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.

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.

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].

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.

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.

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.

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.

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.

Decadal Analysis of Age-Adjusted Mortality Rates for Acute and Chronic Kidney Disease in Brazil, 2000-2021.

Introduction Renal failure, comprising acute kidney injury (AKI) and chronic kidney disease (CKD), involves a decline or loss of kidney function. AKI is sudden and reversible, with a rapid decline in function over hours to days, while CKD involves persistent abnormalities lasting at least three months. Developing countries are seeing a rise in AKI cases, especially in critically ill patients. Globally, there's a growing occurrence and mortality rate linked to CKD. Methods The study used a retrospective cross-sectional design to analyze AKI and CKD mortality rates in Brazil from 2019 to 2022. Data on population and demographics, including sex and age, were obtained from the Brazilian Institute of Geography and Statistics. Mortality data for kidney diseases were sourced from the Brazilian Hospital Information System. The analysis utilized the Joinpoint Regression Program to calculate average annual percentage changes (AAPCs) and their respective 95% confidence intervals. Weighted Bayesian information criterion was used to determine the significance levels and identify the best-fitting combination of line segments and joinpoints. Results The study findings revealed a significant rise in AKI mortality rates for both males and females, from 2008 to 2021 (APC = 3.16; CI: 2.29 to 5.93), with higher mortality rates recorded among males compared to women over the entire study period. Analyses according to age groups showed that males between the ages 40 to 49 experienced the most rapid increase in mortality during the 2019 - 2021 period (APC = 35.41; CI: 16.72 to 46.57); meanwhile, the most rapid increase in mortality for females was observed from 2019 to 2021, and this was among those aged 30 to 39 (APC = 40.33; CI = 6.48 to 59.78). Furthermore, there was an observable upward trend in mortality related to CKD (APC = 0.70; CI: 0.41 to 1.01), with males consistently having higher mortality rates throughout the entire study period. The elderly population, both males and females, experienced the most rapid increase in CKD-related mortality, with AAPC values of 2.32 (CI: 1.82 to 2.89) for males and 1.62 (CI: 1.08 to 2.10) for females. Conclusion We observed a consistent increase in mortality rates from acute kidney diseases for both males and females since 2008, with males experiencing higher mortality rates overall. The study highlighted the need for further research to understand the underlying factors contributing to these trends. Additionally, interventions targeting modifiable risk factors and improving access to healthcare could help reduce mortality related to renal failure.

Severe COVID-19 Outcomes in Five Latin American Countries in the Postvaccination Era.

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. We analyzed the sociodemographic characteristics, comorbidities, clinical outcomes, and vaccination status of laboratory-confirmed COVID-19 cases from January 2021 to December 2022. We calculated the yearly and quarterly hospitalization rates per 1000 confirmed COVID-19 cases and ICU admissions, use of mechanical ventilators, and mortality rates per 1000 hospitalized cases, with their corresponding 95% confidence interval (CI) of 38,852,831 confirmed COVID-19 cases. Rates of hospitalization, ICU admission, ventilatory support, and death were higher among males than among females (38.2 vs. 32.4, 148.4 vs. 117.7, 282.9 vs. 236.2, and 346.9 vs. 320.1 per 1000, respectively); higher in 2021 than in 2022 (50.7 vs. 19.9, 207.8 vs. 58.2, 441.5 vs. 114.9, and 352.5 vs. 285.2 per 1000, respectively); and in the >50 age group (range: 5.7-18.6, 20.1-71.5, 12.2-67.9, and 353.1-577.4, per 1000) than the <50 age group (range: 2.2-9.3, 5.4-33.2, 41.4-135.8, and 22-243.5 per 1000). Hypertension and diabetes mellitus were the most common comorbidities in Mexico and Colombia. Prevention and treatment strategies for these case profiles could bring benefits from a public health perspective.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

Reference values for heart rate variability in older adults: A systematic review.

Heart rate variability (HRV) is an early marker of risk for various health conditions, and its analysis serves as a valuable tool for assessing older adults. This study aimed to describe the reference values of HRV parameters in older adults through a systematic review of the literature. The review included searches in MEDLINE (via PubMed®), EMBASE, Latin American and Caribbean Health Literature, Scopus, and Web of Science (WOS). Studies presenting reference values for at least one HRV linear analysis measure in older adults were considered eligible. Out of 1618 studies identified, only 11 met the inclusion criteria. Sample sizes of older adults ranged from 21 to 6250 subjects. The HRV measures assessed (mean RR intervals, SDNN, RMSSD, PNN50, LF, HF, and LF/HF ratio) varied significantly between studies, with no standardized methods for HRV analysis. We concluded that reference values for HRV measures in older adults vary widely between studies. The scientific literature on HRV reference values in older adults is still limited, and future studies should standardize assessment methods for HRV measures in this population.

Analysis of proteins in the light of mutations.

Proteins have evolved through mutations-amino acid substitutions-since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function, and structure. This study offers a new viewpoint on how the most recent findings in these areas can be used to explore the impact of mutations on protein sequence, stability, and evolvability. Preliminary results indicate that: (1) mutations can be viewed as sensitive probes to identify 'typos' in the amino-acid sequence, and also to assess the resistance of naturally occurring proteins to unwanted sequence alterations; (2) the presence of 'typos' in the amino acid sequence, rather than being an evolutionary obstacle, could promote faster evolvability and, in turn, increase the likelihood of higher protein stability; (3) the mutation site is far more important than the substituted amino acid in terms of the marginal stability changes of the protein, and (4) the unpredictability of protein evolution at the molecular level-by mutations-exists even in the absence of epistasis effects. Finally, the Darwinian concept of evolution "descent with modification" and experimental evidence endorse one of the results of this study, which suggests that some regions of any protein sequence are susceptible to mutations while others are not. This work contributes to our general understanding of protein responses to mutations and may spur significant progress in our efforts to develop methods to accurately forecast changes in protein stability, their propensity for metamorphism, and their ability to evolve.

Primary central nervous system germ cell tumors in Central America and the Caribbean Region: an AHOPCA 20-year experience.

Background: Primary central nervous system germ cell tumors (GCT) are rare neoplasms in pediatrics. Treatment depends on the histological subtype and extent of the disease. Overall survival (OS) is above 90% for germinomas and 70%-80% for nongerminomatous GCT (NGGCT) in high-income countries (HIC) while data are usually lacking for patients in Low-Middle Income country (LMIC). Objective: This study aims to describe the experience of treating patients with CNS GCT in four of eight countries, members of the Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA), and determine their 5-year OS. Design/methods: We conducted a retrospective chart review of patients treated for CNS GCT. Epidemiological and clinical characteristics, histology, treatment modalities, and outcomes were analyzed. Results: From 2001 to 2021, 48 patients were included: 22 from Guatemala, 18 from Nicaragua, three from the Dominican Republic, and five from El Salvador. Thirty-one (64.6%) were boys; the median age at diagnosis was 10.2 years (range: 1 to 17 years). Presenting symptoms were headaches (n = 24, 50%), visual disturbances (n = 17, 35.4%), vomiting (n = 12, 25%), nausea (n = 8, 16.7%), and diabetes insipidus (n = 7, 14.6%). Two patients with NGGCT presented with precocious puberty. Biopsy or tumor resection was performed in 38 cases (79.2%): 23 (88.4%) germinomas, 11 (78.6%) NGGCT, and four (50%) CNS GCT. Eight patients were diagnosed and treated based on CSF tumor marker elevation; four germinomas (BHCG 11.32-29.41 mUI/mL) and four NGGCT (BHCG 84.43-201.97 mUI/mL or positive AFP > 10 UI/mL). Tumor locations included suprasellar (n = 17, 35.4%), pineal (n = 13, 27.1%), thalamus/basal ganglia (n = 5, 10.4%), other (n = 12, 25%), and one bifocal. Four (8.3%) had metastatic disease, and six had positive CSF; staging data were incomplete in 25 patients (52%). Patients were treated with varied chemotherapy and radiotherapy modalities. Nine patients had incomplete data regarding treatment. Five-year OS was 65% (68% for germinoma, 50.6% for NGGCT, and 85.7% for unclassified GCT). Conclusions: Germinoma was the most common histology, and there was a male predominance. More than half of patients had incomplete staging data and treatment was variable across the region. OS is lower compared to HIC. Standardized treatment protocols will aid in adequate staging and treatment planning, prevent complications, and improve survival.

Feeding protocol for the Amazonian ornamental cichlid Apistogramma cacatuoides and a histological approach to the nutritional condition of larvae.

The aim of this study was to develop a feeding protocol for the larviculture of Apistogramma cacatuoides, using the histological approach to larval nutrition conditions. For this, three experiments were carried out. Experiment 1 was carried out in a randomized design to determine the optimal amount of Artemia nauplii (AN) per larva, and three treatments were evaluated: P1-feeding with 25 A. nauplii per larva (AN/L) during the first 5 days, followed by 50 AN/L from the 6th to the 10th day and 100 AN/L from the 11th to the 20th day; P2 and P3-37 and 50 AN/L during the first 5 days, 75 and 100 AN/L from the 6th to the 10th day and 150 and 200 AN/L from the 11th to the 20th day. Experiment 2 was carried out in a randomized design to determine the daily frequency of feeding and evaluated four feeding frequencies: F1-feeding only once a day (09:00); (F2)-feeding twice a day (09:00 and 17:00); F3-feeding three times a day (09:00, 11:30 and 17:00); and F4-feeding four times a day (09:00, 11: 30, 14:00 and 17:00). Experiment 3 lasted 40 days and was conducted in a randomized design to evaluate three periods for the beginning of the feeding transition: WE10:AN for 10 days, followed by 3 days of co-feeding and commercial feed until the end of the experimental period; WE15:AN for 15 days, followed by 3 days of co-feeding and commercial feed; WE20:AN for 20 days, followed by 3 days of co-feeding and commercial feed. The results of this study showed that, for the best development of the larvae, they should receive the feeding protocol 50-100-200 AN/L (P3) until the 20th day of exogenous feeding. From the 21st day, the transition to inert food should begin with 3 days of co-feeding, and feeding during larviculture should be carried out at a frequency of twice a day; this protocol provided a good nutritional status for the larvae, as shown by the histological approach.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.