Bridging the gap: Prenatal nutrition, myelination, and schizophrenia etiopathogenesis.

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

Patterns and indications of intraoperative nerve monitoring usage during thyroidectomy and parathyroidectomy in Spain: results of a national survey of endocrine surgeons.

We investigated the use patterns and indications of intraoperative neural monitoring (IONM) among endocrine surgeons in Spain. We sent an anonymous web-based survey to endocrine surgeons' members of the Spanish Association of Surgery by email. We analysed 79/ 269 surveys. Respondents had a median age of 52 years and 13 years of surgical experience. Only 32% of respondents performed routinely preoperative laryngoscopy in all thyroidectomies and 19% in all parathyroidectomies. Seventy-five percent of respondents used the intermittent-IONM, and 9.7% used the continuous-IONM. All respondents identified recurrent laryngeal nerve during surgery, and 40% of surgeons routinely identified external branch superior laryngeal nerve (EBSLN) during thyroidectomy. Seventy-eight percent of respondents used IONM always for all thyroidectomies. Only 11% stimulated EBSLN in all cases. Forty-nine percent used IONM always for all parathyroidectomies. The most frequent reasons for not using IONM were the unavailability of IONM, the high cost, and the lack of adding value to their clinical practice. Almost 10% declared not having IONM. The IONM is a reality in Spain, especially the intermittent mode. Its use is superior in thyroid surgery than in parathyroid. Its standardized use is not yet fully established, and routine adherence to standardized guidelines should increase.

Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Observed kinetics for the production of diethyl carbonate from CO2 and ethanol catalyzed by CuNi nanoparticles supported on activated carbon.

Monometallic and bimetallic Cu:Ni catalysts with different Cu:Ni molar ratios (3:1, 2:1, 1:1, 1:2, 1:3) were synthesized by wetness impregnation on activated carbon and characterized by TPR (temperature programmed reduction), XRD (X-ray diffraction) and XPS (X-ray photoelectron spectroscopy). The synthesized catalysts were evaluated in the gas phase production of diethyl carbonate from ethanol and carbon dioxide. The largest catalytic activity was obtained over the bimetallic catalyst with a Cu:Ni molar ratio of 3:1. Its improved activity was attributed to the formation of a Cu-Ni alloy on the surface of the catalyst, evidenced by XPS and in agreement with a previous assignment based on Vegard law and TPR analysis. During the reaction rate experiments, it observed the presence of a maximum of the reaction rate as a function of temperature, a tendency also reported for other carbon dioxide-alcohol reactions. It showed that the reaction rate-temperature data can be adjusted with a reversible rate equation. The initial rate as a function of reactant partial pressure data was satisfactorily adjusted using the forward power law rate equation and it was found that the reaction rate is first order in CO2 and second order in ethanol.

Long-Term Patient Symptoms and Quality of Life in Adults After COVID-19: A Real Life Study.

Objective: To characterize long-term patient-reported symptoms and quality of life, in adults after COVID-19. Material and methods: Cross-sectional study in Cantabria (Northern Spain) including adults with PCR-confirmed SARS-CoV-2 infection (n = 694) with a time period between 4.7 and 24 month post-SARS-CoV-2 diagnosis, and their close contacts (n = 663) (PCR negative and without suspected infection) obtained from simple random sampling of a total of 47,773 cases and 94,301 close contacts. The ISARIC survey was used as screening tool with self-reported "non-feeling fully recovery (NFFR)" defined as primary outcome. Results: 16.57% (n = 115/694) reported NFFR. Most prevalent symptoms were in order of frequency: Fatigue (54.8%); Loss of smell (40.9%); Problems speaking or communicating (29.6%); Loss of taste (28.7%); Confusion/lack of concentration (27.8%); Persistent muscle pain (24.3%) and Shortness of breath/breathlessness (23.5%). When comparing the three ordinal groups (Close contacts, COVID-19 feeling recovered, and COVID-19 NFFR) the prevalence of these symptoms was increasingly higher among each ordinal group (p < 0.001). Female gender was significantly associated with NFFR: (adjusted odds ratio (aOR) = 1.56); as well as older age: aOR per 10 year increment = 1.15. Lastly, they scored on average 9.63 points less in Euroquol. Conclusions: More than 15% of patients in our real-life population-based study, reported NFFR, being female sex and older age independent predictors of this condition. Most symptoms in these patients were in accordance with WHO definition of post COVID-19 condition in adults, and were less prevalent in COVID-19 feeling recovered and close contact respectively, with a statistically significant dose-response pattern, and with a large decrease in quality of life according to Euroquol.

Objetivo: Caracterizar los síntomas y la calidad de vida informados a largo plazo después de un episodio agudo de COVID-19. Métodos: Estudio transversal en Cantabria (norte de España) que incluye adultos con infección por SARS-CoV-2 confirmada por PCR (n = 694) tras un periodo entre 4,7 y 24 meses desde el diagnóstico y sus contactos estrechos (n = 663), obtenidos por muestreo aleatorio simple a partir de 47.773 casos y 94.301 contactos. Se utilizó la encuesta ISARIC, estableciéndose como variable resultado principal la respuesta «no-sentirse completamente recuperado (NSCR)¼. Resultados: El 16,57% (n = 115/694) declararon NSCR. Los síntomas más prevalentes fueron, por orden de frecuencia: fatiga (54,8%), pérdida del olfato (40,9%), problemas para hablar o comunicarse (29,6%), pérdida del gusto (28,7%), confusión/falta de concentración (27,8%), dolor muscular persistente (24,3%) y dificultad para respirar/falta de aire (23,5%). Al comparar los tres grupos ordinales (contactos estrechos, COVID-19 recuperados y COVID-19 NSCR), la prevalencia de estos síntomas fue mayor en cada grupo (p < 0,001). El sexo femenino se asoció significativamente con NSCR: Odds Ratio ajustada (aOR) = 1,56), así como la edad avanzada: aOR por cada 10 años = 1,15. Por último, obtuvieron en Euroquol una puntuación media de 9,63 puntos menos. Conclusiones: Más del 15% de los pacientes reportaron NSCR, siendo el sexo femenino y la edad factores predictores independientes. La mayoría de los síntomas en estos pacientes coincidieron con los de la definición de condición post-COVID-19 de la OMS y fueron menos prevalentes en contactos estrechos y COVID-19 que se sintieron recuperados, con un patrón dosis respuesta, y con una menor calidad de vida según Euroquol.

Near infrared spectroscopy (NIRS) and machine learning as a promising tandem for fast viral detection in serum microsamples: A preclinical proof of concept.

Fast detection of viral infections is a key factor in the strategy for the prevention of epidemics expansion and follow-up. Hepatitis C is paradigmatic within viral infectious diseases and major challenges to elimination still remain. Near infrared spectroscopy (NIRS) is an inexpensive, clean, safe method for quickly detecting viral infection in transmission vectors, aiding epidemic prevention. Our objective is to evaluate the combined potential of machine learning and NIRS global molecular fingerprint (GMF) from biobank sera as an efficient method for HCV activity discrimination in serum. GMF of 151 serum biobank microsamples from hepatitis C patients were obtained with a FT-NIR spectrophotometer in reflectance mode. Multiple scatter correction, smoothing and Saviztsky-Golay second derivative were applied. Spectral analysis included Principal Component Analysis (PCA), Bootstrap and L1-penalized classification. Microsamples of 70 µl were sufficient for GMF acquisition. Bootstrap evidenced significant difference between HCV PCR positive and negative sera. PCA renders a neat discrimination between HCV PCR-positive and negative samples. PCA loadings together with L1-penalized classification allow the identification of discriminative bands. Active virus positive sera are associated to free molecular water, whereas water in solvation shells is associated to HCV negative samples. Divergences in the water matrix structure and the lipidome between HCV negative and positive sera, as well as the relevance of prooxidants and glucose metabolism are reported as potential biomarkers of viral activity. Our proof of concept demonstrates that NIRS GMF of hepatitis C patients' sera aided by machine learning allows for efficient discrimination of viral presence and simultaneous potential biomarker identification.

Chitosan-Tricarbocyanine-Based Nanogels Were Able to Cross the Blood-Brain Barrier Showing Its Potential as a Targeted Site Delivery Agent.

Targeting drugs to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). The cutting edge in nanotechnology generates optimism to overcome the growing challenges in biomedical sciences through the effective engineering of nanogels. The primary objective of the present report was to develop and characterize a biocompatible natural chitosan (CS)-based NG that can be tracked thanks to the tricarbocyanine (CNN) fluorescent probe addition on the biopolymer backbone. FTIR shed light on the chemical groups involved in the CS and CNN interactions and between CNN-CS and tripolyphosphate, the cross-linking agent. Both in vitro and in vivo experiments were carried out to determine if CS-NGs can be utilized as therapeutic delivery vehicles directed towards the brain. An ionic gelation method was chosen to generate cationic CNN-CS-NG. DLS and TEM confirmed that these entities' sizes fell into the nanoscale. CNN-CS-NG was found to be non-cytotoxic, as determined in the SH-SY5Y neuroblastoma cell line through biocompatibility assays. After cellular internalization, the occurrence of an endo-lysosomal escape (a crucial event for an efficient drug delivery) of CNN-CS-NG was detected. Furthermore, CNN-CS-NG administered intraperitoneally to female CF-1 mice were detected in different brain regions after 2 h of administration, using fluorescence microscopy. To conclude, the obtained findings in the present report can be useful in the field of neuro-nanomedicine when designing drug vehicles with the purpose of delivering drugs to the CNS.

Heterogeneous Communication Network Architecture for the Management of Electric Vehicle Charging Stations: Multi-Aggregator Management in Microgrids with High Photovoltaic Variability Based on Multiple Solar Radiation Sensors.

Electric power systems with a high penetration of photovoltaic generation and a relevant fleet of electric vehicles face significant stability challenges, particularly in mountainous areas where the variability of photovoltaic resources is pronounced. This study presents a novel methodology to strategically place electric vehicle aggregators along a feeder. This approach considers electrical variables and the dynamics of cloud movements within the study area. This innovative methodology reduces the substation's power load demand and significantly improves the end user's voltage levels. The improvements in voltage regulation and reduced demand on the substation provide clear benefits, including increased system resilience, better integration of renewable energy sources, and enhanced overall efficiency of the electric grid. These advantages are particularly critical in regions with high levels of photovoltaic generation and are important in promoting sustainable electric vehicle charging infrastructure. When analyzing different load scenarios for the IEEE European Low Voltage Test Feeder system, the consideration of distributed aggregators based on cloud movements decreased the power required at the substation by 21.25%, and the voltage drop in loads was reduced from 6.9% to 4.29%. This research underscores the critical need to consider both the variability and geographical distribution of PV resources in the planning and operation of electrical systems with extensive PV generation.

Juvenile Justice-Based Interdisciplinary Collective Care: An Innovative Approach.

Mental health concerns among juvenile-justice-involved youth (JJIY) continue to be a major health crisis in the United States (US). While scholarship has explored mental health concerns among JJIY, and the link to negative life outcomes, there are gaps in the existing research, particularly in effective interventions and models aimed at addressing both the mental health concerns and criminogenic risk contributing to recidivism and other negative life outcomes of this population. In this paper, we present Justice-Based Interdisciplinary Collective Care (JBICC), an innovative framework to address both the mental health needs and delinquent behavior of youth offenders. The model bridges community partners, with the purpose of informing future interventions, implementations, and research in this area. Increased justice-based interdisciplinary collective collaboration between the juvenile justice system and community programs/organizations would be a major benefit to youth offenders and their families. We also focus on the need for cultural responsiveness to be interwoven throughout all aspects of treatment. JBICC offers an opportunity to expanded services outside traditional settings and methods to ensure that youth offenders and their families receive validating and culturally responsive access to services.

Inhibin B and antiMüllerian hormone as surrogate markers of fertility in male and female Crohn's disease patients: a case-control study.

Background: Several studies suggest that women with Crohn disease (CD) have reduced fertility due to decreased ovarian reserve, among other causes. On the other hand, male CD patients could have difficulties conceiving. The present study aimed to test the effect of CD on both male and female fertility potential, Sertoli cell function and ovarian reserve, assessed by inhibin-B (IB) plus IB:FSH ratio (IFR) and antiMüllerian hormone (AMH), respectively. Sexual dysfunction (SD) was studied as secondary endpoint. Methods: We performed a cross-sectional, case-control study. Serum IB levels plus IFR were measured in 58 men with CD and compared to 25 age-matched healthy controls (HC). Serum AMH levels were measured in 50 women with CD and in 30 HC matched by age. SD was assessed by means of the International Index of Erectile Function (IIFE-15) in males and the Index of Female Sexual Function (IFSF) in women. Results: A total of 108 CD patients and 55 HC were included. IB serum levels were significantly lower in CD men than in HC (177 ± 58 vs. 234 ± 75 pg./mL, p = 0.001). IFR was also decreased in CD patients compared to HC (58.27 ± 59.5 vs. 91.35 ± 60.04, p = 0.014). Women with CD > 30 years had lower serum AMH levels compared to HC (1.15 ± 0.74 vs. 2.14 ± 1.68 ng/mL, p = 0.033). In addition, CD women >30 years presented a serum AMH < 2 ng/mL more frequently than HC (90% vs. 40%, p = 0.004). The prevalence of SD was significantly higher among both male and female CD patients compared to HC, without association to fertility potential. Age was the only predictor of low ovarian reserve. Conclusion: Testicular Sertoli cell function assessed through serum IB levels and IFR is decreased in CD male patients compared to HC, regardless of age. Age > 30 years is the single independent predictor of reduced ovarian reserve in women with CD. These results should be confirmed in further studies in order to properly counsel patients with CD and desire for offspring.

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

Design and characterization of BSA-mycophenolic acid nanocomplexes: Antiviral activity exploration.

The interactions between bovine serum albumin (BSA) and mycophenolic acid (MPA) were investigated in silico through molecular docking and in vitro, using fluorescence spectroscopy. Dynamic light scattering and scanning electron microscopy were used to figure out the structure of MPA-Complex (MPA-C). The binding affinity between MPA and BSA was determined, yielding a Kd value of (12.0 ± 0.7) µM, and establishing a distance of 17 Å between the BSA and MPA molecules. The presence of MPA prompted protein aggregation, leading to the formation of MPA-C. The cytotoxicity of MPA-C and its ability to fight Junín virus (JUNV) were tested in A549 and Vero cell lines. It was found that treating infected cells with MPA-C decreased the JUNV yield and was more effective than free MPA in both cell line models for prolonged time treatments. Our results represent the first report of the antiviral activity of this type of BSA-MPA complex against JUNV, as assessed in cell culture model systems. MPA-C shows promise as a candidate for drug formulation against human pathogenic arenaviruses.

Impacto de la pandemia por COVID-19 en el implante de dispositivos cardiacos implantables y las activaciones de la monitorización a distancia / Impact of the COVID-19 pandemic on implantation of cardiac implantable electronic devices and remote monitoring activations

Introducción y objetivos La monitorización a distancia (MD) de los dispositivos cardiacos implantables (DCI) se considera más fiable, eficiente y segura que los convencionales seguimientos presenciales, aunque su implantación es aún subóptima. Este estudio pretende analizar el impacto de la pandemia de COVID-19 en las tasas de implantes y activaciones de MD de DCI en España. Métodos Se utilizó el Registro COVID-19 de MD en España para analizar el número mensual de todos los implantes de DCI y activaciones de MD desde enero de 2018 hasta diciembre de 2021 en España. Se sumaron los datos de los 5 principales fabricantes de DCI y se analizaron de manera descriptiva. Resultados Se registró un total de 205.345 DCI. El número de implantes disminuyó bruscamente (48,2%) con el confinamiento (marzo a junio de 2020) y aumentó progresivamente después hasta compensar la reducción previa, excepto en marcapasos y desfibriladores automáticos implantables (DAI), con una pérdida agregada (2020-2021) del 7 y el 3%, respectivamente, respecto a la media anual. Aumentaron la terapia de resincronización cardiaca con desfibrilador (TRC-D, 17%) y con marcapasos (TRC-P, 4,5%) a los 2 años. El porcentaje de activaciones de MD aumentó del 24,5% en 2018 al 49,0% en 2021, con un fuerte aumento durante el confinamiento. Las tasas de activación de MD aumentaron invariablemente durante el confinamiento con todos los dispositivos: marcapasos (el 14,4 frente al 37,2%; p<0,001); DAI (el 75,6 frente al 94,2%; p<0,001); TRC-D/TRC-P (del 68,6/44,2% al 81,6/61%; p<0,001), y Holters implantables (el 50,2 frente al 68,7%; p<0,001). Conclusiones La significativa reducción de los implantes que se produjo durante el confinamiento se recuperó gradualmente después, excepto los de marcapasos y DAI. La pandemia de COVID-19 impulsó la MD de todos los DCI en España. (AU)

Introduction and objectives Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is considered more reliable, efficient, and safer than conventional in-person follow-up. However, the implementation of RM is still suboptimal. This study aimed to analyze the impact of the COVID-19 pandemic on the rates of CIED implants and RM activations in Spain. Methods The COVID-19 RM Spain Registry was used to analyze the monthly number of all CIED implantations and RM activations from January 2018 to December 2021. A descriptive analysis was performed using aggregated data from the five major CIED manufacturers. Results A total of 205 345 CIEDs were recorded. The number of implants decreased sharply (48.2%) during the pandemic lockdown (March-June 2020) but gradually increased thereafter, compensating for the previous reduction. However, pacemakers and implantable cardiac defibrillators (ICD) showed an aggregate loss of 7% and 3%, respectively, from the annual average during 2020-2021. In contrast, cardiac resynchronization therapy defibrillators (CRT-D) increased by 17%, and pacemakers (CRT-P) by 4.5% over the 2-year period. The percentage of RM activations increased from 24.5% in 2018 to 49.0% in 2021, with a sharp increase during the lockdown. The RM activation rates consistently increased during the lockdown for all devices: pacemakers (14.4% vs 37.2%; P<.001); ICD (75.6% vs 94.2%; P<.001); CRT-D/CRT-P (68.6-44.2% vs 81.6-61%; P<.001), and implantable loop recorders (50.2% vs 68.7%; P<.001). Conclusions The significant decline in implants during the lockdown gradually recovered, except for pacemakers and ICD. However, the COVID-19 pandemic boosted RM for all CIEDs in Spain. (AU)

Pilot trial results of D-HOMES: a behavioral-activation based intervention for diabetes medication adherence and psychological wellness among people who have been homeless.

Introduction: People living with type 2 diabetes who experience homelessness face a myriad of barriers to engaging in diabetes self-care behaviors that lead to premature complications and death. This is exacerbated by high rates of comorbid mental illness, substance use disorder, and other physical health problems. Despite strong evidence to support lay health coach and behavioral activation, little research has effectively engaged people living with type 2 diabetes who had experienced homelessness (DH). Methods: We used community engaged research and incremental behavioral treatment development to design the Diabetes HOmeless MEdication Support (D-HOMES) program, a one-on-one, 3 month, coaching intervention to improve medication adherence and psychological wellness for DH. We present results of our pilot randomized trial (with baseline, 3 mo., 6 mo. assessments) comparing D-HOMES to enhanced usual care (EUC; brief diabetes education session and routine care; NCT05258630). Participants were English-speaking adults with type 2 diabetes, current/recent (<24 mo.) homelessness, and an HbA1c_7.5%. We focused on feasibility (recruitment, retention, engagement) and acceptability (Client Satisfaction Questionnaire, CSQ-8). Our primary clinical outcome was glycemic control (HbA1c) and primary behavioral outcome was medication adherence. Secondary outcomes included psychological wellness and diabetes self-care. Results: Thirty-six eligible participants enrolled, 18 in each arm. Most participants identified as Black males, had high rates of co-morbidities, and lived in subsidized housing. We retained 100% of participants at 3-months, and 94% at 6-months. Participants reported high satisfaction (mean CSQ-8 scores=28.64 [SD 3.94] of 32). HbA1c reduced to clinically significant levels in both groups, but we found no between group differences. Mean blood pressure improved more in D-HOMES than EUC between baseline and 6 mo. with between group mean differences of systolic -19.5 mmHg (p=0.030) and diastolic blood pressure -11.1 mmHg (p=0.049). We found no significant between group differences in other secondary outcomes. Conclusion: We effectively recruited and retained DH over 6 months. Data support that the D-HOMES intervention was acceptable and feasible. We observe preliminary blood pressure improvement favoring D-HOMES that were statistically and clinically significant. D-HOMES warrants testing in a fully powered trial which could inform future high quality behavioral trials to promote health equity. Clinical trial registration: https://clinicaltrials.gov/study/NCT05258630?term=D-HOMES&rank=1, identifier NCT05258630.

An Apple and Acáchul Berry Snack Rich in Bioaccessible Antioxidants and Folic Acid: A Healthy Alternative for Prenatal Diets.

A fruit leather (apple and acáchul berry) oriented toward women of reproductive age was developed. The snack was supplemented with an ingredient composed of folic acid (FA) and whey proteins (WPI) to ensure the required vitamin intake to prevent fetal neural tube defects. In order to generate a low-calorie snack, alternative sweeteners were used (stevia and maltitol). The fruit leather composition was determined. Also, an in vitro digestion process was carried out to evaluate the bioaccessibility of compounds with antioxidant capacity (AC), total polyphenols (TPCs), total monomeric anthocyanins (ACY), and FA. The quantification of FA was conducted by a microbiological method and by HPLC. The leather contained carbohydrates (70%) and antioxidant compounds, mainly from fruits. Bioaccessibility was high for AC (50%) and TPCs (90%), and low for ACY (17%). Regarding FA, bioaccessibility was higher for WPI-FA (50%) than for FA alone (37%), suggesting that WPI effectively protected the vitamin from processing and digestion. Furthermore, the product was shown to be non-cytotoxic in a Caco-2 cell model. The developed snack is an interesting option due to its low energy intake, no added sugar, and high content of bioactive compounds. Also, the supplementation with WPI-FA improved the conservation and bioaccessibility of FA.

Contraceptive Recommendations for Women with Immune-Mediated Inflammatory Diseases: A Delphi Consensus.

INTRODUCTION: Immune-mediated inflammatory diseases (IMID) are a group of disorders characterized by chronic inflammation caused by an altered immune regulation in targeted organs or systems. IMID itself could have an implied increased risk of venous thromboembolism (VTE) and this risk varies throughout the course of the disease as well as with some contraceptive methods and treatments. The aim of this study was to present some key considerations in relation to contraception in women with IMID. METHODS: This was an exploratory study conducted in Spain following the online modified Delphi methodology with two rounds of participation. Four questionnaires were designed for each medical specialty: gastroenterology, rheumatology, dermatology, and gynecology. Each questionnaire was divided in three domains: general recommendations about IMID, specific recommendations, and contraceptive methods for patients with IMID. A 5-point Likert scale measured agreement with each statement, with an 80% agreement threshold. Following the first round, the percentage of each response was calculated for every item. Subsequently, a second round was conducted to reach a consensus on the items for which discrepancies were observed. RESULTS: A total of 52 and 50 experts participated in the first and second round, respectively. Participants agreed on the existence of a higher risk of VTE in inflammatory bowel diseases, psoriasis, and rheumatoid arthritis diseases. Regarding recommendations for contraceptive methods in patients with IMID, experts considered the hormonal intrauterine device (IUD) as a first-line contraceptive (80.0%) and low doses of progesterone-only pills if the latter is not recommended (88.0%). Most of the interviewees concurred on the importance of the patients' contraceptive needs during the disease course (98.1%). CONCLUSION: Raising awareness and promoting a multidisciplinary relationship among the physicians involved in the therapeutic decisions by considering all the risk factors when prescribing a contraceptive method is important to prevent VTE in women with IMID.

Sex differences in autism-like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication and repetitive and restricted behaviors. Sex dimorphism in the brain, including midbrain dopaminergic circuits, can explain differences in social behavior impairment and stereotypic behaviors between male and female individuals with ASD. These abnormal patterns may be due to alterations in dopamine synthesis in the ventral tegmental area (VTA) and substantia nigra (SN). We used an autism-like mouse model by prenatal valproic acid (VPA) exposure. CD1 pregnant female mice were injected with 500 mg/kg VPA or 0.9% NaCl as a vehicle on gestational day 12.5. In the offspring, on postnatal day 31, we examined the social and repetitive behaviors and the number of tyrosine hydroxylase (TH)-positive cells in VTA and SN by sex. Male VPA mice showed impaired social behavior and increased repetitive behaviors when compared to male vehicles. In females, we did not find statistically significant differences in social or repetitive behaviors between the groups. Male VPA mice had fewer TH+ cells in the SN than control-vehicle mice. Interestingly, no cellular changes were observed between females. This study supports the notion that sex dimorphism of certain brain regions is involved in the etiopathogenesis and clinical presentation of ASD.

Experimental and in silico approaches for the buffalo whey protein-folic acid complexation elucidation. Molecular changes impacting on protein structure and functionality.

Using a buffalo whey proteins concentrate (BWPC) as a nanocarrier of labile bioactive compounds as vitamins constitutes a very innovative approach with potential application in the food and nutraceutical industries. This work aims to deepen the knowledge of the phenomena occurring in the complexation process of vitamin B9 with BWPC, providing valuable information on the molecular and functional properties of complexes and intervening substances. For such purpose, analytical (SEC-FPLC, Fluorescence spectroscopy, FTIR, DLS, UV-vis spectroscopy) and in-silico methods (molecular docking) were performed to get complementary data. Five types of proteins were identified in the BWPC. Folic acid (FA) interacted with BWPC in buffer pH 7 through H-bonds and hydrophobic interactions, inducing conformational changes and modifying the secondary and tertiary protein structure. The resultant BWPC-FA complexes showed a size distribution in the nanoscale (100-150 nm) with no aggregation. Molecular docking showed that lactoferrin had the highest FA binding affinity. Complexation did not reduce the antioxidant activity of intervening substances. Indeed, the radical scavenging capacity of BWPC-FA was 20 % higher than single BWPC. The obtained results provide relevant data enabling the adding value of the main effluent of buffalo dairy industries.

Non-invasive estimation of atrial fibrillation driver position using long-short term memory neural networks and body surface potentials.

BACKGROUND AND OBJECTIVE: Atrial Fibrillation (AF) is a supraventricular tachyarrhythmia that can lead to thromboembolism, hearlt failure, ischemic stroke, and a decreased quality of life. Characterizing the locations where the mechanisms of AF are initialized and maintained is key to accomplishing an effective ablation of the targets, hence restoring sinus rhythm. Many methods have been investigated to locate such targets in a non-invasive way, such as Electrocardiographic Imaging, which enables an on-invasive and panoramic characterization of cardiac electrical activity using recording Body Surface Potentials (BSP) and a torso model of the patient. Nonetheless, this technique entails some major issues stemming from solving the inverse problem, which is known to be severely ill-posed. In this context, many machine learning and deep learning approaches aim to tackle the characterization and classification of AF targets to improve AF diagnosis and treatment. METHODS: In this work, we propose a method to locate AF drivers as a supervised classification problem. We employed a hybrid form of the convolutional-recurrent network which enables feature extraction and sequential data modeling utilizing labeled realistic computerized AF models. Thus, we used 16 AF electrograms, 1 atrium, and 10 torso geometries to compute the forward problem. Previously, the AF models were labeled by assigning each sample of the signals a region from the atria from 0 (no driver) to 7, according to the spatial location of the AF driver. The resulting 160 BSP signals, which resemble a 64-lead vest recording, are preprocessed and then introduced into the network following a 4-fold cross-validation in batches of 50 samples. RESULTS: The results show a mean accuracy of 74.75% among the 4 folds, with a better performance in detecting sinus rhythm, and drivers near the left superior pulmonary vein (R1), and right superior pulmonary vein (R3) whose mean sensitivity bounds around 84%-87%. Significantly good results are obtained in mean sensitivity (87%) and specificity (83%) in R1. CONCLUSIONS: Good results in R1 are highly convenient since AF drivers are commonly found in this area: the left atrial appendage, as suggested in some previous studies. These promising results indicate that using CNN-LSTM networks could lead to new strategies exploiting temporal correlations to address this challenge effectively.