Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Estimating the Prevalence of Dementia in New Zealand Using Capture-Recapture Analysis on Routinely Collected Health Data.

OBJECTIVES: Community based dementia prevalence studies are expensive and resource intensive. Aotearoa New Zealand (NZ) has never had a community based dementia prevalence study representing all major ethnic groups. In recent years, dementia prevalence estimates have been derived from routinely collected health data but issues of underdiagnosis and undercoding limit their utility. Capture-recapture techniques can estimate the number of dementia cases missing from health datasets by modelling the ascertained overlaps between linked data sources. METHODS: Three routinely collected national health data sets-interRAI, Public hospital discharges, and Pharmaceuticals-were linked and all prevalent cases of dementia in NZ for the year 1 January 2021-31 December 2021 were identified. Capture-recapture analysis fitted eight loglinear models to the data, with the best fitting model used to estimate the number of prevalent cases missing from all three datasets. RESULTS: We estimated that almost half (47.8%) of dementia cases are not present in any of the three datasets. Dementia prevalence increased from 3.7% to 7.1% (95% CI 6.9%-7.4%) in the NZ 60+ population and from 4.9% to 9.2% (95% CI 8.9%-9.6%) in the NZ 65+ population when missing cases were included. Estimates of missing cases were significantly higher (p < 0.001) in Maori (49.2%), Pacific peoples (50.6%) and Asian (59.6%) compared to Europeans (46.4%). CONCLUSIONS: This study provides updated estimates of dementia prevalence in NZ and the proportion of undiagnosed dementia in NZ, highlighting the need for better access to dementia assessment and diagnosis.

Considerations for the development of guidance on dose level selection for developmental and reproductive toxicity studies.

In 2022, the European Chemicals Agency issued advice on the selection of high dose levels for developmental and reproductive toxicity (DART) studies indicating that the highest dose tested should aim to induce clear evidence of reproductive toxicity without excessive toxicity and severe suffering in parental animals. In addition, a recent publication advocated that a 10% decrease in body weight gain should be replaced with a 10% decrease in bodyweight as a criterion for dose adequacy. Experts from the European Centre for Ecotoxicology and Toxicology of Chemicals evaluated these recent developments and their potential impact on study outcomes and interpretation and identified that the advice was not aligned with OECD test guidelines or with humane endpoints guidance. Furthermore, data analysis from DART studies indicated that a 10% decrease in maternal body weight during gestation equates to a 25% decrease in body weight gain, which differs from the consensus of experts at a 2010 ILSI/HESI workshop. Dose selection should be based on a biological approach that considers a range of other factors. Excessive dose levels that cause frank toxicity and overwhelm homeostasis should be avoided as they can give rise to effects that are not relevant to human health assessments.

Child and adolescent COVID-19 vaccination coverage by educational setting, United States.

OBJECTIVES: The COVID-19 pandemic changed the setting of education for many children in the U.S. Understanding COVID-19 vaccination coverage by educational setting is important for developing targeted messages, increasing parents' confidence in COVID-19 vaccines, and protecting all children from severe effects of COVID-19 infection. STUDY DESIGN/METHODS: Using data from the Household Pulse Survey (n = 25,173) collected from December 9-19, 2022, January 4-16, 2023, and February 1-13, 2023, this study assessed factors associated with COVID-19 vaccination and reasons for non-vaccination among school-aged children 5-11 and adolescents 12-17 by educational setting. RESULTS: Among children 5-11 years, COVID-19 vaccination coverage was higher among those who received in-person instruction (53.7%) compared to those who were homeschooled (32.5%). Furthermore, among adolescents 12-17 years, COVID-19 vaccination coverage was higher among those who received in-person instruction (73.5%) or virtual/online instruction (70.1%) compared to those who were homeschooled (51.0%). Children and adolescents were more likely to be vaccinated if the parental respondent had been vaccinated compared to those who had not. Among children and adolescents who were homeschooled, main reasons for non-vaccination were concern about side effects (45.4-51.6%), lack of trust in COVID-19 vaccines (45.0-50.9%), and lack of trust in the government (32.7-39.2%). CONCLUSIONS: Children and adolescents who were home-schooled during the pandemic had lower vaccination coverage than those who attended school in person, and adolescents who were home-schooled had lower vaccination coverage than those who received virtual instruction. Based on the reasons for non-vaccination identified in this study, increasing parental confidence in vaccines, and reducing barriers to access are important for supporting COVID-19 vaccination for school-age children.

Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP). / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

High unrecognized SARS-CoV-2 exposure of newly admitted and hospitalized psychiatric patients.

BACKGROUND: Patients with pre-existing mental disorders are at higher risk for SARS-CoV-2 infection and adverse outcomes, and severe mental illness, including mood and psychosis spectrum disorders, is associated with increased mortality risk. Despite their increased risk profile, patients with severe mental illness have been understudied during the pandemic, with limited estimates of exposure in inpatient settings. OBJECTIVE: The aim of this study was to describe the SARS-CoV-2 seroprevalence and antibody titers, and pro-inflammatory cytokine concentrations of newly admitted or hospitalized psychiatric inpatients without known history of COVID-19 infection, using robust quantitative multi-antigen assessments, and compare patients' exposure to that of hospital staff. METHODS: This multi-centric, cross-sectional study compared SARS-CoV-2 seroprevalence and titers of 285 patients (University Psychiatric Centre Duffel [UPCD] N = 194; Assistance-Publique-Hopitaux de Paris [AP-HP] N = 91), and 192 hospital caregivers (UPCD N = 130; AP-HP N = 62) at two large psychiatric care facilities between January 1st and the May 30th 2021. Serum levels of SARS-CoV-2 antibodies against Spike proteins (full length), spike subunit 1 (S1), spike subunit 2 (S2), spike subunit 1 receptor binding domain (S1-RBD) and Nucleocapsid proteins were quantitatively determined using an advanced capillary Western Blot technique. To assess the robustness of the between-group seroprevalence differences, we performed sensitivity analyses with stringent cut-offs for seropositivity. We also assessed peripheral concentrations of IL-6, IL-8 and TNF-a using ELLA assays. Secondary analyses included comparisons of SARS-CoV-2 seroprevalence and titers between patient diagnostic subgroups, and between newly admitted (hospitalization ≤ 7 days) and hospitalized patients (hospitalization > 7 days) and correlations between serological and cytokines. RESULTS: Patients had a significantly higher SARS-CoV-2 seroprevalence (67.85 % [95% CI 62.20-73.02]) than hospital caregivers (27.08% [95% CI 21.29-33.77]), and had significantly higher global SARS-CoV-2 titers (F = 29.40, df = 2, p < 0.0001). Moreover, patients had a 2.51-fold (95% CI 1.95-3.20) higher SARS-CoV-2 exposure risk compared to hospital caregivers (Fisher's exact test, P < 0.0001). No difference was found in SARS-CoV-2 seroprevalence and titers between patient subgroups. Patients could be differentiated most accurately from hospital caregivers by their higher Spike protein titers (OR 136.54 [95% CI 43.08-481.98], P < 0.0001), lower S1 (OR 0.06 [95% CI 0.02-0.15], P < 0.0001) titers and higher IL-6 (OR 3.41 [95% CI 1.73-7.24], P < 0.0001) and TNF-α (OR 34.29 [95% CI 5.00-258.87], P < 0.0001) and lower titers of IL-8 (OR 0.13 [95% CI 0.05-0.30], P < 0.0001). Seropositive patients had significantly higher SARS-COV-2 antibody titers compared to seropositive hospital caregivers (F = 19.53, df = 2, P < 0.0001), while titers were not different in seronegative individuals. Pro-inflammatory cytokine concentrations were not associated with serological status. CONCLUSION: Our work demonstrated a very high unrecognized exposure to SARS-CoV-2 among newly admitted and hospitalized psychiatric inpatients, which is cause for concern in the context of highly robust evidence of adverse outcomes following COVID-19 in psychiatric patients. Attention should be directed toward monitoring and mitigating exposure to infectious agents within psychiatric hospitals.

Bisphenols as promoters of the dysregulation of cellular junction proteins of the blood-testis barrier in experimental animals: A systematic review of the literature.

Daily, people are exposed to chemicals and environmental compounds such as bisphenols (BPs). These substances are present in more than 80% of human fluids. Human exposure to BPs is associated with male reproductive health disorders. Some of the main targets of BPs are intercellular junction proteins of the blood-testis barrier (BTB) in Sertoli cells because BPs alter the expression or induce aberrant localization of these proteins. In this systematic review, we explore the effects of BP exposure on the expression of BTB junction proteins and the characteristics of in vivo studies to identify potential gaps and priorities for future research. To this end, we conducted a systematic review of articles. Thirteen studies met our inclusion criteria. In most studies, animals treated with bisphenol-A (BPA) showed decreased occludin expression at all tested doses. However, bisphenol-AF treatment did not alter occludin expression. Cx43, ZO-1, ß-catenin, nectin-3, cortactin, paladin, and claudin-11 expression also decreased in some tested doses of BP, while N-cadherin and FAK expression increased. BP treatment did not alter the expression of α and γ catenin, E-cadherin, JAM-A, and Arp 3. However, the expression of all these proteins was altered when BPA was administered to neonatal rodents in microgram doses. The results show significant heterogeneity between studies. Thus, it is necessary to perform more research to characterize the changes in BTB protein expression induced by BPs in animals to highlight future research directions that can inform the evaluation of risk of toxicity in humans.

Lipoprotein profile assessed by 1H NMR, BMI and blood pressure are associated with vascular alterations in children with familial hypercholesterolaemia.

BACKGROUND AND AIMS: Children with familial hypercholesterolaemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C) concentrations since birth, which increases the risk of cardiovascular disease in adulthood. Arterial injury and stiffness parameters, including carotid intima media thickness (cIMT), pulse wave velocity (PWV) and distensibility (DIST), can be detected early in childhood. We studied the associations between cIMT, PWV and DIST with the lipoprotein profile assessed by proton nuclear magnetic resonance (1H NMR) and with influential variables such as blood pressure (BP) or body mass index (BMI) in children with FH. METHODS AND RESULTS: In this cross-sectional study, we included 201 children (96 with FH and 105 non-FH controls). Clinical history, physical examination and standard biochemical studies were performed. FH genetic testing was performed when clinically indicated. Carotid ultrasonography and an advanced lipoprotein profile by 1H NMR were performed. Multivariate and classification methods were used. There were no differences between cIMT, PWV and DIST between FH and non-FH children. FH children presented more total LDL and large, medium and small particles. Small LDL particles, BMI and systolic BP determined the presence of pathological IMT in the FH group. LDL size, high-density lipoproteins and very low-density lipoprotein particles together with blood pressure determined the presence of pathological arterial wall elasticity. CONCLUSIONS: Alterations in lipoprotein parameters assessed by are associated with early structural and functional arterial characteristics in children with FH. BMI and BP act as boosting factors. Cardiovascular prevention should start early in children with FH, encompassing all components of a healthy lifestyle.

Melatonin and Vitamins as Protectors against the Reproductive Toxicity of Bisphenols: Which Is the Most Effective? A Systematic Review and Meta-Analysis.

Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.

Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Performance Comparison of Different Flat Plate Solar Collectors by Means of the Entropy Generation Rate Using Computational Fluid Dynamics.

In this work, a numerical analysis of three different flat plate solar collectors was conducted using their entropy generation rates. Specifically, the Computational Fluid Dynamics (CFD) technique was used to compare the detailed performance of conventional and zigzag tube geometries of flat plate solar collectors (FPCs) in terms of their entropy generation rates. The effects of fluid viscosity, heat transfer, and heat loss of the flat plate solar collectors were considered for the local and global entropy generation rate analyses. Variations on the inlet volumetric flow rate of the FPCs from 1.0 to 9.0 L/min were simulated under the average solar radiation for one year in the state of Guanajuato, Mexico. The results illustrate and discuss the temperatures, pressures, and global entropy generation rates for volumetric flow variations. The velocity, temperature, and pressure distributions and the maps of the local entropy generation rates inside the collectors are presented and analyzed for the case with a flow rate of 3.0 L/min. These results demonstrate that the zigzag geometries achieved higher outlet temperatures and greater entropy generation rates than the conventional geometry for all the volumetric flow rates considered.

[Burnout syndrome increase during COVID-19 pandemic in attending Internal Medicine physicians]. / Aumento del síndrome de burnout en los adjuntos de Medicina Interna durante la pandemia de COVID-19.

Introduction: Burnout is a psychosocial syndrome caused by stressful situations in the workplace. It affects 30% to 60% of medical professionals. The aim of this study is to carry out a comparative analysis of its frequency before and after the COVID-19 outbreak in Spanish internal medicine attending physicians. Methods: Surveys that included the Maslach Burnout Inventory were sent via email and associated social networks to physicians who were members of the Spanish Society of Internal Medicine in 2019 and 2020. Results: A non-significant increase in burnout was observed (38.0% vs. 34.4%). However, an increase in low personal fulfilment was observed (66.4% vs. 33.6%; p = 0.002), a dimension associated with the prevention of psychiatric morbidity, in addition to two others: emotional fatigue and depersonalization, which can negatively affect patient care. Conclusions: It is essential to address this syndrome individually and institutionally.

Ultrasound Doppler enthesitis shows sensitivity to change after biological therapy in spondyloarthritis and psoriatic arthritis patients.

OBJECTIVE: To explore the sensitivity to change in power Doppler (PD) enthesitis in active spondyloarthritis (SpA) and psoriatic arthritis (PsA) patients. METHOD: This was a longitudinal study in patients with SpA and PsA with active disease [patients starting or switching to biological disease-modifying anti-rheumatic drugs (bDMARDs)]. The MAdrid Sonographic Enthesitis Index (MASEI) was performed at baseline and at 3 and 6 month visits. The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. Reliability analysis among three readers was performed with ultrasound (US)-recorded videos. RESULTS: US examinations of 25 patients were included; 16 (64%) had SpA and nine (36%) PsA. The median (interquartile range, IQR) age was 49 (41-61) years, and 13 patients (52%) were female. The median (IQR) 28-joint Disease Activity Score of 3.6 (2.3-4.2), Bath Ankylosing Spondylitis Disease Activity Index of 6.7 (6.1-7.4), and C-reactive protein value of 8.2 (1.6-20) reflected moderate to high disease activity at baseline. Both MASEI and OMERACT PD enthesitis improved significantly at 3 and 6 month follow-up (p < 0.05) and showed sensitivity to change (standard error of measurement = 0.47 and 0.61, respectively). Improvement in clinical activity outcomes was significantly associated with decreases in MASEI and OMERACT PD enthesitis counts (p < 0.05). The MASEI and OMERACT PD definitions had excellent reliability (kappa = 0.918 and 0.865, respectively). CONCLUSION: PD enthesitis significantly improved at 3 and 6 month follow-up in patients undergoing bDMARD therapy. Both MASEI and OMERACT PD US enthesitis reflect response to treatment.

Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis.

OBJECTIVE: To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA). METHODS: Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment. Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W52, and every 6 months thereafter until treatment discontinuation, regardless of the reason. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum levels during the early stages and clinical outcomes (non-clinically important improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. RESULTS: Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/mL vs 7.1 (4.3-11.3) µg/mL, respectively;p = 0.007). ITL<6.7 µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3-3.9); ii) shorter drug survival (5.0 years (95% CI 3.8-6.2) vs 7.0 years (95% CI 4.8-6.9; p = 0.04), and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95% CI: 1.2-10.2). CONCLUSION: Low serum ITL at W12 were associated with long-term clinical failure in patients with axSpA, due to secondary inefficacy.

Transit along the vas deferens results in a high percentage of filiform spermatozoa with compacted chromatin in the rooster (Gallus domesticus).

The present work aimed to evaluate the chromatin compaction of rooster spermatozoa along the male reproductive tract, and to study the vas deferens lining cells, potentially involved in sperm maturation. Chromomycin A3 (CMA3) was used to determine the chromatin compaction of spermatozoa from testis (T), proximal (including epididymis, V1), intermediate (V2) and distal (V3) vas deferens, and ejaculate (E). Six Birchen Leonesa roosters were used. E was obtained in vivo by dorso-ventral massage. V1, V2 and V3 sperm were obtained post mortem (six pairs of vasa deferentia), by flushing. T was obtained by washing the testes, cut in halves. The fixed cells were stained with CMA3 and propidium iodide for flow cytometry assessment. Results showed higher (P P P.

Study protocol for a randomized controlled trial of the NEIVATECH virtual reality system to improve visual function in children with anisometropic amblyopia.

BACKGROUND: Interest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia. METHODS: We aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex. DISCUSSION: The NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children. TRIAL REGISTRATION: This protocol was registered with ClinicalTrials.gov ( NCT04819386 ) on 29 March 2021.

Maternal perinatal exposure to bisphenol S induces an estrogenic like effect in glucose homeostasis in male offspring.

Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). However, the recent studies have reported a possible association between BPS and disturbed glucose homeostasis, indicating that it may be a risk factor for type 1 and type 2 diabetes mellitus, obesity, and gestational diabetes mellitus. Nevertheless, the role of BPS in glucose metabolism remains controversial. In this study, we investigated the glucose metabolism of male Wistar rats born from dams that were BPS-exposed (groups: BPS-L (0.05 mg/kg/day), BPS-H (20 mg/kg/day)) during pregnancy and lactation. We observed that both BPS treated groups of animals presented a significant decrease in anogenital distance/weight1/3 , as compared to control animals, although no alterations in testosterone levels were observed. Furthermore, the BPS-L group presented a significant decrease in body weight from postnatal day (PND) 21 to adult stage. In addition, a significant increase in glucose tolerance, pancreatic ß-cell proliferation, the frequency of small islets, and the average ß-cell size at PND 36 was observed in this group. However, no changes in insulin serum levels and percentage of ß-cells were recorded. Furthermore, these changes were not preserved at the adult stage (PND 120). The results suggest that the administration of low doses of BPS during the perinatal period induced an estrogenic like effect, with males apparently becoming more female-like in their responses to a glucose challenge.

Urinary tract infections caused by anaerobic bacteria. Utility of anaerobic urine culture.

Urinary tract infections (UTIs) caused by anaerobic bacteria have scarcely been reported. Since anaerobic bacteria are commensals of the genitourinary tract, their presence in a urine sample adds ambiguity in making a definitive diagnosis of anaerobic UTI. It is well known that standard urine culture is the gold standard method for the detection, identification, and antimicrobial susceptibility testing of uropathogens. Nonetheless, both the difficulties in establishing them as pathogens and the scarcity of reported anaerobic UTI cases led to the discontinuation of routine urine culture under an anaerobic atmosphere (UCAA). On the other hand, it is important to emphasize that culture-independent methods, such as proteomics and molecular technics, may detect anaerobes directly on a urine sample. Anaerobes are not included in guidelines for the diagnosis and management of UTIs. At the same time, as fastidious uropathogens and antibiotic resistance become more common, accurate pathogen identification becomes even more important for effective UTI treatment. As a result, we conducted a review of the clinical context, pathogen antimicrobial susceptibility, and treatment of patients with anaerobic UTIs. Because UCAA is a contentious topic, we narrowed our search to cases with both negative standard urine culture and positive UCAA.

Environmental Impact of UV Filters. / Impacto de los filtros ultravioleta en el entorno natural.

UV filters are used daily by millions of people. Not all of these filters, however, are 100% biodegradable, and many wastewater treatments plants are ill-equipped to filter them properly. As a result, UV filters are increasingly reaching the environment. Various types have been detected in soil, continental water, oceans, and numerous organisms, including algae, corals, fish, mammals, and even land birds. In addition, some filters, benzophenone-3 and octocrylene in particular, are toxic to these organisms. Toxic effects include coral bleaching and interference with metabolic, enzymatic, and reproductive activities in practically all organisms. Preliminary data suggest that UV filters may be bioaccumulating in humans, as they have been detected in urine and breast milk. It should be noted, however, that research into the environmental impact of UV filters holds challenges and limitations.

Management of early gestations with low beta-human chorionic gonadotropin conceived by assisted reproductive technologies: performance of M4 predictive model.

OBJECTIVES: To assess the safety and performance of the M4 model for classifying as high risk or low risk for ectopic pregnancy (EP) pregnancies conceived by assisted reproductive technologies (ART) that present with low beta-human chorionic gonadotropin (ß-hCG) concentration in early gestation. METHODS: This was a prospective cohort study of 243 pregnancies conceived by ART with low ß-hCG levels (5-50 IU/L) at 4 + 0 to 4 + 2 weeks' gestation. After subsequent ß-hCG testing at 48 h, pregnancies were classified according to the M4 model into the following categories: (i) high risk, probable EP/persistent pregnancy of unknown location (PPUL), when the risk for EP was ≥ 5%; (ii) low risk, probable intrauterine pregnancy (IUP), when the risk of EP was < 5% and the likelihood of IUP was greater than that of a failed pregnancy of unknown location (FPUL); and (iii) low risk, probable FPUL, when the risk of EP was < 5% and the likelihood of a FPUL was greater than that of an IUP. The predictive performance of the M4 model for EP and its ability to discriminate between high- and low-risk pregnancies was assessed using the final pregnancy outcome at 11 to 13 weeks of gestation as reference, which was classified as EP/PPUL, FPUL or IUP. RESULTS: The sensitivity and specificity of the M4 model in detecting a high-risk pregnancy (EP/PPUL) were 60.0% (95% CI, 43.6-74.4%) and 79.8% (95% CI, 73.8-84.7%), respectively. The area under the receiver-operating-characteristics curve of the M4 model for discriminating between high-risk and low-risk (FPUL/IUI) pregnancies was 0.72 (95% CI, 0.62-0.81). The model had a positive likelihood ratio of 2.97 (95% CI, 2.03-4.36) and a negative likelihood ratio of 0.50 (95% CI, 0.33-0.76). The kappa index was 0.30 (95% CI, 0.16-0.43), indicating a low degree of agreement between the model classification and the final diagnosis. No serious adverse events related directly to the application of the M4 model were observed, although 14 pregnancies classified ultimately as high risk had been categorized initially as low risk by the M4 model. Of these, seven resolved with expectant management, five with methotrexate (MTX) and two required laparoscopic surgery (one after failure of medical treatment with MTX and one after deviation from the follow-up protocol). There were no cases of EP/PPUL with additional complications or need for blood or other blood product transfusion. Of the 243 ART pregnancies with low ß-hCG concentration in early gestation, only 47 (19.3%) had an IUP, half (24/47) of which had an early miscarriage, resulting in only 9.5% (23/243) cases having an ongoing pregnancy. CONCLUSIONS: Application of the M4 model in pregnancies conceived by ART with low ß-hCG concentration in early gestation showed limited capacity in classifying them as being at low or high risk for EP, therefore, its use in pregnancies of this type is not recommended. No serious adverse events or complications related to the use of the model were observed. These pregnancies have a low probability of ending in an IUP as well as a high rate of early miscarriage. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.