Emerging Contributions of Pluripotent Stem Cells to Reproductive Technologies in Veterinary Medicine.

The generation of mature gametes and competent embryos in vitro from pluripotent stem cells has been successfully achieved in a few species, mainly in mice, with recent advances in humans and scarce preliminary reports in other domestic species. These biotechnologies are very attractive as they facilitate the understanding of developmental mechanisms and stages that are generally inaccessible during early embryogenesis, thus enabling advanced reproductive technologies and contributing to the generation of animals of high genetic merit in a short period. Studies on the production of in vitro embryos in pigs and cattle are currently used as study models for humans since they present more similar characteristics when compared to rodents in both the initial embryo development and adult life. This review discusses the most relevant biotechnologies used in veterinary medicine, focusing on the generation of germ-cell-like cells in vitro through the acquisition of totipotent status and the production of embryos in vitro from pluripotent stem cells, thus highlighting the main uses of pluripotent stem cells in livestock species and reproductive medicine.

Correlations between ambient air pollution and the prevalence of hospitalisations and emergency room visits for respiratory diseases in children: a systematic review.

OBJECTIVE: It is known that exposure to air pollution is associated with an increased risk for cardiovascular and respiratory diseases. This review aimed to summarise observational studies on the impact of short and long-term exposure to ambient air pollution on prevalence of hospitalisations and/or emergency department visits caused by respiratory diseases in children and adolescents. SOURCES: Pubmed, Scopus, Embase and Cochrane Library databases were searched for the years 2018 to December 2022, including studies in any language. SUMMARY OF THE FINDINGS: A total of 15 studies published between 2018 and 15 January 2022 were included in this review. PM2.5 was the most type of particulate matter studied. Short-term exposure to PM2,5, PM10, NO2, SO2 and O3, even at concentrations less than the current health-based guidelines, was significantly correlated with increased risk of outpatient/hospital visits and hospitalisations for respiratory diseases by children. CONCLUSIONS: Our findings emphasise the importance and urgency of long-term control of air pollution and pollution-related diseases, especially among children and adolescents. There is a need for further research employing more homogeneous methodologies for assessing exposure and outcome measurements, in order to enable systematic reviews with meta-analysis.

Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice.

Sodium-glucose cotransporter, type 2 inhibitors (SGLT2i) are emerging as the gold standard for treatment of type 2 diabetes (T2D) with renal protective benefits independent of glucose lowering. We took a high-level approach to evaluate the effects of the SGLT2i, empagliflozin (EMPA) on renal metabolism and function in a prediabetic model of metabolic syndrome. Male and female 12-wk-old TallyHo (TH) mice, and their closest genetic lean strain (Swiss-Webster, SW) were treated with a high-milk-fat diet (HMFD) plus/minus EMPA (@0.01%) for 12-wk. Kidney weights and glomerular filtration rate were slightly increased by EMPA in the TH mice. Glomerular feature analysis by unsupervised clustering revealed sexually dimorphic clustering, and one unique cluster relating to EMPA. Periodic acid Schiff (PAS) positive areas, reflecting basement membranes and mesangium were slightly reduced by EMPA. Phasor-fluorescent life-time imaging (FLIM) of free-to-protein bound NADH in cortex showed a marginally greater reliance on oxidative phosphorylation with EMPA. Overall, net urine sodium, glucose, and albumin were slightly increased by EMPA. In TH, EMPA reduced the sodium phosphate cotransporter, type 2 (NaPi-2), but increased sodium hydrogen exchanger, type 3 (NHE3). These changes were absent or blunted in SW. EMPA led to changes in urine exosomal microRNA profile including, in females, enhanced levels of miRs 27a-3p, 190a-5p, and 196b-5p. Network analysis revealed "cancer pathways" and "FOXO signaling" as the major regulated pathways. Overall, EMPA treatment to prediabetic mice with limited renal disease resulted in modifications in renal metabolism, structure, and transport, which may preclude and underlie protection against kidney disease with developing T2D.NEW & NOTEWORTHY Renal protection afforded by sodium glucose transporter, type 2 inhibitors (SGLT2i), e.g., empagliflozin (EMPA) involves complex intertwined mechanisms. Using a novel mouse model of obesity with insulin resistance, the TallyHo/Jng (TH) mouse on a high-milk-fat diet (HMFD), we found subtle changes in metabolism including altered regulation of sodium transporters that line the renal tubule. New potential epigenetic determinants of metabolic changes relating to FOXO and cancer signaling pathways were elucidated from an altered urine exosomal microRNA signature.

Frankincense (Boswellia serrata) Extract Effects on Growth and Biofilm Formation of Porphyromonas gingivalis, and Its Intracellular Infection in Human Gingival Epithelial Cells.

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

Could poor glycaemic control be a predictor of walking speed decline in older adults? Evidence from the English Longitudinal Study of Ageing.

AIM: Although diabetes is a risk factor for walking speed decline in older adults, it remains unclear how glycaemic control [assessed by glycated haemoglobin (HbA1c)] might affect the long-term trajectories of walking speed. We investigated whether the glycaemic control status accelerates the walking speed decline and whether this decline differs depending on previous mobility conditions. MATERIALS AND METHODS: In total, 3202 individuals aged ≥60 years from the English Longitudinal Study of Ageing (ELSA) were classified at baseline and after 4 and 8 years of follow-up according to glycaemic control status as 'without diabetes' (no self-reported diabetes and HbA1c <6.5%), 'good glycaemic control' (self-reported diabetes and HbA1c ≥6.5% and <7.0%) and 'poor glycaemic control' (PGC) (self-reported diabetes and HbA1c ≥7.0%). The generalized linear mixed models verified the walking speed trajectories in m/s. A second analysis was performed, including only participants without slowness at baseline (>0.8 m/s). RESULTS: Compared with the status 'without diabetes', the annual walking speed decline was -0.015 m/s for PGC and -0.011 m/s for good glycaemic control, totalling -0.160 and -0.130 m/s, respectively, over 8 years. Among those without slowness at baseline, only PGC had a significant walking speed decline, corresponding to -0.014 m/s per year and -0.222 m/s over 8 years. CONCLUSIONS: Poor glycaemic control is a discriminator of walking speed decline in older adults, regardless of previous mobility conditions. It may serve as an early screening tool for those at risk of decreased functional performance later in life.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

COVID-19 cases, vaccination, and SARS-CoV-2 in wastewater: insights from a Brazilian municipality.

Vaccines combatting COVID-19 demonstrate the ability to protect against disease and hospitalization, and reduce the likelihood of death caused by SARS-CoV-2. In addition, monitoring viral loads in sewage emerges as another crucial strategy in the epidemiological context, enabling early and collective detection of outbreaks. The study aimed to monitor the viral concentration of SARS-CoV-2 in untreated sewage in a Brazilian municipality. Also, it attempted to correlate these measurements with the number of clinical cases and deaths resulting from COVID-19 between July 2021 and July 2022. SARS-CoV-2 viral RNA was quantified by RT-qPCR. Pearson's correlation was performed to analyze the variables' relationship using the number of cases, deaths, vaccinated individuals, and viral concentration of SARS-CoV-2. The results revealed a significant negative correlation (p < 0.05) between the number of vaccinated individuals and the viral concentration of SARS-CoV-2, suggesting that after vaccination, the RNA viral load concentration was reduced in the sample population by the circulating concentration of wastewater. Consequently, wastewater monitoring, in addition to functioning as an early warning system for the circulation of SARS-CoV-2 and other pathogens, can offer a novel perspective that enhances decision-making, strengthens vaccination campaigns, and contributes to authorities establishing systematic networks for monitoring SARS-CoV-2.

Heart failure worsens leg muscle strength and endurance in coexistence patients with COPD and heart failure reduced ejection fraction.

Purpose: Exercise intolerance and dyspnoea are clinical symptoms in both heart failure (HF) reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD), which are suggested to be associated with musculoskeletal dysfunction. We tested the hypothesis that HFrEF + COPD patients would present lower muscle strength and greater fatigue compared to compared to the COPD group. Methods: We included 25 patients with HFrEF + COPD (100% male, age 67.8 ± 6.9) and 25 patients with COPD alone (100% male, age 66.1 ± 9.1). In both groups, COPD severity was determined as moderate-to-severe according to the GOLD classification (FEV1/FVC < 0.7 and predicted post-bronchodilator FEV1 between 30%-80%). Knee flexor-extensor muscle performance (torque, work, power and fatigue) were measured by isokinetic dynamometry in age and sex-matched patients with HFrEF + COPD and COPD alone; Functional capacity was assessed by the cardiopulmonary exercise test, the 6-min walk test (6MWT) and the four-minute step test. Results: The COPD group exhibited reduced lung function compared to the HFrEF + COPD group, as evidenced by lower FEV1/FVC (58.0 ± 4.0 vs. 65.5 ± 13.9; p < 0.0001, respectively) and FEV1 (51.3 ± 17.0 vs. 62.5 ± 17.4; p = 0.026, respectively) values. Regarding musculoskeletal function, the HFrEF + COPD group showed a knee flexor muscles impairment, however this fact was not observed in the knee extensors muscles. Power peak of the knee flexor corrected by muscle mass was significantly correlated with the 6MWT (r = 0.40; p < 0.05), number of steps (r = 0.30; p < 0.05) and work ratepeak (r = 0.40; p < 0.05) in the HFrEF + COPD and COPD groups. Conclusion: The presence of HFrEF in patients with COPD worsens muscular weakness when compared to isolated COPD.

The Burden of Chagas Disease in the Contemporary World: The RAISE Study.

Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.

Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 µg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.

The economic burden of Chagas disease: A systematic review.

BACKGROUND: Chagas disease (CD) is a neglected disease affecting millions worldwide, yet little is known about its economic burden. This systematic review is part of RAISE project, a broader study that aims to estimate the global prevalence, mortality, and health and economic burden attributable to chronic CD and Chronic Chagas cardiomyopathy. The objective of this study was to assess the main costs associated with the treatment of CD in both endemic and non-endemic countries. METHODS: An electronic search of the Medline, Lilacs, and Embase databases was conducted until 31st, 2022, to identify and select economic studies that evaluated treatment costs of CD. No restrictions on place or language were made. Complete or partial economic analyses were included. RESULTS: Fifteen studies were included, with two-thirds referring to endemic countries. The most commonly investigated cost components were inpatient care, exams, surgeries, consultation, drugs, and pacemakers. However, significant heterogeneity in the estimation methods and presentation of data was observed, highlighting the absence of standardization in the measurement methods and cost components. The most common component analyzed using the same metric was hospitalization. The mean annual hospital cost per patient ranges from $25.47 purchasing power parity US dollars (PPP-USD) to $18,823.74 PPP-USD, and the median value was $324.44 PPP-USD. The lifetime hospital cost per patient varies from $209,44 PPP-USD for general care to $14,351.68 PPP-USD for patients with heart failure. DISCUSSION: Despite the limitations of the included studies, this study is the first systematic review of the costs of CD treatment. The findings underscore the importance of standardizing the measurement methods and cost components for estimating the economic burden of CD and improving the comparability of cost components magnitude and cost composition analysis. Finally, assessing the economic burden is essential for public policies designed to eliminate CD, given the continued neglect of this disease.

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy.

The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient's samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions.

Gene duplication, gene loss, and recombination events with variola virus shaped the complex evolutionary path of historical American horsepox-based smallpox vaccines.

IMPORTANCE: Modern smallpox vaccines, such as those used against mpox, are made from vaccinia viruses, but it is still unknown whether cowpox, horsepox, or vaccinia viruses were used in the early 20th century or earlier. The mystery began to be solved when the genomes of six historical smallpox vaccines used in the United States from 1850 to 1902 were determined. Our work analyzed in detail the genomes of these six historical vaccines, revealing a complex genomic structure. Historical vaccines are highly similar to horsepox in the core of their genomes, but some are closer to the structure of vaccinia virus at the ends of the genome. One of the vaccines is a recombinant virus with parts of variola virus recombined into its genome. Our data add valuable information for understanding the evolutionary path of current smallpox vaccines and the genetic makeup of the potentially extinct group of horsepox viruses.

Porcine Germ Cells Phenotype during Embryonic and Adult Development.

Primordial germ cells (PGCs) are the precursors of gametes. Due to their importance for the formation and reproduction of an organism, understanding the mechanisms and pathways of PGCs and the differences between males and females is essential. However, there is little research in domestic animals, e.g., swine, regarding the epigenetic and pluripotency profiles of PGCs during development. This study analyzed the expression of epigenetic and various pluripotent and germline markers associated with the development and differentiation of PGCs in porcine (pPGCs), aiming to understand the different gene expression profiles between the genders. The analysis of gonads at different gestational periods (from 24 to 35 days post fertilization (dpf) and in adults) was evaluated by immunofluorescence and RT-qPCR and showed phenotypic differences between the gonads of male and female embryos. In addition, the pPGCs were positive for OCT4 and VASA; some cells were H3k27me3 positive in male embryos and adult testes. In adults, the cells of the testes were positive for germline markers, as confirmed by gene expression analysis. The results may contribute to understanding the pPGC pathways during reproductive development, while also contributing to the knowledge needed to generate mature gametes in vitro.

Total Mercury Content in the Tissues of Freshwater Chelonium (Podocnemis expansa) and a Human Health Risk Assessment for the Amazon Population in Brazil.

Researchers recognize the silent, negative and deleterious effects caused by mercury pollution in gold mining areas. Freshwater turtles are culturally part of the diet of riverside populations in the Amazon region and this area presents mercury (Hg) pollution issues mainly due to gold mining activities. Thus, this research aimed to evaluate the total mercury (THg) content in the different organs of Amazonian giant river turtle (Podocnemis expansa) and carry out a human health risk assessment associated with the consumption of these animals. This study was conducted in the Vila Balbina, municipality of Presidente Figueiredo, state of Amazonas, Brazil. Skin (n = 28), muscle (n = 19) and brain (n = 2) samples were analyzed by Atomic Absorption Spectrometry (TDA-AAS) and a DMA-80™ mercury analyzer was used for the total mercury determinations. The average values found for THg in the skin, muscle and brain samples were, respectively, 0.1045 mg·kg-1, 0.1092 mg·kg-1 and 0.0601 mg·kg-1. Thus, THg was observed even though the P. expansa were kept in captivity, possibly due to previous contamination by air, water and food. The Hazard Quotient (HQ) was calculated considering a 9.07 g·day-1 intake dose of P. expansa and the consumption of turtles once a week showed an HQ = 2.45, which may cause long-term injuries to human health. Although the muscle concentrations were below the maximum limit established by the World Health Organization (WHO) and Brazilian regulatory agencies, it is important to evaluate consumption factors such as amount ingested, frequency and animal gender, which may cause a potential risk to regular consumers due to mercury bioaccumulation. The WHO may consider various aspects in order to warn the Amazon population about the severity and silent hazard of this metal, especially due to the importance of this matrix in the region. This region urgently needs government actions to inhibit clandestine mining and to prevent future serious, chronic health problems of the entire population.

P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis.

In mice, oral Toxoplasma gondii infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to T. gondii-induced ileitis. Cysts of the ME49 strain of T. gondii were used to induce ileitis. The infected mice were euthanized on day 8 and ileal tissue and peripheral blood were collected for histopathological and immunohistochemical analyses. Ileal contractility, inflammatory mediators, inflammasome activation, quantitative PCR analysis of gene expression, and fecal microbiota were assessed using appropriate techniques, respectively. The infected P2X7-/- mice had greater disease severity, parasitic burden, liver damage, and intestinal contractility than the infected wild-type (WT) mice. Infection increased serum IL-6 and IFN-γ and tissue caspase-1 but not NLRP3 in P2X7-/- mice compared to WT mice. Bacteroidaceae, Rikenellaceae, and Rhodospirillales increased while Muribaculaceae and Lactobacillaceae decreased in the infected WT and P2X7-/- mice. Bacteroidia and Tannerellaceae increased in the P2X7-/- mice with ileitis. By contrast, Clostridiales and Mollicutes were absent in the P2X7-/- mice but increased in the WT mice. P2X7 protects mice against T. gondii infection by activating the inflammasome and regulating the local and systemic immune responses. Specific gut bacterial populations modulated by P2X7 determine disease severity.

Efeito da reabilitação cardiopulmonar e metabólica em pacientes que apresentaram dessaturação da oxihemoglobina induzida pelo exercício após alta hospitalar pela COVID-19: série de casos / Effect of cardiopulmonary and metabolic rehabilitation in patients with exercise-induced oxyhemoglobin desaturation after hospital discharge from COVID-19: case series

INTRODUÇÃO: A dessaturação da oxihemoglobina induzida pelo exercício em pacientes pós-COVID-19 parece estar associada à redução da difusão e dos volumes pulmonares, à maior dispneia e baixa capacidade funcional, sendo relacionada à maior mortalidade e pior prognóstico. A reabilitação cardiopulmonar e metabólica (RCPM) é relevante, pois visa restaurar a funcionalidade, tolerância ao esforço e a qualidade de vida (QV). OBJETIVO: Verificar os efeitos da RCPM em pacientes que apresentaram dessaturação da oxihemoglobina induzida pelo exercício após alta hospitalar pela COVID-19 e ainda observar a diferença entre os treinamentos contínuo de moderada intensidade (TCMI) e o intervalado de alta intensidade (TIAI) na tolerância ao esforço, nos sintomas e na QV. MÉTODOS: Trata-se do relato de uma série de 4 casos que foram hospitalizados por COVID-19 e que após alta hospitalar apresentaram dessaturação da oxihemoglobina induzida pelo esforço durante o teste do degrau de 6 minutos (TD6). Os pacientes foram avaliados por meio de espirometria de repouso, mensuração da força da musculatura inspiratória, TD6, teste da caminhada de 6 minutos (TC6), teste de repetições máximas do quadríceps e bíceps braquial e responderam ao questionário SF-36 de QV. Submetidos a um protocolo de treinamento contendo treino da musculatura inspiratória e treino resistido para grandes grupos musculares, adicionalmente, 2 pacientes fizeram TCMI (com 60-80% da frequência cárdica de reserva (FCR)) e 2 TIAI (com 40% da FCR na fase off, durante 4 minutos e 80 a 100%, na fase on, durante 2 minutos) em esteira por 30 minutos e, por fim, após 3 meses foram reavaliados. RESULTADOS: Observouse aumento da tolerância ao esforço, da força muscular inspiratória e periférica, além da melhora da QV e redução dos sintomas em todos os pacientes após a RCPM, porém houve incrementos maiores nos pacientes submetidos ao TIAI comparados ao TCMI na distância percorrida em metros (caso 1- 156 (23% de incremento); caso 3 - 168 (40%)) versus (caso 2 e 4 - 60 metros, com incrementos de 9% e 14%, respectivamente) e maior número de degraus (caso 1- 28 (23% de aumento); caso 3- 37 (34%)) versus (caso 2 ­ 2 (2% incremento); caso 4 - 15 (21%)). CONCLUSÃO: A RCPM apresentou efeitos positivos, com incremento da capacidade funcional e melhora da QV, além da redução dos sintomas durante o esforço, particularmente nos pacientes submetidos ao TIAI.

INTRODUCTION: Exercise-induced oxyhemoglobin desaturation in post-COVID-19 patients appears to be associated with reduced diffusion and lung volumes, greater dyspnea and low functional capacity, being related to higher mortality and worse prognosis. Cardiopulmonary and metabolic rehabilitation (CPMR) is relevant, as it aims to restore functionality, exercise tolerance and quality of life (QoL). OBJECTIVE: To verify the effects of CPMR in patients who presented exercise-induced oxyhemoglobin desaturation after hospital discharge due to COVID-19 and also to observe the difference between moderate-intensity continuous training (MICT) and high intensity interval training (HIIT) on effort tolerance, symptoms and QoL. METHODS: This is the report of a series of 4 cases who were hospitalized for COVID-19 and who, after hospital discharge, presented exertion-induced oxyhemoglobin desaturation during the 6-minute step test (6MST). Patients were assessed using spirometry at rest, measurement of inspiratory muscle strength, 6MST, 6-minute walk test (6MWT), quadriceps and biceps brachii maximum repetitions test, and answered the SF-36 QoL questionnaire. Submitted to a training protocol containing training of the inspiratory muscles and resistance training for large muscle groups, additionally, 2 patients underwent CMIT (with 60-80% of heart rate reserve) and 2 HIIT (with 40% of HR reserve in the off, for 4 minutes and 80 to 100%, in the on phase, for 2 minutes) on a treadmill for 30 minutes, finally, after 3 months, they were reassessed. RESULTS: There was an increase in effort tolerance, inspiratory and peripheral muscle strength, in addition to an improvement in QoL and a reduction in symptoms in all patients after CPMR, but there were greater increments in patients submitted to HIIT compared to CMIT in the distance covered in meters (case 1 - 156 (23% increment); case 3 - 168 (40%)) versus (case 2 and 4 - 60 meters, with increments of 9% and 14%, respectively) and greater number of steps (case 1 - 28 (23% increase); case 3- 37 (34%)) versus (case 2 ­ 2 (2% increment); case 4 - 15 (21%)). CONCLUSION: CPMR had positive effects, with an increase in functional capacity and improvement in QoL, in addition to a reduction in symptoms during exertion, particularly in patients undergoing HIIT.

Is dynapenic abdominal obesity a risk factor for cardiovascular mortality? A competing risk analysis.

BACKGROUND: Dynapenic abdominal obesity has been shown as a risk factor for all-cause mortality in older adults. However, there is no evidence on the association between this condition and cardiovascular mortality. OBJECTIVE: We aimed to investigate whether dynapenic abdominal obesity is associated with cardiovascular mortality in individuals aged 50 and older. METHODS: A longitudinal study with an 8-year follow-up was conducted involving 7,030 participants of the English Longitudinal Study of Ageing study. Abdominal obesity and dynapenia were respectively defined based on waist circumference (> 102 cm for men and > 88 cm for women) and grip strength (< 26 kg for men and < 16 kg for women). The sample was divided into four groups: non-dynapenic/non-abdominal obesity (ND/NAO), non-dynapenic/abdominal obesity (ND/AO), dynapenic/non-abdominal obesity (D/NAO) and dynapenic/abdominal obesity (D/AO). The outcome was cardiovascular mortality. The Fine-Grey regression model was used to estimate the risk of cardiovascular mortality as a function of abdominal obesity and dynapenia status in the presence of competing events controlled by socio-demographic, behavioural and clinical variables. RESULTS: The risk of cardiovascular mortality was significantly higher in individuals with D/AO compared with ND/NAO (SHR 1.85; 95% CI: 1.15-2.97). D/NAO was also associated with cardiovascular mortality (SHR: 1.62; 95% CI: 1.08-2.44). CONCLUSION: Dynapenic abdominal obesity is associated with cardiovascular mortality, with a larger effect size compared to dynapenia alone in individuals older than 50 years. Thus, prevention strategies and clinical interventions that enable mitigating the harmful effects of these conditions should be adopted to diminish such risk.

Serious lesions in Green turtles (Chelonia mydas) afflicted by fatal Spirorchiidiasis found stranded in south and southeastern Brazil.

Several diseases have been reported as affecting endangered wild sea turtle population worldwide, including spirorchiidiasis. This parasitic infection results in serious circulatory disorders in sea turtles, as well as tissue damage due to the presence of spirorchiids eggs. However, few reports of organs severely affected by tissue replacement caused by granulomatous inflammatory processes due to spirorchiidiasis in sea turtles are available. In this regard, this study describes massive lesions in 16 juvenile green turtles from southeastern Brazil presenting no other detectable diseases or injuries, associated to parasitic compression of air spaces, parasitic thyroid atrophy, parasitic encephalic compression and parasitic splenic lymphoid depletion. These rare injuries were categorized as extremely severe, affecting most spirorchiidiasis-infected organs. Spirorchiidiasis was, thus, noted herein as capable of causing a variety of lethal injuries to vital or extremely important organs in sea turtles. Spirorchiidiasis should, therefore, also be considered a potential cause of death in stranded green sea turtle monitoring efforts.

Highly water-soluble dapsone nanocrystals: Towards innovative preparations for an undermined drug.

Dapsone (DAP)is a dual-function drug substance; however, its limited water solubility may impair its bioavailability. Drug nanocrystals are an alternative to overcome this limitation. Herein, a DAP nanosuspension was prepared using adesign space approach aiming to investigate the influence of raw material properties and process parameters on the critical quality attributes of the drugnanocrystals. Optimized nanocrystals with 206.3 ± 6.7 nm using povacoat™ as stabilizer were made. The nanoparticles were characterized by dynamic light scattering, laser diffraction, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and saturation solubility. Compared to the raw material, the nanocrystals were 250-times smaller. Meanwhile, its crystalline state remained basically unchanged even after milling and drying. The nanosuspension successfully maintained its physical stability inlong-termandaccelerated stability studiesover, 4 and 3 months. Furthermore, toxicity studiesshowed low a toxicity at a20 mg/kg. As expected for nanocrystals, the size reduction improvedsaturation solubility3.78 times in water. An attempt to scale up from lab to pilot scale resulted nanocrystals of potential commercial quality. In conclusion, the present study describes the development of dapsone nanocrystals for treating infectious and inflammatory diseases. The nanocrystal formuation can be scaled up for commercial use.