the pulpal conditions were clinically classified as normal, reversible pulpitis, pulpitis at the stage of transition, irreversible pulpitis and necrosis. Results: Lack of correlation was observed between the clinical and histopathologic diagnoses in the cases classified as reversible and at the stage of transition, which histologically consisted of irreversible lesions or degenerative alterations. All the cases clinically classified as irreversible corresponded to the histologic diagnoses. Conclusion: It was concluded that the correlation between clinical and histopathologic diagnosis of dental pulp was shown to be controversial, even though the semiotechnique used had been imperative for guidance about the irreversibility of pulpal lesion.