AAV-Mediated Expression of miR-17 Enhances Neurite and Axon Regeneration In Vitro.

Neurodegenerative disorders, including traumatic injuries to the central nervous system (CNS) and neurodegenerative diseases, are characterized by early axonal damage, which does not regenerate in the adult mammalian CNS, leading to permanent neurological deficits. One of the primary causes of the loss of regenerative ability is thought to be a developmental decline in neurons' intrinsic capability for axon growth. Different molecules are involved in the developmental loss of the ability for axon regeneration, including many transcription factors. However, the function of microRNAs (miRNAs), which are also modulators of gene expression, in axon re-growth is still unclear. Among the various miRNAs recently identified with roles in the CNS, miR-17, which is highly expressed during early development, emerges as a promising target to promote axon regeneration. Here, we used adeno-associated viral (AAV) vectors to overexpress miR-17 (AAV.miR-17) in primary cortical neurons and evaluate its effects on neurite and axon regeneration in vitro. Although AAV.miR-17 had no significant effect on neurite outgrowth and arborization, it significantly enhances neurite regeneration after scratch lesion and axon regeneration after axotomy of neurons cultured in microfluidic chambers. Target prediction and functional annotation analyses suggest that miR-17 regulates gene expression associated with autophagy and cell metabolism. Our findings suggest that miR-17 promotes regenerative response and thus could mitigate neurodegenerative effects.

Adesão de pacientes idosos polimedicados: como eles se comportam frente à tomada de medicamentos? / Adherence of polymedicated older adults: how do they behave regarding medication intake?

Resumo Objetivo Analisar a associação entre a adesão à terapia medicamentosa com nível de entendimento e complexidade da prescrição, bem como avaliar a concordância entre dois questionários de adesão aplicados a pessoas idosas polimedicadas. Método Trata-se de estudo transversal, com pessoas idosas atendidas no ambulatório de geriatria de um hospital universitário do Rio de Janeiro, Brasil. Nesses pacientes foi avaliado a adesão à terapia medicamentosa (Brief Medication Questionarie - BMQ e Instrumento de Avaliação da Atitude frente à tomada de remédios - IAAFTR), o conhecimento sobre os medicamentos prescritos e a complexidade da farmacoterapia. Para análise estatística foram utilizados testes qui-quadrado e exato de Fisher sendo considerado o nível de significância de p-valor ≤0,05. A concordância entre os dois métodos de adesão foi avaliada pelo índice Kappa. Resultados Dos 49 idosos entrevistados, 75,5% eram mulheres, hipertensão arterial (82%) e diabetes (37%) as doenças mais prevalentes. Observou-se pelos testes BMQ e IAAFTR que 35% e 45% dos pacientes, respectivamente, eram aderentes a terapia medicamentosa. Não houve concordância de resultado entre os métodos de adesão. Grande parte dos pacientes apresentou bom nível de informação sobre seus medicamentos, porém, a maioria deles foi considerada não aderente. Não foi observado associação estatisticamente significativa entre a complexidade da prescrição frente a adesão e ao nível de informação sobre medicamentos. Conclusão A adesão a terapia medicamentosa é um processo multifatorial e as ferramentas de avaliação de adesão e de outros fatores que a influência deve ser criteriosamente escolhida de acordo com a população de estudo, pois em nosso trabalho elas apresentaram respostas diferenciadas.

Abstract Objective To analyze the association between medication therapy adherence and level of understanding and complexity of the prescription, as well as to assess the agreement between two adherence questionnaires administered to polymedicated older adults. Method This is a cross-sectional study involving older adults attending the geriatrics outpatient clinic at a university hospital in Rio de Janeiro, Brazil. In these patients, medication therapy adherence (assessed using the Brief Medication Questionnaire - BMQ and the Instrument for Assessing Attitudes Toward Medication Taking - IAAFTR), knowledge about prescribed medications, and pharmacotherapy complexity were evaluated. Statistical analysis was conducted using Chi-square tests and Fisher's Exact test, with a significance level set at p-value ≤ 0.05. The agreement between the two adherence methods was assessed using the Kappa index. Results Of the 49 interviewed older adults, 75.5% were women, with arterial hypertension (82%) and diabetes (37%) being the most prevalent conditions. According to the BMQ and IAAFTR tests, 35% and 45% of patients, respectively, were adherent to medication therapy. There was no agreement in the results between the adherence methods. A large proportion of patients exhibited a good level of information about their medications; however, the majority of them were considered non-adherent. No statistically significant association was observed between prescription complexity and adherence, nor between the level of medication information and adherence. Conclusion Medication therapy adherence is a multifactorial process, and the assessment tools for adherence and other influencing factors should be carefully chosen according to the study population, as they exhibited different responses in our work.

Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment.

Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, - 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization.

Efficacy of an Educational Intervention for Sodium Restriction in Patients with Hypertension: A Randomized Controlled Trial.

There is sound evidence showing the efficacy of non-pharmacological interventions in lowering blood pressure (BP); however, adherence is usually poor. Interventions to induce behavioral changes aim to improve the ability to read labels, choose foods, and eat low-sodium meals, reinforcing adherence to sodium restriction. In this randomized parallel-controlled trial, we assessed the effectiveness of an educational intervention using the Dietary Sodium Restriction Questionnaire (DSRQ) scores. A follow-up period of 6 months was conducted. Participants were randomized into (1) an educational intervention provided by a registered dietitian on individual visits and dietary planning; (2) a control group with the usual care and dietary recommendations. Patients underwent 24-h ambulatory BP monitoring, 12-h fasting blood tests, spot urine collection, and assessment using DSRQ. We randomized 120 participants (67.5% women and 68.3% Caucasians), and 25 participants were lost to follow-up. The 24-h sodium urinary excretion changed in the control (Δ -1610 mg/day; 95% confidence interval [CI] -1800 to -1410) and intervention groups (Δ -1670 mg/day; 95% CI -1800 to -1450) over time. There was no significant difference in the 24-h estimated sodium between groups. In hypertensive patients, DSRQ-based educational intervention is effective for improving the ability to detect and overcome obstacles to a low-sodium restriction diet but is as effective as dietary recommendations for lowering sodium.

Body image of women during breastfeeding: analysis supported by nursing theory.

OBJECTIVE: To describe and interpret a woman's perception of her body image during the breastfeeding process. METHOD: Descriptive qualitative study conducted at a university hospital in the Southeast region, Brazil. Forty-three puerperal women who were breastfeeding were interviewed. The interviews were submitted to lexical analysis using the IRAMUTEQ software and interpreted based on the Interactive Theory of Breastfeeding. RESULTS: Women report dissatisfaction with changes in body image during breastfeeding. But they also value and want to keep breastfeeding because of the benefits for the child. Finally, several women express the desire to perform plastic surgery in the future because of these body changes. CONCLUSION: The woman's perception of her body image as satisfactory/unsatisfactory indicates that body changes cover the breastfeeding process with feelings of ambiguity.Body changes are perceived by women in a personal, subjective and complex way.

Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity.

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.

Prevalence of vitamin A deficiency in women of childbearing age in Brazil: a systematic review and meta-analysis.

Vitamin A is an essential micronutrient, especially during pregnancy. We aimed to assess the prevalence of vitamin A deficiency in Brazilian women of childbearing age. We conducted a systematic review with meta-analysis of studies that assessed vitamin A deficiency in women of childbearing age following the registered protocol (CRD42020171856). Independent peer researchers selected the studies retrieved from MEDLINE, Embase, Scopus and other sources. Data from the eligible studies were extracted in pairs and assessed for methodological quality. The prevalence of vitamin A deficiency (< 0·70 µmol/l or <0·20 µg/dl) and 95 % CI was combined by meta-analysis, and heterogeneity was estimated by I2. Out of 3610 screened records, thirty-two studies were included, which assessed 12 577 women from 1965 to 2017, mostly in maternity hospitals. Main limitations of the studies were in sample frame (30/32) and sampling method (29/32). Deficiency occurred in 13 % (95 % CI 9·4, 17·2 %; I² = 97 %) of all women and was higher in pregnant women (16·1 %; 95 % CI 5·6, 30·6 %; I² = 98 %) than non-pregnant women (12·3 %; 95 % CI 8·4, 16·8 %; I² = 96 %). The prevalence increased according to the decade, from 9·5 % (95 % CI 1·9­21·6 %; I² = 98 %) up to 1990, 10·8 % (95 % CI 7·9, 14·2 %; I² = 86 %) in the 2000s and 17·8 % (95 % CI 8·7, 29·0 %; I² = 98 %) in the 2010s. Over 10 % of Brazilian women in childbearing age were deficient in vitamin A. Higher prevalence was observed in pregnant women, and deficiency seemed to be increasing over the decades. Low representativeness of the studies, mainly based on convenience sampling that included pregnant, postpartum, lactating and non-pregnant women, as well as high heterogeneity, limits the findings.

Body image of women during breastfeeding: analysis supported by nursing theory / Imagen corporal de la mujer durante la lactancia: análisis apoyado en la teoría de enfermería / Imagem corporal da mulher durante amamentação: análise suportada em teoria de enfermagem

ABSTRACT Objective: To describe and interpret a woman's perception of her body image during the breastfeeding process. Method: Descriptive qualitative study conducted at a university hospital in the Southeast region, Brazil. Forty-three puerperal women who were breastfeeding were interviewed. The interviews were submitted to lexical analysis using the IRAMUTEQ software and interpreted based on the Interactive Theory of Breastfeeding. Results: Women report dissatisfaction with changes in body image during breastfeeding. But they also value and want to keep breastfeeding because of the benefits for the child. Finally, several women express the desire to perform plastic surgery in the future because of these body changes. Conclusion: The woman's perception of her body image as satisfactory/unsatisfactory indicates that body changes cover the breastfeeding process with feelings of ambiguity.Body changes are perceived by women in a personal, subjective and complex way.

RESUMEN Objetivo: Describir e interpretar la percepción de la mujer sobre su imagen corporal durante el proceso de lactancia. Método: Estudio cualitativo descriptivo realizado en un hospital universitario de la región Sudeste de Brasil. Se entrevistaron 43 puérperas que estaban amamantando. Las entrevistas fueron sometidas a análisis léxico utilizando el software IRAMUTEQ e interpretada con base en la Teoría Interactiva de la Lactancia Materna. Resultados: Las mujeres relatan insatisfacción con los cambios en la imagen corporal durante la lactancia. Pero también valoran y quieren seguir amamantando por los beneficios para el niño. Y varios expresan el deseo de realizarse una cirugía plástica en el futuro ante estos cambios corporales. Conclusión: La percepción de la mujer sobre su imagen corporal como satisfactoria/insatisfactoria indica que los cambios corporales envuelven el proceso de lactancia con sentimientos de ambigüedad. Los cambios corporales son percibidos por las mujeres de manera personal, subjetiva y compleja.

RESUMO Objetivo: Descrever e interpretar a percepção da mulher acerca da sua imagem corporal durante o processo de amamentar. Método: Estudo descritivo qualitativo realizado em hospital universitário da região sudeste, Brasil. Foram entrevistadas 43 puérperas que estavam amamentando.As entrevistas foram submetidas à análise lexical com o softwareIRAMUTEQ e interpretadas baseadas na Teoria Interativa de Amamentação. Resultados: As mulheres referem insatisfação com as mudanças na imagem corporal durante a amamentação. Mas também, valorizam e desejam manter a amamentação devido as vantagens para o filho. E várias expressam o desejo de realizar cirurgia plástica futuramente frente a essas mudanças corporais. Conclusão: A percepção da mulher sobre suaimagem corporal como satisfatória/ insatisfatória aponta que as mudanças corporais revestem o processo de amamentação de sentimentos de ambiguidade.As mudanças corporais são percebidas pelas mulheres de forma pessoal, subjetiva e complexa.

Csk αC Helix: A Computational Analysis of an Essential Region for Conformational Transitions.

Conformational changes are an essential feature for the function of some dynamic proteins. Understanding the mechanism of such motions may allow us to identify important properties, which may be directly related to the regulatory function of a protein. Also, this knowledge may be employed for a rational design of drugs that can shift the balance between active and inactive conformations, as well as affect the kinetics of the activation process. Here, the conformational changes in carboxyl-terminal Src kinase, the major catalytic repressor to the Src family of kinases, was investigated, and it was proposed as a functionally related hypothesis. A Cα Structure-Based Model (Cα-SBM) was applied to provide a description of the overall conformational landscape and further analysis complemented by detailed molecular dynamics simulations. As a first approach to Cα-SBM simulations, reversible transitions between active (closed) and inactive (open) forms were modeled as fluctuations between these two energetic basins. It was found that, in addition to the interdomain Carboxyl-terminal SRC Kinase (Csk) correlated motions, a conformational change in the αC helix is required for a complete conformational transition. The result reveals this as an important region of transition control and domain coordination. Restrictions in the αC helix region of the Csk protein were performed, and the analyses showed a direct correlation with the global conformational changes, with this location being propitious for future studies of ligands. Also, the Src Homology 3 (SH3) and SH3 plus Src Homology 2 (SH2) domains were excluded for a direct comparison with experimental results previously published. Simulations where the SH3 was deleted presented a reduction of the transitions during the simulations, while the SH3-SH2 deletion vanishes the Csk transitions, corroborating the experimental results mentioned and linking the conformational changes with the catalytic functionality of Csk. The study was complemented by the introduction of a known kinase inhibitor close to the Csk αC helix region where its consequences for the kinetic behavior and domain displacement of Csk were verified through detailed molecular dynamics. The findings describe the mechanisms involving the Csk αC helix for the transitions and also support the dynamic correlation between SH3 and SH2 domains against the Csk lobes and how local energetic restrictions or interactions in the Csk αC helix can play an important role for long-range motions. The results also allow speculation if the Csk activity is restricted to one specific conformation or a consequence of a state transition, this point being a target for future studies. However, the αC helix is revealed as a potential region for rational drug design.

Cervicovaginal loads of Gardnerella spp. are increased in immunocompetent women with persistent high-risk human papillomavirus infection.

Introduction. Two high-oncogenic-risk human papilomavirus (hrHPV) genotypes - HPV16 and HPV18 - cause most of the cases of cervical cancer worldwide. Bacterial vaginosis is associated with increased hrHPV persistence, although the mechanism underlying this association remains unclear. Gardnerella spp. are detected in nearly all cases of bacterial vaginosis and are the major source of cervicovaginal sialidases. The NanH1 gene is present in virtually all Gardnerella sialidase-producing strains and has been proposed as a potential marker for persistent hrHPV infection.Hypothesis. Gardnerella spp. load and the NanH1 gene are associated with hrHPV persistence.Aim. To compare the cervicovaginal load of Gardnerella spp. and the frequency of the NanH1 gene between women with persistent HPV16 and/or HPV18 infection and those who cleared the infection after 11 months.Methodology. Among a population of 1638 HPV screened, we detected 104 with positive HPV16 and/or HPV18 results. Samples were obtained at two time points (baseline and at a median of 11 months at follow-up) and tested using the Linear Array HPV Genotyping kit (Roche Molecular Systems, Pleasanton, CA, USA). Based on their HPV16/HPV18 status at enrolment and follow-up, participants were assigned to 'persistence' or 'clearance' groups. We used cervicovaginal fluid samples obtained upon enrolment to determine the load of the 23 s rRNA gene of Gardnerella spp. and the presence of the NanH1 gene using real-time polymerase chain reaction (PCR). We compared Gardnerella spp. loads and NanH1 frequency between the groups by, respectively, Mann-Whitney and chi-squared tests, with a P-value <0.05 considered to be significant.Results. Of the 104 participants who were positive for HPV16/HPV18, 73 (70.2 %) persisted with at least 1 of the baseline genotypes at follow-up, while 31 (29.8 %) cleared the infection in this time frame. Participants in the persistence group had significantly higher loads of Gardnerella spp. [5.8E+02 (0-3.0E+05) copies µl-1] than those in the clearance group [9.9E+01 (0-7.7E+04) copies µl-1] (P=0.03). The baseline frequency of NanH1 was higher in the persistence' (n=46, 63.0 %) than in the clearance (n=14, 45.2 %) group, although this was not statistically significant (P=0.09).Conclusion. These findings reinforce the negative effect of vaginal microbiota for the clearance of hrHPV and indicate a possible association between sialidase-producing species with hrHPV persistence.

Characteristics associated with Lactobacillus iners-dominated vaginal microbiota.

OBJECTIVE: The protective role of Lactobacillus iners in the vaginal microbiota has been questioned. Recent studies have shown that L. iners is the dominating taxon in a large subset of women worldwide. The aim of this study was to identify sociodemographic, behavioural and clinical variables associated with L. iners-dominated community state type (CST) III in Brazilian women of reproductive age. PARTICIPANTS AND METHODS: This study leveraged microbiota compositional data generated by sequencing of the V3-V4 16S rRNA gene from vaginal samples collected from 442 participants enrolled in a previous cross-sectional study that included 609 women in five geographical regions of Brazil. A total of 167 (27.4%) participants were excluded from the current study as they did not present a Lactobacillus-dominated vaginal microbiota. Data on sociodemographic and behavioural characteristics of the study population were obtained through face-to-face interviews. Participants were assigned to two study groups: those with L. iners-dominated CST III (n=222) and those with three distinct CSTs (I, II or V) dominated by another Lactobacillus spp. (n=220). Logistic regression analysis using a stepwise method was performed to test association between CST III and participants' characteristics, considering their OR and 95% CIs. RESULTS: Among the population characteristics assessed, L. iners-dominated CST III was independently associated with having two or more sexual partners (OR 3.27; 95% CI 1.50 to 7.11) and microscopic detection of Candida sp. on vaginal smears (OR 2.24; 95% CI 1.02 to 4.89). Other characteristics were inversely associated with CST III, including condom use (OR 0.59; 95% CI 0.38 to 0.91), higher educational level (OR 0.61; 95% CI 0.41 to 0.91) and diet containing milk/dairy intake (OR 0.43; 95% CI 0.20 to 0.90). CONCLUSION: Unprotected sex practices, number of sexual partners and lower educational levels may be useful for identifying women with L. iners-dominated microbiota and its suboptimal protective properties. L. iners microbiota does not seem to provide optimal protection against Candida sp. colonisation, warranting further investigation.

Frequency of receiving requested data for a systematic review and associated factors: A cross-sectional study.

This study aimed to assess the frequency of receiving requested data for a systematic review and associated factors. We contacted the authors of studies in need of additional data via e-mail. The primary outcome was the success in receiving the requested data according to the time until receipt. We estimated the hazard ratio (HR) and 95% confidence interval (CI) for success in each variable compared to the reference category, with weighted Cox proportional hazards models using Stata (version 14.2). Out of 164 studies contacted, 110 replied (67.1%), and 51 sent requested data (31.1%). Median time to receive a response or withdraw contact was 36.0 days (interquartile range: 17.5, 142.5). Higher success ratio was observed in studies published as scientific papers (HR = 3.01, 95% CI = [1.18, 7.70]), in more than one publication (HR = 2.00, 95% CI = [1.14, 3.51]), and contacted by personal e-mail (HR = 2.85, 95% CI = [1.34, 6.07]). Three or more contact attempts led to lower success ratio (HR = 0.19, 95% CI = [0.11, 0.35]) than one or two. Requesting data for a systematic review was time-consuming and effective in three out of ten studies. Fewer contacts were more successful than insisting.

pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment.

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.

Prevalence of childhood obesity in Brazil: systematic review and meta-analysis

Abstract Objective: To estimate the prevalence of childhood obesity in Brazil by means of a systematic review of representative studies. Sources: We searched for population-based studies that assessed obesity in Brazilian children aged < 10 years in MEDLINE, EMBASE, Scopus and other sources up to September, 2019. Paired researchers selected studies, extracted data and assessed the quality of these studies. Meta-analysis of prevalence and confidence interval (95% CI) was calculated, weighted by the population sizes using Freeman-Tukey double-arccosine transformation. Heterogeneity (I2) and publication bias were investigated by meta-regression and Egger's test, respectively. Summary of the findings: 53 studies were included (n = 122,395), which were held from 1986 to 2015 and limited mainly due to inadequate response rates. Prevalence of obesity in the threedecade period was of 8.2% ([95% CI]: 8.1-8.4%, I2 = 98.5%). Higher prevalence was observed in boys (9.7% [9.4-9.9%], I2 = 97.4%) than girls (7.3% [7.1 7.5%], I2 = 96.1%). Prevalence increased according to the decade (1990: 6.5% [6.0-7.0 %], I2 = 96.8%; 2000: 7.9% [7.7-8.0 %], I2 = 98.8%; 2010: 12.0% [11.5-12.6 %], I2 = 95.8%), and Brazilian region (Northeast: 6.4% [6.2−6.7%], I2 = 98.1%; North: 6.7% [6.3−7.2%], I2 = 98.8%; Southeast:10.6% [10.2−11.0%], I2 = 98.2%; South: 10.1 [9.7−10.4%], I2 = 97.7%). Heterogeneity was affected by age and region (p < 0.05) and publication bias was discarded (p = 0.746). Conclusion: For every 100 Brazilian children, over eight had obesity in the three-decade period and 12 in each 100 had childhood obesity in more recent estimates. Higher prevalence occurred in boys, recent decades and more developed Brazilian regions.

High frequency of spin bias in controlled trials of cannabis derivatives and their synthetic analogues: A meta-epidemiologic study.

OBJECTIVE: To investigate the frequency and perform a qualitative analysis of spin bias in publications of controlled trials assessing the therapeutic use of cannabis derivatives and their synthetic analogues. STUDY DESIGN AND SETTING: Meta-epidemiologic study carried out at the Universidade Federal de São Paulo, Brazil. RESULTS: A total of 65 publications with at least one efficacy primary outcome were considered. The results analysis for the primary outcome indicated statistically significant effects in 44.6% (29/65) of the publications, and 70.7% (45/65) of the conclusions were considered favorable to the intervention. Among the 36 publications that found statistically nonsignificant results for the primary outcome, 44.4% (16/36) presented conclusions favorable to or recommending the intervention, which represents spin bias according to the definition adopted in this study. Qualitative analysis of the 16 studies with spin bias showed selective outcomes reporting (elevating secondary outcomes that had positive results or reporting only subgroup results), deviations from the planned statistical analysis, and failure to consider or report uncertainty in the estimates of treatment effects. CONCLUSION: The frequency of spin bias among publications of controlled trials with statistically nonsignificant results assessing the therapeutic use of cannabis derivatives and their synthetic analogues reached 44.4%. When not observed by readers, such deviation can lead to misconduct in clinical practice through the adoption of interventions that are not effective or whose effectiveness is uncertain.

Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity.

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.

Membrane interactions of Ocellatins. Where do antimicrobial gaps stem from?

The antimicrobial peptides Ocellatin-LB1, -LB2 and -F1, isolated from frogs, are identical from residue 1 to 22, which correspond to the -LB1 sequence, whereas -LB2 carries an extra N and -F1 additional NKL residues at their C-termini. Despite the similar sequences, previous investigations showed different spectra of activities and biophysical investigations indicated a direct correlation between both membrane-disruptive properties and activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. This study presents experimental evidence as well as results from theoretical studies that contribute to a deeper understanding on how these peptides exert their antimicrobial activities and how small differences in the amino acid composition and their secondary structure can be correlated to these activity gaps. Solid-state NMR experiments allied to the simulation of anisotropic NMR parameters allowed the determination of the membrane topologies of these ocellatins. Interestingly, the extra Asn residue at the Ocellatin-LB2 C-terminus results in increased topological flexibility, which is mainly related to wobbling of the helix main axis as noticed by molecular dynamics simulations. Binding kinetics and thermodynamics of the interactions have also been assessed by Surface Plasmon Resonance and Isothermal Titration Calorimetry. Therefore, these investigations allowed to understand in atomic detail the relationships between peptide structure and membrane topology, which are in tune within the series -F1 > > -LB1 ≥ -LB2, as well as how peptide dynamics can affect membrane topology, insertion and binding.

Epimers l- and d-Phenylseptin: How the relative stereochemistry affects the peptide-membrane interactions.

In recent decades, several epimers of peptides containing d-amino acids have been identified in antimicrobial sequences, a feature which has been associated with post-translational modification. Generally, d-isomers present similar or inferior antimicrobial activity, only surpassing their epimers in resistance to peptidases. The naturally occurring l-Phenylseptin (l-Phes) and d-Phenylseptin (d-Phes) peptides (FFFDTLKNLAGKVIGALT-nh2) were reported with d-epimer showing higher activity against Staphylococcus aureus and Xanthomonas axonopodis in comparison with the l-epimer. In this study, we combine structural (CD, solution NMR), orientational (solid-state NMR) and biophysical (ITC, DSC and DLS) studies to understand the role of the d-phenylalanine in the increase of the antimicrobial activity. Although both peptides are structurally similar in the helical region ranging from D4 to the C-terminus, significant structural differences were observed near the peptides' N-termini (which encompasses the FFF motif). Specific aromatic interactions involving the phenylalanine side chains of d-Phes is responsible to maintaining the F1-F3 residues on the hydrophobic face of the peptide, increasing its amphipathicity when compared to the l-epimer. The higher capability of d-Phes to exert an efficient anchoring in the hydrophobic core of the phospholipid bilayer indicates a pivotal role of the N-terminus in enhancing the interaction between the d-peptide and the membrane interface in relation to its epimer.

Self-report instruments for assessing adherence to warfarin therapy: a systematic review.

BACKGROUND: The assessment of adherence to warfarin therapy is useful in clinical practice due to its wide variability in dose-response and risks of complications. The aim of this study was to investigate validated instruments used to assess adherence to warfarin therapy. METHODS: Information was collected from the MEDLINE (PubMed), LILACS, EMBASE, and Cochrane Library databases. Search strategies were applied for each database, with no time limit or language restriction. Inclusion criteria consisted of study participants of ≥ 18 years of age, from both sexes, on chronic anticoagulation with warfarin for any indication and the use of validated instruments to assess adherence to warfarin therapy. Exclusion criteria consisted of duplicate articles, narrative or systematic reviews, and meta-analyses, as well as case reports/series and experimental studies involving animals. Two independent reviewers performed the following steps: evaluation of titles/abstracts, selection of studies after full reading, data extraction, and evaluation of potential bias. Discrepancies were resolved by a third reviewer. RESULTS: Overall, 19 articles were selected for this systematic review, including 17 cross-sectional studies, one cohort study, and one quasi-experimental study, published from 2009 to 2019. The validated instruments identified in this review were Morisky Medication Adherence Scale (MMAS), the eight-item Morisky Medication Adherence Scale (MMAS-8), Measurement of Treatment Adherence (MTA), and Brief Medication Questionnaire (BMQ). Only MMAS-8 was tested for reliability, using the internal consistency assessment, with Cronbach's α range 0.56-0.71. CONCLUSIONS: This review highlighted a gap in knowledge regarding the scarcity of validated instruments to assess adherence to warfarin therapy. Limitations were found in instruments that comprised the assessment of the isolated use of medication and the lack of analysis of other relevant therapeutic aspects. Future studies are needed to develop and validate more comprehensive instruments in an attempt to assess adherence to warfarin therapy. PROSPERO: Registration number CRD42019128324.