Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells.

During mitosis, chromatin condensation is accompanied by a global arrest of transcription. Recent studies suggest transcriptional reactivation upon mitotic exit occurs in temporally coordinated waves, but the underlying regulatory principles have yet to be elucidated. In particular, the contribution of sequence-specific transcription factors (TFs) remains poorly understood. Here we report that Brn2, an important regulator of neural stem cell identity, associates with condensed chromatin throughout cell division, as assessed by live-cell imaging of proliferating neural stem cells. In contrast, the neuronal fate determinant Ascl1 dissociates from mitotic chromosomes. ChIP-seq analysis reveals that Brn2 mitotic chromosome binding does not result in sequence-specific interactions prior to mitotic exit, relying mostly on electrostatic forces. Nevertheless, surveying active transcription using single-molecule RNA-FISH against immature transcripts reveals differential reactivation kinetics for key targets of Brn2 and Ascl1, with transcription onset detected in early (anaphase) versus late (early G1) phases, respectively. Moreover, by using a mitotic-specific dominant-negative approach, we show that competing with Brn2 binding during mitotic exit reduces the transcription of its target gene Nestin Our study shows an important role for differential binding of TFs to mitotic chromosomes, governed by their electrostatic properties, in defining the temporal order of transcriptional reactivation during mitosis-to-G1 transition.

A dual-function SNF2 protein drives chromatid resolution and nascent transcripts removal in mitosis.

Mitotic chromatin is largely assumed incompatible with transcription due to changes in the transcription machinery and chromosome architecture. However, the mechanisms of mitotic transcriptional inactivation and their interplay with chromosome assembly remain largely unknown. By monitoring ongoing transcription in Drosophila early embryos, we reveal that eviction of nascent mRNAs from mitotic chromatin occurs after substantial chromosome compaction and is not promoted by condensin I. Instead, we show that the timely removal of transcripts from mitotic chromatin is driven by the SNF2 helicase-like protein Lodestar (Lds), identified here as a modulator of sister chromatid cohesion defects. In addition to the eviction of nascent transcripts, we uncover that Lds cooperates with Topoisomerase 2 to ensure efficient sister chromatid resolution and mitotic fidelity. We conclude that the removal of nascent transcripts upon mitotic entry is not a passive consequence of cell cycle progression and/or chromosome compaction but occurs via dedicated mechanisms with functional parallelisms to sister chromatid resolution.

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

Food-Related Quality of Life and Its Predictors in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with dietary restrictions and food- and drink-driven daily life limitations. Food-related quality of life (FR-QoL) is still an under-addressed issue in IBD. AIM: We aimed to study determinants of FR-QoL in an IBD cohort, namely objective measures of disease activity. METHODS: A cross-sectional case-control study was conducted in a Tertiary Hospital, including adult patients with IBD (cases) and blood donors or subjects referred for colorectal polypectomies (controls). Participants answered an anonymous multimodal questionnaire including sociodemographic and clinical data, the validated FR-QoL-29, and the SIBDQ tools. Patients' disease activity was previously assessed by a physician using symptom-based scores and biomarkers (Harvey-Bradshaw index, partial Mayo score, fecal calprotectin). RESULTS: A total of 239 patients with IBD and 126 controls were included. Patients with active disease had poorer FR-QoL than patients in remission (80.0 [56.0-99.0] vs. 103.5 [81.0-129.9], p < 0.001). Still, patients with IBD had significantly lower FR-QoL compared with controls (99.0 [76.0-126.0] vs. 126.0 [102.8-143.0], p < 0.001), irrespective of disease activity. FR-QoL correlated with health-related quality of life, measured by SIBDQ (r = 0.490, p < 0.001), and was significantly impaired by patients' depressive humor (84.0 [61.0-112.0] vs. 108.0 [88.0-130.5], p < 0.001). Globally, FR-QoL compromise was mostly related to persistent worries about food, concerns about food-related symptoms, and life disruption due to eating and drinking. CONCLUSIONS: Patients with IBD showed significant FR-QoL impairment, irrespective of disease type and activity. Related psychosocial factors, such as the patient's affective status and fear around eating, warrant a need for a multidisciplinary approach to IBD, including tailored nutritional counseling.

A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

Interactions between carnivore species: limited spatiotemporal partitioning between apex predator and smaller carnivores in a Mediterranean protected area.

BACKGROUND: There is need of information on ecological interactions that keystone species such as apex predators establish in ecosystems recently recolonised. Interactions among carnivore species have the potential to influence community-level processes, with consequences for ecosystem dynamics. Although avoidance of apex predators by smaller carnivores has been reported, there is increasing evidence that the potential for competitive-to-facilitative interactions is context-dependent. In a protected area recently recolonised by the wolf Canis lupus and hosting abundant wild prey (3 ungulate species, 20-30 individuals/km2, together), we used 5-year food habit analyses and 3-year camera trapping to (i) investigate the role of mesocarnivores (4 species) in the wolf diet; (ii) test for temporal, spatial, and fine-scale spatiotemporal association between mesocarnivores and the wolf. RESULTS: Wolf diet was dominated by large herbivores (86% occurrences, N = 2201 scats), with mesocarnivores occurring in 2% scats. We collected 12,808 carnivore detections over > 19,000 camera trapping days. We found substantial (i.e., generally ≥ 0.75, 0-1 scale) temporal overlap between mesocarnivores-in particular red fox-and the wolf, with no support for negative temporal or spatial associations between mesocarnivore and wolf detection rates. All the species were nocturnal/crepuscular and results suggested a minor role of human activity in modifying interspecific spatiotemporal partitioning. CONCLUSIONS: Results suggest that the local great availability of large prey to wolves limited negative interactions towards smaller carnivores, thus reducing the potential for spatiotemporal avoidance. Our study emphasises that avoidance patterns leading to substantial spatiotemporal partitioning are not ubiquitous in carnivore guilds.

Attachment, suicidal behavior, and self-harm in childhood and adolescence: a study of a cohort of Brazilian schoolchildren.

BACKGROUND: Attachment influences the development and the formation of the self and subjectivity and, just as early adverse events, may be related to the occurrence of mental disorders, suicidal behavior, and self-harm throughout life. This study aimed to analyze the effect of mental representation of attachment in children on suicidal behavior and self-harm throughout childhood and adolescence, considering the mediating role of internalizing problems. METHODS: Based on a cohort of 500 students (mean age 8 years, SD 1.2) sampled from public schools in a Brazilian southeastern metropolis, 316 children were followed for eight years in three waves (2006, 2008, 2012). The following data from the research baseline (2005) were used: family drawing, maternal and family variables, and sociodemographic data. The mental representation of attachment (independent variable) was measured by the Family Drawing Global Scale, discriminating between secure attachment and non-secure attachment. Suicidal behavior/self-harm (dependent variable) and internalizing problems were evaluated in three research waves through CBCL and YSR (ASEBA). Descriptive analysis, calculation of frequencies and p-values of the variables of interest, as well as modeling of structural equations, were performed. RESULTS: The prevalence throughout the study was: 17.1% [CI 13.3-20.8] for suicidal ideation and 8.9% [CI 5.6 - 12.2] for self-harm; there was a recurrence at one time in 16.5% [IC 12.6 - 20.3] and in two or more moments in 4.1% [CI 2.0 - 6.3] of the sample. Female gender (p = 0.035), internalizing disorders (p < 0.01), and non-secure attachment (p = 0.035) were associated with the occurrence of suicidal behavior/self-harm. The modeling indicated that 92,2% of the total effect of attachment (p = 0.069) on suicidal behavior/self-harm was due to direct effect, the other 7,8% of the effect being mediated by internalizing problems, adjusted for the confounding variables sex, skin color/race, and social stratum. The total effect showed a positive value, which indicates an increase in suicidal behavior/self-harm when the non-secure attachment is present. The approximate OR of non-secure attachment on the total effect (direct + indirect) was 1.15, indicating that, when adjusting for confounding variables, there was a 15% increase in suicidal behavior/self-injury from non-secure attachment. CONCLUSIONS: The study supports the hypothesis that there is a relationship between disruptive attachment patterns (non-secure attachment) developed during infancy and suicidal and self-harm behavior during childhood and adolescence. These findings validate the concern about the first thousand days of childhood as a critical period for child growth and development, but also for the mental health of children and adolescents.

Impact of the SARS-CoV-2 on the journey of high-risk colon cancer patients within the scope of the Unified Health System in Brazil.

BACKGROUND: Colon cancer is an important cause of mortality related to cancer. During the COVID-19 pandemic, an important reallotment of assistance resources was necessary to tackle the crisis, directly impacting medical practice all over the globe. OBJECTIVE: To assess the impact of the Sars-Cov-2 pandemic on the time between diagnosis and the beginning of systemic treatment in patients diagnosed with high-risk colon neoplasia. METHODS: This is a retrospective study based on the analysis of medical records of patients diagnosed with colon neoplasia who required systemic treatment and were treated between March 2019 and March 2022, in a reference Oncology unit of the Brazilian Unified Health System. The study's population was divided into two groups: (I) Pre-COVID-19: diagnoses made between March 2019 and February 2020, (II) COVID-19: diagnoses made between March 2020 and March 2022. RESULTS: The sample consisted of 228 patients, 108 (47.97%) of whom were diagnosed during pre-COVID-19 and 118 (52.21%) diagnosed during the two years-period of COVID-19. Regarding the time between colonoscopy and surgery, the time between surgery and first consultation in clinical oncology, and the time between requesting and beginning of systemic treatment, a statistically significant reduction was observed during the COVID-19 period. CONCLUSION: A decrease in time between diagnosis and systemic treatment of patients with colorectal cancer during the COVID-19 pandemic was observed. Yet, even with this improvement, the time to begin treatment remains greater than the recommended by the current guidelines, regardless of the time of diagnosis (before or after the pandemic), which negatively impacts the disease outcome.

Effect of increasing doses of chitosan to grazing beef steers on the relative population and transcript abundance of Archaea and cellulolytic and amylolytic bacterias.

This paper aims to investigate the influence of increasing chitosan doses on the relative proportion and abundance of cellulotytic, amylolytic bacteria, and Archaea transcripts for grazing cattle. Five rumen cannulated crossbread steers [3.6 months and 300 ± 25 kg body LW (live weight), mean ± standard deviation] were used in a 5 × 5 latin square design, randomly assigned to treatment sequence containing chitosan added to 0, 400, 800, 1200, or 1600 mg/kg concentrate. There was the effect of chitosan on the population of Fibrobacter succinogenes, Ruminococcus albus, and Archaea. The lowest population of these bacteria of 576.60 mg/kg DM (dry matter), 1010.40 mg/kg DM, and 634.80 mg/kg DM were noted when chitosan was added at levels of 3.87, 4.16, and 3.52. Except for Ruminococcus albus, which was not affected by increasing chitosan doses, supplementation of this additive in the concentrate quadratically increased the relative abundance of Fibrobacter succinogenes and Archaea Supplemental 740 mg CHI/kg concentrate for grazing steers receiving concentrate at 150 grams/100 kg LW is recommended to promote minimal effect on the relative population and abundance of cellulolytics and amylomatics and to restrict Archaea growth.

The neurotoxic mechanism of Jack Bean Urease in insects involves the interplay between octopaminergic and dopaminergic pathways.

In the last decades, the entomotoxicity of JBU and its derived peptides became an object of study, due mainly to the ubiquitous interaction of these compounds with different species of insects and their potential as natural insecticides. In this work, we investigated the neurotoxic effects of JBU in Nauphoeta cinerea cockroaches by dissecting pharmacologically the monoaminergic pathways involved. Selective pharmacological modulators for monoaminergic pathways in in vivo and ex vivo experimental models were employed. Thus, the analysis of N. cinerea neurolocomotory behavior demonstrated that JBU (1.5 and 3 µg/g) induces a significant decrease in the exploratory activity. In these assays, pretreatment of animals with phentolamine, SCH23390 or reserpine, interfered significantly with the response of JBU. Using in vivo abductor metathoracic preparations JBU (1.5 µg/g) induced progressive neuromuscular blockade, in 120 min recordings. In this set of experiments, the previous treatment of the animals with phentolamine, SCH23390 or reserpine, completely inhibited JBU-induced neuromuscular blockade. The recordings of spontaneous compound neural action potentials in N. cinerea legs showed that JBU, only in the smallest dose, significantly decreased the number of potentials in 60 min recordings. When the animals were pretreated with phentolamine, SCH23390, or reserpine, but not with mianserin, there was a significant prevention of the JBU-inhibitory responses on the action potentials firing. Meanwhile, the treatment of the animals with mianserin did not affect JBU's inhibitory activity. The data presented in this work strongly suggest that the neurotoxic response of JBU in N. cinerea involves a cross talking between OCTOPAMIN-ergic and DOPAMIN-ergic nerve systems, but not the SEROTONIN-ergic neurotransmission. Further molecular biology studies with expression of insect receptors associated with voltage clamp techniques will help to discriminate the selectivity of JBU over the monoaminergic transmission.

Compromised Mitotic Fidelity in Human Pluripotent Stem Cells.

Human pluripotent stem cells (PSCs), which include both embryonic and induced pluripotent stem cells, are widely used in fundamental and applied biomedical research. They have been instrumental for better understanding development and cell differentiation processes, disease origin and progression and can aid in the discovery of new drugs. PSCs also hold great potential in regenerative medicine to treat or diminish the effects of certain debilitating diseases, such as degenerative disorders. However, some concerns have recently been raised over their safety for use in regenerative medicine. One of the major concerns is the fact that PSCs are prone to errors in passing the correct number of chromosomes to daughter cells, resulting in aneuploid cells. Aneuploidy, characterised by an imbalance in chromosome number, elicits the upregulation of different stress pathways that are deleterious to cell homeostasis, impair proper embryo development and potentiate cancer development. In this review, we will summarize known molecular mechanisms recently revealed to impair mitotic fidelity in human PSCs and the consequences of the decreased mitotic fidelity of these cells. We will finish with speculative views on how the physiological characteristics of PSCs can affect the mitotic machinery and how their suboptimal mitotic fidelity may be circumvented.

Induced aneuploidy in neural stem cells triggers a delayed stress response and impairs adult life span in flies.

Studying aneuploidy during organism development has strong limitations because chronic mitotic perturbations used to generate aneuploidy usually result in lethality. We developed a genetic tool to induce aneuploidy in an acute and time-controlled manner during Drosophila development. This is achieved by reversible depletion of cohesin, a key molecule controlling mitotic fidelity. Larvae challenged with aneuploidy hatch into adults with severe motor defects shortening their life span. Neural stem cells, despite being aneuploid, display a delayed stress response and continue proliferating, resulting in the rapid appearance of chromosomal instability, a complex array of karyotypes, and cellular abnormalities. Notably, when other brain-cell lineages are forced to self-renew, aneuploidy-associated stress response is significantly delayed. Protecting only the developing brain from induced aneuploidy is sufficient to rescue motor defects and adult life span, suggesting that neural tissue is the most ill-equipped to deal with developmental aneuploidy.

The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Factors Related to Smoking Cessation.

BACKGROUND: Smoking cessation is not an easy accomplishment. However, the benefits are several for those who do it, such as cardiovascular risk reduction 1 year after quitting smoking. This study aimed to verify the factors related to smoking cessation in civil servants of The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: This study had a longitudinal design using data from a prospective cohort of civil servants (ELSA-Brasil). Our variable of interest was smoking cessation. The relationship between socio-demographic characteristics, job stress, health-related variables, legislation, and smoking cessation was analyzed by Cox proportional hazard models. The analyses were stratified by gender. Second-hand smoke exposure, age, education, excessive alcohol consumption, common mental disorder, and smoking control law were the variables considered in the final model. RESULTS: Information of 2020 women and 2429 men was analyzed. Individuals without second-hand smoke exposure, with up to 49 years of age, with higher education, without excessive alcohol consumption, without common mental disorders, and who initiated smoking in 1989 or after the smoking control law had a higher risk of stopping smoking. The risks magnitudes were higher for women. CONCLUSIONS: Our study reinforces the necessity of alcohol consumption regulation, the relevance of Public Health Policies, and the need for more smoking cessation measures focused on men, on people with mental disorders, alcoholism, and older adults. Also, our results did not show significant risks regarding the psychosocial working environment.

Prevalence of children with special healthcare needs: An epidemiological survey in Brazil.

PURPOSE: We aimed to estimate the prevalence and delineate the profile of children with special healthcare needs (CSHCN) in the three municipalities of Brazil's southern and southeastern regions from 2015 to 2017. DESIGN AND METHODS: This cross-sectional study included 6853 children aged 0-11 years. Participants were selected through complex sampling in 32 primary healthcare units. The Brazilian version of the Children with Special Healthcare Needs Screener© and a questionnaire were used to identify sociodemographic and family characteristics, health status, and health services utilization. Simple and multiple logistic regression models were used to evaluate the association between family and child characteristics and prevalence (P < 0.05). RESULTS: The prevalence of CSHCN was 25.3% (95% confidence interval: 21.0-30.0). Most participants required health services or were on long-term medication for a current chronic condition; approximately 53% of CSHCN had no formally recorded diagnoses. The most frequent health problems were respiratory conditions, asthma, and allergies. Approximately 60% of the CSHCN patients underwent follow-up examinations of the specialties pneumology, pediatrics, otorhinolaryngology, speech therapy, neurology, and psychology. Children of school age, of male sex, with premature birth, with a history of recurrent hospitalization, from non-nuclear families, and from underprivileged social classes were identified as risk factors for classification as CSHCN. PRACTICE IMPLICATION: These results contribute to the unprecedented mapping of these children in healthcare networks in Brazil. CONCLUSION: The high prevalence of CSHCN in medium and large municipalities in the southern and southeastern regions was associated with the child's previous health conditions and family structure.

Development of Neurogenic Detrusor Overactivity after Thoracic Spinal Cord Injury Is Accompanied by Time-Dependent Changes in Lumbosacral Expression of Axonal Growth Regulators.

Thoracic spinal cord injury (SCI) results in urinary dysfunction, which majorly affects the quality of life of SCI patients. Abnormal sprouting of lumbosacral bladder afferents plays a crucial role in this condition. Underlying mechanisms may include changes in expression of regulators of axonal growth, including chondroitin sulphate proteoglycans (CSPGs), myelin-associated inhibitors (MAIs) and repulsive guidance molecules, known to be upregulated at the injury site post SCI. Here, we confirmed lumbosacral upregulation of the growth-associated protein GAP43 in SCI animals with bladder dysfunction, indicating the occurrence of axonal sprouting. Neurocan and Phosphacan (CSPGs), as well as Nogo-A (MAI), at the same spinal segments were upregulated 7 days post injury (dpi) but returned to baseline values 28 dpi. In turn, qPCR analysis of the mRNA levels for receptors of those repulsive molecules in dorsal root ganglia (DRG) neurons showed a time-dependent decrease in receptor expression. In vitro assays with DRG neurons from SCI rats demonstrated that exposure to high levels of NGF downregulated the expression of some, but not all, receptors for those regulators of axonal growth. The present results, therefore, show significant molecular changes at the lumbosacral cord and DRGs after thoracic lesion, likely critically involved in neuroplastic events leading to urinary impairment.

Evaluation of online content of proctological disorders in the Portuguese language.

INTRODUCTION: health literacy has an increasing relevance as the disseminated access to online contents may impact on community health. This study aimed to evaluate the suitability of the online content of benign proctological disorders. METHODS: the platforms Google© and YouTube™ were searched using the keywords hemorrhoidal disease, anal fistula, anal fissure, anal pruritus and fecal incontinence. Each page was analyzed for: interactivity, credibility, readability and content adequacy. For each video, the content, reactions and comments of the users were analyzed. Three validated scales were applied: Simple Measure of Gobbledygook (SMOG); Suitability Assessment of Materials (SAM), and quality criteria for consumer health information on treatment choices (DISCERN). RESULTS: a total of 127 webpages and 113 videos were evaluated. Forty webpages (31.50 %) included images and ten (37.04 %) had informative videos. The SMOG scale had an average value of 9.91 ± 0.94, which estimates the need for ten years of schooling for comprehension and 64 webpages (52.07 %) presented a reading level higher than the recommended B1. The mean SAM score was 39.46 ± 11.2 % and the DISCERN scale averaged 40.33 ± 5.69, corresponding to a reasonable content. Only 20 pages (15.75 %) included interactivity tools and 44 (34.64 %) contained bibliographic references. The videos posted by patients (n = 67, 59.2 %) had the highest number of views and positive comments whereas videos from health professionals (n = 21; 18.75 %) had the highest proportion of requests for additional information. DISCUSSION: online content regarding benign proctological disorders is globally inappropriate for the health literacy level of the Portuguese population, both at the written and reading levels.

ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants.

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) participant's profile regarding self-rated health: a multiple correspondence analysis.

BACKGROUND: Self-rated health (SRH) - one of the most common health indicators used to verify health conditions - can be influenced by several types of socioeconomic conditions, thereby reflecting health inequalities. This study aimed to evaluate the participant profiles regarding the association between self-rated health and social and occupational characteristics of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Cross-sectional design, including 11,305 individuals. Self-rated health was categorized as good, fair, and poor. The relationship between socio-demographic, psychosocial work environment, health-related variables, and self-rated health was analyzed by multiple correspondence analysis (stratified by age: up to 49 years old and 50 years old or more). RESULTS: For both age strata, group composition was influenced by socioeconomic conditions. Poor SRH was related to lower socioeconomic conditions, being women, black self-declared race/ethnicity, being non-married/non-united, low decision authority, low skill discretion, and obesity. CONCLUSION: To promote health, interventions should focus on reducing existing socioeconomic, race, and gender inequalities in Brazil.

Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients.

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta-CEBPB, KRAS proto-oncogene, GTPase-KRAS and suppressor of cytokine signaling 1-SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.