Preterm birth is the leading cause of mortality and disability in newborn and infants. Having a short cervix increases the risk of preterm birth, which can be accessed by a transvaginal ultrasound ...scan during the second trimester. In women with a short cervix, vaginal progesterone and pessary can both reduce this risk, which progesterone more established than cervical pessary. The aim of this study is to compare the use of vaginal progesterone alone versus the association of progesterone plus pessary to prevent preterm birth in women with a short cervix.
This is a pragmatic open-label randomized controlled trial that will take place in 17 health facilities in Brazil. Pregnant women will be screened for a short cervix with a transvaginal ultrasound between 18
until 22
weeks of gestational age. Women with a cervical length below or equal to 30 mm will be randomized to the combination of progesterone (200 mg) and pessary or progesterone (200 mg) alone until 36 + 0 weeks. The primary outcome will be a composite of neonatal adverse events, to be collected at 10 weeks after birth. The analysis will be by intention to treat. The sample size is 936 women, and a prespecified subgroup analysis is planned for cervical length (= < or > 25 mm). Categorical variables will be expressed as a percentage and continuous variables as mean with standard deviation. Time to delivery will be assessed with Kaplan-Meier analysis and Cox proportional hazard analysis.
In clinical practice, the combination of progesterone and pessary is common however, few studies have studied this association. The combination of treatment might act in both the biochemical and mechanical routes related to the onset of preterm birth.
Brazilian Clinical Trial Registry (ReBec) RBR-3t8prz, UTN: U1111-1164-2636, 2014/11/18.
Mutations of GBA1 , the gene encoding glucocerebrosidase, represent a common genetic risk factor for developing the synucleinopathies Parkinson disease (PD) and dementia with Lewy bodies. PD patients ...with or without GBA1 mutations also exhibit lower enzymatic levels of glucocerebrosidase in the central nervous system (CNS), suggesting a possible link between the enzyme and the development of the disease. Previously, we have shown that early treatment with glucocerebrosidase can modulate α-synuclein aggregation in a presymptomatic mouse model of Gaucher-related synucleinopathy (Gba1 ᴰ⁴⁰⁹ⱽ/ᴰ⁴⁰⁹ⱽ) and ameliorate the associated cognitive deficit. To probe this link further, we have now evaluated the efficacy of augmenting glucocerebrosidase activity in the CNS of symptomatic Gba1 ᴰ⁴⁰⁹ⱽ/ᴰ⁴⁰⁹ⱽ mice and in a transgenic mouse model overexpressing A53T α-synuclein. Adeno-associated virus-mediated expression of glucocerebrosidase in the CNS of symptomatic Gba1 ᴰ⁴⁰⁹ⱽ/ᴰ⁴⁰⁹ⱽ mice completely corrected the aberrant accumulation of the toxic lipid glucosylsphingosine and reduced the levels of ubiquitin, tau, and proteinase K-resistant α-synuclein aggregates. Importantly, hippocampal expression of glucocerebrosidase in Gba1 ᴰ⁴⁰⁹ⱽ/ᴰ⁴⁰⁹ⱽ mice (starting at 4 or 12 mo of age) also reversed their cognitive impairment when examined using a novel object recognition test. Correspondingly, overexpression of glucocerebrosidase in the CNS of A53T α-synuclein mice reduced the levels of soluble α-synuclein, suggesting that increasing the glycosidase activity can modulate α-synuclein processing and may modulate the progression of α-synucleinopathies. Hence, increasing glucocerebrosidase activity in the CNS represents a potential therapeutic strategy for GBA1 -related and non- GBA1 –associated synucleinopathies, including PD.
Background
Prematurity is considered to be the leading cause of death in children under 5 years of age, with one child dying every 2 s. Smoking is known to be one of the factors associated with ...prematurity, with both immediate and late consequences. However, it is difficult to obtain concrete data on the relationship between smoking and spontaneous preterm birth.
Objective
The aim of this study was to evaluate the influence of active and passive smoking on spontaneous preterm birth.
Methods
This was a multicenter, cross‐sectional complementary study that included data on preterm births in 20 maternity hospitals in Brazil between 2011 and 2012. The relationship between smoking category (people who smoke PWS; people who smoke indirectly PWSI; and people who do not smoke PWDNS) and sociodemographic characteristics, birth, and neonatal data was assessed. Statistical analysis was performed using frequencies, percentages, the χ2 test, and stepwise comparisons, with a significance level of 5%.
Results
The original study included 5295 pregnant participants and their preterm infants. There were 1491 spontaneous preterm births (SPBs); 1191 preterm rupture of membranes; 1468 therapeutic preterm births; and 1146 term births. The proportion of women who were PWS during pregnancy was 13.5%, and 31.6% were PWSI. Pregnant individuals who smoked and who smoked indirectly had a higher incidence of SPBs (61.2%) compared with PWDNS (48.4%; P < 0.0001); however, multivariate analysis did not confirm causality.
Conclusions
This study did not confirm that smoking during pregnancy increases the risk of SPB. PWSI also did not have an increased incidence of spontaneous preterm birth or adverse neonatal outcomes.
Synopsis
Active and passive smoking during pregnancy are associated with, but do not directly cause, spontaneous preterm birth..
Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model ...of Gaucher disease (Gba1D409V/D409V) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant α-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (Gba1D409V/D409V) and heterozygous (Gba1D409V/+ and Gba1+/−) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of Gba1D409V/D409V mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in GBA1 can cause Parkinson disease-like α-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for GBA1-associated synucleinopathies.
Introduction
Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria that enter the bloodstream and establish infections in the inner linings or valves of the heart, ...including blood vessels. Despite the availability of modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Oral microbiota is considered one of the most significant risk factors for IE. The objective of this study was to evaluate the microbiota present in root canal (RC) and periodontal pocket (PP) clinical samples in cases with combined endo-periodontal lesions (EPL) to detect species related to IE using NGS.
Methods
Microbial samples were collected from 15 RCs and their associated PPs, also from 05 RCs with vital pulp tissues (negative control, NC). Genomic studies associated with bioinformatics, combined with structuring of a database (genetic sequences of bacteria reported for infective endocarditis), allowed for the assessment of the microbial community at both sites. Functional prediction was conducted using PICRUSt2.
Results
Parvimonas
,
Streptococcus
, and
Enterococcus
were the major genera detected in the RCs and PPs
.
A total of 79, 96, and 11 species were identified in the RCs, PPs, and NCs, respectively. From them, a total of 34 species from RCs, 53 from PPs, and 2 from NCs were related to IE. Functional inference demonstrated that CR and PP microbiological profiles may not be the only risk factors for IE but may also be associated with systemic diseases, including myocarditis, human cytomegalovirus infection, bacterial invasion of epithelial cells, Huntington’s disease, amyotrophic lateral sclerosis, and hypertrophic cardiomyopathy. Additionally, it was possible to predict antimicrobial resistance variants for broad-spectrum drugs, including ampicillin, tetracycline, and macrolides.
Conclusion
Microorganisms present in the combined EPL may not be the only risk factor for IE but also for systemic diseases. Antimicrobial resistance variants for broad-spectrum drugs were inferred based on PICRUSt-2. State-of-the-art sequencing combined with bioinformatics has proven to be a powerful tool for conducting studies on microbial communities and could considerably assist in the diagnosis of serious infections.
Clinical relevance
Few studies have investigated the microbiota in teeth compromised by combined endo-periodontal lesions (EPL), but none have correlated the microbiological findings to any systemic condition, particularly IE, using NGS techniques. In such cases, the presence of apical periodontitis and periodontal disease can increase IE risk in susceptible patients.
Background
This study was conducted to compare the microbiomes, the levels of lipopolysaccharides (LPS), lipoteichoic acid (LTA), and cytokines (interleukin IL‐1β and tumor necrosis factor‐alpha ...TNF‐α), before and after chemomechanical preparation (CMP) of the root canals (RC) and their associated periodontal pockets (PP) in teeth with combined EPL.
Materials
Samples were taken from 10 RC and PP, before and after CMP. The microbiomes (next‐generation sequencing, V3‐V4 hypervariable region of the 16S rRNA gene), microbiome diversity (bioinformatics analyses), LPS (limulus amebocyte lysate), LTA, IL‐1β, and TNF‐α (ELISA) were evaluated. A statistical analysis was performed with significance level set at 5%.
Results
The most abundant phyla in both sites were Firmicutes and Proteobacteria. Comparative studies of bacterial genera species revealed that some increased and others decreased after CMP at both sites. A 3% reduction in Gram‐negative bacteria (RC) and a 4% increase in Gram‐positive bacteria (PP) were detected. LPS levels were 4.4 times higher in PP than in the RC. LTA was detected in all samples investigated. Higher levels of IL‐1β and TNF‐α were detected in both sites at baseline. After CMP, LPS, LTA, IL‐1β and TNF‐α were reduced in both sites.
Conclusion
The microbial community in the RC and PP in teeth with combined EPL indicated a similarity between both sites. CMP effectively reduced the microbial load and the LPS levels from teeth with EPL, and consequently diminished the cytokine levels. The reduction in LTA levels in the RC and PP proved challenging.
Background. Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations. ...Methods. We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays. Results. Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth–associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers.
The objective of this study was to determine incidence and risk factors associated with spontaneous preterm birth (sPTB). It was a prospective multicentre cohort study performed in five Brazilian ...referral maternity hospitals and enrolling nulliparous women at 19-21 weeks. Comprehensive maternal data collected during three study visits were addressed as potentially associated factors for sPTB. Bivariate and multivariate analysis estimated risk ratios. The main outcomes measures were birth before 37 weeks due to spontaneous preterm labour or premature rupture of membranes (sPTB). The comparison group was comprised of women with term births (≥37weeks). Outcome data was available for 1,165 women, 6.7% of whom had sPTB, 16% had consumed alcohol and 5% had used other illicit drugs during the first half of pregnancy. Current drinking at 19-21 weeks (RR 3.96 95% CI 1.04-15.05) and a short cervix from 18-24 weeks (RR 4.52 95% CI 1.08-19.01) correlated with sPTB on bivariate analysis. Increased incidence of sPTB occurred in underweight women gaining weight below quartile 1 (14.8%), obese women gaining weight above quartile 3 (14.3%), women with a short cervix (<25 mm) at 18-24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the first half of pregnancy (40%). Cervical length (RR
4.52 95% CI 1.08-19.01) was independently associated with sPTB. In conclusion, the incidence of sPTB increased in some maternal phenotypes, representing potential groups of interest, the focus of preventive strategies. Similarly, nulliparous women with a short cervix in the second trimester require further exploration.
Objective
The objective of this study was to evaluate the microbiological profile of root canals indicated for endodontic retreatment due to secondary endodontic infections evidenced by the presence ...of chronic apical periodontitis (G1) or for prosthetic reasons, without clinical and radiographic signs of endodontic reinfection (G2).
Methods
Microbiological samples were collected from thirty teeth (
N
=30) out of which 15 were indicated for retreatment due to the presence of chronic apical periodontitis (G1) and 15 were indicated exclusively for prosthetic reasons (G2). Samples were collected from root canals before (S1), after chemomechanical preparation (S2), and after 30 days of intracanal medication composed of calcium hydroxide and 2% chlorhexidine gel (S3). The molecular analysis was performed using Nested-PCR for the detection of 17 bacterial species. The efficacy of each stage of the retreatment in reducing the microbial load was verified by counting colony-forming units (CFU). The statistical analysis considered a significance level of 5%.
Results
The results showed that bacteria were detected in 100% of the cases in S1, in both groups, by Nested PCR. The most frequently found species in S1 in both groups were
Enterococcus faecalis
,
Fusobacterium nucleatum
,
Porphyromonas gingivalis
,
Aggregatibacter actinomycetemcomitans
, and
Parvimonas micra
. The microbial load of G1 was higher than G2 in the initial samples (S1). Endodontic retreatment was effective in reducing the microbial load in G1 and G2. Statistically significant associations were found between specific bacteria and clinical signs and symptoms.
Conclusion
It was concluded that the microbial community present in the root canal of teeth indicated for endodontic retreatment is mixed and heterogeneous. G1 and G2 differ in the number of species per case and microbial load.
Clinical relevance
Endodontic retreatment was effective in reducing the microbial load. Statistically significant associations were found between specific bacteria and clinical signs and symptoms.
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