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INTRODUCTION: Although a well-established component of bone metabolism, the efficacy and safety of vitamin D supplementation for the prevention of fractures in elderly healthy individuals is still unclear. PURPOSE: To perform a meta-analysis comparing vitamin D supplementation with placebo and its contributions on fracture incidence. METHODS: This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under protocol CRD42023484979. We systematically searched PubMed, Embase, and Cochrane Central databases from inception to November 2023 for randomized controlled trials (RCTs) comparing vitamin D supplementation versus placebo in individuals with 60 years of age or more and without bone related medical conditions such as cancer and osteoporosis. RESULTS: Seven RCTs with 71,899 patients were included, of whom 36,822 (51.2%) were women. There was no significant difference in total fracture incidence (RR 1.03; 95% CI 0.93-1.14; p = 0.56; I2 = 58%) between groups or subgroups. However, women had an increased risk for hip fractures (164 vs. 121 events; RR 1.34; 95% CI 1.06-1.70; p = 0.01; I2 = 0%). There was no significant difference in non-vertebral fractures, osteoporotic fractures development, or falls (RR 1.02; 95% CI 0.94-1.12; p = 0.6; I2 = 47%; RR 0.97; 95% CI 0.87-1.08; p = 0.63; I2 = 0%; RR 1.01; 95% CI 0.97-1.04; p = 0.66; I2 = 55%, respectively). CONCLUSION: Vitamin D supplementation does not reduce the total fracture development rate in the elderly healthy population, and it may increase the incidence of hip fractures among elderly healthy women. This finding suggests refraining from prescribing high intermittent doses of vitamin D, without calcium, to individuals aged 60 or older with unknown vitamin D serum concentration or osteoporosis status and inadequate calcium intake.
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This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42 e and 49 b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory inâ vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.
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The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter hypertrophy (MH). Twenty-six women complaining about lower third facial enlargement due to MH, received 75 U of BoNT-A (abobotulinum toxin) in each masseter muscles. After 3 months, patients were randomly assigned to receive a second treatment session of Saline Solution: (G1; n = 11) or BoNT-A: (G2; n = 12). Muscle thickness (ultrasound), electrical activity (electromyography; EMG), masticatory performance, and subjective perception of MH were evaluated. Follow-up was performed at 1, 3 and 6 months. Muscle thickness, EMG activity, and masticatory performance were analyzed using ANOVA two-way and Sidak test as post-hoc. Masticatory performance was analyzed by the Friedman's test and Mann-Whitney test. Regarding inter-groups comparisons, there was a significant decrease in the left masseter muscle thickness in the G2 group at the 6 month follow-up (p < 0.02). For EMG, significant differences were evident at the 6 month assessment, with higher masseter activity for G1 (p < 0.05). For masticatory performance, no significant differences were observed throughout the study (p > 0.05) and a higher improvement in subjective perception of MH was observed in the 1 month follow-up for G2 (p < 0.05). In conclusion, BoNT-A is effective for MH, however multiple injections cause functional adverse effects in masseter muscle.
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Toxinas Botulínicas Tipo A , Eletromiografia , Hipertrofia , Músculo Masseter , Humanos , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/patologia , Músculo Masseter/anormalidades , Feminino , Hipertrofia/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Adulto , Mastigação/efeitos dos fármacos , Pessoa de Meia-Idade , Resultado do Tratamento , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Injeções IntramuscularesRESUMO
Background: Resistance training with instability (REI) emerged as a promising training modality for older adults aiming to counteract age-related changes. Objectives: We compared the effects of 12 weeks of REI and traditional resistance exercise (RE) on muscle strength in older adults with cognitive impairment. We further explored if total training volume (TTV) significantly differs among training groups. Methods: This is a secondary analysis of the REI study. Participants were randomly assigned to REI (n=22) or RE (n=23). RE protocol involved moderate-intensity, free-weight, and machines-based resistance exercises (3 sets, 10-15 repetitions). REI received a similar training protocol, in which exercises were simultaneously performed with instability/unstable devices (e.g., squat exercise under a foam pad or Bosu® ball). Maximal isometric strength and isokinetic parameters were assessed at baseline and after completion of a 12-week intervention through a hydraulic handgrip and isokinetic dynamometer, respectively. TTV (sets × repetitions × load) was computed based on external training load over the 12 weeks. Results: No differences were observed between groups (p=.35) after the intervention. Over 12 weeks, REI and RE improved isometric handgrip strength (p<.001) and isokinetic performance (p=.04). We also did not find differences in the TTV between training groups (p=.28). Conclusion: We demonstrated that both REI and RE training induced similar gains in muscle strength. Combining unstable surfaces/instability devices did not hamper TTV, which may have clinical applications in the context of exercise for older adults.
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Introduction: Glycemia is an important factor among critically ill patients in the intensive care unit (ICU). There is conflicting evidence on the preferred strategy of blood glucose control among patients with diabetes in the ICU. We aimed to conduct a meta-analysis comparing tight with liberal blood glucose in critically ill patients with diabetes in the ICU. Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing tight versus liberal blood glucose control in critically ill patients with diabetes from inception to December 2023. We pooled odds-ratios (OR) and 95% confidence intervals (CI) with a random-effects model for binary endpoints. We used the Review Manager 5.17 and R version 4.3.2 for statistical analyses. Risk of bias assessment was performed with the Cochrane tool for randomized trials (RoB2). Results: Eight RCTs with 4474 patients were included. There was no statistically significant difference in all-cause mortality (OR 1.11; 95% CI 0.95-1.28; P = .18; I² = 0%) between a tight and liberal blood glucose control. RoB2 identified all studies at low risk of bias and funnel plot suggested no evidence of publication bias. Conclusion: In patients with diabetes in the ICU, there was no statistically significant difference in all-cause mortality between a tight and liberal blood glucose control. PROSPERO registration: CRD42023485032.
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Ochratoxin A (OTA) is a toxin produced by several Aspergillus species, mainly those belonging to section Circumdati and section Nigri. The presence of OTA in cheese has been reported recently in cave cheese in Italy. As artisanal cheese production in Brazil has increased, the aim of this study was to investigate the presence of ochratoxin A and related fungi in artisanal cheese consumed in Brazil. A total of 130 samples of artisanal cheeses with natural moldy rind at different periods of maturation were collected. Of this total, 79 samples were collected from 6 producers from Canastra region in the state of Minas Gerais, since this is the largest artisanal cheese producer region; 13 samples from one producer in the Amparo region in the state of São Paulo and 36 samples from markets located in these 2 states. Aspergillus section Circumdati occurred in samples of three producers and some samples from the markets. A. section Circumdati colony counts varied from 102 to 106 CFU/g. Molecular analysis revealed Aspergillus westerdijkiae (67 %) as the most frequent species, followed by Aspergillus ostianus (22 %), and Aspergillus steynii (11 %). All of these isolates of A. section Circumdati were able to produce OTA in Yeast Extract Sucrose Agar (YESA) at 25 °C/7 days. OTA was found in 22 % of the artisanal cheese samples, ranging from 1.0 to above 1000 µg/kg, but only five samples had OTA higher than 1000 µg/kg. These findings emphasize the significance of ongoing monitoring and quality control in the artisanal cheese production process to minimize potential health risks linked to OTA contamination.
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Aspergillus , Queijo , Contaminação de Alimentos , Microbiologia de Alimentos , Ocratoxinas , Ocratoxinas/biossíntese , Ocratoxinas/análise , Queijo/microbiologia , Queijo/análise , Brasil , Aspergillus/metabolismo , Contaminação de Alimentos/análise , Contagem de Colônia MicrobianaRESUMO
INTRODUCTION: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD. AREAS COVERED: Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi, aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD. EXPERT OPINION: Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.
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Doença de Chagas , Descoberta de Drogas , Resistência a Medicamentos , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Nitroimidazóis/farmacologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Tripanossomicidas/farmacologia , Humanos , Animais , Descoberta de Drogas/métodos , Desenvolvimento de MedicamentosRESUMO
BACKGROUND: This study aimed to elucidate the effects of botulinum toxin A (BoNT-A) treatment for patients diagnosed with masseter hypertrophy on the temporalis muscle, with a particular focus on assessing alterations in muscle thickness, electromyographic (EMG) activity, and the development of muscle pain. METHODS: The present randomized triple-blinded clinical trial enrolled 26 female participants aged between 25 and 50 years complaining about masseter hypertrophy. Participants received 75U of BoNT-A (abobotulinumtoxinA) in both masseter muscles and after three months were randomized to receive a second treatment session of saline solution (S-BoNT-A) or BoNT-A (M-BoNT-A). Longitudinal assessments included temporalis muscle thickness through ultrasound, EMG activity, subjective pain, and masseter prominence severity after one, three, and six months of the first injection session. Muscle thickness, EMG, and subjective pain were analysed using two-way ANOVA with repeated measures and post hoc Sidak test, and for masseter prominence severity, Friedman and Mann-Whitney tests were used. RESULTS: Regarding inter-group comparisons, a higher muscle thickness (p < 0.02) and a higher EMG activity (p < 0.01) were found in the M-BoNT-A group at the 6-month follow-up. For subjective pain assessments, inter-group comparisons showed a higher prevalence of painful regions in M-BoNT-A group at the 6-month follow-up (p < 0.02). No significant differences were found in masseter prominence severity at the 6 months assessment between groups. CONCLUSION: BoNT-A treatment for masseter hypertrophy lead to structural and functional changes in the temporalis muscle, presenting higher changes after multiple injections of this treatment. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20 years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.
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Infecções Comunitárias Adquiridas , Meningite Pneumocócica , Recidiva , Streptococcus pneumoniae , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Adulto , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/classificação , Estudos Retrospectivos , Feminino , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Fatores de Risco , Sorogrupo , Antibacterianos , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/classificaçãoRESUMO
The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.