How did coronavirus disease 2019 affect autonomic balance in young individuals? Analysis by heart rate variability

SUMMARY OBJECTIVE: The aim of this study was to demonstrate the effect of coronavirus disease 2019 on the cardiovascular autonomic system using heart rate variability in young individuals. METHODS: The study was designed retrospectively by scanning the 24-h Holter electrocardiography records of patients who applied to the Ankara Abdurrahman Yurtaslan Oncology Education and Research Hospital Cardiology outpatient clinic. The study group consisted of 492 patients under the age of 40 years, who did not have additional comorbidities or medication use and had prolonged symptoms after coronavirus disease 2019 during the pandemic. The control group, including 401 patients, was determined during the pre-pandemic period (before December 2019). Heart rate variability parameters were evaluated by scanning the 24-h Holter electrocardiography records of the patients and compared with the non-coronavirus disease 2019 group. RESULTS: The median age of participants was 30 years. Standard deviation of normal RR intervals (SDNN) ≤100 ms was more prevalent in the study group (27 (6.7%) vs 73 (14.8%), p<0.001). In univariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.41, 95%CI 1.52-3.83), p<0.001] and age [(OR 1.04, 95%CI 1.01-1.07), p=0.016] had a significant effect on the probability of SDNN≤100. In multivariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.42, 95%CI 1.52-3.85), p<0.001] and age [(OR 2.42, 95%CI 1.52-3.85), p=0.016] had a significant effect on the probability of SDNN≤100. Frequency domain measures such as, high-frequency values were significantly higher in the study group (p=0.029). The study group's low-frequency/high frequency ratio was significantly lower (p=0.019). The low-frequency/high-frequency ratio's cut-off value was ≤2.77. for determining the differentiation between coronavirus disease 2019 positive and negative cases in the receiver operating characteristic analysis. The sensitivity rate was 80.7%. The area under the curve value is 0.546 (p=0.019). CONCLUSION: This study showed that coronavirus disease 2019 causes reduced heart rate variability and increased parasympathetic activity in young patients. This may explain the prolonged symptoms after coronavirus disease 2019 infection.

Nuclear compensatory evolution driven by mito-nuclear incompatibilities.

Mitochondrial function relies on the coordinated expression of mitochondrial and nuclear genes, exhibiting remarkable resilience despite high mitochondrial mutation rates. The nuclear compensation mechanism suggests deleterious mitochondrial alleles drive compensatory nuclear mutations to preserve mito-nuclear compatibility. However, prevalence and factors conditioning this phenomenon remain debated due to its conflicting evidence. Here, we investigate how mito-nuclear incompatibilities impact substitutions in a model for species radiation. Mating success depends on genetic compatibility (nuclear DNA) and spatial proximity. Populations evolve from partially compatible mito-nuclear states, simulating mitochondrial DNA (mtDNA) introgression. Mutations do not confer advantages nor disadvantages, but individual fecundity declines with increasing incompatibilities, selecting for mito-nuclear coordination. We find that selection for mito-nuclear compatibility affects each genome differently based on their initial state. In compatible gene pairs, selection reduces substitutions in both genomes, while in incompatible nuclear genes, it consistently promotes compensation, facilitated by more mismatches. Interestingly, high mitochondrial mutation rates can reduce nuclear compensation by increasing mtDNA rectification, while substitutions in initially compatible nuclear gene are boosted. Finally, the presence of incompatibilities accelerates species radiation, but equilibrium richness is not directly correlated to substitution rates, revealing the complex dynamics triggered by mitochondrial introgression and mito-nuclear coevolution. Our study provides a perspective on nuclear compensation and the role of mito-nuclear incompatibilities in speciation by exploring extreme scenarios and identifying trends that empirical data alone cannot reveal. We emphasize the challenges in detecting these dynamics and propose analyzing specific genomic signatures could shed light on this evolutionary process.

Características y supervivencia de adultos con cáncer diferenciado de tiroides en un hospital de Perú / Characteristics and survival of adults with differentiated thyroid cancer in a Peruvian hospital

RESUMEN El propósito del estudio fue describir las características clínicas, anatomopatológicas, tratamiento y supervivencia de los pacientes con cáncer de tiroides diferenciado. Se realizó un estudio de cohorte retrospectiva con datos de 150 pacientes de un hospital peruano entre los años 2010 al 2020. Se describieron las características y supervivencia (método de Kaplan-Meier). La media de edad fue 48,3 años, 130 (86,7%) fueron mujeres y el tipo histológico más frecuente fue el papilar 94,6%. El 74,2% tenían estadio TNM I, 70,7% tiroidectomía total y 68,7% recibió yodo radiactivo. La supervivencia global a los 5 años fue 89,3%, siendo menor en aquellos con estadio TNM IV y mayor en los que usaron yodo radiactivo. En conclusión, en un hospital de Cusco, el cáncer diferenciado de tiroides fue más frecuente en mujeres y la supervivencia fue menor en comparación con reportes de otros países.

ABSTRACT This study aimed at studying the clinical and anatomopathological characteristics, treatment and survival of patients with differentiated thyroid cancer. A retrospective cohort study was conducted with data from 150 patients from a Peruvian hospital between the years 2010 to 2020. Characteristics and survival (Kaplan-Meier method) were described. The mean age was 48.3 years, 130 participants (86.7%) were women and the most frequent histologic type was papillary 94.6%. Of the participants, 74.2% had TNM stage I, 70.7% had total thyroidectomy and 68.7% received radioactive iodine. Overall survival at 5 years was 89.3%, being lower in those with TNM stage IV and higher in those who used radioactive iodine. In conclusion, in a hospital in Cusco, differentiated thyroid cancer was more frequent in women and survival was lower compared to reports from other countries.

Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Predictors of autosomal dominant polycystic kidney disease progression: a Brazilian single-center cohort / Preditores de progressão da doença renal policística autossômica dominante: uma coorte brasileira de centro único

Abstract Introduction: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. Methods: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. Results: The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome. Conclusions: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.

Resumo Introdução: É importante identificar fatores de risco para progressão da doença renal policística autossômica dominante (DRPAD). Entretanto, são escassos os estudos que avaliam esse assunto utilizando amostra brasileira. Portanto, o objetivo deste estudo foi identificar fatores de risco para desfechos renais e óbito em coorte brasileira de pacientes com DRPAD. Métodos: Os pacientes tiveram o primeiro atendimento médico entre janeiro/2002 e dezembro/2014, sendo acompanhados até dezembro/2019. Associações entre variáveis clínicas e laboratoriais com desfecho primário (redução sustentada de pelo menos 57% na TFGe em relação ao valor basal, necessidade de diálise ou transplante renal) e desfecho secundário (óbito por qualquer causa) foram analisadas pelo modelo de regressão múltipla de Cox. Entre 80 pacientes com DRPAD, foram excluídos aqueles menores de 18 anos, com TFG <30 mL/min/1,73 m2 e/ou aqueles com dados ausentes. Foram acompanhados 70 pacientes. Resultados: Fatores independentemente associados aos desfechos renais foram: comprimento renal total - Razão de Risco (HR) ajustada com intervalo de confiança de 95% (IC 95%): 1,137 (1,057-1,224), taxa de filtração glomerular - HR (IC 95%): 0,970 (0,949-0,992) e nível sérico de ácido úrico - HR (IC 95%): 1,643 (1,118-2,415). Diabetes mellitus - HR (IC 95%): 8,115 (1,985-33,180) e TFG - HR (IC 95%): 0,957 (0,919-0,997) foram associados ao desfecho secundário. Conclusões: Esses achados corroboram a hipótese de que comprimento renal total, TFG e nível sérico de ácido úrico podem ser importantes preditores prognósticos de DRPAD em uma coorte brasileira, o que pode ajudar a selecionar pacientes que necessitam de acompanhamento mais próximo.

Prevalence and metabolic risk factors of chronic kidney disease among a Mexican adult population: a cross-sectional study in primary healthcare medical units.

Introduction: The intricate relationship between obesity and chronic kidney disease (CKD) progression underscores a significant public health challenge. Obesity is strongly linked to the onset of several health conditions, including arterial hypertension (AHTN), metabolic syndrome, diabetes, dyslipidemia, and hyperuricemia. Understanding the connection between CKD and obesity is crucial for addressing their complex interplay in public health strategies. Objective: This research aimed to determine the prevalence of CKD in a population with high obesity rates and evaluate the associated metabolic risk factors. Material and Methods: In this cross-sectional study conducted from January 2017 to December 2019 we included 3,901 participants of both sexes aged ≥20 years who were selected from primary healthcare medical units of the Mexican Social Security Institute (IMSS) in Michoacan, Mexico. We measured the participants' weight, height, systolic and diastolic blood pressure, glucose, creatinine, total cholesterol, triglycerides, HDL-c, LDL-c, and uric acid. We estimated the glomerular filtration rate using the Collaborative Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Results: Among the population studied, 50.6% were women and 49.4% were men, with a mean age of 49 years (range: 23-90). The prevalence of CKD was 21.9%. Factors significantly associated with an increased risk of CKD included age ≥60 years (OR = 11.70, 95% CI [9.83-15.93]), overweight (OR = 4.19, 95% CI [2.88-6.11]), obesity (OR = 13.31, 95% CI [11.12-15.93]), abdominal obesity (OR = 9.25, 95% CI [7.13-11.99]), AHTN (OR = 20.63, 95% CI [17.02-25.02]), impaired fasting glucose (IFG) (OR = 2.73, 95% CI [2.31-3.23]), type 2 diabetes (T2D) (OR = 14.30, 95% CI [11.14-18.37]), total cholesterol (TC) ≥200 mg/dL (OR = 6.04, 95% CI [5.11-7.14]), triglycerides (TG) ≥150 mg/dL (OR = 5.63, 95% CI 4.76-6.66), HDL-c <40 mg/dL (OR = 4.458, 95% CI [3.74-5.31]), LDL-c ≥130 mg/dL (OR = 6.06, 95% CI [5.12-7.18]), and serum uric acid levels ≥6 mg/dL in women and ≥7 mg/dL in men (OR = 8.18, 95% CI [6.92-9.68]), (p < 0.0001). These factors independently contribute to the development of CKD. Conclusions: This study underscores the intricate relationship between obesity and CKD, revealing a high prevalence of CKD. Obesity, including overweight, abdominal obesity, AHTN, IFG, T2D, dyslipidemia, and hyperuricemia emerged as significant metabolic risk factors for CKD. Early identification of these risk factors is crucial for effective intervention strategies. Public health policies should integrate both pharmacological and non-pharmacological approaches to address obesity-related conditions and prevent kidney damage directly.

A New Mixture Model With Cure Rate Applied to Breast Cancer Data.

We introduce a new modelling for long-term survival models, assuming that the number of competing causes follows a mixture of Poisson and the Birnbaum-Saunders distribution. In this context, we present some statistical properties of our model and demonstrate that the promotion time model emerges as a limiting case. We delve into detailed discussions of specific models within this class. Notably, we examine the expected number of competing causes, which depends on covariates. This allows for direct modeling of the cure rate as a function of covariates. We present an Expectation-Maximization (EM) algorithm for parameter estimation, to discuss the estimation via maximum likelihood (ML) and provide insights into parameter inference for this model. Additionally, we outline sufficient conditions for ensuring the consistency and asymptotic normal distribution of ML estimators. To evaluate the performance of our estimation method, we conduct a Monte Carlo simulation to provide asymptotic properties and a power study of LR test by contrasting our methodology against the promotion time model. To demonstrate the practical applicability of our model, we apply it to a real medical dataset from a population-based study of incidence of breast cancer in São Paulo, Brazil. Our results illustrate that the proposed model can outperform traditional approaches in terms of model fitting, highlighting its potential utility in real-world scenarios.

Femora nutrient foramina and aerobic capacity in giant extinct xenarthrans.

Nutrient foramina are small openings in the periosteal surface of the mid-shaft region of long bones that traverse the cortical layer and reach the medullary cavity. They are important for the delivery of nutrients and oxygen to bone tissue and are crucial for the repair and remodeling of bones over time. The nutrient foramina in the femur's diaphysis are related to the energetic needs of the femur and have been shown to be related to the maximum metabolic rate (MMR) of taxa. Here, we investigate the relationship between nutrient foramen size and body mass as a proxy to the aerobic capacity of taxa in living and extinct xenarthrans, including living sloths, anteaters, and armadillos, as well as extinct xenarthrans such as glyptodonts, pampatheres, and ground sloths. Seventy femora were sampled, including 20 from extant taxa and 50 from extinct taxa. We obtained the blood flow rate (Q̇) based on foramina area and performed PGLS and phylogenetic ANCOVA in order to explore differences among mammalian groups. Our results show that, among mammals, taxa commonly associated with lower metabolism like living xenarthrans showed relatively smaller foramina, while the foramina of giant extinct xenarthrans like ground sloths and glyptodonts overlapped with non-xenarthran placentals. Consequently, Q̇ estimations indicated aerobic capacities comparable to other placental giant taxa like elephants or some ungulates. Furthermore, the estimation of the MMR for fossil giant taxa showed similar results, with almost all taxa showing high values except for those for which strong semi-arboreal or fossorial habits have been proposed. Moreover, the results are compatible with the diets predicted for extinct taxa, which indicate a strong consumption of grass similar to ungulates and in contrast to the folivorous or insectivorous diets of extant xenarthrans. The ancestral reconstruction of the MMR values indicated a lack of a common pattern for all xenarthrans, strongly supporting the occurrence of low metabolic rates in extant forms due to their particular dietary preferences and arboreal or fossorial habits. Our results highlight the importance of considering different evidence beyond the phylogenetic position of extinct taxa, especially when extinct forms are exceptionally different from their extant relatives. Future studies evaluating the energetic needs of giant extinct xenarthrans should not assume lower metabolic rates for these extinct animals based solely on their phylogenetic position and the observations on their extant relatives.

Análise Comparativa do ECG com o Holter na avaliação da Frequência Cardíaca na Insuficiência Cardíaca com Fração de Ejeção Reduzida e Ritmo Sinusal / Comparative Analysis of ECG and Holter Monitoring in the Assessment of Heart Rate in Heart Failure with Reduced Ejection Fraction and Sinus Rhythm

Resumo Fundamento A frequência cardíaca (FC) na insuficiência cardíaca com fração de ejeção reduzida (ICFEr) e ritmo sinusal apresenta valor prognóstico. Entretanto, o método de mensuração é debatido na literatura. Objetivos Comparar em pacientes com ICFEr e ritmo sinusal a FC no Holter com três eletrocardiogramas de repouso: ECG1, ECG2 e ECG3. Metodologia Estudo transversal com 135 pacientes portadores de insuficiência cardíaca com fração de ejeção ≤ 40% e ritmo sinusal. A FC foi avaliada por ECG e Holter. Análises incluíram o coeficiente de correlação intraclasse (CCI), regressão robusta, raiz do erro quadrático médio, Bland-Altman e a área sobre a curva ROC. Adotou-se nível de significância de 0,05 e o ajuste de Bonferroni-Holm para minimizar erros tipo I. Resultados As medianas [intervalo interquartil] de idade e fração de ejeção foram de 65 anos [16] e 30% [11], respectivamente. O CCI dos 3 ECG foi de 0,922 (intervalo de confiança de 95%: 0,892; 0,942). Os coeficientes de regressão robusta para ECG1 e ECG3 foram 0,20 (intervalo de confiança de 95%: 0,12; 0,29) e 0,21 (intervalo de confiança de 95%: 0,06; 0,36). O R2 robusto foi de 0,711 (intervalo de confiança de 95%: 0,628; 0,76). Na análise de concordância de Bland-Altman, os limites de concordância foram de −17,0 (intervalo de confiança de 95%: −19,0; −15,0) e 32,0 (intervalo de confiança de 95%: 30,0; 34,0). A área sob a curva ROC foi de 0,896 (intervalo de confiança de 95%: 0,865; 0,923). Conclusão A FC do ECG mostrou alta concordância com a FC do Holter, validando seu uso clínico em pacientes com ICFEr e ritmo sinusal. Contudo, a concordância foi subótima em um terço dos pacientes com FC inferior a 70 bpm pelo ECG, devendo ser considerada a realização de Holter neste contexto.

Abstract Background Heart rate (HR) has shown prognostic value in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm. However, the method of measurement is debated in the literature. Objectives To compare HR on Holter with 3 resting electrocardiograms (ECG1, ECG2, and ECG3) in patients with HFrEF and sinus rhythm. Methods This was a cross-sectional study with 135 patients with heart failure with ejection fraction ≤ 40% and sinus rhythm. HR was assessed by ECG and Holter. Analyses included intraclass correlation coefficient (ICC), robust regression, root mean squared error, Bland-Altman, and area under the receiver operating characteristic (ROC) curve. A significance level of 0.05 and Bonferroni-Holm adjustment were adopted to minimize type I errors. Results The median [interquartile range] age and ejection fraction were 65 years [16] and 30% [11], respectively. The ICC of the 3 ECGs was 0.922 (95% confidence interval: 0.892; 0.942). The robust regression coefficients for ECG1 and ECG3 were 0.20 (95% confidence interval: 0.12; 0.29) and 0.21 (95% confidence interval: 0.06; 0.36). The robust R2 was 0.711 (95% confidence interval: 0.628; 0.76). In the Bland-Altman agreement analysis, the limits of agreement were −17.0 (95% confidence interval: −19.0; −15.0) and 32.0 (95% confidence interval: 30.0; 34.0). The area under the ROC curve was 0.896 (95% confidence interval: 0.865; 0.923). Conclusion The HR on ECG showed high agreement with the HR on Holter, validating its clinical use in patients with HFrEF and sinus rhythm. However, agreement was suboptimal in one third of patients with HR below 70 bpm on ECG; thus, 24-hour Holter monitoring should be considered in this context.

Determining Sex from Thai Radius: Discriminant Function Analysis Including the Dry Bone Weight as an Effective Variant / Determinación del Sexo a Partir del Radio Tailandés: Análisis de Función Discriminante que Incluye el Peso del Hueso Seco como Variante Eficaz

SUMMARY: In forensic anthropology, the radius bone has been shown to determine the sex of human remains in a number of different populations. The dry mass and growth of long bones, including the radius, are associated with sex hormone levels; however, the use of bone weight to determine sex has not been sufficiently investigated. The aim of this study was to apply bone morphometric parameters, including maximum length of radius (MLR), circumference at the midshaft of radius (CMR), and weight of radius (WR), to 400 sample radii from a Northeastern Thai population. Univariate and multivariate discriminant functions of all parameters were systemically applied. Equations for calculating sex classification were also determined. Descriptive data analysis showed significant sexual dimorphism in all variables (p < 0.05). The canonical correlation was highest in CMR (0.772) and the ratio of weight to length (0.747). Multivariate discriminant function analysis showed that the measured indices of the right radius were slightly greater than those of the left radius. The parameters demonstrating the highest values of the standardized canonical discriminant function coefficients were CMR (Rt. = 0.496, Lt. 0.431) and WR (Rt. = 0.681, Lt. = 0.715). Moreover, the results of the multivariable (stepwise method) indicated that the best accuracy rates for using combinations of CMR and WR were 94 % (right side) and 92 % (left side). In conclusion, the weight of the radius (rather than the length) is an effective parameter in determining sex.

En antropología forense, se ha demostrado que el hueso radio determina el sexo de los restos humanos en varias poblaciones diferentes. La masa seca y el crecimiento de los huesos largos, incluido el radio, están asociados con los niveles de hormonas sexuales; sin embargo, el uso del peso de los huesos para determinar el sexo no se ha investigado suficientemente. El objetivo de este estudio fue aplicar parámetros morfométricos óseos, incluida la longitud máxima del radio (LMR), la circunferencia en la mitad del radio (CMR) y el peso del radio (PR), a 400 radios de muestra de una población del noreste de Tailandia. Se aplicaron sistémicamente funciones discriminantes univariadas y multivariadas de todos los parámetros. También se determinaron ecuaciones para calcular la clasificación por sexo. El análisis descriptivo de los datos mostró un dimorfismo sexual significativo en todas las variables (p < 0,05). La correlación canónica fue mayor en CMR (0,772) y la relación peso-longitud (0,747). El análisis de función discriminante multivariante mostró que los índices del radio derecho eran ligeramente mayores que los del radio izquierdo. Los parámetros que demostraron los valores más altos de los coeficientes de la función discriminante canónica estandarizada fueron CMR (Rt. = 0,496, Lt. 0,431) y PR (Rt. = 0,681, Lt. = 0,715). Además, los resultados del método multivariable (método paso a paso) indicaron que las mejores tasas de precisión al usar combinaciones de CMR y PR fueron del 94 % (lado derecho) y del 92 % (lado izquierdo). En conclusión, el peso del radio (más que la longitud) es un parámetro eficaz para determinar el sexo.

Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

[Box: see text].

Affective Implications of Human-Animal Relationship on Pig Welfare: Integrating Non-Linear Heart Rate Variability Measures.

The human-animal relationship is crucial for animal welfare. Gentle handling enhances pigs' comfort while rough handling causes fear and stress. This study examined how different human-animal relationship qualities affect the behavior and heart rate variability (linear and non-linear parameters) of 36 nursery pigs. Over six weeks, pigs experienced positive (n = 12), minimal (n = 12), or negative (n = 12) human handling. Their responses to handlers were then assessed in an experimental arena with four phases: habituation, exposure to the handler standing and sitting, and forced interaction. Pigs subjected to negative handling exhibited increased fear-related behaviors, spending less time in contact with the handler. They also exhibited heightened stress responses, with greater LF/HF ratio and Lmean values compared with positively handled pigs. Conversely, gently handled pigs displayed affiliative behaviors, accepting more strokes, and higher parasympathetic activation, indicated by greater RMSSD/SDNN and SampEn values, suggesting a more positive affective state. Minimally handled pigs exhibited some behavioral similarities to gently handled pigs, although physiological data indicated that the interaction was likely more rewarding for the gently handled pigs. These results emphasize the impact of human-animal relationships on pig welfare and highlight the value of incorporating non-linear heart rate variability parameters in such evaluations.

The impact of settleable atmospheric particulate on the energy metabolism, biochemical processes, and behavior of a sentinel mangrove crab.

We use the sentinel mangrove crab, Minuca rapax, as a model to investigate the effects of metallic settleable particulate matter (SePM) on wetland. Multiple levels of energetic responses, including (i) metabolic rate and energy budget, (ii) oxidative stress, and (iii) behavioral response by righting time, were assessed as well as the metal and metalloid content in crabs exposed to 0, 0.1 and 1 g.L-1 of SePM, under emerged and submerged conditions over five days, simulating the rigors of the intertidal habitat. Al, Fe, Mn, Cr, and Y exhibited a concentration-dependent increase. Metal concentrations were higher in submerged crabs due to the continuous ingestion of SePM and direct exposure through gills. Exposure concentration up to 1 g.L-1 decreased metabolic rate and enzymatic activities, reduced assimilation efficiency and energy for maintenance, and induces a slower response to righting time, probably by metal effects on nervous system and energy deficits. In conclusion, SePM exposure affects the redox status and physiology of M. rapax depending on he submersion regime and SePM concentration. The disruption to the energy budget and the lethargic behavior in M. rapax exposed to SePM implies potential ecological alterations in the mangrove ecosystem with unknown consequences for the local population.

Strategies to promote contraception use by female volunteers in Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia trial.

BACKGROUND/AIMS: Including women of childbearing age in a clinical trial makes it necessary to consider two factors from a bioethical perspective: first, the lack of knowledge about the potential teratogenic effects of an investigational product, and also, the principle of justice not to exclude any population from the benefits of research. The most common way to address this issue is by requiring volunteers to use contraceptives before, during, and a few weeks after the clinical trial. This work presents all the strategies used to promote contraception use and prevent pregnancy during the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia clinical trial. Two characteristics of this trial make it of special interest for closely monitoring contraception use. One is that the trial lasted more than 7 years, and the other is that participants could be carriers of the E280A PSEN1 mutation, leading to a mild cognitive impairment as early as their late 30s. METHODS: An individual medical evaluation to select the contraception method that best fits the volunteer was carried out during the screening visit, remitting to the gynecologist when necessary. All non-surgical contraception methods were supplied by the sponsor. Staff were trained on contraception counseling, correctly dispensing contraceptive drugs to volunteers, and identifying, reporting, and following up on pregnancies. Two comprehensive educational campaigns on contraception use were performed, and the intervention included all volunteers. In addition, volunteers were asked on an annual survey to evaluate the dispensing procedure. Finally, the effectiveness of these strategies was retrospectively evaluated, comparing by extrapolation the number of pregnancies presented throughout the trial with the General Fertility Rate in Colombia. RESULTS: A total of 159 female volunteers were recruited. All strategies were implemented as planned, even during the COVID-19 contingency. Ten pregnancies occurred during the evaluation period (2015-2021). Two were planned; the rest were associated with a potential therapeutic failure or incorrect use of contraceptive methods for a contraceptive failure of 0.49% per year. Sixty percent of pregnancies led to an abortion, either miscarriage or therapeutic abortion. However, there was not enough data to associate the pregnancy outcome with the administration of the investigational product. Finally, we observed a lower fertility rate in women participating in the trial compared to the Colombian population. CONCLUSION: The lower rates of contraceptive failure and the decrease in the incidence of pregnancies in women participating in the trial compared to the Colombian population across the 7 years of evaluation suggest that the strategies used in API ADAD Colombia were adequate and effective in addressing contraception use.

A pilot study using the LASCA technique to analyze stress using heart rate variability.

In the quest to uncover biological cues that help explain organic changes brought on by an external stimulus, like stress, new technologies have become necessary. The Laser Speckle Contrast Analysis (LASCA) approach is one of these technologies that may be used to analyze biological data, including respiratory rate (RR) intervals, and then use the results to determine heart rate variability (HRV Thus, to evaluate the stress brought on by physical activity, this study used the LASCA approach. A stress induction procedure involving physical exertion was employed, and the results were compared to other established techniques (cortisol analysis and ECG signal) to verify the LASCA methodology as a tool for measuring HRV and stress. The study sample comprised 27 willing participants. The technique involving LASCA allowed for the non-invasive (non-contact) acquisition of HRV and the study of stress. Furthermore, it made it possible to gather pertinent data, such as recognizing modifications to the thermoregulation, peripheral vasomotor tonus, and renin-angiotensin-aldosterone systems that were brought on by elevated stress and, as a result, variations in HRV readings.

Determinants of Neonatal and Postneonatal Mortality in Northeastern Brazil: A Cohort Study of Newborns Admitted to the Neonatal Intensive Care Unit.

Despite advances in neonatology, neonatal mortality from preventable causes remains high in the North and Northeast regions of Brazil. This study aimed to analyze the determinants associated with neonatal and postneonatal mortality in newborns admitted to a neonatal intensive care unit. A cohort study was carried out in a capital in the Brazilian Northeast from 2013 to 2018. The outcome studied was death. Poisson regression was performed in the multivariate analysis of variables. Four hundred and eighty newborns were eligible, and 8.1% (39 newborns) died. Among them, 34 died in the neonatal period. The determinants that remained significantly associated with neonatal and postneonatal mortality in the final adjustment model (p < 0.05) were history of abortion, perinatal asphyxia, early neonatal sepsis and umbilical venous catheterization. All causes of this outcome were preventable. The neonatal mortality rate, although it did not include twins, neonates with malformations incompatible with life and other conditions, was 3.47 deaths per thousand live births (95% CI:1.10-8.03‱), well below the national average. In this study, pregnant women from different social classes had in common a private plan for direct access to health services, which provided them with excellent care throughout pregnancy and postnatal care. These results indicate that reducing neonatal mortality is possible through public policies with strategies that promote improvements in access to health services.

The Total Denervation of the Ischemic Kidney Induces Differential Responses in Sodium Transporters' Expression in the Contralateral Kidney in Goldblatt Rats.

The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCß, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl- cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.

Uterine tone: A neglected criterion for the selection of bovine embryo transfer recipients.

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1-3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen-thawed in vivo-produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p < .02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B-mode and Doppler-mode did not significantly predict pregnancy rates on D35 (p < .6 and p < .5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p < .08 and p < .06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p > .05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation.