Redefining the Role of Ornithine Aspartate and Vitamin E in Metabolic-Dysfunction-Associated Steatotic Liver Disease through Its Biochemical Properties.

It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation.

Objective: To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods: We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results: Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion: Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

Does Swimming Exercise Impair Bone Health? A Systematic Review and Meta-Analysis Comparing the Evidence in Humans and Rodent Models.

BACKGROUND: The effect of swimming on bone health remains unclear, namely due to discrepant findings between studies in humans and animal models. OBJECTIVE: The aim of this systematic review and meta-analysis is to identify the available evidence on the effects of swimming on bone mass, geometry and microarchitecture at the lumbar spine, femur and tibia in both humans and rodent animal models. METHODS: The study followed PRISMA guidelines and was registered at PROSPERO (CRD4202236347 and CRD42022363714 for human and animal studies). Two different systematic literature searches were conducted in PubMed, Scopus and Web of Science, retrieving 36 and 16 reports for humans and animal models, respectively. RESULTS: In humans, areal bone mineral density (aBMD) was similar between swimmers and non-athletic controls at the lumbar spine, hip and femoral neck. Swimmers' tibia diaphysis showed a higher cross-sectional area but lower cortical thickness. Inconsistent findings at the femoral neck cortical thickness were found. Due to the small number of studies, trabecular microarchitecture in human swimmers was not assessed. In rodent models, aBMD was found to be lower at the tibia, but similar at the femur. Inconsistent findings in femur diaphysis cross-sectional area were observed. No differences in femur and tibia trabecular microarchitecture were found. CONCLUSION: Swimming seems to affect bone health differently according to anatomical region. Studies in both humans and rodent models suggest that tibia cortical bone is negatively affected by swimming. There was no evidence of a negative effect of swimming on other bone regions, both in humans and animal models.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease.

BACKGROUND: Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM: To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS: Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS: Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION: Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.

Body Composition Changes in Adolescents Who Underwent Bariatric Surgery: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: The purpose of this review and meta-analysis is to characterize the changes in body composition of children and adolescents who underwent bariatric surgery and identify possible negative effects of performing this procedure during pediatric ages. RECENT FINDINGS: Bariatric surgery in children and adolescents is an emerging strategy to promote higher and faster body weight and fat mass losses. However, possible negative effects usually observed in surgical patients' muscle-skeletal system raise a major concern perform this intervention during growth. Despite these possible issues, most experimental studies and reviews analyze bariatric surgery's effectiveness only by assessing anthropometric outcomes such as body weight and BMI, disregarding the short- and long-term impact of bariatric surgery on all body composition outcomes. Bariatric surgery is effective to reduce fat mass in adolescents, as well as body weight, waist circumference, and BMI. Significant reduction in lean mass and fat-free mass is also observed. Bone mass seems not to be impaired. All outcomes reduction were observed only in the first 12 months after surgery. Sensitivity analysis suggests possible sex and type of surgery-related differences, favoring a higher fat mass, body weight, and BMI losses in boys and in patients who underwent RYGB.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation

Abstract Objective To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

O arquétipo do mestre-aprendiz - Considerações sobre a vivência / The master-apprentice archetype ­ Considerations about the experience / El arquetipo del maestro-aprendiz ­ Consideraciones sobre la vivencia

A partir de sua experiência como professora e como aluna, a autora tece reflexões sobre o campo de interação constelado pelo arquétipo do mestre-aprendiz. O "Teatro Arquetípico", ou "Mitodrama", é apresentado tal como é formulado por sua autora, tal como tem sido realizado numa disciplina do curso de graduação em Psicologia, e tal como pode ser enriquecido em alguns aspectos por contribuições de Erich Neumann sobre a fase do self corporal e de Juana Elbein dos Santos sobre o sistema Nagô. O artigo faz ainda algumas considerações sobre as relações e as diferenças entre a psicoterapia e a pedagogia, e termina por ressaltar a importância da palavra que "rasga a fantasia", permitindo o fluir da elaboração simbólica embasada no vivido.

Drawing from her experience as both a professor and a student, the author reflects upon the field of interaction constellated by the master-apprentice archetype. The "Archetypal Theater", or "Mythodrama", is presented as it is formulated by its author, as it is implemented in a course within the undergraduate Psychology program at the University of Sao Paulo, and as it can be enriched in certain aspects by contributions from Erich Neumann regarding the phase of the body-self and from Juana Elbein dos Santos regarding the Nagô system. The article also offers some considerations on the relationships and differences between psychotherapy and pedagogy and concludes by emphasizing the importance of the words, which allow the flow of symbolic elaboration grounded on experience.

A partir de su experiencia como profesora y como alumna, la autora teje reflexiones sobre el campo de interacción constelado por el arquetipo del maestro-aprendiz. El "Teatro Arquetípico", o "Mitodrama", se presenta tal como es formulado por su autora, tal como ha sido realizado en una disciplina del curso de graduación en Psicología, y tal como puede ser enriquecido en algunos aspectos por contribuciones de Erich Neumann sobre la fase del self corporal y de Juana Elbein dos Santos sobre el sistema Nagô. El artículo hace aún algunas consideraciones sobre las relaciones y diferencias entre la psicoterapia y la pedagogía, y termina por resaltar la importancia de la palabra que "rasga la fantasia", permitiendo el fluir de la elaboración simb6lica basada en lo vivido.

Impact of Long-Term Swimming Exercise on Rat Femur Bone Quality.

Considering the conflicting evidence regarding the potential long-term detrimental effect of swimming during growth on femur quality and fracture risk, our aim was to investigate the effect of eight months of swimming on femur quality. Twenty male eight-week-old Wistar rats were assigned into a swimming (SW; n = 10; 2 h/day, 5 days/week) or active control group (CG; n = 10, housed with running wheel) for eight months. Plasma osteocalcin and C-terminal telopeptide of type I collagen concentrations (ELISA) were assessed at baseline, four, and eight months of protocol. Femur structure (micro-computed tomography), biomechanical properties (three-point bending), and cellular density (histology) were determined after the protocol. SW displayed a lower uncoupling index, suggesting higher bone resorption, lower empty lacunae density, cortical and trabecular femur mass, femur length and cortical thickness, and higher cortical porosity than CG (p < 0.05). Although both biomarkers' concentrations decreased in both groups throughout the experiment (p < 0.001), there were no significant differences between groups (p > 0.05). No differences were also found regarding biomechanical properties, bone marrow adiposity, and osteocyte and osteoclast densities (p > 0.05). Long-term swimming was associated with unbalanced bone turnover and compromised femur growth, lower femur mass, and deteriorated cortical bone microarchitecture. However, femur trabecular microarchitecture and biomechanical properties were not affected by swimming.

Ornithine Aspartate and Vitamin-E Combination Has Beneficial Effects on Cardiovascular Risk Factors in an Animal Model of Nonalcoholic Fatty Liver Disease in Rats.

Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1ß, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.

Bone Tissue Responsiveness To Mechanical Loading-Possible Long-Term Implications of Swimming on Bone Health and Bone Development.

PURPOSE OF REVIEW: To revisit the bone tissue mechanotransduction mechanisms behind the bone tissue response to mechanical loading and, within this context, explore the possible negative influence of regular swimming practice on bone health, particularly during the growth and development period. RECENT FINDINGS: Bone is a dynamic tissue, responsive to mechanical loading and unloading, being these adaptative responses more intense during the growth and development period. Cross-sectional studies usually report a lower bone mass in swimmers compared to athletes engaged in weigh-bearing sports. However, studies with animal models show contradictory findings about the effect of swimming on bone health, highlighting the need for longitudinal studies. Due to its microgravity characteristics, swimming seems to impair bone mass, but mostly at the lower limbs. It is unkown if there is a causal relationship between swimming and low BMD or if other confounding factors, such as a natural selection whithin the sport, are the cause.

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 µg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 µg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

Comparison of Climacteric Symptoms, Quality of Life, and Self-Care Attitudes before and during the COVID-19 Pandemic.

OBJECTIVES: This study aimed to compare the climacteric symptoms, quality of life indices, and self-care attitudes in women before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study was conducted between January 2020 and September 2021. The sample consisted of 342 climacteric women who were divided into two groups: before the pandemic (BP group; n = 62) and during the pandemic (DP group; n = 280). The Menopause Rating Scale and Women's Health Questionnaire were used to measure the health-related quality of life and degree of climacteric symptoms reported by women. RESULTS: During the COVID-19 pandemic, women were able to decrease their somatic symptoms derived from the climacteric period (BP group: 7.84 ± 4.46, DP group: 5.94 ± 9.20; P = 0.003). CONCLUSIONS: There was no worsening in the self-reported symptoms, quality of life, and self-care attitudes of climacteric women because of the COVID-19 pandemic. Moreover, only somatic symptoms decreased during the pandemic.

Nosocomial meningitis in intensive care: a 10-year retrospective study and literature review.

BACKGROUND: Nosocomial meningitis is a medical emergency that requires early diagnosis, prompt initiation of therapy, and frequent admission to the intensive care unit (ICU). METHODS: A retrospective study was conducted in adult patients diagnosed with nosocomial meningitis who required admission to the ICU between April 2010 and March 2020. Meningitis/ventriculitis and intracranial infection were defined according to Centers for Disease Control and Prevention guidelines. RESULTS: An incidence of 0.75% of nosocomial meningitis was observed among 70 patients. The mean patient age was 59 years and 34% were ≥65 years. Twenty-two percent of patients were in an immunocompromised state. A clear predisposing factor for nosocomial meningitis (traumatic brain injury, basal skull fracture, brain hemorrhage, central nervous system [CNS] invasive procedure or device) was present in 93% of patients. Fever was the most frequent clinical feature. A microbiological agent was identified in 30% of cases, of which 27% were bacteria, with a predominance of Gram-negative over Gram-positive. Complications developed in 47% of cases, 24% of patients were discharged with a Glasgow coma scale <14, and 37% died. There were no clear clinical predictors of complications. Advanced age (≥65 years old) and the presence of complications were associated with higher hospital mortality. CONCLUSIONS: Nosocomial meningitis in critical care has a low incidence rate but high mortality and morbidity. In critical care patients with CNS-related risk factors, a high level of suspicion for meningitis is warranted, but diagnosis can be hindered by several confounding factors.

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

Bovine Colostrum Supplementation Improves Bone Metabolism in an Osteoporosis-Induced Animal Model.

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.

Associations between nutrition, energy expenditure and energy availability with bone mass acquisition in dance students: a 3-year longitudinal study.

Three years of study showed that female and male vocational dancers displayed lower bone mass compared to controls, at forearm, lumbar spine and femoral neck. Energy intake was found to positively predict bone mass accruals only in female dancers at femoral neck. Vocational dancers can be a risk population to develop osteoporosis. PURPOSE: To determine whether risk factors normally associated with low bone mass in athletic populations (i.e. nutrition intake, energy expenditure and energy availability) are significant predictors of bone mass changes in vocational dance students. METHODS: The total of 101 vocational dancers (63 females, 12.8 ± 2.2 years; 38 males, 12.7 ± 2.2 years) and 115 age-matched controls (68 females, 13.0 ± 2.1 years; 47 males, 13.0 ± 1.8 years) were monitored for 3 consecutive years. Bone mass parameters were measured annually at impact sites (femoral neck, FN; lumber spine, LS) and non-impact site (forearm) using DXA. Nutrition (3-day record), energy expenditure (accelerometer), energy availability and IGF-1 serum concentration (immunoradiometric assays) were also assessed. RESULTS: Female and male vocational dancers had consistently reduced bone mass at all anatomical sites (p < 0.001) than controls. IGF-1 did not differ between male vocational dancers and controls, but female dancers showed it higher than controls. At baseline, calcium intake was significantly greater in female vocational dancers than controls (p < 0.05). Male vocational dancers' fat and carbohydrate intakes were significantly lower than matched controls (p < 0.001 and p < 0.05, respectively). Energy availability of both female and male vocational dancers was within the normal range. A significant group effect was found at the FN regarding energy intake (p < 0.05) in female dancers. No significant predictors were found to explain bone mass differences in males. CONCLUSION: Our 3-year study revealed that both female and male vocational dancers displayed lower bone mass compared to controls, at both impact and non-impact sites. The aetiology of these findings may be grounded on factors different than those usually considered in athletic populations.

The role of 68Gallium-prostate-specific membrane antigen positron emission tomography on staging of high-risk localized prostate cancer: for all high-risk patients or would it be better to select them?

BACKGROUND: According to pathologico-clinical features, patients diagnosed with localized prostate cancer (PCa) are stratified into distinct risk groups (low-risk, intermediate-risk or high-risk). Data have demonstrated that 68Gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET/CT) is superior to conventional radiological exams (CT or MRI and bone scintigraphy) in the primary staging of high-risk localized PCa. However, it is still unknown if in a population of high-risk PCa, there would be a subgroup of patients with a higher probability of identifying metastatic disease by the 68Ga-PSMA PET/CT. MATERIALS AND METHODS: Data from patients with localized PCa who underwent 68GA-PSMA PET/CT for primary staging from four institutions were retrospectively collected. We selected patients with at least one D'Amico classification risk factor (International Society of Urological Pathology ≥ IV and/or prostate-specific antigen > 20 ng/ml). To detect an association between extent of disease and number of risk factors as well as International Society of Urological Pathology prostate cancer grade, contingency tables were used, and Fisher Exact Test was performed. RESULTS: Between 2016 and 2020, 60 patients underwent a 68GA-PSMA PET/CT for primary staging of high-risk localized PCa. Regarding the number of risk factors, 37 patients (62%) had one risk factor, and 23 (38%) had two risk factors. In the subgroup of patients with metastatic disease (n = 22), those with two risk factors had higher incidence of metastatic disease, and it was statistically significant (p = 0.011). CONCLUSION: This retrospective analysis demonstrated that 68GA-PSMA PET/CT was able to identify advanced disease in more than one-third of patients with high-risk disease especially those with two adverse risk factors.

Caracterização físico-química, fitoquímica e avaliação da eficácia antimicrobiana de um gargarejo fitoterápico / Physico-chemical characterization, phytochemistry and evaluation of the antimicrobial efficacy of an herbal medicine gargle / Caracterización fisicoquímica, fitoquímica y evaluación de la eficacia antimicrobiana de unas gárgaras de hierbas medicinales

RESUMO Objetivo: Considerando a importância dos produtos naturais de uso tradicional, o trabalho propôs a avaliação de parâmetros de qualidade e atividade antimicrobiana in vitro do gargarejo produzido no Centro de Educação Popular (Cenep), Nova Palmeira (PB), e utilizado para o tratamento de afecções da orofaringe e amígdalas. Metodologia: Três amostras de gargarejo foram analisadas para avaliar o aspecto microbiológico sendo realizada a contagem de micro-organismos viáveis, por semeadura em profundidade. Materiais e métodos: A avaliação da atividade antimicrobiana in vitro contra S. pyogenes foi realizada utilizando o método de difusão em ágar e os parâmetros físico-químicos determinados foram pH, resíduo seco, densidade, bem como a caracterização fitoquímica. Resultados: Apresentaram contagem microbiana dentro dos limites estabelecidos pela Farmacopeia. A atividade antimicrobiana contra S. pyogenes apresentou halos de inibição variando de 10,5 a 18,6 mm para amostra diluída e pura, respectivamente. Os parâmetros físico-químicos apresentaram pH 4,39 ± 0,16; o resíduo seco de 13,4 % a 15,4 %; e a densidade de 1,013 ± 0,010. O perfil fitoquímico foi caracterizado pela presença de taninos, alcaloides e flavonoides. Conclusões: O gargarejo apresentou-se adequado para uso, tendo em vista os parâmetros microbiológicos, físico-químicos, fitoquímicos apresentados, bem como a comprovação da eficácia antimicrobiana adequada ao uso terapêutico proposto.

SUMMARY Aim: Considering the importance of natural products of traditional use, the work proposed the evaluation of quality parameters and in vitro antimicrobial activity of the gargle produced at the Popular Education Center (Cenep), Nova Palmeira (PB), and used for the treatment of oropharynx and tonsil disorders. Methodology: Three gargle samples were analyzed, in order to evaluate the microbiological aspect, the count of viable microorganisms was performed, by pour plate method. Materials and methods: The evaluation of antimicrobial activity in vitro against S. pyogenes was performed using the agar diffusion method and the physicochemical parameters determined were pH, dry residue, density, as well as phytochemical characterization. Results: They had microbial counts within the limits established by the pharmacopoeia. The antimicrobial activity against S. pyogenes had inhibition halos ranging from 10.5 to 18.6 mm for diluted and pure samples, respectively. The physical-chemical parameters showed pH 4.39 ± 0.16; the dry residue of 14.43 ± 1.00; and the density of 1.013 ± 0.010. The phytochemical profile was characterized by the presence of tannins, alkaloids and flavonoids. Conclusion: Thus, the gargle was suitable for use, considering the microbiological, physical-chemical, phytochemical parameters presented, as well as the proof of antimicrobial efficacy suitable for the proposed therapeutic use.

RESUMEN Objetivo: Considerando la importancia de los productos naturales de uso tradicional, el trabajo propuso la evaluación de los parámetros de calidad y la actividad antimicrobiana in vitro de la gárgaras producidas en el Centro de Educación Popular (Cenep), Nova Palmeira (PB), y utilizadas para el tratamiento de los trastornos de la orofaringe y las amígdalas. Metodología: Se analizaron tres muestras de gárgaras para evaluar el aspecto microbiológico, se realizó el recuento de microorganismos viables, sembrando en profundidad. Materiales y métodos: La evaluación de la actividad antimicrobiana in vitro contra S. pyogenes se hizo mediante el método de difusión en agar y los parámetros fisicoquímicos determinados fueron pH, residuo seco, densidad, así como caracterización fitoquímica. Resultados: Hubo recuentos microbianos dentro de los límites establecidos por la Farmacopea. La actividad antimicrobiana contra S. pyogenes tenía halos de inhibición que oscilaban entre 10,5 y 18,6 mm para muestras diluidas y puras, respectivamente. Los parámetros físico-químicos mostraron un pH que oscila entre 4,39 ± 0,16; el residuo seco del 14,43 ± 1,00; y la densidad de 1,013 ± 0,010. El perfil fitoquímico se caracterizó por la presencia de taninos, alcaloides y flavonoides. Conclusión: Por lo tanto, la gárgara demostró ser adecuada para su uso, considerando los parámetros microbiológicos, fisicoquímicos, fitoquímicos presentados, así como la prueba de la eficacia antimicrobiana adecuada para el uso terapéutico propuesto.

Understanding the mechanism of action of peptide (p-BthTX-I)2 derived from C-terminal region of phospholipase A2 (PLA2)-like bothropstoxin-I on Gram-positive and Gram-negative bacteria.

Based on the antimicrobial activity of bothropstoxin-I (BthTX-I) and on the premise that a C-terminal peptide of Lys49 myotoxin can reproduce the antimicrobial activity of the parent protein, we aimed to study the mechanism of action of a peptide derived from the C-terminal region of the myotoxin BthTX-I [(p-BthTX-I)2, sequence: KKYRYHLKPFCKK, disulfide-linked dimer] against Gram-positive and Gram-negative bacteria. Fluorescence quenching technique showed that the carboxyfluorescein labeled-peptide [CF-(p-BthTX-I)2] when incubated with E. coli displayed a superior penetration activity than when incubated with S. aureus. Cell death induced by the peptide (p-BthTX-I)2 showed a loss of membrane integrity in E. coli and S. aureus; however, the mechanisms of cell death were different, characterized by the presence of necrosis-like and apoptosis-like deaths, respectively. Scanning electron microscopy studies in E. coli and S. aureus showed morphological changes in the cells, with superficial deformities, appearance of wrinkles and bubbles, and formation of vesicles. Our results demonstrate that the mechanism of action of the peptide (p-BthTX-I)2 is different in Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Knowledge of the mechanism of action of these peptides is important, since they are promising prototypes for new antimicrobial drugs.