Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews.

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.

Postweaning Development Influences Endogenous VPAC1 Modulation of LTP Induced by Theta-Burst Stimulation: A Link to Maturation of the Hippocampal GABAergic System.

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6-7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?

Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity (EA) triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of EA were induced: (1) interictal-like EA evoked by Mg2+ withdrawal and K+ elevation to 6 mM in the superfusion medium or (2) ictal-like EA induced by bicuculline (10 µM). Both EA patterns induced and LTP-like effect on CA1 synaptic transmission prior to LTP induction. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA in synaptosomes isolated from these slices. EA enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser845 phosphorylation and the GluA1/GluA2 ratio. Flotillin-1 and caveolin-1 were markedly decreased concomitantly with a marked increase in gephyrin levels and a less prominent increase in PSD-95. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting that altered LTP post-seizures is a relevant target for antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.

Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.

Study of the renal Parenchymal volume during the human fetal period.

OBJECTIVE: To evaluate the renal parenchymal area in human fetuses, providing a descriptive analysis on the renal area development by demographic factors during the second gestational trimester. MATERIAL AND METHODS: We analyzed 84 fetuses (44 males and 40 females), for a total of 168 renal units evaluated in terms of longitudinal length, superior pole width, inferior pole width and thickness. Renal volume was calculated by ellipsoid formula. After renal pelvis dissection, length and width were evaluated; as pelvis is free of urine, we considered thickness as 1mm. Renal pelvis volume was also calculated by ellipsoid formula. Renal parenchymal area was assessed by excluding the volume of the renal pelvis from the total renal volume. We performed the statistical analysis by simple linear regression assessing the association between the variables analyzed with the fetal age. RESULTS: Gestational age ranged from 12 to 23 weeks post conception. Mean renal parenchymal area of the right kidney was 666.22mm3 (45.86 to 2375.35mm3) and for the left kidney was 606.76mm3 (68.63 to 2402.57mm3). No statistical difference was observed between the sides (p-value = 0.3456) or genders (p-value = 0.07429). Linear regression between renal parenchymal volume and gestational age was positive for right kidney (y = 133.74x-1479.94 / r² = 0.4009) and left kidney (y = 149.53x-1761.59 / r² = 0.4591). CONCLUSIONS: The linear regression analysis indicated that renal parenchymal area correlated significantly and positively with fetal age, weight and crown-rump length with no statistical differences between gender or laterality. These growth curves provide a reference for functional volume of the kidney during fetal period.

Study of the renal parenchymal volume during the human fetal period

ABSTRACT Objective: To evaluate the renal parenchymal area in human fetuses, providing a descriptive analysis on the renal area development by demographic factors during the second gestational trimester. Material and Methods: We analyzed 84 fetuses (44 males and 40 females), for a total of 168 renal units evaluated in terms of longitudinal length, superior pole width, inferior pole width and thickness. Renal volume was calculated by ellipsoid formula. After renal pelvis dissection, length and width were evaluated; as pelvis is free of urine, we considered thickness as 1mm. Renal pelvis volume was also calculated by ellipsoid formula. Renal parenchymal area was assessed by excluding the volume of the renal pelvis from the total renal volume. We performed the statistical analysis by simple linear regression assessing the association between the variables analyzed with the fetal age. Results: Gestational age ranged from 12 to 23 weeks post conception. Mean renal parenchymal area of the right kidney was 666.22mm3 (45.86 to 2375.35mm3) and for the left kidney was 606.76mm3 (68.63 to 2402.57mm3). No statistical difference was observed between the sides (p-value = 0.3456) or genders (p-value = 0.07429). Linear regression between renal parenchymal volume and gestational age was positive for right kidney (y = 133.74x-1479.94 / r2 = 0.4009) and left kidney (y = 149.53x-1761.59 / r2 = 0.4591). Conclusions: The linear regression analysis indicated that renal parenchymal area correlated significantly and positively with fetal age, weight and crown-rump length with no statistical differences between gender or laterality. These growth curves provide a reference for functional volume of the kidney during fetal period.

The magnitude of syphilis: from prevalence to vertical transmission.

INTRODUCTION: In 2013, the World Health Organization (WHO) reported that 1.9 million pregnant women were infected with syphilis worldwide, of which 66.5% had adverse fetal effects in cases of untreated syphilis. Congenital syphilis contributes significantly to infant mortality, accounting for 305,000 perinatal deaths worldwide annually. AIM: To estimate the prevalence of syphilis in parturients, the incidence of congenital syphilis and the vertical transmission rate. MATERIAL AND METHODS: a cross-sectional study with data collected from 2041 parturients who had undergone treatment between 2012 and 2014 in the maternity section of the Pedro Ernesto Hospital of the State University of Rio de Janeiro, in the metropolitan area of Rio de Janeiro. The inclusion criterion was positive VDRL and treponemal test in a hospital environment. RESULTS: the prevalence of syphilis in pregnant women was 4.1% in 2012, 3.1% in 2013 and 5% in 2014, with official reporting of 15.6%, 25.0% and 48.1%, respectively. The incidence of congenital syphilis (CS) was 22/1,000 in live births (LB) in 2012; 17/1,000 LB in 2013 and 44.8/1,000 LB in 2014. CS underreporting during the period was 6.7%. Vertical transmission occurred in 65.8% of infants from infected mothers. It was concluded that, in 34.6% of the CS cases, maternal VDRL titers were = 1/4. CONCLUSION: Results demonstrate the magnitude of the disease, fragility of the reporting system in the assessment of the actual prevalence, impact on perinatal outcomes, and they are a warning about the real situation of syphilis, which is still underestimated in the State.

Profile of Brazilian smokers in the National Program for Tobacco Control.

OBJECTIVE: The treatment of tobacco addiction in Brazil has expanded in recent years; however, we must increase knowledge about the characteristics of individuals who adhere to cessation programs in order to adjust treatments to specific characteristics of the target population that favor success. The aim of this study was to describe the characteristics of smokers who present to Brazilian public health units seeking help to quit smoking based on the experience of a primary health care unit that covers a poor community in the city of Rio de Janeiro. METHODS: Data were collected at a Teaching Health Center from January 03 2012 to January 03 2014. RESULTS: Mean patient age was 49.32 ± 11.82 years, and 71% were women. About half of the participants successfully quit smoking (n=125, 51%). Higher levels of nicotine dependence were associated with lower levels of smoking cessation. There was a notable decrease in the probability of remaining smoking throughout the first month of treatment. After 3 weeks of treatment, only 19% had not quit smoking. The probability of quitting smoking decreases by 2% for every additional year of age. CONCLUSION: There is a need to revise and expand current strategies to make them more effective in preventing smoking since childhood.

Age-period-cohort analysis of suicide rates in Rio de Janeiro, Brazil, 1979-1998.

BACKGROUND: Recent studies in Brazil have demonstrated that suicide rates have been rising over the last years. The objective of this study was to investigate trends in suicide from 1979 to 1998 in Rio de Janeiro State, with emphasis on age, period, and cohort effects. METHOD: Age-specific suicide rates from 1979 to 1998 were estimated for males and females based on mortality data obtained from the Brazilian Mortality Information System, and population counts from the 1980, 1991 and 2000 censuses. Poisson regression and graphical methods were used to evaluate age, period and cohort effects. RESULTS: Suicide rates increased steadily with age, particularly among males. In both males and females, age-adjusted suicide rates decreased until 1992. In 1993, rates started to rise. Cohort effects showed that younger generations had significantly lower rates of suicide than older ones. CONCLUSION: The recent rise in suicide rates might be a result of the increasing levels of firearm availability, drug use, and unemployment. Follow-up over longer periods and powerful epidemiological studies are needed to sustain the implication of socio-economic changes in the observed features.