Desfechos obstétricos adversos durante a COVID-19: uma série de casos retrospectiva / Adverse obstetric outcomes during COVID-19: a retrospective case series / Resultados obstétricos adversos durante el COVID-19: serie de casos retrospectiva

Objetivo: analisar as características e os desfechos obstétricos adversos em gestantes/puérperas infectadas pelo SARS-CoV-2 em serviço de referência. Método: série de casos retrospectiva entre gestantes com Covid-19 em um hospital universitário em Minas Gerais, Brasil, atendidas no serviço de 2020 a 2021, coletados em abril de 2022, empregando-se estatística descritiva para análise dos dados através do Statistical Package for the Social Science. Resultados: incluídas 26 gestantes, em sua maioria brancas, que tiveram como principais desfechos obstétricos adversos a internação em UTI (43,5%), parto prematuro (34,6%), dado reestratificado de semanas para dias para investigar o encurtamento da gestação, onde constatou-se média de 38,6 dias potenciais de gravidez perdidos dos 280 dias ideais, e ainda 15,4% evoluíram para óbito materno. Conclusão: o estudo proporcionou evidenciar a necessidade de vigilância e atenção às gestantes com foco nos principais desfechos adversos, podendo-se intervir em tempo oportuno para diminuir adversidades.

Objective: to analyze the characteristics and adverse obstetric outcomes in pregnant/puerperal women infected by SARS-CoV-2 at a reference service. Method: a retrospective case series conducted among pregnant women with Covid-19 in a university hospital from Minas Gerais, Brazil, treated at the service from 2020 to 2021. The cases were collected in April 2022 employing descriptive statistics for data analysis in the Statistical Package for the Social Science. Results: a total of 26 pregnant women were included, mostly white-skinned, whose main adverse obstetric outcomes were admission to the ICU (43.5%), premature birth (34.6%) and data restratified from weeks to days to investigate shortening of pregnancy, where a mean of 38.6 potential days of pregnancy were lost out of the ideal 280 days, and 15.4% resulted in maternal death. Conclusion: the study provided evidence of the need for surveillance and care for pregnant women with a focus on the main adverse outcomes, enabling timely intervention to reduce adversities.

Objetivo: analizar las características y resultados obstétricos adversos en gestantes/puérperas infectadas por SARS-CoV-2 en un servicio de referencia. Método: serie de casos retrospectiva entre gestantes con Covid-19 en un hospital universitario de Minas Gerais, Brasil, atendidas en el servicio de 2020 a 2021. Los datos se recolectaron en abril de 2022, se utilizó estadística descriptiva para analizar los datos mediante el Statistical Package for the Social Science. Resultados: se incluyeron 26 gestantes, la mayoría de raza blanca, cuyos principales resultados obstétricos adversos fueron ingreso a UCI (43,5%), parto prematuro (34,6%), dato reestratificado de semanas a días para investigar el acortamiento de la gestación, que arrojó como resultado un promedio de 38,6. Se comprobó que se perdieron en promedio 38,6 días potenciales de embarazo de los 280 días ideales, y muerte materna (15,4%). Conclusión: la evidencia que proporcionó el estudio indica que es necesario vigilar y atender a las gestantes enfocándose en los principales resultados adversos, lo que permite intervenir de forma oportuna para reducir adversidades.

Methotrexate might become the sole treatment option for leukemia following the occurrence of Stevens-Johnson syndrome.

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment. CASE REPORT: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the "BFM 2009" protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing. CONCLUSION: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.

Cereal bar enriched with ora-pro-nóbis (Pereskia aculeata Miller): physicochemical and sensory characterization.

Ora-pro-nobis (OPN) is an unconventional food plant with high nutritional value, and its nutritional composition can be altered according to cultivation. Cereal bars are a popular nutrient-poor foods, and OPN could be incorporated to improve the nutritional quality. This study aimed to evaluate the physicochemical characteristics and sensory acceptability of cereal bars enriched with OPN flour (OpnF) from different forms of cultivation. OpnF was obtained by dehydrating and grinding OPN leaves collected in rural (ROpnF) and urban (UOpnF) municipalities. Two formulations of cereal bars, peanut flavor (Bpn) and mango flavor (Bmg), each with 10% OpnF, were prepared. The macronutrients and mineral composition, oxalate content, water activity, texture, color profile, and acceptability were evaluated. ROpnF had the highest protein, iron, and manganese content, whereas UOpnF had the highest ash and magnesium content. The oxalic acid/calcium ratio was 1.43 and did not imply calcium bioavailability. In addition to nutritional and protein values, Bpn and Bmg presented a good sensory acceptability index of > 77.5% with market potential. Bmg has the highest mineral content and is a source of iron, manganese, and magnesium. OpnF can be used in cereal bars and potentially improve nutritional attributes and used in other foods in a similar way.

Characterizing lipid constituents of B. moojeni snake venom: a comparative approach for chemical and biological investigations.

Snake venoms are complex mixtures majorly composed of proteins with well-studied biological effects. However, the exploration of non-protein components, especially lipids, remains limited despite their potential for discovering bioactive molecules. This study compares three liquid-liquid lipid extraction methods for both chemical and biological analyses of Bothrops moojeni snake venom. The methods evaluated include the Bligh and Dyer method (methanol, chloroform, water), considered standard; the Acunha method, a modification of the Bligh and Dyer protocol; and the Matyash method (MTBE/methanol/water), featuring an organic phase less dense than the aqueous phase. Lipidomic analysis using liquid chromatography with high-resolution mass spectrometry (LC-HRMS) system revealed comparable values of lipid constituents' peak intensity across different extraction methods. Our results show that all methods effectively extracted a similar quantity of lipid species, yielding approximately 17-18 subclasses per method. However, the Matyash and Acunha methods exhibited notably higher proportions of biologically active lipids compared to the Bligh and Dyer method, particularly in extracting lipid species crucial for cellular structure and function, such as sphingomyelins and phosphatidylinositol-phosphate. In conclusion, when selecting a lipid extraction method, it is essential to consider the study's objectives. For a biological approach, it is crucial to evaluate not only the total quantity of extracted lipids but also their quality and biological activity. The Matyash and Acunha methods show promise in this regard, potentially offering a superior option for extracting biologically active lipids compared to the Bligh and Dyer method.

Enhancing affordability and profit in a non-cooperative, coordinated, hypothetical pediatric vaccine market via sequential optimization.

This study considers a hypothetical global pediatric vaccine market where multiple coordinating entities make optimal procurement decisions on behalf of countries with different purchasing power. Each entity aims to improve affordability for its countries while maintaining a profitable market for vaccine producers. This study analyzes the effect of several factors on affordability and profitability, including the number of non-cooperative coordinating entities making procuring decisions, the number of market segments in which countries are grouped for tiered pricing purposes, how producers recover fixed production costs, and the procuring order of the coordinating entities. The study relies on a framework where entities negotiate sequentially with vaccine producers using a three-stage optimization process that solves a MIP and two LP problems to determine the optimal procurement plans and prices per dose that maximize savings for the entities' countries and profit for the vaccine producers. The study's results challenge current vaccine market dynamics and contribute novel alternative strategies to orchestrate the interaction of buyers, producers, and coordinating entities for enhancing affordability in a non-cooperative market. Key results show that the order in which the coordinating entities negotiate with vaccine producers and how the latter recuperate their fixed cost investments can significantly affect profitability and affordability. Furthermore, low-income countries can meet their demands more affordably by procuring vaccines through tiered pricing via entities coordinating many market segments. In contrast, upper-middle and high-income countries increase their affordability by procuring through entities with fewer and more extensive market segments. A procurement order that prioritizes entities based on the descending income level of their countries offers higher opportunities to increase affordability and profit when producers offer volume discounts.

In vitro evaluation of the selective cytotoxicity and genotoxicity of three synthetic ortho-nitrobenzyl derivatives in human cancer cell lines, with and without metabolic activation.

Although the presence of nitro groups in chemicals can be recognized as structural alerts for mutagenicity and carcinogenicity, nitroaromatic compounds have attracted considerable interest as a class of agents that can serve as source of potential new anticancer agents. In the present study, the in vitro cytotoxicity, genotoxicity, and mutagenicity of three synthetic ortho-nitrobenzyl derivatives (named ON-1, ON-2 and ON-3) were evaluated by employing human breast and ovarian cancer cell lines. A series of biological assays was carried out with and without metabolic activation. Complementarily, computational predictions of the pharmacokinetic properties and druglikeness of the compounds were performed in the Swiss ADME platform. The MTT assay showed that the compounds selectively affected selectively the cell viability of cancer cells in comparison with a nontumoral cell line. Additionally, the metabolic activation enhanced cytotoxicity, and the compounds affected cell survival, as demonstrated by the clonogenic assay. The comet assay, the cytokinesis-block micronucleus assay, and the immunofluorescence of the γ-H2AX foci formation assay have that the compounds caused chromosomal damage to the cancer cells, with and without metabolic activation. The results obtained in the present study showed that the compounds assessed were genotoxic and mutagenic, inducing double-strand breaks in the DNA structure. The high selectivity indices observed for the compounds ON-2 and ON-3, especially after metabolic activation with the S9 fraction, must be highlighted. These experimental biological results, as well as the theoretical properties predicted for the compounds have shown that they are promising anticancer candidates to be exploited in additional studies.

Assessment of Body Condition in a Threatened Dolphin Population in an Anthropized Area in Southeastern Brazil.

Sepetiba Bay, located in southwestern Rio de Janeiro state, in southeastern Brazil, is a region of extreme anthropogenic impact, and is home to a large population of Guiana dolphins, which face increasing and cumulative pressures on their physical health. Cetacean body condition provides a useful indicator for the evaluation of the conservation status of marine mammals. Given this, the present study quantified the proportion of dolphins with different body condition scores and assessed temporal variation in these scores between 2017 and 2022 through the analysis of photographic records. We analyzed the photographs and identified the individuals using FinFindR and classified each individual based on its apparent body condition. A total of 29,737 photographs were taken during the study, and 79 individuals were identified, of which 68.35% were in poor condition. The evidence suggests that the Guiana dolphins are in relatively poor condition overall, possibly reflecting the cumulative impact of human activities in Sepetiba Bay.

Episodic memory improvement in illiterate adults attending late-life education irrespective of low socioeconomic status: insights from the PROAME study.

The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. Objective: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. Methods: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. Results: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. Conclusion: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.

A maioria das pessoas com demência vive em países de baixa/média renda, onde recursos essenciais para a saúde cerebral, como educação de qualidade, ainda não são amplamente acessíveis. No Brasil, o analfabetismo ainda é frequente, especialmente em comunidades de baixo nível socioeconômico. O estudo PROAME teve como objetivo explorar a educação básica tardia em pessoas analfabetas como ferramenta para o aumento da reserva cognitiva. Objetivo: Investigar a relação entre nível socioeconômico com aprendizado e com desempenho em testes cognitivos, em adultos analfabetos. Métodos: Este estudo clínico de seis meses (NCT04473235) contou com 108 participantes inscritos no projeto Educação para Jovens e Adultos (EJA), dos quais 77 completaram os testes. O nível socioeconômico de cada participante foi medido usando-se: o Índice de Qualidade de Vida Urbana, o Índice de Desenvolvimento Humano Municipal e o nível socioeconômico doméstico. Avaliações cognitivas incluíram: o Teste de Recordação Seletiva Livre e Guiada (TRSLG), uma lista de palavras para avaliar leitura e a matriz Beta III. Resultados: A amostra era predominantemente feminina, com idade média de 58,5. Os participantes melhoraram a leitura (p=0,01) e o TRSLG (p=0,003). Com relação à memoria episódica, as mulheres tiveram resultados superiores aos dos homens (p=0,007) e participantes mais jovens melhoraram mais que seus colegas mais velhos (p=0,001). Não foi observada nenhuma relação entre o nível socioeconômico e o desempenho cognitivo. Conclusão: Independentemente do nível socioeconômico, participantes obtiveram resultados positivos após frequentar a educação básica. Isso sugere que a educação tardia pode ser uma medida preventiva não farmacológica importante, especialmente em países de baixa/média renda.

The protective and destructive critical processes of female labor in small-scale fishing in coast Pernambuco, Brazil. / Processos críticos protetores e destrutivos no trabalho das pescadoras artesanais do litoral Pernambucano, Brasil.

This study aims to analyze the protective and destructive critical processes of 34 water women in the municipalities of Cabo de Santo de Agostinho and Ipojuca, Pernambuco, Brazil, from February/21 to August/22. The work process stages were systematized by the work flowchart, and we employed Breilh's critical processes matrix to organize the data. The destructive processes identified in the general domain were injustice and socio-environmental vulnerability, such as the economic development model, the Suape Industrial Port Complex, the 2019 oil spill crime disaster, the COVID-19 pandemic, and the difficult access to public policies; in the particular domain: overloads and extended working hours, use of rudimentary equipment and tools, and unequal gender, class, and race relationships; in the singular domain: physical and mental illnesses and deaths. The protective processes identified in the general domain were sustainable development objectives, public health, and social assistance policies; in the particular domain, group work and processing, consumption for subsistence; in the singular domain, fishing as a therapeutic, pleasurable, and sharing process. The study highlighted the central issues of the water women and the need to establish public policies targeting their care.

Objetivou-se analisar os processos críticos, protetores e destrutivos do trabalho de 34 mulheres das águas nos municípios de Cabo de Santo de Agostinho e Ipojuca (PE), de fevereiro de 2021 a agosto de 2022. As etapas do processo de trabalho foram sistematizadas pelo fluxograma do trabalho e organizadas na matriz de processos críticos de Breilh. Os processos destrutivos, no domínio geral, foram: injustiça e vulnerabilização socioambiental como modelo de desenvolvimento econômico, o Complexo Industrial Portuário de Suape, o desastre-crime de petróleo ocorrido em 2019, a pandemia de COVID-19 e dificuldade de acesso às políticas públicas; no particular: jornadas e sobrecargas de trabalho, uso de equipamentos e ferramentas rudimentares e relações desiguais de gênero, classe e raça; no singular: adoecimentos físicos, mentais e mortes. Os processos protetores, no domínio geral: os objetivos de desenvolvimento sustentável, políticas públicas de saúde e assistência social; no particular: trabalho e beneficiamento em grupo, consumo para subsistência; no singular: a pesca como processo terapêutico, prazeroso e de partilha. O estudo destacou os problemas centrais das mulheres das águas e a necessidade do estabelecimento de políticas públicas voltadas ao seu cuidado.

Use of the Ishii Test for screening sarcopenia in older adults: a systematic review with meta-analysis of diagnostic test accuracy (DTA) studies.

BACKGROUND: The Ishii Test is recommended by the European Working Group on Sarcopenia in Older People (EWGSOP2), however the use of this technique is still little explored in the clinical context and the scientific literature. OBJECTIVE: We aimed to verify the use of the Test of Ishii in screening for sarcopenia in older adults. METHODS: We searched three electronic databases and two reviewers independently screened and assessed the studies. Studies with older adults (60 years or more) of both genders, no year or language restriction and which aimed to evaluate sarcopenia using the Ishii Test and another diagnostic criteria were selected. A summary of the ROC curve, sensitivity and specificity were performed using the MedCalc and SPSS software programs, respectively. RESULTS: A total of 3,298 references were identified in the database, 278 by manually searching, and finally 11 studies were included for the review. The screening test showed good sensitivity and specificity in both genders. All studies showed values above the considered value for the Area Under the Curve (AUC) results, without discriminating power (0.500). Four studies used the original values, and five studies developed a new cut-off point. A summary of the AUC curve showed the diamond close to one, indicating that the Ishii test has good performance for screening sarcopenia (I2=83,66%; p<0.001; 95%CI: 69.38 to 91.28 for men; and I2=60.04%; p<0.001; 95%CI: 13.06 to 81.63 for women). CONCLUSION: The Ishii Test can be considered a useful tool for the early identification of sarcopenia in older adults. However, further studies are still needed to understand the behavior of this screening tool. TRIAL REGISTRATION: CRD42023424392.

Equidae pythiosis in Brazil and the world: a systematic review of the last 63 years (1960-2023).

This systematic review compiles reports of clinical pythiosis in horses, mules and donkeys from 1960 to 2023 worldwide, focusing on Brazil. We searched databases and included 71 articles detailing clinical characteristics, geographic distribution, epidemiology, diagnostic methods, therapies, and outcomes. The results showed that publications on equine pythiosis have significantly increased since 2010. Brazil reported the highest incidence, comprising 55% of cases, predominantly in the southern, northeastern, and central-western regions during summer and autumn. Cutaneous pythiosis was the most prevalent form, generally presenting as single lesions in the appendicular region, and affected females more than males. Diagnosis typically involved histopathology, used alone or with other methods. Various treatments have been employed, with surgery, often combined with chemotherapy and immunotherapy, being the most common. Notably, 80.84% of treated animals recovered, highlighting the effectiveness of these therapies in enhancing survival rates. The limitations of the study included the lack of data in published case reports, which made it difficult to collect and calculate epidemiological data. Additionally, we recognize that pythiosis in Brazil is underreported, since this disease does not have mandatory notification and several cases are not registered and/or reported in the literature. Lastly, it is hypothesized that equid pythiosis may be more widespread than currently known, and its real occurrence in Brazil remains uncertain.

Unearthing the power of microbes as plant microbiome for sustainable agriculture.

In recent years, research into the complex interactions and crosstalk between plants and their associated microbiota, collectively known as the plant microbiome has revealed the pivotal role of microbial communities for promoting plant growth and health. Plants have evolved intricate relationships with a diverse array of microorganisms inhabiting their roots, leaves, and other plant tissues. This microbiota mainly includes bacteria, archaea, fungi, protozoans, and viruses, forming a dynamic and interconnected network within and around the plant. Through mutualistic or cooperative interactions, these microbes contribute to various aspects of plant health and development. The direct mechanisms of the plant microbiome include the enhancement of plant growth and development through nutrient acquisition. Microbes have the ability to solubilize essential minerals, fix atmospheric nitrogen, and convert organic matter into accessible forms, thereby augmenting the nutrient pool available to the plant. Additionally, the microbiome helps plants to withstand biotic and abiotic stresses, such as pathogen attacks and adverse environmental conditions, by priming the plant's immune responses, antagonizing phytopathogens, and improving stress tolerance. Furthermore, the plant microbiome plays a vital role in phytohormone regulation, facilitating hormonal balance within the plant. This regulation influences various growth processes, including root development, flowering, and fruiting. Microbial communities can also produce secondary metabolites, which directly or indirectly promote plant growth, development, and health. Understanding the functional potential of the plant microbiome has led to innovative agricultural practices, such as microbiome-based biofertilizers and biopesticides, which harness the power of beneficial microorganisms to enhance crop yields while reducing the dependency on chemical inputs. In the present review, we discuss and highlight research gaps regarding the plant microbiome and how the plant microbiome can be used as a source of single and synthetic bioinoculants for plant growth and health.

Surgical Management Of Congenital Thoracic Disorders: A 15-Year Center Experience.

INTRODUCTION: Congenital thoracic disorders represent a spectrum of fetal lung bud development abnormalities, which may affect breathing capacity and quality of life. We aim to evaluate the impact of surgery in the treatment of 4 major congenital conditions. MATERIALS AND METHODS: We performed a retrospective cohort analysis of patients who underwent surgical treatment in our tertiary center, from 2007 to 2022. RESULTS: Over the 15-year period, we treated 33 patients, with a male predominance of 55%. 22 patients (67%) were asymptomatic. When symptomatic, the recurrence of respiratory infections was the most common clinical presentation (18%). In 13 patients (39%), diagnosis was achieved through fetal ultrasonography. This study encompassed 13 patients with pulmonary sequestration (39%), 11 patients with bronchogenic cysts (33%), 7 patients with congenital pulmonary airway malformation (21%) and 2 patients with congenital lobar emphysema (6%). Considering solely lung malformation conditions, we accounted 22 patients with a median age of 3 [1-67] years-old. Surgery comprised bilobectomy (9%), lobectomy (77%), lobectomy with wedge resection (5%), segmentectomy (5%) and wedge resection (5%). Concerning bronchogenic cysts, we treated 11 patients with a median age of 19 [14-66] years-old. We identified 1 hilar, 1 intrapulmonary and 9 mediastinal lesions, of which 4 were paraesophageal, 4 were subcarinal and 1 was miscellaneous. Overall, surgery was conducted by thoracotomy in 61% of patients, VATS in 33% and RATS in 6%. The median drainage time was 3 [1-40] days and median hospital stay was 4 [1-41] days. There were no cases of mortality. Ensuing, 94% of patients experienced clinical improvement after surgery. CONCLUSION: Early diagnosis of congenital thoracic malformations increased considerably with the improvement in imaging technology and prenatal screening. Treatment may include expectant conservative treatment. However, in selected cases, surgery may play an important role in symptomatic control and prevention of disease progression.

In Vitro Propagation of "Salsaparrilha" [Herreria salsaparrilha Mart. (Asparagaceae)]: An Antisyphilitic Medicinal Species.

An efficient procedure for in vitro propagation of Herreria salsaparrilha Martius was established from single-node explants (fourth and fifth nodes from apex to the base) derived from donor plants maintained under shading-house conditions. After surface sterilization, explants are inoculated in test tubes containing 15 mL of Murashige and Skoog (MS) medium without growth regulators. Cultures are maintained under 35 µmol m-2 s-1 irradiance, a 16/8-h light/dark light regime, at 26 ± 2 °C. The subcultures are carried out under the same conditions, adding 6-benzyladenine 1.0 mg/L and Phytagel® 2.8 g/L. Shoots are elongated and rooted by transferring individual shoots to half-strength MS medium without growth regulators. After 25-30 days, elongated rooted shoots are transferred to plastic pots containing 25-30 mL of sterile distilled water, covered with a transparent plastic bag, and kept under the same growth room conditions for 2 days. Plants are transferred to cups containing autoclaved and washed sand and kept in a shading house (50% light interception) for acclimatization. True-to-type adult plants were successfully recovered under ex vitro conditions.

An Integrated DAIDS Laboratory Oversight Framework: Application of the DAIDS GCLP Guidelines.

The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials. .

Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma.

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.

Low levels of potentially toxic elements in workers are associated with self-reported health outcomes.

Occupational exposure to toxic elements can adversely affect health. The current study evaluated blood concentrations of potentially toxic elements (PTE) including As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn in formal and informal workers. Additionally, the study investigated the associations between blood PTE concentrations and reported health outcomes in the study population. The exposed group included women engaged in informal jewelry welding within their homes in Limeira, São Paulo state, Brazil (n = 36) and men who worked at a steel company in Volta Redonda, Rio de Janeiro state, Brazil (n = 22). The control group comprised residents of the same neighborhoods as the workers but without occupational exposure to chemicals (n = 28 in Limeira; n = 27 in Volta Redonda). Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (TQ ICP-MS) was used to determine PTE concentrations in blood samples. Glycemia, insulin, and lipid profile tests were performed. All participants completed questionnaires on household risk and reported morbidity. The blood concentrations of Cd, As, and Pb, as well as glycemia, were higher in informal workers than in control subjects. No significant differences were observed between formal workers and control subjects. A robust Poisson regression model, adjusted for variables suggested by a Directed Acyclic Graph, disclosed associations of blood lead and arsenic concentrations with the prevalence of neurological manifestations in Limeira. Blood lead levels > 2.6 µg dL-1 were associated with 2.3 times the prevalence of self-reported neurological manifestations (95 % CI: 1.17-4.58; p = 0.02) than lower blood lead concentrations. Furthermore, a positive association between blood cadmium concentrations and glycemia was observed. Informal occupational exposure to these elements may indicate an increased risk of developing diseases. Monitoring exposure and implementing interventions to reduce PTE exposure in the work environment represent significant steps toward prevention.

Preliminary snapshot reveals a relationship between multidrug-resistance and biofilm production among enterobacteriaceae isolated from fecal samples of farm-raised poultry in ceará, Brazil.

Antimicrobial resistance and biofilm formation by microbial pathogens pose a significant challenge to poultry production systems due to the persistent risk of dissemination and compromise of bird health and productivity. In this context, the study aimed to investigate the occurrence of different multiresistance phenotypes and the biofilm-forming ability of Enterobacteriaceae isolated from broiler chicken excreta in poultry production units in Ceará, Brazil. Samples were collected from three distinct broiler breeding facilities and subjected to isolation, identification, antibiotic susceptibility testing, phenotypic screening for ß-lactamases enzymes, and biofilm formation evaluation. Seventy-one strains were identified, being Escherichia coli (37 %) and Proteus mirabilis (32 %), followed by Klebsiella pneumoniae (11 %), Providencia stuartii (9 %), Klebsiella aerogenes (6 %), Alcaligenes faecalis (4 %), and Salmonella sp. (1 %). A significant proportion (87 %) of multiresistant strains were detected. For the phenotypic evaluation of ß-lactamases production, strains with resistance to second and third-generation cephalosporins and carbapenems were tested. About 4 of 6 and 10 of 26 were positive for inducible chromosomal AmpC ß-lactamase and extended-spectrum ß-lactamase (ESBL), respectively. Regarding biofilm formation, it was observed that all MDR strains were capable of forming biofilm. In this sense. the potential of these MDR bacteria to develop biofilms becomes a significant concern, representing a real threat to both human and animal health, as biofilms offer stability, antimicrobial protection, and facilitate genetic transfer.

Negative effects of cigarette butt leachate on freshwater phytoplankton communities.

We experimentally tested the effects of different concentrations of cigarette butt leachate on freshwater phytoplankton chlorophyll-a, species richness, cell density, and community composition. For this, we sampled the phytoplankton from a eutrophic lake and acclimated it for 24 h in microcosms. We then conducted the experiment in microcosms maintained for 96 h. The experiment consisted of four treatments: control and leachate from 1 butt L-1 (T1), 5 butts L-1 (T5), and 10 butts L-1 (T10), which were prepared by diluting a stock solution of leachate from 50 butts L-1. We found that algal chlorophyll-a content was not affected by different leachate concentrations. In contrast, phytoplankton cell density decreased in a dose-dependent manner as concentrations of the leachate increased. Similarly, the number of species was highest in the control group relative to all other treatments, with T1 and T5 showing higher species richness than T10. Additionally, the exposition to different concentrations of the leachate impacted community composition across all treatments in comparison to the control group. Our results suggest that cigarette butt leachate alters the number of cells and species, as well as the distribution of abundance, without necessarily reducing chlorophyll-a concentrations. Our findings indicate that to gain a comprehensive understanding of the effects of cigarette butt leachate on freshwater ecosystems, it is essential to evaluate more realistic scenarios that incorporate aquatic communities, rather than isolated species.