Hospital wastewater as source of human pathogenic bacteria: A phenotypic and genomic analysis of international high-risk clone VIM-2-producing Pseudomonas aeruginosa ST235/O11.

Pseudomonas aeruginosa belong to the special pathogen group capable of causing serious infections, with high mortality rates. The aim of this study was to describe the antibiotic resistance and genomic characteristics of Pseudomonas aeruginosa belonging to international high-risk clone ST235 (GPAE0131 isolate), obtained from hospital wastewater. P. aeruginosa GPAE0131 was isolated from ward tertiary hospital in Brazil and the antibiotic resistance profile was determined by the disc-diffusion method. Genomic characteristics related to antibiotic resistance and virulence factors were evaluated by genomic DNA sequencing on the Illumina MiSeq platform and bioinformatic analysis. GPAE0131 isolate showed resistance to piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, ciprofloxacin, levofloxacin and tobramycin. Resistome comprehend of resistance genes to ß-lactams (blaVIM-2, blaOXA-4, blaOXA-488, blaPDC-35), aminoglycosides (aph(3')-IIb, aac(6')-IIc, aac(6')-Ib9, aadA1), fosfomycin (fosA), chloramphenicol (catB7) and sulfonamides (sul1). Genome comparisons evidence insertion of blaVIM-2 and blaOXA-4 genes. GPAE0131 isolate was predicted to be pathogenic to humans and several virulence factors were found, including encoding gene for ExoU and exotoxin A. All of these features into a pathogenic international high-risk clone (ST235), classified as critical priority, stands out as public health concern due to the widespread dispersal of human pathogens through wastewater. It is suggested that mitigating measures be implemented, such as the treatment of hospital sewage and the addition of tertiary treatment, to prevent the escape of pathogens at this level into the environment.

Rapid colorimetric polymyxin B microelution directly from positive blood bottles: because patients with serious infections should not have to wait for results of culture-based methodologies.

PURPOSE: To evaluate the performance of the rapid colorimetric polymyxin B microelution (RCPEm) in determining polymyxin B resistance directly from Enterobacterales-positive blood cultures. METHODS: A set volume of positive blood culture bottles (diluted 1:10) was inoculated into a glucose-broth-phenol red solution (NP solution), where a polymyxin B disk was previously eluted (final concentration of 3 µg/mL). Test was read each 1 h for up to 4 h. Color change from red/orange to yellow indicated resistant isolates. Results were compared to the reference method, broth microdilution (BMD), performed from colonies grown on solid media from the same blood culture bottle. RESULTS: One hundred fifty-two Enterobacterales-positive blood cultures were evaluated, 22.4% (34/152) of them resistant to polymyxin B (including 6.6% with borderline MICs). When performing directly from positive blood cultures (RCPEm-BC), specificity and sensitivity were 99.1% and 94.1%, respectively. Of note, 79.4% (27/34) of truly resistant isolates required 3 h of incubation, compared to the 18 ± 2 h incubation that microtiter plates of BMD demand before reading can be performed. CONCLUSIONS: RCPEm directly from blood cultures has great potential to be part of the routine of clinical microbiology laboratories to establish polymyxin B susceptibility, impacting outcome of patients with bloodstream infections caused by carbapenem-resistant Enterobacterales.

Evaluation of the ceftazidime/avibactam and meropenem susceptibility by MALDI-TOF MS directly from positive blood cultures.

The purpose of this study was to evaluate the MBT-ASTRA to determine susceptibility to ceftazidime/avibactam (CZA) and meropenem (MEM) of Enterobacterales directly from positive blood cultures (BC). Bacterial suspension was incubated with antibiotic and analyzed by MALDI-TOF MS. The relative growth was calculated and cutoff values were determined to categorize isolates as "S," "I," and "R." Klebsiella spp. with CZA 20/8 mg/L and 1.5-h incubation presented 1 (5.9%) major discrepancy and 96.3% category agreement; other species required 2.5 h for 100% category agreement. For MEM, 4 mg/L and 1.5h were necessary, demonstrating 2 (6.67%) minor discrepancies and 93.3% categorical agreement.

Combined ultrasound and electric field stimulations improve pain and functional capacity in immediate cesarean delivery: a randomized clinical trial, double-blind, and placebo-controlled / Terapia combinada de estimulação elétrica por meio do ultrassom melhora a dor e a capacidade funcional no pós-parto imediato de cesariana: ensaio clínico randomizado, duplo-cego e placebo

ABSTRACT BACKGROUND AND OBJECTIVES: Wound complications and pharmacological pain relief methods used at the skin surgical site after cesarean delivery may result in women's physical and emotional burden. Thus, nonpharmacological treatments must be explored to avoid these complications and side effects on maternal health. The objective of this study was to investigate the effects of Combined Ultrasound and Electric Field Stimulation (CUSEFS) on cicatricial pain and functional capacity in immediate cesarean delivery. METHODS: This study has a randomized clinical trial, double-blind, and placebo-controlled design. Thirty women (25.7±5.0 years) in immediate postpartum were randomly assigned to three groups: Control (CG, n:9), CUSEFS (TG, n:11), and Placebo (PG, n:10). CUSEFS was performed once for 20 minutes. Cicatricial pain (McGill Pain Questionnaire) and functional capacity (Functional Capacity Check) was assessed at baseline, after the intervention, and after 30 minutes. Cohen's (d) and Mixed-design analysis of variance were used to compare groups. RESULTS: Immediately after the intervention, TG showed a decrease in cicatricial pain compared with CG in sensory (d:3.8 to 4.0), affective (d:4.0), and total categories (d:3.9). In functional capacity, TG had less difficulty than CG at walking (d:0.6) and lying down (d:1.1), and PG at rest (d: 0.9). CONCLUSION: CUSEFS might be a resource for managing cicatricial pain and functional capacity in immediate cesarean delivery. Further studies with longer duration and different CUSEFS doses/parameters are required.

RESUMO JUSTIFICATIVA E OBJETIVOS: As complicações na ferida e o uso de métodos farmacológicos de alívio da dor no local cirúrgico após a cesariana podem resultar em sobrecarga física e emocional para a mulher. Assim, tratamentos não farmacológicos devem ser explorados para evitar essas complicações e efeitos adversos à saúde materna. O objetivo deste estudo foi investigar os efeitos da terapia combinada de estimulação elétrica por meio do ultrassom (CUSEFS) na dor cicatricial e na capacidade funcional no pós-parto imediato de cesariana. MÉTODOS: Este estudo possui um desenho de ensaio clínico randomizado, duplo-cego e controlado por placebo. Trinta mulheres (25,7±5,0 anos) em pós-parto imediato de cesariana foram distribuídas aleatoriamente em três grupos: Controle (CG, n:9), CUSEFS (TG:11) e Placebo (PG, n:10). O CUSEFS foi realizado uma vez por 20 minutos. A dor cicatricial (Questionário de Dor McGill) e a capacidade funcional (Functional Capacity Check) foram avaliadas no início, após a intervenção e após 30 minutos. As análises de variância de design misto e Cohen (d) foram usadas para comparar os grupos. RESULTADOS: Imediatamente após a intervenção, o TG apresentou diminuição na dor cicatricial em relação ao CG nas categorias sensorial (d:3,8 a 4,0), afetiva (d:4,0) e total (d:3,9). Na capacidade funcional, o TG apresentou menor dificuldade que o CG na marcha (d:0,6) e deitado (d:1,1), e que o PG em repouso (d:0,9). CONCLUSÃO: O CUSEFS pode ser um recurso para o manejo da dor cicatricial e da capacidade funcional imediatamente após a cesariana. Além disso, são necessários mais estudos com maior duração e diferentes doses/parâmetros de CUSEFS.

Detection of polymyxins resistance among Enterobacterales: evaluation of available methods and proposal of a new rapid and feasible methodology.

BACKGROUND: Fast and accurate detection of polymyxins resistance is necessary as they remain the last resources to treat infections caused by Carbapenem-resistant Enterobacterales in many regions. We evaluated the rapid colorimetric polymyxin B elution (RCPE) and developed its miniaturized version, RCPE microelution (RCPEm), aiming to detect polymyxins resistance among Enterobacterales. METHODS: The methodologies consist of exposing the bacterial population in a solution (NP solution) where polymyxin B disks were previously eluted to obtain a concentration of 2 µg/mL for RCPE and 3 µg/mL for RCPEm. RESULTS: Two hundred sixty-seven Enterobacterales were evaluated, 90 (33.7%) resistant to polymyxin B by broth microdilution. It was observed 0.6% of major error (ME) by RCPE, with a specificity of 99.4%. The miniaturized version (RCPEm) presented the same ME and specificity values, but slightly higher sensitivity (97.8% vs. 95.6%) with 2.2% of very major error (VME). CONCLUSIONS: RCPE and RCPEm proved to be useful alternatives to determine polymyxin B susceptibility in clinical microbiology laboratories, presenting low cost, being easy to perform, and demanding short incubation time.

Copper-Catalyzed Synthesis of Pyrrolo[1,2-c]quinazolines and Pyrrolo[2,1-a]isoquinolines and Antiplasmodial Evaluation.

Reactions involving C(sp3)-H bonds of azaarenes have been widely studied in recent years as they allow direct functionalization of these N-heterocycles without the use of harsh reaction conditions. In this work, we describe the C(sp3)-H functionalization of 4-methylquinazolines and 1-benzylisoquinolines, employing α-substituted ß-nitrostyrenes catalyzed by inexpensive copper acetate. Under the optimized condition, 21 pyrrolo[1,2-c]quinazolines, as well as an imidazo[1,2-c]quinazoline and 4 pyrrolo[2,1-a]isoquinolines, were obtained in moderate to good yields. Furthermore, the biological activity of the pyrrolo[1,2-c]quinazolines was evaluated against Plasmodium falciparum, and promising results were obtained.

The Brazilian Portuguese version of the Pregnancy Mobility Index: Cross-cultural adaptation and psychometric evaluation - a validation study.

BACKGROUND: The Pregnancy Mobility Index (PMI) was developed to assess mobility in pregnant women in the Netherlands. At present, no similar questionnaire is available in Brazil. OBJECTIVE: The present study aimed to translate, cross-culturally adapt, and evaluate the psychometric properties of a Brazilian PMI. DESIGN AND SETTING: The present study was a validation study conducted at the Universidade Federal do Paraná and a public maternity ward in Curitiba, Brazil. METHODS: Text translation and cross-cultural adaptation followed international guidelines. Construct validity, internal consistency, and inter- and intra-rater reliability tests included 97 women. The Pelvic Girdle Questionnaire, Multidimensional Pain Evaluation Scale, Schober's test, and lumbar spine range of motion assessment were administered on the first day. Intra-rater reliability (n = 19) was measured after 15 days. Exploratory factor analysis was performed, and the correlation matrix was analyzed using Pearson's coefficient. RESULTS: Pregnant women (88%) understood the cultural adaptation process. The internal consistency was high (Cronbach's alpha > 0.90), construct validity was moderate, with significant correlation between lumbar spine range of motion (r = 0.283-0.369) and Schober's test (r = -0.314), and high correlation between the Multidimensional Pain Evaluation Scale (r = -0.650 and -0.499) and Pelvic Girdle Questionnaire (r = -0.737). Intra- and inter-rater reliabilities were excellent (intraclass correlation coefficient = 0.932 and 0.990, respectively). CONCLUSION: The Brazilian version of the PMI was successfully translated with excellent reliability and moderate-to-high construct validity. It is an important tool for assessing mobility in pregnant women. CLINICAL TRIAL: RBR-789tps (Validation study), https://ensaiosclinicos.gov.br/rg/RBR-789tps.

Direct Detection of KPC Peak from Positive Blood Cultures Using MALDI-TOF MS: Are We There Yet?

Detecting carbapenemase-associated carbapenem resistance is a subject of major clinical and epidemiological concern as it influences therapeutic choice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed as a means to assess bacterial resistance mechanisms. We aimed to detect the KPC enzyme directly from positive blood cultures using MALDI-TOF MS. To do so, 102 clinical Enterobacteria were evaluated, including 59 blaKPC positives. Proteins were extracted using formic acid, isopropyl alcohol, and water (17:33:50) and spotted onto a steel target plate using the double-layer sinapinic acid technique. Two parameters were considered: (i) the visual detection of a clear peak with the expected KPC m/z and (ii) the evaluation of the relative intensity of the ions in the peak. A peak was observed in 56/59 blaKPC-positive isolates (94.9% sensitivity), with no false-positive results (100% specificity). When considering intensity, with a cut-off ≥120 (a.u.), sensitivity was 94.9% and specificity was 95.3%. We proposed a "buffer" zone, with intermediate values of intensity (115 to 125) reaching 100% sensitivity and specificity. The detection of KPC peaks directly from positive blood cultures using MALDI-TOF MS is feasible and rapid, which may improve appropriate patient therapy and antimicrobial stewardship.

Nursing Home Residence, Overweight and Cognitive Status are Related to Falls in Older Adults: A Cross-sectional Study.

BACKGROUND: Nursing home residents are likely to differ from community older adults when their gait parameters are compared, as nursing home residents present more falls. AIM: The study aim was to identify the main fall (occurrence predictors) (anthropometrics, functional and gait-related parameters) between older adults living in community and nursing homes during self-selected (SSWS) and fast walking speeds (FWS). METHODS: A hundred and sixty-five older adults were selected from the community (n = 92) and nursing home (n = 73) with and without fall history. They were assessed for fall history, functionality, cognitive status, and several gait parameters in SSWS and FWS conditions. RESULTS: Fallers differed from non-fallers in the SSWS, while such differences were not evidenced during the FWS. Cadence and stride width did not differ when living backgrounds were compared. Nursing home residents walked slower than their non-institutionalized peers, regardless of fall history or walking speed. Besides, binary logistic regression analysis showed that living in a nursing home, age, body mass index (BMI), mini-mental state examination (MMSE), and step width were related to falls in the SSWS. On the other hand, living in a nursing home, having a larger BMI and having low MMSE scores were fall predictors in the FWS. CONCLUSION: Fall occurrence can be identified by factors related to living in nursing homes, cognitive status, BMI, and gait parameters, at the SSWS. Cognitive status and BMI are related to falls in the FWS for those living in nursing homes.

Are the spatiotemporal gait parameters at different walking speeds capable of predicting variations in cognitive status by the mini-mental state examination?

BACKGROUND: Several studies have reported the association between cognition and gait; however, most are limited to investigating gait in just one speed, usually the self-selected one, and commonly, only the general score of cognitive tests is used. AIMS: Investigate the relationship between the spatiotemporal gait parameters at different speeds (self-selected and fast walking speeds) and cognitive status in older adults. METHODS: Cross-sectional study. Two hundred and ninety-five older adults (70.9 ± 7.2 years; 82.3% women) were evaluated according to cognitive status (Mini-Mental State Examination, MMSE) and spatiotemporal gait parameters. RESULTS: Data analysis indicates that the spatiotemporal gait parameters (stride length, step time, and single support time) were able to predict cognitive status, assessed by the MMSE general score and its subdomain (temporal and spatial orientation) at both walking speeds. CONCLUSIONS: The spatiotemporal gait parameters were associated with cognitive status, assessed by the MMSE (general score and temporal and spatial orientation), regardless of the walking conditions. The model's variance was significant and with a large effect size. Stride length and step time were identified as the variables with the best explanatory factors. Therefore, it is concluded that greater cognitive performance is associated with longer stride lengths and faster step times.

A set of antibiotic-resistance mechanisms and virulence factors in GES-16-producing Klebsiella quasipneumoniae subsp. similipneumoniae from hospital wastewater revealed by whole-genome sequencing.

Klebsiella quasipneumoniae subsp. similipneumoniae has emerged as a human pathogen and sporadic isolates from non-clinical sources were reported. Here, we described the phenotypic- and genomic-characteristics of a multidrug-resistant (MDR) and potentially hypervirulent (MDR-hv) Klebsiella quasipneumoniae subsp. similipneumoniae (KqA1) isolated from hospital wastewater. The antibiotic susceptibility profile of KqA1 was investigated using disk-diffusion method, broth microdilution method, and agar dilution method, and the genetic characteristics of antimicrobial resistance, mobile genetics elements, and virulence were evaluated by genomic DNA sequencing on the Illumina® NovaSeq6000 platform as well as by bioinformatic analysis. Resistome analyses revealed the presence of genes related to resistance to ß-lactams, aminoglycosides, quinolones, tetracyclines, sulfonamides, trimethoprim, chloramphenicol, macrolides, and fosfomycin. New genetic contexts to blaGES-16 (carbapenemase gene) and to fosA (fosfomycin resistance gene) were described. A set of mechanisms that can contribute to antibiotic resistance, commonly detected in Klebsiella spp., was also found including chromosomal mutations, efflux systems, proteins, and regulators. Moreover, KqA1 presented genes related to tolerance to metals (arsenic, copper, nickel, cobalt, magnesium, cadmium, zinc, tellurium, selenium) and to biocides (quaternary-ammonium compounds). The isolate was classified as potentially hypervirulent due to a wide range of virulence factors found associated to regulation, motility, biofilm, effector delivery systems, immune modulation, nutritional/metabolic factors, adherence, invasion, and competitive advantage. The occurrence of MDR-hv KqA1 in hospital wastewater points out how this environment matrix plays a crucial role in the maintenance and selection of critical bacterial pathogens. Regarding One Health perspective, it is evident the need for multidisciplinary implementation of control measures for antibiotic-resistant bacteria, not only in hospital settings but also in a general environmental context to mitigate the dissemination of MDR and hv bacteria.

The Brazilian Portuguese version of the Pregnancy Mobility Index: Cross-cultural adaptation and psychometric evaluation - a validation study

ABSTRACT BACKGROUND: The Pregnancy Mobility Index (PMI) was developed to assess mobility in pregnant women in the Netherlands. At present, no similar questionnaire is available in Brazil. OBJECTIVE: The present study aimed to translate, cross-culturally adapt, and evaluate the psychometric properties of a Brazilian PMI. DESIGN AND SETTING: The present study was a validation study conducted at the Universidade Federal do Paraná and a public maternity ward in Curitiba, Brazil. METHODS: Text translation and cross-cultural adaptation followed international guidelines. Construct validity, internal consistency, and inter- and intra-rater reliability tests included 97 women. The Pelvic Girdle Questionnaire, Multidimensional Pain Evaluation Scale, Schober's test, and lumbar spine range of motion assessment were administered on the first day. Intra-rater reliability (n = 19) was measured after 15 days. Exploratory factor analysis was performed, and the correlation matrix was analyzed using Pearson's coefficient. RESULTS: Pregnant women (88%) understood the cultural adaptation process. The internal consistency was high (Cronbach's alpha > 0.90), construct validity was moderate, with significant correlation between lumbar spine range of motion (r = 0.283-0.369) and Schober's test (r = -0.314), and high correlation between the Multidimensional Pain Evaluation Scale (r = -0.650 and -0.499) and Pelvic Girdle Questionnaire (r = -0.737). Intra- and inter-rater reliabilities were excellent (intraclass correlation coefficient = 0.932 and 0.990, respectively). CONCLUSION: The Brazilian version of the PMI was successfully translated with excellent reliability and moderate-to-high construct validity. It is an important tool for assessing mobility in pregnant women. CLINICAL TRIAL: RBR-789tps (Validation study), https://ensaiosclinicos.gov.br/rg/RBR-789tps.

Physiological gait test: an effective method for analyzing balance, locomotion, and neuromuscular disorders in rats and a comparison to the elevated beam test / Teste de marcha fisiológica: um método eficaz para analisar distúrbios de equilíbrio, locomoção e neuromusculares em roedores

The evaluation of animal locomotor activity is a behavioral tool widely used to measure the mechanisms underlying a particular disease, disorder, or injury, as well as the effects of exposure to a xenobiotic. The elevated beam test is one of the most used tests in rodents to assess balance and motor coordination. Despite being inexpensive and utilizing a simple apparatus, the high beam test requires a long period of animal training and habituation. The development and characterization of an alternative test, namely the gait test, has the potential to circumvent the time and effort required for animal training, deeming it an effective, inexpensive, and fast method for the analysis of behaviors that are comparably assessed by the high beam test. Therefore, the present study focused on determining the effectiveness and feasibility of the gait test for assessing rodent locomotion and balance as a replacement for the elevated beam test. For this purpose, male rats were divided into three groups: one control group exposed to a saline solution (NaCl 0.9%) and two experimental groups exposed to a single dose of either 0.2 or 1.0 mg/kg of ivermectin intraperitoneally for induction of locomotor disturbance. The high beam and gait tests were performed 15 min and 24 h after drug administration. Results show that the experimental groups had difficulty performing the tasks of either test at both time points analyzed compared to the control groups. At the high beam, experimental animals had trouble maintaining balance and walking. At the gait test, experimental animals showed alterations in gait, which were quantitated by: (a) shortening of step length, (b) decrease of stride, (c) altered step symmetry, and (d) altered stride area. Such results are indicative of compensatory efforts and were comparable between both tests. Altogether, the data indicate that the gait test meets all requirements for assessing motor coordination in rodents. The gait test is therefore validated as a complement to the elevated beam test for the study and analysis of neurodegenerative impairment and other disorders involving neuromuscular disturbances.(AU)

A avaliação da atividade locomotora animal é uma ferramenta comportamental bastante utilizada para mensurar os mecanismos subjacentes a uma determinada doença, distúrbio ou lesão e efeitos da exposição a um xenobiótico. Um dos testes mais utilizados em roedores para avaliar o equilíbrio e coordenação motora é o teste da trave elevada que, apesar de ser um teste barato e que exige um aparato simples, é necessário um longo período de treino e habituação dos animais. O desenvolvimento e caracterização de um teste alternativo, chamado de teste da marcha, tem o potencial de contornar o tempo e o esforço necessários ao treino dos animais, considerando-o um método eficaz, barato e rápido para a análise de comportamentos avaliados comparativamente pelo alto teste de feixe. Portanto, o presente estudo concentrou-se em determinar a eficácia e viabilidade do teste de marcha para avaliação da locomoção e equilíbrio de roedores em substituição ao teste da trave elevada. Para isso, ratos machos foram divididos em 3 grupos, sendo 1 grupo controle exposto à solução salina (NaCl 0,9%) e 2 grupos experimentais expostos à dose única de 0,2 e 1,0 mg/kg de ivermectina por via intraperitoneal para indução da alteração locomotora. Os testes de trave elevada e marcha foram realizados 15 min e 24 h após a administração da droga. Os resultados mostram que os grupos experimentais tiveram dificuldade em realizar as tarefas de qualquer teste em ambos os momentos analisados em comparação com os grupos de controle. Na trave elevada, os animais experimentais tiveram dificuldade em manter o equilíbrio e andar. No teste de marcha, os animais experimentais apresentaram alterações na marcha, que foram quantificadas por: (a) encurtamento do comprimento da passada, (b) diminuição da passada, (c) alteração da simetria da passada e (d) alteração da área da passada. Tais resultados são indicativos de esforços compensatórios e foram comparáveis entre os dois testes. Em conjunto, os dados indicam que o teste de marcha atende a todos os requisitos para avaliação da coordenação motora em roedores. O teste de marcha é, portanto, validado como um complementar para o teste da trave elevada e para o estudo e análise de comprometimento neurodegenerativo e outros distúrbios envolvendo distúrbios neuromusculares.(AU)

Novel Dual AChE and ROCK2 Inhibitor Induces Neurogenesis via PTEN/AKT Pathway in Alzheimer's Disease Model.

Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease. Acetylcholinesterase inhibitors (AChEIs) are a major class of drugs used in AD therapy. ROCK2, another promising target for AD, has been associated with the induction of neurogenesis via PTEN/AKT. This study aimed to characterize the therapeutic potential of a novel donepezil-tacrine hybrid compound (TA8Amino) to inhibit AChE and ROCK2 protein, leading to the induction of neurogenesis in SH-SY5Y cells. Experiments were carried out with undifferentiated and neuron-differentiated SH-SY5Y cells submitted to treatments with AChEIs (TA8Amino, donepezil, and tacrine) for 24 h or 7 days. TA8Amino was capable of inhibiting AChE at non-cytotoxic concentrations after 24 h. Following neuronal differentiation for 7 days, TA8Amino and donepezil increased the percentage of neurodifferentiated cells and the length of neurites, as confirmed by ß-III-tubulin and MAP2 protein expression. TA8Amino was found to participate in the activation of PTEN/AKT signaling. In silico analysis showed that TA8Amino can stably bind to the active site of ROCK2, and in vitro experiments in SH-SY5Y cells demonstrate that TA8Amino significantly reduced the expression of ROCK2 protein, contrasting with donepezil and tacrine. Therefore, these results provide important information on the mechanism underlying the action of TA8Amino with regard to multi-target activities.

Clinical-Functional Vulnerability, Functional Capacity, and Falls in Octogenarians with Different Physical Activity Levels-A Cross-Sectional Study.

AIM: To compare differences between frailty, functional capacity, and fall prevalence among community-dwelling oldest-old adults regarding their physical activity levels. METHODS: Two hundred and thirty-nine octogenarians (80+ years) were allocated according to their physical activity as insufficiently active (<150 min week-1; n = 98; 84.4 ± 3.7 years), active (150 to 300 min week-1, n = 81, 83.9 ± 3.1 years), and very active (>300 min week-1, n = 60; 83.8 ± 3.4 years). Frailty (CFVI-20 questionnaire), functional capacity (Five Times Sit-to-Stand Test, Timed Up and Go, Balance, and handgrip strength), fall history, and physical activity were assessed. RESULTS: The insufficiently active group was the frailest and presented the worst functional performance compared to the other groups. The fall prevalence was higher in the insufficiently active (60.9%) compared to the active (26.4%) and very active (12.7%) groups. CONCLUSIONS: The group of insufficiently active octogenarians showed the greatest frailty, worst functional capacity, and higher fall prevalence than the active and very active groups. The engagement in physical activity of at least 300 min week-1 is essential to reverse or minimize the deleterious effects of aging on frailty, functional capacity, and falls in octogenarians.

Evaluation of the effectiveness of surveillance policies to control the COVID-19 pandemic in São Paulo, Brazil.

BACKGROUND: Surveillance efforts are essential to pandemic control, especially where the state is the primary health provider, such as Brazil. When public health testing guidelines limit molecular tests, there are reductions in detection efforts aimed at early recognition, isolation, and treatment of those infected with the virus. This study evaluates the effectiveness of surveillance policies to control the COVID-19 pandemic in São Paulo. METHODS: We conducted an interrupted time series analysis with a segmented regression model to analyze if changes in the state's guidelines improved RT-PCR testing outcomes in Brazil's most affluent and largest state, São Paulo. Anonymized daily data on the RT-PCR tests conducted in public laboratories belonging to the state-wide network from March 1, 2020 to June 5, 2021 were extracted from the Sao Paulo State open-source database, while the data on the genomic sequences were obtained from GISAID. We then aggregated these data for the 17 regional health departments in the state to evaluate regional-level outcomes. RESULTS: The public health system restricted RT-PCR testing to hospitalized cases in the first months. Testing was expanded to permit symptomatic testing of non-hospitalized persons only in July 2020, but a statistically significant increase in surveillance efforts was not observed. Case definition was expanded to allow case confirmation based on clinical, laboratory and image data criteria other than an RT-PCR test without increasing the testing effort for asymptomatic suspicious cases in September 2020. There was an increase in the mean volume of testing in each RHD, but the test positivity rate increased due to insufficient testing expansion. Results also show an uneven improvement in testing outcomes following these changes across the state's regional health departments. CONCLUSIONS: Evidence suggests that lower RT-PCR testing and genomic surveillance efforts are associated with areas characterized by a higher population concentration and a greater population reliance on the public health system. Our results highlight the need to structure health surveillance and information systems for disease control and prevention in emergency settings considering local demographics and vulnerabilities. In high prevalence settings, efforts at identifying and including vulnerable populations in routine and enhanced surveillance programs during COVID-19 must be significantly improved.

MALDI-TOF mass spectrometry for direct KPC detection among Enterobacterales.

In this study, we evaluate a method for the KPC enzyme detection, using MALDI-TOF MS, for Enterobacterales. A total of 300 clinical Enterobacterales isolates were selected. The collection included 259 carbapenemase-producing (157 KPC and 102 non-KPC) and 41 carbapenemase non-producing isolates. Bacterial proteins were extracted from Mueller-Hinton agar plates using formic acid, isopropyl alcohol, and water (17:33:50). Samples were prepared with a double layer of synapinic acid. Analyses were performed using a Microflex LT mass spectrometer (Bruker Daltonics) and flexAnalysis 4.0 software (Bruker Daltonics). Statistical analyses were performed using SPSS Software. A distinctive peak at m/z 28,643-28,731 was found in all 157 KPC-producing isolates, and it was consistently absent in the 143 KPC non-producing group. KPC-producing peak intensities ranged from 77 to 3893. Considering an intensity cutoff value ≥ 120 for the presence of KPC, this methodology presented 98.09% and 97.90% of sensitivity and specificity, respectively.

Association between Domains of the Clinical-Functional Vulnerability Index and Falls History in Older Adults: A Cross-Sectional Study.

Objectives: The study aimed to determine which domains, sets, and isolated or combined questions of the Clinical-Functional Vulnerability Index (CFVI-20) are associated with falls history in older adults. Methods: Instruments used were the CFVI-20 assessment and reported falls during the last year. The receiver operating characteristics (ROC) curves identified the performance of the CFVI-20 domains and questions in identifying older adults with and without falls history, while logistic regression identified relevant questions to identify fall history. Results: This study included 1725 individuals (71.9 ± 7.3 years). The area under the curve (AUC) between the CFVI-20 and fall history was 0.69. The mobility domain presented the largest AUC (0.71; p < 0.01), and most isolated domains showed low AUCs (0.51 to 0.58). Isolated questions were limited to identifying fallers. The regression analysis identified 7 questions of the CFVI-20 with falls. Conclusions: The CFVI-20 general score identified older adults with a fall history. When considered in isolation, most domains were limited to identifying falls, except for the mobility domain. Combining the CFVI-20 questions enabled identification of fallers.

Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer's Disease and Future Perspectives.

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease conceptualized as a continuous process, ranging from mild cognitive impairment (MCI), to the mild, moderate, and severe clinical stages of AD dementia. AD is considered a complex multifactorial disease. Currently, the use of cholinesterase inhibitors (ChEI), such as tacrine, donepezil, rivastigmine, and galantamine, has been the main treatment for AD patients. Interestingly, there is evidence that ChEI also promotes neuroprotective effects, bringing some benefits to AD patients. The mechanisms by which the ChEI act have been investigated in AD. ChEI can modulate the PI3K/AKT pathway, which is an important signaling cascade that is capable of causing a significant functional impact on neurons by activating cell survival pathways to promote neuroprotective effects. However, there is still a huge challenge in the field of neuroprotection, but in the context of unravelling the details of the PI3K/AKT pathway, a new scenario has emerged for the development of more efficient drugs that act on multiple protein targets. Thus, the mechanisms by which ChEI can promote neuroprotective effects and prospects for the development of new drug candidates for the treatment of AD are discussed in this review.

Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli.

This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.