Prepregnancy maternal BMI and trajectories of BMI-for-age in children up to four years of age: findings from the 2015 Pelotas (Brazil) birth cohort.

BACKGROUND: The aims of the study were to: (a) describe BMI-for-age trajectories in children up to four years of age; (b) evaluate the association between prepregnancy maternal BMI and the BMI-for-age trajectories. METHODS: Data from 3218 (75.3% of the original cohort) children from the Pelotas 2015 Birth Cohort were analyzed. Prepregnancy BMI (kg/m2) was measured on the perinatal interview. Z-scores of BMI-for-age were calculated for children at three months, 1, 2 and 4 years. Trajectories were identified using a semi-parametric group-based modeling approach. Multinomial logistic regression was used to test the association between prepregnancy BMI (weight excess: BMI ≥ 25 kg/m2) and BMI-for-age trajectories. RESULTS: Four trajectories of the BMI-for-age, in z-score, were identified and represent children in the "increasing", "adequate", "stabilized" and "risk for weight excess" group. A total of 196 children (7.1%) belonged to the group that was at risk of weight excess. Adjusted analyses showed that children whose mothers presented prepregnancy weight excess had 2.36 (95%CI 1.71; 3.24) times more risk of belonging to group "risk for weight excess" when compared to those children whose mothers presented underweight/normal weight before pregnancy. CONCLUSION: The risk of weight excess in children up to 4 years of age were greater in mothers who presented prepregnancy weight excess.

Guidelines of the Brazilian Society of Surgical Oncology for anatomopathological, immunohistochemical, and molecular testing in female tumors.

INTRODUCTION: Precision medicine has revolutionized oncology, providing more personalized diagnosis, treatment, and monitoring for patients with cancer. In the context of female-specific tumors, such as breast, ovarian, endometrial, and cervical cancer, proper tissue collection and handling are essential for obtaining tissue, immunohistochemical (IHC), and molecular data to guide therapeutic decisions. OBJECTIVES: To establish guidelines for the collection and handling of tumor tissue, to enhance the quality of samples for histopathological, IHC, genomic, and molecular analyses. These guidelines are fundamental in informing therapeutic decisions in cancer treatment. METHOD: The guidelines were developed by a multidisciplinary panel of renowned specialists between June 12, 2013 and February 12, 2024. Initially, the panel deliberated on critical and controversial topics related to conducting precision medicine studies focusing on female tumors. Subsequently, 22 pivotal topics were identified within the framework and assigned to groups. These groups reviewed relevant literature and drafted preliminary recommendations. Following this, the recommendations were reviewed by the coordinators and received unanimous approval. Finally, the groups made the final adjustments, classified the level of evidence, and ranked the recommendations. CONCLUSION: The collection of surgical samples requires minimum quality standards to enable histopathological, IHC, genomic, and molecular analyses. These analyses provide crucial data for informing therapeutic decisions, significantly impacting potential survival gains for patients with female tumors.

Consumption of ultra-processed foods and mental health of pregnant women from the South of Brazil.

The objective of this study is to evaluate the association between the consumption of ultra-processed foods (UPF) and the mental health of pregnant women from the South of Brazil. This is a cross-sectional study carried out in Criciúma, Brazil, through face-to-face interviews, from April to December 2022. Pregnant women aged 18 or older who underwent prenatal care in the forty-eight basic health care units of the municipality and who were in their third trimester of pregnancy were included. High consumption of UPF was considered as six or more items or subgroups of UPF consumed on the day before the interview, using the Nova-UPF screener. The mental health variables were depressive symptoms, stress, sadness and anxiety. Crude and adjusted analyses were conducted using the Fisher's exact test and the Poisson regression with robust variance. In total, 428 pregnant women were studied; most of them were aged between 20 and 25 years and were white. Pregnant women who presented high consumption of UPF were 1·42-fold (95 % CI 1·06, 1·92) more likely to experience anxiety and presented a prevalence 56 % (95 % CI 1·18, 2·07) higher of stress when compared with those who did not present high consumption of UPF. The prevalence of depressive symptoms and feelings of sadness was 1·31-fold (95 % CI 1·08, 1·60) and 3·41-fold (95 % CI 1·77, 6·58) higher among those with high consumption of UPF, respectively. The results suggest that diet quality is associated with the mental health of pregnant women. Promoting joint actions focused on food and nutritional education, and mental health, for pregnant women, is necessary.

Uterine transposition for fertility preservation in pelvic cancers.

OBJECTIVE: To review rates of uterine preservation and gonadal function, surgical outcomes, and pregnancy outcomes in patients undergoing surgical uterine transposition. METHODS: A structured search and analysis of the published literature on uterine transposition was conducted. Information on study type, sample size, patient characteristics, clinical indications, details of the surgical technique, trans-operative and post-operative results, success rates in preserving reproductive organ function and fertility were extracted. RESULTS: A total of 18 cases were reported to date. Patients' median age was 29 (range 3-38) years. Rectal cancers accounted for 9 (50%) cases of published cases of uterine transposition, followed by 6 (33%) cervical squamous cell carcinomas, 1 (6%) vaginal squamous cell carcinoma, 1 (6%) sacral yolk sac tumor, and 1 (6%) pelvic liposarcoma. The median time for uterine transposition to the upper abdomen was 150 (range 80-360) min, and 90 (range 80-310) min for organ reimplantation in the pelvis. Cervical ischemia occurred in 5 (27.8%) cases, being the most commonly reported complication. The median follow-up time was 25 months, and three patients achieved spontaneous pregnancies resulting in successful gestations, out of five patients who were reported as having tried. One patient experienced recurrence and succumbed to the tumor during treatment. CONCLUSIONS: Uterine transposition is a feasible and safe surgical approach that offers patients undergoing pelvic radiotherapy an option to preserve gonadal and uterine function, with the potential for spontaneous pregnancy.

Cognitive-behavioral therapy for treating hypertension: a systematic review and meta-analysis.

The aim of the study is to investigate whether cognitive behavioral therapy (CBT) can help in reducing blood pressure (BP) in patients with hypertension, both systolic blood pressure (SBP) and diastolic blood pressure (DBP), this being the primary outcome. This was a systematic review with a meta-analysis that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The keywords used for the searches were CBT and hypertension and their respective synonyms, and were applied to the Pubmed, EMBASE and Web of Science databases. Eligibility and data extraction were performed by two independent researchers. They assessed the risk of bias using the Cochrane's RoB 2 tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of the evidence. The data was pooled on the basis that all the analyses had a random effects model. Twenty-two studies were included in this review. In the meta-analysis, 11 studies were included in the analyses of the BP outcomes (SBP and DBP), five studies were included in the follow-up evaluation, and two studies in the body mass index (BMI) analysis. The searches included a total of 2897 patients. The studies presented a high risk of bias and very low quality of evidence. We observed an effect of -0.65 (95% CI: -0.91; -0.39) for CBT-based interventions on SBP with high heterogeneity (I2 85%) and a higher effect of -0.78% (95% CI: -1.13; -0.43) on DBP with even greater heterogeneity (I2 92%). We observed that CBT did have an effect on reducing BP and BMI in hypertensive adults. However, due to the considerable heterogeneity between the studies, the high risk of bias, and the low overall quality of evidence, confidence in these findings should be limited.

Credibility assessment of patient-specific computational modeling using patient-specific cardiac modeling as an exemplar.

Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also be used to construct virtual cohorts of patients, for in silico evaluation of medical product safety and/or performance. Methods and frameworks have recently been proposed for evaluating the credibility of M&S in healthcare applications. However, such efforts have generally been motivated by models of medical devices or generic patient models; how best to evaluate the credibility of PSMs has largely been unexplored. The aim of this paper is to understand and demonstrate the credibility assessment process for PSMs using patient-specific cardiac electrophysiological (EP) modeling as an exemplar. We first review approaches used to generate cardiac PSMs and consider how verification, validation, and uncertainty quantification (VVUQ) apply to cardiac PSMs. Next, we execute two simulation studies using a publicly available virtual cohort of 24 patient-specific ventricular models, the first a multi-patient verification study, the second investigating the impact of uncertainty in personalized and non-personalized inputs in a virtual cohort. We then use the findings from our analyses to identify how important characteristics of PSMs can be considered when assessing credibility with the approach of the ASME V&V40 Standard, accounting for PSM concepts such as inter- and intra-user variability, multi-patient and "every-patient" error estimation, uncertainty quantification in personalized vs non-personalized inputs, clinical validation, and others. The results of this paper will be useful to developers of cardiac and other medical image based PSMs, when assessing PSM credibility.

Modelling the interaction between stem cells derived cardiomyocytes patches and host myocardium to aid non-arrhythmic engineered heart tissue design.

Application of epicardial patches constructed from human-induced pluripotent stem cell- derived cardiomyocytes (hiPSC-CMs) has been proposed as a long-term therapy to treat scarred hearts post myocardial infarction (MI). Understanding electrical interaction between engineered heart tissue patches (EHT) and host myocardium represents a key step toward a successful patch engraftment. EHT retain different electrical properties with respect to the host heart tissue due to the hiPSC-CMs immature phenotype, which may lead to increased arrhythmia risk. We developed a modelling framework to examine the influence of patch design on electrical activation at the engraftment site. We performed an in silico investigation of different patch design approaches to restore pre-MI activation properties and evaluated the associated arrhythmic risk. We developed an in silico cardiac electrophysiology model of a transmural cross section of host myocardium. The model featured an infarct region, an epicardial patch spanning the infarct region and a bath region. The patch is modelled as a layer of hiPSC-CM, combined with a layer of conductive polymer (CP). Tissue and patch geometrical dimensions and conductivities were incorporated through 10 modifiable model parameters. We validated our model against 4 independent experimental studies and showed that it can qualitatively reproduce their findings. We performed a global sensitivity analysis (GSA) to isolate the most important parameters, showing that the stimulus propagation is mainly governed by the scar depth, radius and conductivity when the scar is not transmural, and by the EHT patch conductivity when the scar is transmural. We assessed the relevance of small animal studies to humans by comparing simulations of rat, rabbit and human myocardium. We found that stimulus propagation paths and GSA sensitivity indices are consistent across species. We explored which EHT design variables have the potential to restore physiological propagation. Simulations predict that increasing EHT conductivity from 0.28 to 1-1.1 S/m recovered physiological activation in rat, rabbit and human. Finally, we assessed arrhythmia risk related to increasing EHT conductivity and tested increasing the EHT Na+ channel density as an alternative strategy to match healthy activation. Our results revealed a greater arrhythmia risk linked to increased EHT conductivity compared to increased Na+ channel density. We demonstrated that our modeling framework could capture the interaction between host and EHT patches observed in in vitro experiments. We showed that large (patch and tissue dimensions) and small (cardiac myocyte electrophysiology) scale differences between small animals and humans do not alter EHT patch effect on infarcted tissue. Our model revealed that only when the scar is transmural do EHT properties impact activation times and isolated the EHT conductivity as the main parameter influencing propagation. We predicted that restoring physiological activation by tuning EHT conductivity is possible but may promote arrhythmic behavior. Finally, our model suggests that acting on hiPSC-CMs low action potential upstroke velocity and lack of IK1 may restore pre-MI activation while not promoting arrhythmia.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

Additional coils mitigate elevated defibrillation threshold in right-sided implantable cardioverter defibrillator generator placement: a simulation study.

AIMS: The standard implantable cardioverter defibrillator (ICD) generator (can) is placed in the left pectoral area; however, in certain circumstances, right-sided cans may be required which may increase defibrillation threshold (DFT) due to suboptimal shock vectors. We aim to quantitatively assess whether the potential increase in DFT of right-sided can configurations may be mitigated by alternate positioning of the right ventricular (RV) shocking coil or adding coils in the superior vena cava (SVC) and coronary sinus (CS). METHODS AND RESULTS: A cohort of CT-derived torso models was used to assess DFT of ICD configurations with right-sided cans and alternate positioning of RV shock coils. Efficacy changes with additional coils in the SVC and CS were evaluated. A right-sided can with an apical RV shock coil significantly increased DFT compared to a left-sided can [19.5 (16.4, 27.1) J vs. 13.3 (11.7, 19.9) J, P < 0.001]. Septal positioning of the RV coil led to a further DFT increase when using a right-sided can [26.7 (18.1, 36.1) J vs. 19.5 (16.4, 27.1) J, P < 0.001], but not a left-sided can [12.1 (8.1, 17.6) J vs. 13.3 (11.7, 19.9) J, P = 0.099). Defibrillation threshold of a right-sided can with apical or septal coil was reduced the most by adding both SVC and CS coils [19.5 (16.4, 27.1) J vs. 6.6 (3.9, 9.9) J, P < 0.001, and 26.7 (18.1, 36.1) J vs. 12.1 (5.7, 13.5) J, P < 0.001]. CONCLUSION: Right-sided, compared to left-sided, can positioning results in a 50% increase in DFT. For right-sided cans, apical shock coil positioning produces a lower DFT than septal positions. Elevated right-sided can DFTs may be mitigated by utilizing additional coils in SVC and CS.

Uterine transposition for fertility and ovarian function preservation after radiotherapy.

OBJECTIVE: To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation. METHODS: This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2-4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines. RESULTS: Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19-37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications. CONCLUSIONS: Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.

Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing.

Disruption of CCR5 or CXCR4, the main human immunodeficiency virus type 1 (HIV-1) co-receptors, has been shown to protect primary human CD4+ T cells from HIV-1 infection. Base editing can install targeted point mutations in cellular genomes, and can thus efficiently inactivate genes by introducing stop codons or eliminating start codons without double-stranded DNA break formation. Here, we applied base editors for individual and simultaneous disruption of both co-receptors in primary human CD4+ T cells. Using cytosine base editors we observed premature stop codon introduction in up to 89% of sequenced CCR5 or CXCR4 alleles. Using adenine base editors we eliminated the start codon in CCR5 in up to 95% of primary human CD4+ T cell and up to 88% of CD34+ hematopoietic stem and progenitor cell target alleles. Genome-wide specificity analysis revealed low numbers of off-target mutations that were introduced by base editing, located predominantly in intergenic or intronic regions. We show that our editing strategies prevent transduction with CCR5-tropic and CXCR4-tropic viral vectors in up to 79% and 88% of human CD4+ T cells, respectively. The engineered T cells maintained functionality and overall our results demonstrate the effectiveness of base-editing strategies for efficient and specific ablation of HIV co-receptors in clinically relevant cell types.

Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. AIMS: The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. METHODS: The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). KEY RESULTS: The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. CONCLUSIONS: These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. IMPLICATIONS: These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

Nova diet quality scores and risk of weight gain in the NutriNet-Brasil cohort study.

OBJECTIVE: To assess the prospective association of two diet quality scores based on the Nova food classification with BMI gain. DESIGN: The NutriNet-Brasil cohort is an ongoing web-based prospective study with continuous recruitment of participants aged ≥ 18 years since January 2020. A short 24-h dietary recall screener including 'yes/no' questions about the consumption of whole plant foods (WPF) and ultra-processed foods (UPF) was completed by participants at baseline. The Nova-WPF and the Nova-UPF scores were computed by adding up positive responses regarding the consumption of thirty-three varieties of WPF and twenty-three varieties of UPF, respectively. Participants reported their height at baseline and their weight at both baseline and after approximately 15 months of follow-up. A 15-month BMI (kg/m2) increase of ≥5 % was coded as BMI gain. SETTING: Brazil. PARTICIPANTS: 9551 participants from the NutriNet-Brasil cohort. RESULTS: Increasing quintiles of the Nova-UPF score were linearly associated with higher risk of BMI gain (relative risk Q5/Q1 = 1·34; 95 % CI 1·15, 1·56), whereas increasing quintiles of the Nova-WPF score were linearly associated with lower risk (relative risk Q5/Q1 = 0·80; 95 % CI 0·69, 0·94). We identified a moderate inverse correlation between the two scores (-0·33) and a partial mediating effect of the alternative score: 15 % for the total effect of the Nova-UPF score and 25 % for the total effect of the Nova-WPF score. CONCLUSIONS: The Nova-UPF and Nova-WPF scores are independently associated with mid-term BMI gain further justifying their use in diet quality monitoring systems.

A novel web-based 24-h dietary recall tool in line with the Nova food processing classification: description and evaluation.

OBJECTIVE: This paper describes the first web-based self-completed 24-h recall designed to categorise food intake according to Nova groups - Nova24h - and its agreement with a reference tool in estimating the dietary relative contribution of the four Nova food groups (% of total energy intake). DESIGN: Comparisons of estimates of dietary relative contributions of Nova groups obtained by Nova24h and one standard interviewer-led 24-h recall. SETTING: Nationwide adult cohort study in Brazil. PARTICIPANTS: The subjects were 186 participants of the NutriNet Brasil Cohort Study (n 186). RESULTS: No statistically significant differences were observed between the Nova24h and the reference tool mean contributions of unprocessed or minimally processed foods (52·3 % v. 52·6 %), processed culinary ingredients (11·6 % v. 11·9 %), processed foods (17·1 % v. 14·7 %) and ultra-processed foods (19·0 % v. 20·9 %). Intraclass correlation coefficients between individual estimates obtained for each Nova group showed moderate to good agreement (0·54-0·78). Substantial or almost perfect agreement between the tools was seen regarding the ability to rank participants according to quintiles of contribution of each Nova group (PABAK 0·69-0·81). CONCLUSIONS: Nova24h is a suitable tool for estimating the dietary relative energy contribution of Nova food groups in the NutriNet Brasil cohort. New studies are necessary to verify its adequacy in other populations.

Is the adherence to the food practices recommended by the dietary guidelines for the Brazilian population associated with diet quality?

PURPOSE: The Brazilian Food Guide (BFG)'s messages are mostly qualitative and focused on food practices, such as meal planning, cooking, and eating modes. This study sough to investigate whether the adherence to these food practices is aligned with diet quality. METHODS: A quota-based subsample of the NutriNet-Brasil Cohort (n = 2052) completed the Food Practices Brazil Scale (FPBr), a 24-item scale assessing the adherence to healthy eating practices recommended by the BFG. Four possible frequency-based answers are given and a score ranging from 0 to 72 is calculated by summing them (FPBr-score). Data from web-based 24-h recalls were used for calculating the usual percentage of energy intake (%energy) of ten food groups based on the level of food processing: plant-based unprocessed or minimally processed foods; processed foods; ultra-processed foods; fruits; vegetables; whole grains; beans and other legumes; nuts; red meat; and table sugar. The association between quartiles of the FPBr-score and food groups' %energy was analysed through crude and adjusted linear regression models. RESULTS: Except for red meat, all the other food groups were linearly associated with the FPBr-score in the expected direction. For example, adjusted means for the %energy of plant-based unprocessed or minimally processed foods were 26.7% (CI95% 25.9-27.5) and 36.8% (CI95% 36.0-37.6) among those classified in the first and fourth quartiles of the FPBr-score, respectively. For ultra-processed foods, these percentages were 27.0 (CI95% 26.3-27.8) against 17.5 (CI95% 16.7-18.3). CONCLUSIONS: These results support the use of messages based on practices and behaviors in Food-Based Dietary Guidelines. At the same time, they call attention to the importance of policies that enable people to adopt healthier food practices.

Effects of fetal bovine serum on trophectoderm and primitive endoderm cell allocation of in vitro-produced bovine embryos.

Supplementing embryonic culture medium with fetal bovine serum (FBS) renders this medium undefined. Glucose and growth factors present in FBS may affect the results of cell differentiation studies. This study tested the hypothesis that FBS supplementation during in vitro culture (IVC) alters cell differentiation in early bovine embryo development. Bovine embryos were produced in vitro and randomly distributed into three experimental groups at 90 h post insemination (90 hpi): the KSOM-FBS group, which consisted of a 5% (v/v) FBS supplementation; the KSOM33 group, with the renewal of 33% of medium volume; and the KSOM-Zero group, without FBS supplementation nor renewal of the culture medium. The results showed that the blastocyst rate (blastocyst/oocytes) at 210 hpi in the KSOM-FBS group was higher than in the KSOM-Zero group but not different from the KSOM33 group. There were no significant changes in metabolism-related aspects, such as fluorescence intensities of CellROX Green and MitoTracker Red or reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+). Immunofluorescence analysis of CDX2 revealed that the lack of FBS or medium supplementation reduced the number of trophectoderm (TE) cells and total cells. Immunofluorescence analysis revealed a reduction of SOX17-positive cell numbers after FBS supplementation compared with the KSOM33 group. Therefore, we concluded that FBS absence reduced blastocyst rates; however, no reduction occurred when there was a 33% volume renewal of the medium at 90 hpi. We also concluded that FBS supplementation altered TE and primitive endoderm cell allocation during early bovine embryo development.

The effectiveness of continuous positive airway pressure for treating obstructive sleep apnoea in pregnancy: A systematic review.

BACKGROUND: Obstructive sleep apnoea (OSA) occurs in 15-20% of pregnant women living with obesity. As global obesity prevalence increases, OSA in pregnancy is concurrently increasing, yet remains under-diagnosed. The effects of treating OSA in pregnancy are under-investigated. AIM: A systematic review was conducted to determine whether treating pregnant women with OSA using continuous positive airway pressure (CPAP) will improve maternal or fetal outcomes, compared with no treatment or delayed treatment. MATERIALS AND METHODS: Original studies in English published until May 2022 were included. Searches were conducted in Medline, PubMed, Scopus, the Cochrane Library and clinicaltrials.org. Maternal and neonatal outcome data were extracted, and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach (PROSPERO registration: CRD42019127754). RESULTS: Seven trials met inclusion criteria. Use of CPAP in pregnancy appears to be well tolerated with reasonable adherence. Use of CPAP in pregnancy may be associated with both a reduction in blood pressure and pre-eclampsia. Birthweight may be increased by maternal CPAP treatment, and preterm birth may be reduced by treatment with CPAP in pregnancy. CONCLUSION: Treatment of OSA with CPAP in pregnancy may reduce hypertension and, preterm birth, and may increase neonatal birthweight. However, more rigorous definitive trial evidence is required to adequately assess the indication, efficacy, and applications of CPAP treatment in pregnancy.

Development of a new non invasive prognostic stroke scale (NIPSS) including triage elements for sleep apnea and peripheral artery disease.

BACKGROUND: Although sleep apnea and peripheral artery disease are prognostic factors for stroke, their added benefit in the acute stage to further prognosticate strokes has not been evaluated. OBJECTIVES: We tested the accuracy in the acute stroke stage of a novel score called the Non-Invasive Prognostic Stroke Scale (NIPSS). PATIENTS AND METHODS: Prospective cohort with imaging-confirmed ischemic stroke. Clinical data, sleep apnea risk score (STOPBANG) and blood pressure measures were collected at baseline. Primary outcome was the 90-day modified Rankin Scale (mRS), with poor outcome defined as mRS 3-6. Area under the ROC curve (AUC) was calculated for NIPSS and compared to six other stroke prognostic scores in our cohort: SPAN-100 index, S-SMART, SOAR, ASTRAL, THRIVE, and Dutch Stroke scores. RESULTS: We enrolled 386 participants. After 90 days, there were 56% with poor outcome, more frequently older, female predominant and with higher admission National Institute of Health Stroke Scale (NIHSS). Four variables remained significantly associated with primary endpoint in the multivariable model: age (OR 1.87), NIHSS (OR 7.08), STOPBANG category (OR 1.61), and ankle-braquial index (OR 2.11). NIPSS AUC was 0.86 (0.82-0.89); 0.83 (0.79-0.87) with bootstrapping. When compared to the other scores, NIPSS, ASTRAL, S-SMART and DUTCH scores had good abilities in predicting poor outcome, with AUC of 0.86, 0.86, 0.83 and 0.82, respectively. THRIVE, SOAR and SPAN-100 scores were fairly predictive. DISCUSSION AND CONCLUSIONS: Non-invasive and easily acquired emergency room data can predict clinical outcome after stroke. NIPSS performed equal to or better than other prognostic stroke scales.

One-carbon metabolism pathway genes and their non-association with the development of amyotrophic lateral sclerosis.

Although of unknown etiology, some mechanisms associated with the metabolic cycle of folate are speculated to be related to the genesis of amyotrophic lateral sclerosis (ALS). Thus, the aim of the study was to analyze the role of genetic polymorphisms rs1051266 in SLC19A1 gene and rs1805087 in MTR gene and their associations with ALS development. A case-control study was conducted with 101 individuals with ALS and 119 individuals without diagnosis of neurodegenerative diseases, from the Brazilian central population. The polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. The results showed no statistically significant differences, even when genotypes were analyzed by the dominant, recessive, codominant, and overdominant inheritance models. It was observed a statistical significance relating alcohol consumption with individuals in the case group (p = 0.01). Therefore, the need for more studies to evaluate the influence of genetic variants is highlighted, seeking to provide information on the etiopathogenesis of ALS.

Efficient adoptive transfer of autologous modified B cells: a new humanized platform mouse model for testing B cells reprogramming therapies.

Here, we report a novel experimental setup to perform adoptive transfer of gene-edited B cells using humanized immune system mice by infusing autologous HIS mouse-derived human B cells "educated" in a murine context and thus rendered tolerant to the host. The present approach presents two advantages over the conventional humanized PBMC mouse models: (i) it circumvents the risk of xenogeneic graft-versus-host reaction and (ii) it mimics more closely human immune responses, thus favoring clinical translation. We show that the frequencies and numbers of transduced B cells in recipient's spleens one week post-transfer are within the range of the size of the pre-immune B cell population specific for a given protein antigen in the mouse. They are also compatible with the B cell numbers required to elicit a sizeable immune response upon immunization. Altogether, our findings pave the way for future studies aiming at assessing therapeutic interventions involving B cell reprogramming for instance by an antibody transgene in a "humanized" hematopoietic setting.