Incidence of urinary incontinence after hip fracture surgery and associated risk factors: a prospective study.

BACKGROUND: The contribution of the postoperative process to developing or worsening urinary incontinence (UI) after hip fracture surgery (HFS) remains unclear. We aimed to evaluate UI incidence and worsening among older patients undergoing HFS, and explore associated risk factors. METHODS: This prospective cohort study included patients ≥ 75 years admitted between October 2019 and October 2021 to the Traumatology Service of three hospitals in the Consorci Sanitari de Alt-Penedès i Garraf (Barcelona, Spain) with hip fracture requiring surgical treatment. UI was assessed using the first two questions of the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) at baseline and at days 30 (± 3 days) and 90 (± 3 days) after HFS. Surgery-related data and post-surgical complications were recorded. RESULTS: A total of 248 patients with a mean (SD) age of 85.8 (6.78) years were included; 77.8% were female and 154 (62.1%) had UI at baseline. After HFS, 3.24% experienced urinary tract infections (UTIs), 3.64%, acute urinary retention (AUR), 8.57%, constipation, and 53.9%, prolonged catheterization (> 24 h). Fifty-eight patients without baseline UI developed UI at 30 days, resulting in a UI incidence of 61.7% (95% CI 51.1-71.54) between days 0 and 30. Of the 248 patients, 146 (59.1%) experienced worsening of UI. AUR and UTIs were identified as risk factors for UI development and worsening after HFS, respectively. CONCLUSION: The incidence of UI in older patients after HFS is significant. Patient management protocols should consider AUR and UTIs to reduce or eliminate the incidence of UI in older patients undergoing HFS.

Impact of COVID-19 on Unaccompanied Immigrant Minors and Families: Perspectives from Clinical Experts and Providers.

The number of unaccompanied immigrant minors (UIMs) and families from Central America seeking asylum in the U.S. continues to rise. This growth, combined with restrictive government policies, led to crowded and suboptimal conditions in Customs and Border Patrol and non-governmental organization facilities. COVID-19 further taxed facilities and exacerbated uncertainty surrounding length of detention, basic human rights, and family reunification. The current project features testimonies from the authors who work as clinical experts and providers in Texas - a top destination for Central American immigrants. In collaboration with a deputy director of a not-for-profit human rights organization, volunteer psychologists, and the director of a humanitarian respite center, we describe challenges faced by administrators and clinical staff in addressing the mental health needs of immigrant children and families during the COVID-19 pandemic. The primary themes identified were anti-immigrant policies that occurred concurrently with COVID-19; difficulty implementing COVID-19 protocols alongside scarcity of supplies and volunteers; increased mental health needs among UIMs and immigrant families; and challenges in UIM placement upon release from custody. Strategies for addressing clinical challenges in the near- and long-term and opportunities for improvement in care systems to immigrant youth, including correcting anti-immigrant policies, addressing ongoing COVID-19 protocols and challenges, meeting mental and physical health needs, facilitating release and reunification for unaccompanied immigrant minors, and maximizing youth resilience through trauma-informed interventions, are presented.

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.

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.

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.

The ventricular-subventricular, subgranular and subcallosal zones: three niches of neural stem cells in the postnatal brain.

In the postnatal brain, three regions show high mitotic activity. These brain areas are neurogenic niches, and each niche harbors a microenvironment favorable for the proliferation and differentiation of neural stem cells. These multipotential cells maintain the capacity to self-renew and generate intermediate precursors that will differentiate into neuronal and glial lineages (astrocytes and oligodendrocytes). The most well-studied niches are the ventricular-subventricular zone (V-SVZ) of the lateral ventricles, the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, and the subcallosal zone (SCZ), located in the limit between the corpus callosum and the hippocampal formation. The discovery of these three neurogenic niches has gained much interest in the field because they may be a therapeutic alternative in neural regeneration and neurodegenerative disorders. In this review, we describe in brief all these regions and explain their potential impact on solving some neurological conditions.

Conduction system pacing, a European survey: insights from clinical practice.

AIMS: The field of conduction system pacing (CSP) is evolving, and our aim was to obtain a contemporary picture of European CSP practice. METHODS AND RESULTS: A survey was devised by a European CSP Expert Group and sent electronically to cardiologists utilizing CSP. A total of 284 physicians were invited to contribute of which 171 physicians (60.2%; 85% electrophysiologists) responded. Most (77%) had experience with both His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Pacing indications ranked highest for CSP were atrioventricular block (irrespective of left ventricular ejection fraction) and when coronary sinus lead implantation failed. For patients with left bundle branch block (LBBB) and heart failure (HF), conventional biventricular pacing remained first-line treatment. For most indications, operators preferred LBBAP over HBP as a first-line approach. When HBP was attempted as an initial approach, reasons reported for transitioning to utilizing LBBAP were: (i) high threshold (reported as >2 V at 1 ms), (ii) failure to reverse bundle branch block, or (iii) > 30 min attempting to implant at His-bundle sites. Backup right ventricular lead use for HBP was low (median 20%) and predominated in pace-and-ablate scenarios. Twelve-lead electrocardiogram assessment was deemed highly important during follow-up. This, coupled with limitations from current capture management algorithms, limits remote monitoring for CSP patients. CONCLUSIONS: This survey provides a snapshot of CSP implementation in Europe. Currently, CSP is predominantly used for bradycardia indications. For HF patients with LBBB, most operators reserve CSP for biventricular implant failures. Left bundle branch area pacing ostensibly has practical advantages over HBP and is therefore preferred by many operators. Practical limitations remain, and large randomized clinical trial data are currently lacking.

Cryopreservation, in addition to protein tyrosine phosphorylation, alters the distribution of phosphatidyl inositol bisphosphate and the localization of cytoskeletal and signaling proteins (gelsolin, tyrosine kinase c-SRC and phospholipase C-ζ) in the perinuclear theca of boar sperm.

Cryopreservation of boar spermatozoa affects the perinuclear theca (PT) and involves several proteins and molecules that play important roles during capacitation and the acrosomal reaction. The objective of the present study was to evaluate whether the deleterious effects of cryopreservation in addition to protein tyrosine phosphorylation are accompanied by changes in the distribution of phosphatidyl inositol bisphosphate (PIP2) and the localization of cytoskeletal and signaling proteins in the perinuclear theca of cryopreserved boar spermatozoa. For this purpose, by immunocytochemistry (IC) the changes in localization of phosphorylated proteins in tyrosine residues, gelsolin, c-SRC kinase and PLC-ζ, as well as in the distribution of phosphatidyl inositol bisphosphate were analyzed in thawed spermatozoa (T) non capacitated (NC), capacitated (C) and in those with acrosomal reaction (AR) and compared with fresh spermatozoa (F) under the same physiological status. Western blotting (WB) and co-immunoprecipitation were performed to confirm the presence of these proteins in PT and to determine the interaction between these molecules. IC showed that immunostaining for phosphorylated proteins significantly increased in the acrosomal region and flagellum in TNC spermatozoa (p < 0.05). The proportion of cells displaying immunolabeling for gelsolin in the acrosomal region decreased after capacitation in cryopreserved spermatozoa; the same change was found (p < 0.05) in the proportion of spermatozoa immunoreactive to PIP2 in the sperm head. c-SRC was observed in the equatorial segment and acrosomal region, subdomains that coincide with the site where phosphorylated proteins were detected. PLC-ζ immunolocalization in fresh spermatozoa underwent changes after capacitation and acrosomal reaction, with a significant increase in the equatorial segment and post-acrosomal region in cryopreserved spermatozoa (p < 0.05). WB analysis indicated the presence of gelsolin, c-SRC and PLC-ζ in PT; besides, we confirmed that gelsolin co-immunoprecipitated with c-SRC and PLC-ζ, which changes according to the physiological state of spermatozoa. As a conclusion, cryopreservation together with increased immunodetection of tyrosine phosphorylated proteins decreases the detection of PIP2 and alters the immunolocalization patterns of gelsolin, c-SRC and PLC-ζ in the PT in boar spermatozoa.

Association between Clinical Frailty Scale (CFS) and clinical presentation and outcomes in older inpatients with COVID-19.

BACKGROUND: Frailty is a physiological condition characterized by a decreased reserve to stressors. In patients with COVID-19, frailty is a risk factor for in-hospital mortality. The aim of this study was to assess the relationship between clinical presentation, analytical and radiological parameters at admission, and clinical outcomes according to frailty, as defined by the Clinical Frailty Scale (CFS), in old people hospitalized with COVID-19. MATERIALS AND METHODS: This retrospective cohort study included people aged 65 years and older and admitted with community-acquired COVID-19 from 3 March 2020 to 31 April 2021. Patients were categorized using the CFS. Primary outcomes were symptoms of COVID-19 prior to admission, mortality, readmission, admission in intensive care unit (ICU), and need for invasive mechanical ventilation. Analysis of clinical symptoms, clinical outcomes, and CFS was performed using multivariable logistic regression, and results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 785 included patients, 326 (41.5%, 95% CI 38.1%-45.0%) were defined as frail (CFS ≥ 5 points): 208 (26.5%, 95% CI 23.5%-29.7%) presented mild-moderate frailty (CFS 5-6 points) and 118 (15.0%, 95% CI 12.7%-17.7%), severe frailty (7-9 points). After adjusting for epidemiological variables (age, gender, residence in a nursing home, and Charlson comorbidity index), frail patients were significantly less likely to present dry cough (OR 0.58, 95% CI 0.40-0.83), myalgia-arthralgia (OR 0.46, 95% CI 0.29-0.75), and anosmia-dysgeusia (OR 0.46, 95% CI 0.23-0.94). Confusion was more common in severely frail patients (OR 3.14; 95% CI 1.64-5.97). After adjusting for epidemiological variables, the risk of in-hospital mortality was higher in frail patients (OR 2.79, 95% CI 1.79-4.25), including both those with mild-moderate frailty (OR 1.98, 95% CI 1.23-3.19) and severe frailty (OR 5.44, 95% CI 3.14-9.42). Readmission was higher in frail patients (OR 2.11, 95% CI 1.07-4.16), but only in mild-moderate frailty (OR 2.35, 95% CI 1.17-4.75).. CONCLUSION: Frail patients presented atypical symptoms (less dry cough, myalgia-arthralgia, and anosmia-dysgeusia, and more confusion). Frailty was an independent predictor for death, regardless of severity, and mild-moderate frailty was associated with readmission.

Severe Spontaneous Hematomas in Patients Hospitalized with COVID-19.

Objective: To describe the epidemiological, clinical, laboratory, and radiological characteristics, medical treatment, and outcomes of a case series of severe spontaneous hematoma in COVID-19. Material and Methods. This retrospective study included patients hospitalized for COVID-19 who were diagnosed with severe spontaneous bleeding complications by following a standardized treatment protocol that included computed tomography angiography (CTA) from 1 March 2020 to 28 February 2022. The main outcomes were embolization and all-cause mortality. Baseline variables were analyzed for their association with mortality using bivariable logistic regression, and results were expressed as odds ratios (OR) and 95% confidence intervals (CI). Results: In total, 2450 adults were hospitalized for COVID-19 in our center during the study period. 20 patients presented severe and spontaneous intramuscular bleeding (8.1 per 1000 COVID-19 admission vs. 0.47 per 1000 non-COVID-19 admissions, p < 0.001); their median age was 68.5 years (interquartile range (IQR) 63, 80), they had high comorbidity (median Charlson comorbidity index 4.5), and 95% were receiving high doses of heparin. The median interval from COVID-19 symptoms to bleeding was 17 days (IQR 13, 24), and 70% reported cough as a previous symptom. Hypovolemic shock, hypotension, and abdominal pain were the most frequent symptoms of the hematoma. All presented decreased hemoglobin, and 95% required transfusion. Intramuscular hematoma occurred most frequently in the rectus sheath, iliopsoas compartment, and femoral-iliac compartment. All patients underwent embolization; mortality was 45%. We did not identify risk factors associated with an increased risk of death. Conclusion: Although severe bleeding is an uncommon complication of COVID-19, its prevalence is higher than in inpatients without COVID-19, it usually needs embolization, and it is associated with high mortality.

Changes in the levels of free sialic acid during ex vivo lung perfusion do not correlate with pulmonary function. Experimental model.

BACKGROUND: Ex vivo lung perfusion (EVLP) constitutes a tool with great research potential due to its advantages over in vivo and in vitro models. Despite its important contribution to lung reconditioning, this technique has the disadvantage of incurring high costs and can induce pulmonary endothelial injury through perfusion and ventilation. The pulmonary endothelium is made up of endothelial glycocalyx (EG), a coating of proteoglycans (PG) on the luminal surface. PGs are glycoproteins linked to terminal sialic acids (Sia) that can affect homeostasis with responses leading to edema formation. This study evaluated the effect of two ex vivo perfusion solutions on lung function and endothelial injury. METHODS: We divided ten landrace swine into two groups and subjected them to EVLP for 120 min: Group I (n = 5) was perfused with Steen® solution, and Group II (n = 5) was perfused with low-potassium dextran-albumin solution. Ventilatory mechanics, histology, gravimetry, and sialic acid concentrations were evaluated. RESULTS: Both groups showed changes in pulmonary vascular resistance and ventilatory mechanics (p < 0.05, Student's t-test). In addition, the lung injury severity score was better in Group I than in Group II (p < 0.05, Mann-Whitney U); and both groups exhibited a significant increase in Sia concentrations in the perfusate (p < 0.05 t-Student) and Sia immunohistochemical expression. CONCLUSIONS: Sia, as a product of EG disruption during EVLP, was found in all samples obtained in the system; however, the changes in its concentration showed no apparent correlation with lung function.

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues.

Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies or prion diseases, which are caused by an infectious isoform of the innocuous cellular prion protein (PrPC) known as PrPSc. DNA methylation, one of the most studied epigenetic mechanisms, is essential for the proper functioning of the central nervous system. Recent findings point to possible involvement of DNA methylation in the pathogenesis of prion diseases, but there is still a lack of knowledge about the behavior of this epigenetic mechanism in such neurodegenerative disorders. Here, we evaluated by immunohistochemistry the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in sheep and mouse brain tissues infected with scrapie. Expression analysis of different gene coding for epigenetic regulatory enzymes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, TET1, and TET2) was also carried out. A decrease in 5mC levels was observed in scrapie-affected sheep and mice compared to healthy animals, whereas 5hmC displayed opposite patterns between the two models, demonstrating a decrease in 5hmC in scrapie-infected sheep and an increase in preclinical mice. 5mC correlated with prion-related lesions in mice and sheep, but 5hmC was associated with prion lesions only in sheep. Differences in the expression changes of epigenetic regulatory genes were found between both disease models, being differentially expressed Dnmt3b, Hdac1, and Tet1 in mice and HDAC2 in sheep. Our results support the evidence that DNA methylation in both forms, 5mC and 5hmC, and its associated epigenetic enzymes, take part in the neurodegenerative course of prion diseases.

Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes.

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or "long COVID"), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers.

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Male pituitary-gonadal axis dysfunction in post-acute COVID-19 syndrome-Prevalence and associated factors: A Mediterranean case series.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 through angiotensin-converting enzyme 2 receptor can harm testes function. The objectives were to analyse the prevalence of low serum testosterone (LT) and impaired fertility potential (Leydig and Sertoli cells dysfunction, respectively) in coronavirus disease 2019 (COVID-19) male survivors and to evaluate acute infection-related associated factors. Also, we explore its association with post-acute COVID-19 syndrome (PCS) and quality of life (QOL). MATERIALS AND METHODS: Male adults recovered from polymerase chain reaction-confirmed COVID-19 were offered a structured evaluation 8-12 weeks after recovery. The main outcome measure(s) were as follows: LT, defined as total testosterone (TT) < 2 ng/ml or if TT levels 2-4 ng/ml as calculated free testosterone < 6.36 ng/dl; Sertoli cell dysfunction was defined as inhibin-B < 89 pg/ml. Secondary outcome-associated factors were analysed by multiple logistic regression (odds ratio; 95% confidence interval [CI]). QOL was evaluated by SF-36 v.2. RESULTS: One hundred and forty-three patients were evaluated at a median (interquartile range) of 77 days (72-83) after disease onset; 72% of them recovered from severe pneumonia. LT was detected in 41 patients (28.7%; 95% CI: 21.8-36.5). Low levels of inhibin-B were detected in 25 patients (18.1%; 95% CI: 12.5-25.3). After multivariate adjustment, obesity and hypokalaemia were associated with LT, whereas age more than 65 was an independent predictor of Sertoli cell dysfunction. LT or Sertoli cell dysfunction was not associated with PCS. Patients with LT had a lower score in four domains of QOL. CONCLUSIONS: Prevalence of male LT and impaired fertility potential in COVID-19 survivors is high in the medium term. Traditional risk factors and severity markers for COVID-19 could be predictive.

Plasma ACE2 species are differentially altered in COVID-19 patients.

Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.

SARS-CoV-2 infection in early first-trimester miscarriages: a prospective observational study.

RESEARCH QUESTION: Is there an association between SARS-CoV-2 infection and first-trimester miscarriage? DESIGN: This multicentre prospective study included a cohort of women with first-trimester miscarriages registered consecutively by seven Spanish hospitals where universal PCR screening for SARS-CoV-2 infection was implemented with both miscarriages and deliveries. The incidence of SARS-CoV-2 infection among women with first-trimester miscarriages was compared with the rate registered in women on admission to the delivery ward within the same time frame using a mixed-effects Poisson regression analysis, considering 'hospital' as random effect. The characteristics of SARS-CoV-2 positive and negative patients who miscarried were compared through two-sided univariable analyses. RESULTS: A total of 301 miscarriages were registered, 11 (3.7%) to SARS-CoV-2 infected and 290 to non-infected women. In the same time frame as the miscarriages, 1936 deliveries were registered, 44 [2.3%] of them were SARS-CoV-2 infected. No differences in terms of SARS-CoV-2 infection incidence were observed between infected miscarriages and infected deliveries (P = 0.233). Regarding the differences observed between miscarriages in SARS-CoV-2 positive and negative women, more inevitable miscarriages occurred in the group of infected women (36.4% versus 16.5% in non-infected women; P = 0.004), and there was greater surgical management of miscarriages (27.3% versus 8.2% in non-infected women; P = 0.036), probably in line with the greater number of inevitable miscarriages observed in this group. CONCLUSIONS: No association between SARS-CoV-2 infection and risk of first-trimester miscarriage was observed; however, the type of miscarriage seems to differ between SARS-CoV-2 positive and negative women, with inevitable miscarriage being more frequent among infected women.

Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone.

Oligodendrocyte loss and myelin sheet destruction are crucial characteristics of demyelinating diseases. Phenytoin promotes the proliferation of endogenous neural precursor cells in the ventricular-subventricular zone in the postnatal brain that help restore the oligodendroglial population. This study aimed to evaluate whether phenytoin promotes myelin recovery of the corpus callosum of demyelinated adult mice. CD1 male mice were exposed to a demyelinating agent (0.2% cuprizone) for 8 weeks. We assembled two groups: the phenytoin-treated group and the control-vehicle group. The treated group received oral phenytoin (10 mg/kg) for 4 weeks. We quantified the number of Olig2 + and NG2 + oligodendrocyte precursor cells (OPCs), Rip + oligodendrocytes, the expression level of myelin basic protein (MBP), and the muscle strength and motor coordination. The oligodendroglial lineage (Olig2 + cells, NG2 + cells, and RIP + cells) significantly increases by the phenytoin administration when compared to the control-vehicle group. The phenytoin-treated group also showed an increased expression of MBP in the corpus callosum and better functional scores in the horizontal bar test. These findings suggest that phenytoin stimulates the proliferation of OPCs, re-establishes the oligodendroglial population, promotes myelin recovery in the corpus callosum, and improves motor coordination and muscle strength.

A high-fat diet during pregnancy impairs memory acquisition and increases leptin receptor expression in the hippocampus of rat offspring.

A high-fat diet (HFD) during pregnancy influences the neurodevelopment of progeny, particularly in the hippocampus, a brain region involved in cognitive processes. The hippocampus has high levels of leptin receptors (Ob-R) that participate in synaptic plasticity. This study examined the effect of maternal HFD during gestation on Ob-R expression in the CA1 and CA3 hippocampal regions, and its relationship with spatial learning and memory in the offspring. We used 48 rat pups: 24 from dams fed a balanced diet (BD, 6.2% fat) and 24 from those fed an HFD (42% fat) during pregnancy. We recorded weight gain and food intake in each pup every day beginning on postnatal day 3 (PND 3). Memory acquisition was assessed on PND 28 and memory retention on PND 42 in the Morris water maze (MWM). Then, 12 pups per group were selected randomly and subjected to bioimpedance spectroscopy. The remaining offspring was perfused to determine Ob-R expression levels in the CA1 and CA3 hippocampal regions. Interestingly, HFD pups had significantly higher weight gain, food intake, and fat mass than BD offspring. Interestingly, the HFD group showed poor memory performance, which correlated with changes in the Ob-R expression in both hippocampal regions. These data indicate that maternal exposure to HFD impacts neurodevelopmental and cognitive functions of the offspring.