Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor 1 (ESR1), have been studied in different populations with contradictory results. AIMS: To evaluate the influence of FSHR rs6166 (c.2039A>G) and of ESR1 rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS). MATERIALS AND METHODS: Genotyping of the FSHR rs6166 and the ESR1 rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups. RESULTS: We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of FSHR rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the ESR1 rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the FSHR polymorphism (9.2 vs 6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with FSHR or ESR1 genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the FSHR rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs 1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). CONCLUSION: Our data suggest that in the population, FSHR rs6166and ESR1 rs2234693 polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the FSHR rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.

Early prediction of treatment failure in severe community-acquired pneumonia: The PRoFeSs score.

PURPOSE: To identify a single/panel of biomarkers and to provide a point score that, after 48 h of treatment, could early predict treatment failure at fifth day of Intensive Care Unit (ICU) stay in severe community-acquired pneumonia (SCAP) patients. MATERIALS AND METHODS: Single-center, prospective cohort study of 107 ICU patients with SCAP. Primary outcome included death or absence of improvement in Sequential Organ Failure Assessment score by ≥2 points within 5 days of treatment. Biomarkers were evaluated within 12 h of first antibiotic dose (D1) and 48 h after the first assessment (D3). RESULTS: A model based on Charlson's score and a panel of biomarkers (procalcitonin on D1 and D3, B-natriuretic peptide on D1, D-dimer and lactate on D3) had good discrimination for primary outcome in both derivation (AUC 0.82) and validation (AUC 0.76) samples and was well calibrated (X2 = 0.98; df = 1; p = .32). A point score system (PRoFeSs score) built on the estimates of regression coefficients presented good discrimination (AUC 0.81; 95% Confidence Interval 0.72-0.89) for primary outcome. CONCLUSIONS: In SCAP, a combination of biomarkers measured at admission and 48 h later may early predict treatment failure. PRoFeSs score may recognize patients with poor short-term prognosis.

Frailty, body composition and nutritional status in non-institutionalised elderly. / Fragilidad, composición corporal y estado nutricional en ancianos no institucionalizados.

OBJECTIVE: Frailty is a clinical syndrome characterized, among other signs, by involuntary weight loss and decreased muscle strength. The aim of this study was to analyse associations between frailty, body composition and nutritional status in non-institutionalised elderly people in the municipality of Alfândega (Braganza-Portugal). METHOD: Observational, prevalence and association study involving 220 elderly (mean 75.8±6.8 years of age; 68.8% women). Frailty was assessedt according to Fried criteria, body composition by bioelectrical impedance analysis and nutritional status using the Mini Nutritional Assessment Short-Form. RESULTS: The prevalence of frailty was 23.6%. Frail participants had, on average, lower total muscle mass and lower segmental muscle mass (arms and legs) than pre-frail and non-frail (p <.001). From the elderly at risk of malnutrition or undernourished (n=24), the majority (n=13) had frailty syndrome. It was observed that 41.2% of the elderly with low weight were frail. This syndrome prevailed only in 17.1% of the eutrophic persons, increasing again to 22.4% in the overweight group (p <.001). CONCLUSION: The phenotypic profile of frail elderly was characterised by lower muscle mass. The results of our study suggest that both underweight and overweight may be associated with frailty. There is the need to prevent and manage frailty, not only taking into account possible treatable medical causes, but also by intervening in important pillars, such as physical activity, dietary and nutritional problems.

Can we predict pneumococcal bacteremia in patients with severe community-acquired pneumonia?

PURPOSE: This study aimed to evaluate the role of biomarkers as markers of pneumococcal bacteremia in severe community-acquired pneumonia (SCAP). MATERIALS AND METHODS: A prospective, single-center, observational cohort study of 108 patients with SCAP admitted to the intensive care department of a university hospital in Portugal was conducted. Leucocytes, C-reactive protein (CRP), lactate, procalcitonin (PCT), d-dimer, brain natriuretic peptide (BNP), and cortisol were measured within 12 hours after the first antibiotic dose. RESULTS: Fifteen patients (14%) had bacteremic pneumococcal pneumonia (BPP). They had significantly higher levels of median CRP (301 [interquartile range, or IQR], 230-350] mg/L vs 201 [IQR, 103-299] mg/L; P = .023), PCT (40 [IQR, 25-102] ng/mL vs 8 [IQR, 2-26] ng/mL; P < .001), BNP (568 [IQR, 478-2841] pg/mL vs 407 [IQR, 175-989] pg/mL; P = .027), and lactate (5.5 [IQR, 4.5-9.8] mmol/L vs 3.1 [IQR, 1.9-6.2] mmol/L; P = .009) than did patients without BPP. The discriminatory power evaluated by the area under the receiver operating characteristic curve (aROC) for PCT (aROC, 0.79) was superior to lactate (aROC, 0.71), BNP (aROC, 0.67), and CRP (aROC, 0.70). At a cutoff point of 17 ng/mL, PCT showed a sensitivity of 87%, a specificity of 67%, a positive predictive value of 30% and a negative predictive value of 97%, as a marker of pneumococcal bacteremia. CONCLUSIONS: In this cohort, significantly higher PCT, BNP, lactate, and CRP levels were found in BPP, and PCT presented the best ability to identify pneumococcal bacteremia. A PCT serum level lower than 17 ng/mL could identify patients with SCAP unlikely to have pneumococcal bacteremia.

Fragilidad, composición corporal y estado nutricional en ancianos no institucionalizados / Frailty, body composition and nutritional status in non-institutionalised elderly

Objetivo: La fragilidad es un síndrome clínico caracterizado, entre otros signos, por la pérdida involuntaria de peso y fuerza muscular disminuida. El objetivo de este estudio fue analizar asociaciones entre fragilidad, composición corporal y estado nutricional en ancianos no institucionalizados del municipio de Alfândega (Braganza-Portugal). Método: Estudio observacional, de prevalencia y asociación cruzada en el que participaron 220 ancianos (edad media de 75,8±6,8 años; 68,8% mujeres). La fragilidad fue evaluada según el fenotipo de Fried, la composición corporal por impedancia bioeléctrica y el estado nutricional mediante el Mini Nutritional Assessment Short-Form. Resultados: La prevalencia de fragilidad fue del 23,6%. Los participantes frágiles presentaban, en promedio, menor masa muscular total y menor masa muscular por segmentos (brazos y piernas) que los prefrágiles y no frágiles (p<0,001). De aquellos ancianos en riesgo de desnutrición o desnutridos (n=24), la mayoría (n=13) presentaban síndrome de fragilidad. Se observó que el 41,2% de los ancianos con bajo peso eran frágiles. Dicho síndrome prevaleció tan solo en el 17,1% de las personas eutróficas, aumentando de nuevo al 22,4% en el grupo con sobrepeso (p<0,001). Conclusión: El perfil fenotípico de los ancianos frágiles se caracterizó por menor masa muscular. Los resultados de nuestro estudio sugieren que tanto el bajo peso como el sobrepeso podrán conducir a situaciones de fragilidad. Es fundamental prevenir y gestionar la fragilidad, no solo teniendo en cuenta las posibles causas médicas tratables, sino también interviniendo en pilares importantes, como la actividad física y los problemas dietéticos y nutricionales (AU)

Objective: Frailty is a clinical syndrome characterized, among other signs, by involuntary weight loss and decreased muscle strength. The aim of this study was to analyse associations between frailty, body composition and nutritional status in non-institutionalised elderly people in the municipality of Alfândega (Braganza-Portugal). Method: Observational, prevalence and association study involving 220 elderly (mean 75.8±6.8 years of age; 68.8% women). Frailty was assessed according to Fried criteria, body composition by bioelectrical impedance analysis and nutritional status using the Mini Nutritional Assessment Short-Form. Results: The prevalence of frailty was 23.6%. Frail participants had, on average, lower total muscle mass and lower segmental muscle mass (arms and legs) than pre-frail and non-frail (p <.001). From the elderly at risk of malnutrition or undernourished (n=24), the majority (n=13) had frailty syndrome. It was observed that 41.2% of the elderly with low weight were frail. This syndrome prevailed only in 17.1% of the eutrophic persons, increasing again to 22.4% in the overweight group (p <.001). Conclusion: The phenotypic profile of frail elderly was characterised by lower muscle mass. The results of our study suggest that both underweight and overweight may be associated with frailty. There is the need to prevent and manage frailty, not only taking into account possible treatable medical causes, but also by intervening in important pillars, such as physical activity, dietary and nutritional problems (AU)