Search

Background: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. Objective: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. Methods: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test–6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy ( P = 0.154) or improvement in quality of life ( P = 0.783, P = 0.150), but there was greater toxicity ( P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. Conclusions: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose.

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.

Background Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. Methods This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. Results We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p Conclusions Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

We examined whether potent vascular endothelial growth factor (VEGF) blockade mediated by aflibercept, a decoy VEGF receptor (VEGFR) 1/2 moiety with stronger affinity for VEGF than bevacizumab, resulted in antileukemia effects and enhanced the efficacy of systemic chemotherapy. The efficacy of aflibercept alone and in combination with doxorubicin was evaluated in human VEGF-expressing acute myeloid leukemia (AML) cell lines and primary cells xenotransplanted into immunodeficient mice. Aflibercept reduced primary VEGF/VEGFR-positive AML colony formation growth in vitro and inhibited AML xenograft growth up to 93% in association with antiangiogenic and antiproliferative effects, hypoxia, and VEGF sequestration in multiple models. High VEGF-A expression by AML cells promoted in vivo xenograft growth and aflibercept sensitivity. Aflibercept therapy slowed disease progression in two systemic human AML xenograft models and reduced peripheral leukemia disease in a primary relapsed AML model in NOD/SCID/IL2Rγnull mice. Combination aflibercept and doxorubicin enhanced antitumor effects in local xenograft models. Sequential aflibercept followed by doxorubicin resulted in progressive anthracycline accumulation in marrow and extramedullary AML sites and resulted in 2-fold higher drug levels 24 hours after administration. In contrast, tissues (tumor, plasma, marrow) treated with chemotherapy only showed progressive drug clearance over time. Combination aflibercept and doxorubicin also resulted in vascular narrowing, decreased vessel number, and perivascular apoptosis. These data suggest that inefficient drug delivery by leukemia-associated vasculature may mediate chemoresistance and support further clinical evaluation of combination aflibercept and anthracycline therapy in refractory/relapsed AML patients. Mol Cancer Ther; 9(10); 2737–51. ©2010 AACR.

Supplementary Tables 1-3 from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models

Supplementary Methods and References from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models

Supplementary Figure Legends from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models

Supplementary Figures 7-8 from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models

Supplementary Figures 1-6 from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models

OBJECTIVE: To evaluate the relation between sexual function and depressive symptoms in puerperal women during the pandemic period. STUDY DESIGN: Prospective cohort with 125 women evaluated in the immediate postpartum period (before the pandemic - T1) in Hospital de Clinicas de Porto Alegre, 3 months (pandemic onset - T2) and 6 months (pandemic peak - T3) after birth by email and WhatsApp. The Female Sexual Function Index (FSFI) and the Edinburgh Postnatal Depression Scale (EPDS) were applied. RESULTS: Fifty puerperal women participated in the three periods of the study. The median age was 25 years. There was an inverse correlation between the ​​ FSFI and EPDS values at T2 (p < 0.001) and T3 (p < 0.001), demonstrating that the worsening sexual response was secondary to the higher prevalence of depressive symptoms in the puerperium in the COVID-19 pandemic. There was an increase in EPDS scores in the three periods: at T1, the EPDS scores ​​were 5.0 (2.0-9.0), increasing to 7.0 (4.0-14.0) at T2 and 6.5 (3.0-13.0) at T3 (p = 0.004). There was no difference between the FSFI index at the three evaluated times. CONCLUSIONS: Puerperal women are a susceptible subgroup for sexual dysfunction and depressive symptoms, which are correlated to each other and worsen in periods of stress, therefore, it is mandatory to investigate depressive symptoms in puerperal women with sexual complaints, especially during the COVID-19 pandemic.

Rationale: Recent studies of trainee evaluations of medical faculty have demonstrated subtle gender-based word choice differences. However, it is not known if this manifests in major contextual dif...

John Henryism and Superwoman Schema (SWS) are dispositional characteristics adopted to overcome the challenges of chronic psychosocial stress, and have particular salience for African American women. Both show protective and harmful effects on health and share conceptual similarities and distinctions, yet there is no empirical evidence of the potential overlap resulting in uncertainty about the unique roles they may each play concerning the health of African American women.We examined: 1) whether and to what extent John Henryism and SWS represent similar or distinct constructs relevant to the unique sociohistorical and sociopolitical position of African American women, and 2) whether the two differentially predict health outcomes.Data are from a purposive and socioeconomically diverse sample of 208 African American women in the San Francisco Bay Area. First, we conducted a progressive series of tests to systematically examine the conceptual and empirical overlap between John Henryism and SWS: correlation analysis, exploratory factor analysis (EFA), principal component analysis and k-modes cluster analysis. Next, we used multivariable regression to examine associations with psychological distress and hypertension.John Henryism and SWS were moderately correlated with one another (rs = 0.30-0.48). In both EFA and cluster analyses, John Henryism items were distinct from SWS subscale items. For SWS, feeling an obligation to present an image of strength and an obligation to help others predicted higher odds of hypertension (p 0.05); having an intense motivation to succeed predicted lower odds (p = 0.048). John Henryism did not predict hypertension. Feeling an obligation to help others and an obligation to suppress emotions predicted lower levels of psychological distress (p 0.05) whereas John Henryism predicted higher distress (p = 0.002).We discuss the implications of these findings for the measurement of culturally specific phenomena and their role in contributing to the unequal burden of ill health among African American women.

Examine the relationship between Premenstrual Syndrome (PMS) and sleep in different menstrual cycle phases.Case-control survey conducted at the Primary Care Service and Clinical Research Center at Hospital de Clínicas de Porto Alegre with women aged between 18 and 45 years old. Women filled the Brazilian version of the Premenstrual Symptoms Screen Tool (PSST) for the screening of PMS; participants with positive screening completed the Daily Record of Severity of Problems (DRSP) to confirm PMS diagnosis. We applied the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) Brazilian versions in the luteal phase (LP) and follicular phase (FP).69 women were characterized with PMS and 52 without PMS. The risk of poor sleep quality (SQ) was two times higher in women with PMS (

Introduction: Obstetric anal sphincter tear (OAST) is associated with anal incontinence. Episiotomy was proposed as a form of protection of the anal sphincter at delivery; however, several studies have shown that routine use of episiotomy does not reduce the risk of OAST. Objective: This study aims to analyse whether the reduction in the rate of episiotomy in a school hospital in Brazil was associated with an increase in the incidence of obstetric lacerations of the anal sphincter, in addition to associated factors. Methods: Observational, cross-sectional and retrospective study. We included all vaginal deliveries of single pregnancies, cephalic presentation, from 34 weeks of gestational age, performed in 2011-2012 (liberal episiotomy) and 2015-2016 (restricted episiotomy), and compared in relation to the rate of mediolateral episiotomy and OAST. Results: 4268 births were analysed (2043 in 2011-2012 and 2225 in 2015-2016). The episiotomy rate decreased from 59.4% to 44.2% (p ≤ 0.0001). In 2011-2012, there were 10 obstetric anal sphincter lacerations in 2043 births (0.48%), while in the period 2015-2016 there were 31 lacerations in 2225 births (1.39%). There was interaction when comparing the two periods in relation to the episiotomy and the occurrence of OAST (p ≤ 0.0001). Factors associated with OAST were labor induction and shoulder dystocia. Conclusion: There was an increase in the rate of lacerations of the anal sphincter with use of restrictive episiotomy. However, this increase occurred both in deliveries with and in deliveries without episiotomy.

Lichen sclerosus is a chronic and autoimmune dermatitis that develops in the anogenital region. It is related to genital alterations with repercussions in sexuality. We present a case of a 60-year-old woman who had several chronic diseases and had been diagnosed with vulvar lichen sclerosusfor 20 years, with no response to multiple treatments (topical corticosteroids, immuno-modulators). She was submitted to vulvectomy; however, it leads to worsen-ing of her condition, presenting obliterated and fibrosed clitoris, atrophic va-ginal lips, and anal and vulvar fissures. She remained with dyspareunia, de-creased sexual desire and difficulty in orgasm. She underwent sexual therapy, adjustment of antidepressant medication and made intercalated use of topical corticosteroids, topical testosterone andvaginal moisturizers, with partial improvement. From this case we can conclude that, although vulvectomy can be related to some degree of improvement in patients with lichen sclerosus, serious complications can occur.

Objective: To assess the relationship between the timing of elective cesarean section (C-section) and neonatal outcomes in a Brazilian population.Methods: Retrospective cohort study including women with single gestation submitted to elective C-section from January 2013 to December 2016. Eligibility criteria included primiparous mothers and those who previously underwent a C-section, with gestational ages of 37–39 weeks (group I) or ≥ 39 weeks (group II), undergoing antepartum elective C-section without clinical indication. Main Outcomes and Measures: adverse neonatal outcomes (NICU admission, respiratory distress, hypoglycemia, hiperbilirrubinemia, neonatal infection and meconium aspiration syndrome)Results: There were 17,184 live births at Hospital Moinhos de Vento during the study period. Of these, remaining 3,722 C-sections without medical indication in nulliparous women or in those with one previous C-section. Of these, 1,460 were in group I and 2,262 were in group II. Neonatal intensive care unit (NICU) hospitalization, respiratory distress and hyperbilirubinemia were positively associated with group I in relation to group II (p≤0.0001, p=0.001 and p=0.002, respectively). Conclusion: Elective C-section based on maternal request should not be recommended; however, for women who require elective C-section, neonatal outcomes suggest that delivery between 39 and 39+7 weeks is the optimal timing.

The increase in the number of cesarean sections (C-sections) has been reported in developed and under-developed countriesObjective: To assess the relationship between the timing of antepartum elective cesarean section (C-section) and neonatal outcomes in a Brazilian population.Design: Retrospective cohort study.Setting: large obstetric center in Porto Alegre, BrazilParticipants: women with single gestation submitted to elective C-section at a large obstetric from January 2013 to December 2016. Eligibility criteria included primiparous mothers and those who previously underwent a C-section, with gestational ages of 37–39 weeks (group I) or ≥ 39 weeks (group II), undergoing antepartum elective C-section without clinical indication. Participants under 18 years old, with fetal malformation diagnosis or dead fetus were excluded. Neonatal outcomes were compared between both gestational age groups.Exposure: elective C-section.Main Outcomes and Measures: adverse neonatal outcomes (NICU admission, Fetal trauma, respiratory distress, hypoglycemia, hiperbilirrubinemia, neonatal infection, thick meconium and meconium aspiration syndrome)Results: There were 17,184 live births at Hospital Moinhos de Vento during the study period. Of these, 13,457 were excluded (multiparous women, vaginal birth or C-section with medical indication), remaining 3,722 C-sections without medical indication in nulliparous women or in those with one previous C-section (both with no prior vaginal delivery). Of these, 1,460 were in group I and 2,262 were in group II. Most women were white (97.8%) and the median age was 33.0 (95%CI 33.1–33.5) years. Neonatal intensive care unit (NICU) hospitalization, respiratory distress and hyperbilirubinemia were positively associated with group I in relation to group II (p≤0.0001, p=0.001 and p=0.002, respectively). In logistic regression, overall higher gestational age was associated with reduction on odds of NICU admission (unadjusted OR 0.46, 95%CI 0.36-0.59), respiratory distress (unadjusted OR 0.52, 95%CI 0.33-0.78) and hyperbilirubinemia (unadjusted OR 0.35, 95%CI 0.20-0.61).Conclusion: Elective C-section based on maternal request should not be recommended; however, for women who require elective C-section, neonatal outcomes suggest that delivery between 39 and 39+7 weeks is the optimal timing.

To examine the relationship between Premenstrual Syndrome (PMS) and female sexual function (FSF) with the luteal (LP) and follicular phases (FP).We performed a cross-sectional survey using the Female Sexual Function Index (FSFI) questionnaire in the LP and FP. We used the Brazilian's version of the Premenstrual Symptoms Screen Tool (PSST) and the Daily Record of Severity of Problems (DRSP) for diagnosis of PMS.There was no difference in the FSF between groups in both cycle phases. We found an association between LP and worst scores on FSFI.PMS does not affect FSF.

This research explores a previously unidentified integration of approaches to mitigate racial inequity in teachers’ discipline decisions., Harsh exclusionary discipline predicts major negative life outcomes, including adult incarceration and unemployment. This breeds racial inequality because Black students are disproportionately at risk for this type of discipline. Can a combination of policy and psychological interventions reduce this kind of discipline and mitigate this inequality? Two preregistered experiments (Nexperiment1 = 246 teachers; Nexperiment2 = 243 teachers) used an established paradigm to systematically test integration of two and then three policy and psychological interventions to mitigate the consequences of bias (troublemaker labeling and pattern perception) on discipline (discipline severity). Results indicate that the integrated interventions can curb teachers’ troublemaker labeling and pattern prediction toward Black students who misbehave in a hypothetical paradigm. In turn, integration of the three components reduced racial inequality in teachers’ discipline decisions. This research informs scientific theory, public policy, and interventions.

BACKGROUND Half of people living with HIV (PLWH) are cigarette smokers. Stress and craving to smoke are two major predictors of smoking relapse in PLWH. Mindfulness is effective in reducing stress and controlling craving to smoke. Contingency Management (CM) improves cessation in hard-to-treat smokers. Smartphone applications (app) improve access to treatment. OBJECTIVE Guided by the Spiral Technology Action Research Model (Listen, Plan, Do, Act, Study), we sought to adapt an existing evidence-based mindfulness smoking cessation app “Craving to Quit” to PLWH. Appling user-centered participatory mixed methods of qualitative and quantitative design, this study involves “Listen” to PLWH smokers to adapt the content of the app, and “Plan” for the creation of the new app. METHODS We conducted 8 focus groups combined with a brief survey among PLWH smokers (n=59; 47.5% females; >18 years) receiving treatment at an academic clinic. Participants completed a brief survey, then were instructed to download the “Craving to Quit” app and received a demonstration explaining the app content. Focus group discussion explored previous quit attempts, thoughts concerning the app, and perception about adding CM and strategies to track adherence to HIV treatment in the app. Participants were also asked to practice 3 mindfulness exercises and watch 3 videos from the app presented on a big screen in the conference room to discuss their experience, reaction, and concerns. Sessions were audio-taped, transcribed verbatim, and analyzed thematically using NVivo. RESULTS Participants were mostly non-Hispanic black (67.8%), heterosexual (79.7%), on Medicaid (61.0%), heavy alcohol users (30.5%), and depressed (44.1%). In focus group discussion, participants reported multiple drug use (alcohol, marijuana) and being surrounded by smokers as tremendous challenges to quitting, and that nicotine replacement treatment was not helpful. Participants considered mindfulness (RAIN, body scan, loving kindness) helpful in reducing stress, and videos (habit loop, costs benefits, tripping on thoughts) as effective in motivating quit attempts. Participants felt it is necessary to make the app available for free, add information about smoking medications and the effects of smoking on HIV treatment. Participants were supportive of adding CM and considered receiving $20-$50 weekly cash incentives helpful in supporting quit attempts. Participants thought that adding strategies to track adherence to ART helpful, but a few were concerned about confidentiality in case they lost their phone. CONCLUSIONS Findings from this formative qualitative research underscore the need for comprehensive approaches to smoking cessation in PLWH that integrate mindfulness, short-term CM, and strategies to improve adherence to HIV treatment. Further clinical research is needed to test the feasibility and acceptability of comprehensive interventions to address smoking as a key driver of morbidity and mortality in PLWH. CLINICALTRIAL N/A

Effective diffusion of educational innovations is essential for evidence-based practices to have broad impacts on student learning. One of the barriers to such diffusion is the large inertia associated with changing one’s teaching practices. Educational disruptions, such as COVID-19, may lower this barrier by making business-as-usual no longer feasible. Here, we reflect on the ways in which an online community, designed to promote diffusion of educational innovation, supported Advanced Placement (AP) Chemistry teachers in the rapid transition to online instruction necessitated by the pandemic. The lessons learned from supporting teachers as they responded to the pandemic may provide insights into how to better promote and support adoption of reformed teaching strategies.

Introduction: Adolescence and pregnancy increase nutritional needs. Pregnant adolescents have higher energy requirements to maintain maternal health and ensure adequate fetal growth and development. Aim: Identify patterns of diet consumption among Pregnant adolescents. Methods: We carried out a cross-sectional study between November 2014 and July 2016 among teenage mothers. Food intake was analyzed using asemiquantitative food frequency questionnaire (FFQ). We identified the food patterns as a posteriori using cluster analysis. Results: 294 adolescents participated in the study. The mean age was 17.83 ± 1.29 years. Sixty-five percent of participants self-declared as Caucasian and 83.3% were primiparous. Pregestational BMI was 23.71 ± 5.04 kg/m2 , and 42.9% of the sample showed excessive weight gain during pregnancy. Two food patterns were identified, labeled as Traditional Diet and Junk Food. The Traditional Diet was characterized by a higher intake of protein (p = 0.03), magnesium, folate, iron (p ≤ 0.0001), and potassium (p = 0.005). In comparison, the Junk Food pattern had a higher intake of total fat (p ≤ 0.0001). We did not find significant associations between eating patterns and sociodemographic variables or pre-gestational BMI. Conclusion: The study confirmed that pregnant teenagers tend to adopt the food pattern Junk Food, regardless of sociodemographic aspects.

Objective: To evaluate the relationship between pregestational obesity and maternal and fetal outcomes in pregnant adolescents. Methods: Cross-sectional study conducted among puerperal teenagers of a university hospital in Southern Brazil. Structured questionnaires on sociodemographic and obstetric data were applied. Results: We evaluated 500 puerperal adolescents with a mean age of 17.77 ± 1.36. Of these, 31.2% (n=156) had pregestational weight excess. Pregestational weight excess was significantly associated with gestational hypertension (p=0.037) and diabetes (p=0.045), cesarean delivery (p=0.040), and lower adherence to prenatal care (24.7%, p=0.007). Mothers with pregestational weight excess also gained more weight than recommended during pregnancy and had babies with a higher weight (p=0.02) and length (p=0.018). Conclusion: Pregestational weight excess in adolescence is related to unfavorable maternal and fetal outcomes. We emphasize the importance of a closer look at this population still in development to identify nutritional disbalances and promote adequate weight gain.

Background Group B Streptococcus (GBS) is one of the most important causative agents of neonatal sepsis. As administration of prophylactic antibiotics during labor can prevent GBS infection, routine screening for this bacterium in prenatal care before the onset of labor is recommended. However, many women present in labor without having undergone such testing during antenatal care, and the turnaround time of detection methods is insufficient for results to be obtained before delivery. Methods Vaginal and anorectal specimens were collected from 270 pregnant women. Each sample was tested by Xpert GBS, qPCR, and culture for GBS detection. Results The overall prevalence of maternal GBS colonization was 30.7% according to Xpert GBS, 51.1% according to qPCR, and 14.3% according to cultures. Considering the qPCR method as the reference, the Xpert GBS had a sensitivity of 53% and specificity of 93%. Positive Xpert GBS results were correlated to marital status (married or cohabitating) and with prematurity as a cause of neonatal hospitalization. Positive cultures were related with ischemic–hypoxic encephalopathy requiring therapeutic hypothermia. Conclusions Combined enrichment/qPCR and the Xpert GBS rapid test found a high prevalence of GBS colonization. The Xpert GBS technique gives faster results and could be useful for evaluating mothers who present without antenatal GBS screening results and are at risk of preterm labor, thus allowing institution of prophylactic antibiotic therapy.

mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear whether LTP and homeostatic plasticity use a common route to mTORC1-dependent signaling or whether each engage mTORC1 through distinct pathways. Here, we report a unique signaling pathway that specifically couples homeostatic signaling to postsynaptic mTORC1 after loss of excitatory synaptic input. We find that AMPAR blockade, but not LTP-inducing stimulation, induces phospholipase D (PLD)-dependent synthesis of the lipid second messenger phosphatidic acid (PA) in rat cultured hippocampal neurons of either sex. Pharmacological blockade of PLD1/2 or pharmacogenetic disruption of PA interactions with mTOR eliminates mTORC1 signaling and presynaptic compensation driven by AMPAR blockade, but does not alter mTORC1 activation or functional changes during chemical LTP (cLTP). Overexpression of PLD1, but not PLD2, recapitulates both functional synaptic changes as well as signature cellular adaptations associated with homeostatic plasticity. Finally, transient application of exogenous PA is sufficient to drive rapid presynaptic compensation requiring mTORC1-dependent translation of BDNF in the postsynaptic compartment. These results thus define a unique homeostatic signaling pathway coupling mTORC1 activation to changes in excitatory synaptic drive. Our results further imply that more than one canonical mTORC1 activation pathway may be relevant for the design of novel therapeutic approaches against neurodevelopmental disorders associated with mTORC1 dysregulation.SIGNIFICANCE STATEMENTHomeostatic and Hebbian forms of synaptic plasticity are thought to play complementary roles in regulating neural circuit function, but we know little about how these forms of plasticity are distinguished at the single neuron level. Here, we define a signaling pathway that uniquely links mTORC1 with homeostatic signaling in neurons.

Complement deficiencies are uncommon types of primary immunodeficiency. Necrotizing fasciitis is a rare complication in pregnancy characterized by soft tissue invasion and necrosis of the subcutaneous and other adjacent tissues, leading to high mortality rates. We report a case of a 29-year-old pregnant woman with functional deficiency of the C4 complement component and short uterine cervix. Admitted at the hospital with preterm labor, she received multiple doses of immunoglobulin. After 8 weeks, she had a premature membrane rupture, and due to pelvic presentation she had a cesarean. The patient presented multiple obstetric complications, such as operative wound infection, endometritis, sepsis, necrotizing fasciitis and pelvic septic thrombophlebitis. She underwent multiple antimicrobial schemes, a hysterectomy and 4 extensive debridements of the abdominal wall because of significant necrosis. She stayed at the hospital for 101 days (32 of those in ICU in immediate postpartum). 41 days after cesarean, patient was discharged in good conditions. Our case emphasizes individual handling and high multiple doses of immunoglobulin for favorable outcome of the case.

BackgroundMutations in gene regulatory networks often lead to genetic divergence without impacting gene expression or developmental patterning. The rules governing this process of developmental systems drift, including the variable impact of selective constraints on different nodes in a gene regulatory network, remain poorly delineated.ResultsHere we examine developmental systems drift within the cardiopharyngeal gene regulatory networks of two tunicate species,Corella inflataandCiona robusta.Cross-species analysis of regulatory elements suggests thattrans-regulatory architecture is largely conserved between these highly divergent species. In contrast,cis-regulatory elements within this network exhibit distinct levels of conservation. In particular, while most of the regulatory elements we analyzed showed extensive rearrangements of functional binding sites, the enhancer for the cardiopharyngeal transcription factorFoxFis remarkably well-conserved. Even minor alterations in spacing between binding sites lead to loss ofFoxFenhancer function, suggesting that boundtrans-factors form position-dependent complexes.ConclusionsOur findings reveal heterogeneous levels of divergence across cardiopharyngealcis-regulatory elements. These distinct levels of divergence presumably reflect constraints that are not clearly associated with gene function or position within the regulatory network. Thus, levels ofcis-regulatory divergence or drift appear to be governed by distinct structural constraints that will be difficult to predict based on network architecture.

Background: Group B Streptococcus (GBS) is one of the most important causative agents of neonatal sepsis. As administration of prophylactic antibiotics during labor can prevent GBS infection, routine screening for this bacterium in prenatal care before the onset of labor is recommended. However, many women present in labor without having undergone such testing during antenatal care, and the turnaround time of detection methods is insufficient for results to be obtained before delivery. Methods: Vaginal and anorectal specimens were collected from 270 pregnant women. Each sample was tested by Xpert GBS, qPCR, and culture for GBS detection. Results: The overall prevalence of maternal GBS colonization was 30.7% according to Xpert GBS, 51.1% according to qPCR, and 14.3% according to cultures. Considering the qPCR method as the reference, the Xpert GBS had a sensitivity of 53% and specificity of 93%. Positive Xpert GBS results were correlated to marital status (married or cohabitating) and with prematurity as a cause of neonatal hospitalization. Positive cultures were related with ischemic–hypoxic encephalopathy requiring therapeutic hypothermia. Conclusions: Combined enrichment/qPCR and the Xpert GBS rapid test found a high prevalence of GBS colonization. The Xpert GBS technique gives faster results and could be useful for evaluating mothers who present without antenatal GBS screening results and are at risk of preterm labor, thus allowing institution of prophylactic antibiotic therapy. Keywords: Group B Streptococcus ; Streptococcus agalactiae ; Xpert GBS; real-time polymerase chain reaction; antenatal care

Objective To describe a population of pregnant women diagnosed with toxoplasmosis and their respective newborns, describing the hospital protocol for treatment and follow-up. Methods Retrospective cohort of pregnant women with acute toxoplasmosis infection and risk of transplacental transmission who were sent to the Fetal Medicine Group of Hospital de Clínicas de Porto Alegre (HCPA) between - January 1, 2006 and December 31, 2016. All patients with confirmed disease were included. The diagnostic protocol and treatment were applied; a polymerase chain reaction (PCR) analysis of the amniotic fluid was used to diagnose toxoplasmosis and determine the treatment. The newborns were followed up at the pediatric outpatient clinic specializing in congenital infection. The patients who were not followed up or were not born in the HCPA were excluded. Results A total of 65 patients were confirmed to have gestational toxoplasmosis; 40 performed amniocentesis, and 6 (15%) were identified as having positive PCR in the amniotic fluid. In five of those cases, this result associated with the gestational age defined the triple therapy during pregnancy, and in one case, it defined the monotherapy (advanced gestational age). A total of 4 of these newborns were treated from birth with triple therapy for 10months, 1 was not treated (due to maternal refusal), and 1 progressed to death within the first 54 hours of life due to complications of congenital toxoplasmosis. Of the 34 remaining cases with a negative PCR, 33 were treated with monotherapy and 1 was treated with triple therapy (ultrasound findings); of these children, 9 (26.5%) presented negative immunoglobulin G (IgG), 24 (70.6%) presented positive IgG (but none presented positive immunoglobulin M [IgM]), and 1 (2,9%) presented alterations compatible with congenital disease and started treatment with the triple therapy soon after birth. Out of the total sample of 60 patients, among the 25 who did not perform amniotic fluid PCR, 5 were treated with triple therapy (ultrasound findings/prior treatment) and 20 patients were submitted to monotherapy; only two newborns underwent treatment for congenital toxoplasmosis. Among the 65 cases of gestational toxoplasmosis, 6 (9,2%) children had a diagnosis of congenital toxoplasmosis, and 2 patients with triple therapy felt severe adverse effects of the medications. Conclusions The present study suggests that research on PCR screening of the amniotic fluid may be useful to identify patients with a higher potential for fetal complications, who may benefit from the poly-antimicrobial treatment. Patients with negative PCR results must continue to prevent fetal infection with monotherapy, without risk of fetal or maternal impairment. Resumo Objetivo Descrever uma população de pacientes diagnosticadas com toxoplasmose na gestação e seus respectivos recém-nascidos, relatando o protocolo do hospital durante o tratamento e seguimento. Métodos Coorte retrospectiva de gestantes com infecção aguda por toxoplasmose e risco de transmissão transplacentária, encaminhadas para acompanhamento pelo Grupo deMedicina Fetal doHospital de Clínicas de Porto Alegre (HCPA) entre 1o de janeiro de 2006 e 31 de dezembro de 2016. Todas as pacientes comdoença confirmada foram incluídas. O protocolo de diagnóstico e tratamento foi aplicado; uma análise da reação em cadeia da polimerase (RCP) no líquido amniótico foi utilizada para diagnosticar a toxoplasmose e determinar o tratamento. Os recém-nascidos foram acompanhados no ambulatório de pediatria especializadoeminfecções congênitas. Pacientes que não foramseguidas ou cujo parto não foi feito no hospital foram excluídas. Resultados A toxoplasmose gestacional foi confirmada em 65 pacientes; 40 realizaram amniocentese, e 6 (15%) foram identificadas com RCP positiva no líquido amniótico. Este resultado associado à idade gestacional definiu a terapia tríplice durante a gestação em 5 casos, e a monoterapia em 1 caso (por idade gestacional avançada). Quatro destas crianças foram tratadas desde o nascimento com terapia tríplice por 12 meses, 1 não foi tratada (por recusa materna), e 1 evoluiu com óbito dentro das primeiras 54 horas de vida devido a complicações da toxoplasmose congênita. Dos 34 casos remanescentes com RCP negativa, 33 foram tratados com monoterapia, e 1 foi tratado com terapia tríplice (por achados ultrassonográficos); destes recém-nascidos, 9 (26,5%) tiveram imunoglobulina G (IgG) negativa, 24 (70,6%) tiveram IgG positiva, mas nenhum apresentou imunoglobulina M (IgM) positiva, e 1 (2,9%) apresentou alterações compatíveis comdoença congênita e iniciou a terapia tríplice logo após o nascimento. Entre as 25 pacientes que não fizeram RCP no líquido amniótico, 5 foram tratadas com terapia tríplice (por achados ultrassonográficos/ tratamento prévio) e 20 receberam monoterapia; somente 2 recém-nascidos receberam tratamento para toxoplasmose congênita. Entre os 65 casos de toxoplasmose gestacional, 6 (9,2%) recém-nascidos tiveram o diagnóstico de toxoplasmose congênita. Um total de 2 pacientes submetidas à terapia tríplice apresentaram efeitos adversos severos das medicações utilizadas. Conclusão Este estudo sugere que a triagem da RCP para toxoplasmose do líquido amniótico pode ser útil no rastreamento de pacientes com maior potencial para complicações fetais, que podem se beneficiar do tratamento poli antimicrobiano. Pacientes com RCP negativa devem continuar a prevenir a infecção fetal com monoterapia, sem risco de comprometimento fetal ou materno.

Introduction: Pregnancy is a unique situation and involves changes in sexuality. The aim is to evaluate sexual function and satisfaction in pregnant women under prenatal care provided by the public health system. Method: Cross-sectional study with pregnant women receiving ambulatory care in the public health system in the Southern region of Brazil conducted between November 2014 and September 2015. Results: 283 pregnant women were studied. The mean age was 27.7 ± 6.3 years; 64% were white and 31.1% were nulliparous. In the total sample, 8.50% were in the first trimester of pregnancy, 37.4% were in the second trimester, and 54.1% were in the third trimester. The rate of global sexual dysfunction (score < 26 points) was 55.5%, following the application of The Female Sexual Function Index (FSFI). Sexual dysfunction was significantly more prevalent in the third trimester (62%) compared to the first (33.3%) and second (50.9%) trimesters (p = 0.015). There was a significant difference in all domains, except in the desired domain, according to the trimester. Pregnant women in the third trimester showed significantly lower scores compared to those in the first trimester in the domains with significance. Conclusion: The prevalence of sexual dysfunction among pregnant women in the public system was high. Knowing that more than 50% of the pregnant women presented sexual dysfunction, it is essential to approach sexuality during prenatal care involving the couple.

Background: Bernard-Soulier Syndrome (BSS) is a rare autosomal recessively inherited bleeding disorder of platelet function. Pregnancy in BSS is associated with a high risk of serious bleeding for both mother and neonate, and current data show no consensual approach. Aim: To report the case of a pregnant woman with BSS, in order to provide more information about management of these cases. Case Presentation: This case report describes a successful pregnancy outcome in a woman with BSS who was closely monitored throughout pregnancy and postpartum period, and had a judiciously planned birth. Conclusion: Management of BSS during pregnancy is still unclear. However, it is important to strictly control platelet counts and plan the birth in advance.