Vascular contraction of umbilical arteries of pregnant women with preeclampsia.

Objective: Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies. Methods: To investigate the effects of the inhibition of Katp, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin. Results: There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights. Conclusion: In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.

Effectiveness of metformin to pregnant women with PCOS to reduce spontaneous abortion and gestational diabetes mellitus: a protocol for an overview of reviews.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a globally prevalent endocrinological disorder and has been associated with poor pregnancy outcomes, including a higher rate of gestational diabetes and miscarriage. Metformin is among the drugs investigated to improve the prognosis of pregnant women with PCOS. OBJECTIVE: To conduct an overview of systematic reviews examining the effects of metformin versus placebo or no intervention throughout pregnancy among pregnant women with a preconception PCOS diagnosis to reduce the incidence of miscarriage and gestational diabetes. METHODS AND ANALYSIS: We will perform an overview of systematic reviews by searching Embase, PubMed, Virtual Health Library, Cochrane Central Register of Controlled Trials, Trip Database, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature from inception to 17 August 2023. Language, publication status and year indexed or published filters will not be applied. Two reviewers will independently screen and select papers, assess their quality, evaluate their risk of bias and collect the data. The included reviews will be summarised narratively. The quality and risk of bias of the systematic review and meta-analysis studies included will be assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Second Version) and ROBIS (Risk of Bias in Systematic Reviews), respectively. ETHICS AND DISSEMINATION: This overview of reviews will analyse data from systematic reviews on the use of metformin for prepregnancy diagnosis of PCOS to reduce adverse outcomes. As there will be no primary data collection, a formal ethical analysis is unnecessary. The study outcomes will be submitted to a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42023441488.

Vascular contraction of umbilical arteries of pregnant women with preeclampsia

Abstract Objective: Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies. Methods: To investigate the effects of the inhibition of Katp, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin. Results: There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights. Conclusion: In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.

Deficiencies in reporting inclusion/exclusion criteria and characteristics of patients in randomized controlled trials of therapeutic interventions in pressure injuries: a systematic methodological review.

Wound care is a complex procedure and the related research may include many variables. Deficiencies in the sample inclusion and exclusion criteria may limit the generalizability of randomized controlled trials (RCTs) for wound patients in the real world. This study aimed to evaluate deficiencies in reporting the inclusion and exclusion criteria and the characteristics of patients in RCTs of pressure injuries (PI) therapeutic interventions. We conducted a systematic methodological review in which 40 full text RCTs of PI treatment interventions published in English, from 2008 to 2020, were identified. Data on the general characteristics of the included RCTs and data about inclusion/exclusion criteria and characteristics of patients were collected. The inclusion/exclusion criteria were categorized into five domains (definition of disease, precision, safety, ethical/legal and administrative). Study duration (in weeks) was 8.0 (quartile 1: 2.0; quartile 3: 48.0); only 5.0% of the trials mentioned race, skin colour or ethnicity, and 37.5% reported the duration of the wound. Only 9 (22.5%) studies reported the drugs that the included patients were using and 10 (25.0%) RCTs reported adverse events. The presence of the five domains was observed only in 12.5% of RCTs and only 12 (30.0%) had the precision domain. Much more research is required in systematic assessments of the external validity of trials because there is substantial disparity between the information that is provided by RCTs and the information that is required by clinicians. We concluded that there are deficiencies in reporting of data related to inclusion/exclusion criteria and characteristics of patients of RCTs assessing PI therapeutic interventions.

Assessment of healthcare accessibility and travel distance on intrapartum fetal death: a retrospective cohort study / Relación de la accesibilidad de la atención de salud y la distancia de desplazamiento con la muerte fetal durante el parto: un estudio de cohorte retrospectivo / Avaliação do impacto do acesso ao sistema de saúde e da distância percorrida na morte fetal intraparto: estudo retrospectivo de coorte

ABSTRACT Objective. To determine if there was an association between intrapartum stillbirths and both traveled distance for delivery and delivery care accessibility, assessing periods before and during the COVID-19 pandemic. Methods. This is a population-based cohort study. Patients had birth occurring after the onset of labor; the primary outcome was intrapartum stillbirth. City of residence was classified according to the ratio between deliveries performed and total births among its residents; values lower than 0.1 indicated low delivery care accessibility. Travel distance was calculated using the Haversine formula. Education level, maternal age, and birth sex were included. In each period, relative risk was assessed by generalized linear model with Poisson variance. Results. There were 2 267 534 deliveries with birth occurring after the onset of labor. Most patients were between age 20 and 35 years, had between 8 and 11 years of education, and resided in cities with high delivery care accessibility. Low delivery care accessibility increased risk of intrapartum stillbirth in the pre-pandemic (relative risk [RR] 2.02; 95% CI [1.64, 2.47]; p < 0.01) and the pandemic period (RR 1.69; 95% CI [1.09, 2.55]; p = 0.015). This was independent of other risk-increasing factors, such as travel distance and fewer years of education. Conclusions. Low delivery care accessibility is associated with the risk of intrapartum stillbirths, and accessibility reduced during the pandemic. Delivery of patients by family physicians and midwives, as well as official communication channels between primary care physicians and specialists, could improve patient healthcare-seeking behavior.

RESUMEN Objetivo. Determinar si hubo una asociación entre la mortinatalidad durante el parto y la distancia recorrida o la accesibilidad de la atención para el parto, mediante la evaluación de un período anterior y de otro coincidente con la pandemia de COVID-19. Métodos. Se realizó un estudio de cohorte de base poblacional. Se incluyó a las pacientes que dieron a luz tras el inicio de un trabajo de parto; el criterio de valoración principal fue la mortinatalidad durante el parto. Se clasificaron las ciudades de residencia conforme al cociente entre el número de partos atendidos y el total de partos habidos entre sus residentes; los valores inferiores a 0,1 indican que la accesibilidad de la atención del parto es baja. La distancia recorrida para el parto se calculó utilizando la fórmula de Haversine. Se utilizaron datos del nivel de estudios y la edad de la madre y del sexo biológico neonatal. Para cada período, se evaluó el riesgo relativo mediante un modelo lineal generalizado con varianza de Poisson. Resultados. Hubo 2 267 534 partos que se produjeron tras el inicio de un trabajo de parto. La mayoría de las pacientes tenían edades comprendidas entre 20 y 35 años, tenían entre 8 y 11 años de estudios y residían en ciudades donde la accesibilidad de la atención del parto era alta. Una accesibilidad baja de la atención del parto se asoció a un aumento del riesgo de mortinatalidad durante el parto en el período prepandémico (riesgo relativo [RR] = 2,02; IC del 95% = [1,64, 2,47]; p < 0,01) y también durante la pandemia (RR = 1,69; IC del 95% = [1.09, 2.55]; p = 0,015). Este resultado fuer independiente de otros factores que incrementan el riesgo, como la distancia recorrida para dar a luz y un menor nivel de estudios. Conclusiones. Una accesibilidad baja de la atención del parto se asocia a un mayor riesgo de mortinatalidad durante el parto; y se observó una reducción de la accesibilidad durante la pandemia. Los partos asistidos por personal de medicina de familia o de partería y los canales de comunicación oficiales entre el personal médico de atención primaria y el especializado podrían mejorar el comportamiento de las pacientes a la hora de buscar atención de salud.

RESUMO Objetivo. Determinar se existe alguma relação entre a morte fetal intraparto e dois fatores: a distância percorrida para o parto e o acesso à assistência ao parto, avaliando o período antes e durante a pandemia de COVID-19. Métodos. Este é um estudo de coorte de base populacional. As pacientes tiveram parto após o início do trabalho de parto; o desfecho primário foi morte fetal intraparto. A cidade de residência foi classificada de acordo com a razão entre os partos realizados e o total de nascimentos entre os residentes; valores inferiores a 0,1 indicavam baixo acesso à assistência ao parto. A distância percorrida foi calculada usando a fórmula de Haversine. Foram incluídos o nível de escolaridade, a idade materna e o sexo de nascimento. Em cada período, o risco relativo foi avaliado usando um modelo linear generalizado com variância de Poisson. Resultados. Foram registrados 2 267 534 partos com nascimento após o início do trabalho de parto. A maioria das pacientes tinha entre 20 e 35 anos de idade, entre 8 e 11 anos de escolaridade e residia em cidades com alto nível de acesso à assistência ao parto. O baixo acesso à assistência ao parto aumentou o risco de morte fetal intraparto no período anterior à pandemia (risco relativo [RR]: 2,02; intervalo de confiança [IC] de 95%: 1,64-2,47; p < 0,01) e durante a pandemia (RR: 1,69; IC 95%: 1,09-2,55; p = 0,015). Isso ocorreu independentemente de outros fatores de aumento de risco, como a distância percorrida e menor escolaridade. Conclusões. O baixo acesso ao atendimento de parto está associado ao risco de morte fetal intraparto, e a acessibilidade diminuiu durante a pandemia. A realização do parto por médicos de família e obstetrizes, bem como a existência de canais oficiais de comunicação entre médicos de atenção primária e especialistas, poderiam melhorar o comportamento de busca de saúde por parte das pacientes.

Markers of Endothelial Dysfunction Are Attenuated by Resveratrol in Preeclampsia.

Preeclampsia (PE) is characterized by great endothelial dysfunction, decreased nitric oxide (NO) bioavailability, and higher levels of arginase activity. In the present study, we investigated the potential modulatory effects of trans-resveratrol (RSV) on arginase and endothelial dysfunction biomarkers in endothelial cells exposed to plasma from patients with PE and healthy pregnant (HP) women, and umbilical arteries from patients with PE. Human umbilical vein endothelial cells (HUVECs) were incubated with pooled plasma from 10 HP or 10 PE pregnant women and RSV; umbilical arteries from patients with PE were incubated with RSV; intracellular NO and total reactive oxygen species (ROS) levels were assessed using a probe that interacted with these radicals; total arginase activity was evaluated measuring the urea produced; total antioxidant capacity was measured using the ferric reduction ability power (FRAP) assay; and endothelial dysfunction biomarkers were assessed using qPCR in endothelial cells and umbilical arteries. RSV increased NO levels and decreased total arginase activity in endothelial cells incubated with plasma from patients with PE. In addition, RSV increased total antioxidant capacity and downregulated endothelial dysfunction biomarkers, such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3, (CASP-3), in endothelial cells and umbilical arteries from PE patients. RSV treatment positively modulated the L-arginine-NO pathway, decreased arginase activity, and increased antioxidant capacity, in addition to downregulating endothelial dysfunction biomarkers.

Viability of ex-vivo myography as a diagnostic tool for rectus abdominis muscle electrical activity collected at Cesarean section within a diamater cohort study.

BACKGROUND: Ex-vivo myography enables the assessment of muscle electrical activity response. This study explored the viability of determining the physiological responses in muscles without tendon, as rectus abdominis muscle (RAM), through ex-vivo myography to assess its potential as a diagnostic tool. RESULTS: All tested RAM samples (five different samples) show patterns of electrical activity. A positive response was observed in 100% of the programmed stimulation. RAM 3 showed greater weight (0.47 g), length (1.66 cm), and width (0.77 cm) compared to RAM 1, RAM 2, RAM 4 and RAM 5 with more sustained electrical activity over time, a higher percentage of fatigue was analyzed at half the time of the electrical activity. The order of electrical activity (Mn) was RAM 3 > RAM 5 > RAM 1 > RAM 4 > RAM 2. No electrical activity was recorded in the Sham group. CONCLUSIONS: This study shows that it is feasible to assess the physiological responses of striated muscle without tendon as RAM, obtained at C-section, under ex vivo myography. These results could be recorded, properly analyzed, and demonstrated its potential as a diagnostic tool for rectus abdominis muscle electrical activity.

Glibenclamide Increases Nitric Oxide Levels and Decreases Oxidative Stress in an In Vitro Model of Preeclampsia.

(1) Background: The bioavailability of nitric oxide (NO) and oxidative stress are important events related to the pathophysiology of preeclampsia (PE). In this present study, we aimed to evaluate the antioxidant effect of glibenclamide (GB) on the NO synthesis, oxidative stress, and antioxidant capacity in endothelial cells incubated with plasma from preeclamptic (PE) and normotensive pregnant women (NT). (2) Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with a plasma pool from 10 NT and 10 PE pregnant women; NO/NOx quantification and ROS levels were assessed by a fluorescence compound; lipid peroxidation was evaluated employing thiobarbituric acid (TBA); and total antioxidant capacity was measured by ferric reduction ability power (FRAP) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). (3) Results: We found that endothelial cells incubated with plasma from PE showed lower NO and NOx levels compared with the NT group. However, GB treatment increased these levels, as well as the antioxidant capacity. Furthermore, a decrease was observed in ROS generation and lipid peroxidation (4) Conclusions: The GB treatment exerted a positive effect on the NO/NOx production by HUVEC incubated with plasma from NT and PE pregnant women, as well as in the reduction in oxidative stress and increase in the antioxidant capacity.

Modulatory effect of two regimens of magnesium sulfate on the systemic inflammatory response in pregnant women with imminent eclampsia.

OBJECTIVE: This study compared the modulatory effect of two intravenous magnesium sulfate (MgSO4) regimens on the systemic inflammatory response in pregnant women diagnosed with imminent eclampsia. STUDY DESIGN: In a single-blind cross-sectional study, 33 women were allocated according to the Zuspan (n = 16) and Sibai (n = 17) MgSO4 regimens, and treated for 24 h. Blood samples were collected pre-administration of the loading dose, at 24 h of the maintenance dose of MgSO4, and at 48 h, when patients were without treatment. Plasma was used to determine interleukin (IL)-1 beta (IL-1ß), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), heat shock protein (Hsp70), and heme oxygenase-1 (HO-1) by ELISA. RESULTS: The treatment with the Zuspan's regimen didn't change plasma concentrations of TNF-α, IL-10, and Hsp70 in the three-time points studied. However, it decreased IL-1ß at 24 h and 48 h and IL-6 at 48 h, and increased HO-1 concentration at 48 h. On the other hand, compared to the pre-treatment period, Sibai's regimen induced a significant decrease in TNF-α, IL-1ß, IL-6, and Hsp70, while increased HO-1 levels both at 24 h and 48 h and, IL-10 concentration at 48 h. CONCLUSIONS: Sibai's regimen determined an early and efficient immunoregulatory effect on systemic inflammatory response in preeclampsia, suggesting that the maintenance dose of two grams of MgSO4 was better than one gram in the treatment of imminent eclampsia.

Consolidation chemotherapy in postmolar low-risk gestational trophoblastic neoplasia: a systematic review protocol.

INTRODUCTION: Current evidence remains insufficient to strongly demonstrate the benefits of consolidation chemotherapy to all women with low-risk gestational trophoblastic neoplasia (GTN). This protocol outlines a systematic review to investigate whether consolidation chemotherapy is necessary for all patients with postmolar low-risk GTN after human chorionic gonadotropin normalisation with first-line single-agent chemotherapy. METHODS AND ANALYSIS: A search string will be used to search the PubMed (MEDLINE), EMBASE, Web of Sciences, Scopus, LILACS and Cochrane Central Register of Controlled Trials databases. Articles will be screened at the title and abstract level, and then at the full article level by two independent reviewers using inclusion/exclusion criteria. Randomised and non-randomised study designs will be included, while case studies, commentaries, editorials, review articles, animal studies, basic science studies and cross-sectional studies, as well as studies not reporting relapse/recurrence rates and/or whether consolidation chemotherapy was delivered will be excluded. There will be no restrictions on date of publication, geographical location, study setting, or language of publication. The primary outcome is rate of recurrence/relapse. The assessments of randomised controlled trials will be performed using the risk of bias tool from the Cochrane Collaboration. Non-randomised studies will be assessed using the Newcastle-Ottawa scale. The quality of evidence will be assessed using the Grading quality of evidence and strength of recommendations (Grades of Recommendations, Assessment, Development and Evaluation) guidelines. ETHICS AND DISSEMINATION: No formal ethical approval is required as all data collected will be secondary data and analysed anonymously. Results will be disseminated through a peer-reviewed publication and at scientific events. PROSPERO REGISTRATION NUMBER: CRD42020164822.

Vitamin D decreases cell death and inflammation in human umbilical vein endothelial cells and placental explants from pregnant women with preeclampsia cultured with TNF-α.

This study evaluated the impact of vitamin D on Human Umbilical Vein Endothelial Cells (HUVEC) and inflammation in placental explants from women with preeclampsia (PE). HUVEC and explants from 10 late-onset PE (LOPE), 10 early-onset (EOPE), and 10 normotensive (NT) pregnant women were cultured with/without tumor necrosis factor (TNF-α) and VD. Interleukin-1ß (IL-1ß), 18 (IL-18), TNF-α, and TNF-related apoptosis-inducing ligand (TRAIL) were detected by ELISA. High mobility group box 1 (HMGB1) was determined by qPCR/Western blotting, and cell death by flow cytometry. Statistical significance was accepted at p < .05. Compared to the NT group, the endogenous levels of IL-1ß, TNF-α, and IL-18 were higher in the PE group. The stimulus with TNF-α increased cytokines in NT, TNF-α in EOPE/LOPE, IL-18 in LOPE, and all cytokines in HUVEC. TNF-α+VD treatment decreased cytokines in explant and HUVEC supernatants. TRAIL was higher in EOPE versus NT, while TNF-α increased this receptor in NT versus control. In HUVEC, TNF-α increased TRAIL versus control, and TNF-α+VD decreased levels compared to only TNF-α stimulus. Protein expression of HMGB1 was higher in explant cultures treated with TNF-α and decreased after TNF-α+VD treatment in all groups, and gene/protein expression in HUVEC. Gene expression was elevated in EOPE versus NT and LOPE, and TNF-α increased HMGB1 in NT versus control, while TNF-α+VD decreased mRNA levels in EOPE. TNF-α stimulus increased late apoptosis in HUVEC, while VD increased viability. These in vitro observations suggest that VD administration to women with preeclampsia may be beneficial in reducing placental inflammation and cell death.

Pro-angiogenic approach for skeletal muscle regeneration.

The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed.

Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions.

BACKGROUND: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. OBJECTIVES: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). METHODS: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used a random-effects model to pool results across studies and Peto's one-step odds ratio (OR) for event rates below 1%. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence. RESULTS: One hundred and six RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95% confidence interval [CI]: 0.76-1.26, 33 trials, 15,942 participants, moderate certainty of evidence). However, there was a moderate certainty of evidence that CQ/HCQ increases the incidence of cardiac complications (RR: 1.62, 95% CI: 1.10-2.38, 16 trials, 9908 participants). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1.63, 95% CI: - 0.4-6.57, 5 trials, 344 participants, very low certainty of evidence). CONCLUSIONS: CQ and HCQ probably do not increase SAEs, with low frequency of these adverse events on malarial and non-malarial conditions. However, they may increase cardiac complications especially in patients with COVID-19. No clear effect of their use on the incidence of retinopathy was observed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020177818.

Exploring pooled analysis of pretested items to monitor the performance of medical students exposed to different curriculum designs.

Several methods have been proposed for analyzing differences between test scores, such as using mean scores, cumulative deviation, and mixed-effect models. Here, we explore the pooled analysis of retested Progress Test items to monitor the performance of first-year medical students who were exposed to a new curriculum design. This was a cross-sectional study of students in their first year of a medical program who participated in the annual interinstitutional Progress Tests from 2013 to 2019. We analyzed the performance of first-year students in the 2019 test and compared it with that of first-year students taking the test from 2013 to 2018 and encountering the same items. For each item, we calculated odds ratios with 95% confidence intervals; we also performed meta-analyses with fixed effects for each content area in the pooled analysis and presented the odds ratio (OR) with a 95% confidence interval (CI). In all, we used 63 items, which were divided into basic sciences, internal medicine, pediatrics, surgery, obstetrics and gynecology, and public health. Significant differences were found between groups in basic sciences (OR = 1.172 [CI95% 1.005 CI 1.366], p = 0.043) and public health (OR = 1.54 [CI95% CI 1.25-1.897], p < 0.001), which may reflect the characteristics of the new curriculum. Thus, pooled analysis of pretested items may provide indicators of different performance. This method may complement analysis of score differences on benchmark assessments.

Quality of reporting of outcomes in trials of therapeutic interventions for pressure injuries in adults: a systematic methodological survey.

Randomised controlled trials of therapeutic interventions for pressure injuries should include a clear description of outcomes to increase transparency and replicability and improve the construction of scientific evidence. The objective of this study was to assess the completeness of the descriptions of the outcomes of therapeutic interventions in adults with pressure injury (PI) and factors associated with completeness. This was a systematic methodological survey. The completeness of the outcome was assessed according to five criteria: domain (title), specific measure (technique/instrument used), specific metric, or format of the outcome data of each participant that was used for analysis, aggregation (method data from each group were summarised), and time that was used for analysis. Sixty-eight studies were included for analysis. A total of 265 outcomes were reported, and 46 trials (67.6%) had 73 primary outcomes, which were mainly intermediates/substitutes (78.8%). The main outcome evaluated was the ulcer area reduction (36.6%). Approximately 37.2% of the outcomes were incompletely reported, and the least described element was the data aggregation method (72.8%). Only 48.4% of the outcomes with the specified technique had the same reference or validation. Poor quality of reporting outcomes was associated with studies with an older year of publication and a small sample size, single-center studies, and those sponsored by industry. PI studies use many outcomes, mostly surrogates or intermediates, and some of them are incompletely described.

Deleterious effects of gestational diabetes mellitus on the characteristics of the rectus abdominis muscle associated with pregnancy-specific urinary incontinence.

AIMS: To evaluate the effects of gestational diabetes mellitus (GDM) on the structural characteristics of the rectus abdominis muscle (RAM) and its indirect effects on pregnancy-specific urinary incontinence (PSUI). METHODS: A total of 92 pregnant women were divided into four groups, according to their clinical conditions: non-GDM continent, non-GDM associated PSUI, GDM continent and GDM associated PSUI. The muscle morphometry (histochemistry and immunohistochemistry) for the fiber types and collagen fiber distribution, the ultrastructural analysis (transmission electron microscopy), the protein expression of fiber types and calcium signaling (Western blotting), and the content of types I and III collagen fiber (ELISA) in RAM collected at delivery were assessed. RESULTS: The GDM groups presented a significantly increased number of slow fibers and slow-twitch oxidative fiber expression; decreased fiber area, number of fast fibers, and area of collagen; an increase in central nuclei; ultrastructural alterations with focal lesion areas such as myeloid structures, sarcomere disorganization, and mitochondrial alteration. The PSUI groups presented a considerable decrease in types I and III collagen contents and the localization of collagen fiber. CONCLUSIONS: Our data reveal that GDM causes morphological, biochemical and physiological changes in the RAM, and this might predispose women to PSUI.

Alterations in the structural characteristics of rectus abdominis muscles caused by diabetes and pregnancy: A comparative study of the rat model and women.

BACKGROUND AND OBJECTIVE: In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). METHOD: Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. RESULTS: No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. CONCLUSION: Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.

Increased placental mitochondrial fusion in gestational diabetes mellitus: an adaptive mechanism to optimize feto-placental metabolic homeostasis?

INTRODUCTION: Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. METHODS AND RESULTS: Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. CONCLUSIONS: Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Altered maternal metabolism during mild gestational hyperglycemia as a predictor of adverse perinatal outcomes: A comprehensive analysis.

Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers.