Antibodies against Leptospira spp. in Free-living and Captive Broad-snouted Caiman (Caiman latirostris) and Free-living Yacare Caiman (Caiman yacare) in Brazil.

We evaluated antibodies against Leptospira spp. in both free-living and captive Caiman latirostris from Atlantic Forest, and free-living Caiman yacare from Pantanal, Brazil, by using a microscopic agglutination test. Overall seropositivity was 17%, with rates of 36% in captive C. latirostris (n=4/11) and 18% in free-living C. yacare (n=4/22).

Chemical composition and antimicrobial activity of Cordiera myrciifolia leaves against pathogenic bacteria and fungi: Drug potentiation ability and inhibition of virulence.

Cordiera myrciifolia is an abundant species in Northeast Brazil that presents metabolites of biological/therapeutic interest. From this perspective, the present study aimed to investigate the chemical constituents and evaluate the in vitro antimicrobial activity of hexane (HECM) and ethanolic (EECM) extracts of C. myrciifolia leaves. The extracts were analyzed by chromatographic techniques (GC and UPLC) coupled with mass spectrometry. The antimicrobial activity of the extracts and the extracts combined with conventional drugs was evaluated by microdilution. The in vitro effect of the treatments on Candida's morphological transition was verified through cultivation in humid chambers. In HECM, 11 constituents including fatty acids, and triterpenes, including phytosterols, alkanes, tocols, and primary alcohols were identified. Triterpenes represented >40% of the identified constituents, with Lupeol being the most representative. In EECM, 13 constituents were identified, of which eight belonged to the class of flavonoids. High antibacterial activity of HECM was detected against Escherichia coli and Staphylococcus aureus, with Minimum Inhibitory Concentrations of 8 and 16 µg/mL, respectively. The combined activity was more effective when combined with Norfloxacin and Imipenem. In anti-Candida activity, the IC50 of the extracts ranged from 36.6 to 129.1 µg/mL. There was potentiating effect when associated with Fluconazole. Both extracts inhibited the filamentous growth of C. tropicalis at a concentration of 512 µg/mL. C. myrciifolia extracts prove to be candidates for the development of new therapeutic formulations to treat bacterial and fungal infections.

Patterns of virtual reality and Fitbit wearable activity device use after skull base surgery.

KEY POINTS: Virtual reality (VR) and Fitbit devices are well tolerated by patients after skull base surgery. Postoperative recovery protocols may benefit from incorporation of these devices. However, challenges including patient compliance may impact optimal device utilization.

Validation of mutated CEBPA bZIP as a distinct prognosis entity in acute myeloid leukemia: a study by the Spanish PETHEMA registry.

Not available.

[Brazilian Ministry of Health strategy to increase vaccination coverage at bordersEstrategia del Ministerio de Salud de Brasil para aumentar las tasas de cobertura de vacunación en las fronteras]. / Estratégia do Ministério da Saúde do Brasil para aumento das coberturas vacinais nas fronteiras.

Objective: Evaluate the implementation of the Ministry of Health's "Action Plan: Border Vaccination Strategy - Agenda 2022" in the Brazil's 33 twin cities and evaluate the increase in the country's vaccination coverage (VC). Methodology: Pre-post community clinical trial. Implementation of the strategy was analyzed, and pre- and post-intervention VC were compared in two stages: P1 (pre-intervention) and P2 (post-intervention). Based on statistical analyses of P1 and P2 coverage, calculations were made of municipal averages, standard deviation, and difference in VC between the two periods. Results: Integration was observed between the primary health care (PHC), surveillance, immunization, and special indigenous health district (DSEI) teams, although there were difficulties, for example, in relation to migratory flows. While immigration flows present challenges in the areas of immunization, PHC, and DSEI, the difficulties are compounded by the polarization of these services, which hinders intersectoral integration. After carrying out the workshops, a total of 50 977 doses were administered in the general population in the 33 twin cities. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, which may be relevant in terms of increasing VC in Brazil. Conclusion: There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, helping to increase VC in Brazil.

Objetivo: Evaluar la aplicación de la Estrategia de Vacunación en las Fronteras - Agenda 2022, que forma parte del Plan de Acción del Ministerio de Salud en las 33 ciudades hermanas y evaluar el aumento de las tasas de cobertura de vacunación en Brasil. Métodos: Ensayo clínico comunitario realizado antes y después de la intervención correspondiente. Se analizó la aplicación de la estrategia y se compararon las tasas de cobertura de vacunación antes y después de la intervención en dos periodos: P1 (pre-intervención) y P2 (post-intervención). En los análisis estadísticos de la tasa de cobertura de vacunación en P1 y P2 se calcularon los valores de media y desviación estándar de los municipios y la diferencia entre las tasas de cobertura de los dos periodos. Resultados: Se observó una integración entre los equipos de Atención Primaria de Salud, Vigilancia, Inmunización y el Distrito Especial de Salud Indígena (DISEI), pero con dificultades, como las inherentes al flujo migratorio. Cabe destacar que el flujo migratorio es uno de los desafíos en el contexto de la inmunización, la atención primaria de salud y el DISEI, dificultad que se ve agravada por la polarización entre los servicios (inmunización, atención primaria de salud y el DISEI), lo que supone un reto para la integración de los sectores. Por lo que respecta al análisis de las tasas de cobertura de vacunación llevado a cabo después de realizar los talleres, se administró un total de 50 977 dosis a la población general en las 33 ciudades hermanas de Brasil. Hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados después de la intervención, lo que puede ser importante para aumentar las tasas de cobertura de Brasil. Conclusión: Después de la intervención hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados, lo cual influyó en el incremento de las tasas de cobertura de Brasil.

Neural inhibition as implemented by an actor-critic model involves the human dorsal striatum and ventral tegmental area.

Inhibition is implicated across virtually all human experiences. As a trade-off of being very efficient, this executive function is also prone to many errors. Rodent and computational studies show that midbrain regions play crucial roles during errors by sending dopaminergic learning signals to the basal ganglia for behavioural adjustment. However, the parallels between animal and human neural anatomy and function are not determined. We scanned human adults while they performed an fMRI inhibitory task requiring trial-and-error learning. Guided by an actor-critic model, our results implicate the dorsal striatum and the ventral tegmental area as the actor and the critic, respectively. Using a multilevel and dimensional approach, we also demonstrate a link between midbrain and striatum circuit activity, inhibitory performance, and self-reported autistic and obsessive-compulsive subclinical traits.

Prevalence and imaging characteristics of cerebral small vessel disease in a Colombian population aged 40 years and older.

Cerebral small vessel disease is a major contributor to both brain aging and cognitive decline. This study aimed to determine the prevalence of cerebral small vessel disease in a Colombian population over 40 years of age who attended a Radiology and Diagnostic Imaging service for brain MRI between October 2018 and March 2019. This was an observational, cross-sectional and analytical study of 710 adult patients over 40 years of age who attended the Radiology and Diagnostic Imaging service for a brain MRI. The analysed data were obtained from an anonymized database of the service. We studied 710 MRI scans of patients aged between 40 and 104 years. The most frequent risk factor was hypertension (36.2%). Brain abnormalities associated with cerebral small vessel disease, such as white matter hyperintensities, were seen in 56.20% of the population, and brain atrophy was observed in 12.96%. Brain disease prevalence increased with age (23.18% for those aged 55 years, 54.49% for those aged 55-64 years, 69.8% for those aged 65-74 years and 90.53% for those older than 75 years). The prevalence of cerebral small vessel disease in our population was similar to that reported in the world literature, as were the prevalence of the evaluated cardiovascular risk factors. Additionally, we identified an association between hypertension and advanced age with cerebral small vessel disease, with white matter hyperintensities being the most characteristic finding.

Reliability and validity of the Brazilian version of the world health organization disability assessment schedule (WHODAS 2.0) questionnaire for women with urinary incontinence.

PURPOSE: To analyze the reliability and validity of the WHODAS 2.0 instrument for women with urinary incontinence (UI). METHODS: This is a methodological study with Brazilian women with complaints of urge, stress or mixed UI, over 18 years old, without cognitive disorders. The WHODAS 2.0 (36-item version) and the auxiliary instruments were applied through face-to-face and telephone interviews after 7-14 d. The psychometric properties evaluated were: Cronbach's alpha for internal consistency, intraclass correlation coefficient (ICC) for intra-rater test-retest, Spearman's correlation coefficient (rho) for construct validity of WHODAS 2.0 with auxiliary instruments; and ANOVA for discriminative validity with UI severity. RESULTS: 101 women with UI with a mean age of 50.71 ± 10.39 were included. WHODAS 2.0 showed good reliability in all domains and excellent reliability in the total score (>0.80). The intra-evaluator test-retest showed ICC values between 0.59 and 0.87 (p < 0.001). We observed a positive correlation between the WHODAS 2.0 domains and the instruments recommended by International Continence Society (ICS), with greater emphasis on moderate correlation with the Urinary Impact Questionnaire (IUQ-7) subscale (rho = 0.730 p < 0.001). CONCLUSION: The WHODAS 2.0 instrument is a reliable and valid questionnaire for investigating the functioning and disability of women with UI.

The WHODAS 2.0 is a valid and reliable tool for future functioning research with women with urinary incontinence.The WHODAS 2.0 can be used in clinical practice to assess disabilities in women with urinary incontinence.The validation of WHODAS 2.0 reinforces the need for rehabilitation based on the functioning needs of each patient with urinary incontinence.The WHODAS 2.0 assesses functioning based on the biopsychosocial model, supported by the ICF (International Classification of Functioning, Disability and Health).

Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection.

Introduction: Guanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3. It comprises the genes for GBP1-to-3, GBP5 and GBP7. In humans, all GBPs are present in a single cluster on chromosome 1. Brucella abortus is a Gram-negative bacterium known to cause brucellosis, a debilitating disease that affects both humans and animals. Our group demonstrated previously that GBPs present on murine chromosome 3 (GBPchr3) is important to disrupt Brucella-containing vacuole and GBP5 itself is important to Brucella intracellular LPS recognition. In this work, we investigated further the role of GBPs during B. abortus infection. Methods and results: We observed that all GBPs from murine chromosome 3 are significantly upregulated in response to B. abortus infection in mouse bone marrow-derived macrophages. Of note, GBP5 presents the highest expression level in all time points evaluated. However, only GBPchr3-/- cells presented increased bacterial burden compared to wild-type macrophages. Brucella DNA is an important Pathogen-Associated Molecular Pattern that could be available for inflammasome activation after BCV disruption mediated by GBPs. In this regard, we observed reduced IL-1ß production in the absence of GBP2 or GBP5, as well as in GBPchr3-/- murine macrophages. Similar result was showed by THP-1 macrophages with downregulation of GBP2 and GBP5 mediated by siRNA. Furthermore, significant reduction on caspase-1 p20 levels, LDH release and Gasdermin-D conversion into its mature form (p30 N-terminal subunit) was observed only in GBPchr3-/- macrophages. In an in vivo perspective, we found that GBPchr3-/- mice had increased B. abortus burden and higher number of granulomas per area of liver tissue, indicating increased disease severity. Discussion/conclusion: Altogether, these results demonstrate that although GBP5 presents a high expression pattern and is involved in inflammasome activation by bacterial DNA in macrophages, the cooperation of multiple GBPs from murine chromosome 3 is necessary for full control of Brucella abortus infection.

Phytochemical Profile and In Vitro Bioactivities of Wild Asparagus stipularis.

In this study, Asparagus stipularis was characterized concerning its phytochemical composition, antioxidant potential, cytotoxicity, and pancreatic lipase inhibitory activities. Twenty-seven compounds were identified and quantified by HPLC-DAD-MS in the leaf, stem, pericarp, and rhizome of ethanolic extracts. Seven steroidal saponins were detected, and the highest content was quantified in rhizome and pericap. A. stipularis also contained significant amounts of flavonoids in the aerial part. Isorhamnetin tetra-glycoside, quercetin-3-glucosyl-rutinoside, and rutin were the main flavonoid derivatives in leaf, stem, and pericarp extracts, respectively. In addition, eleven phenolic acids were also detected; among them, caffeic acid, protocatechuic acid, p-hydroxybenzoic acid, and ferulic acid were the predominant phenolics, with these having the highest amounts quantified in the rhizome extracts. All the tested extracts possessed antioxidant capacities, with pericarp and rhizome extracts exhibiting the highest activity in DPPH, ABTS, and FRAP assays. The extracts from pericarp and rhizome were revealed to also be the strongest inhibitors of pancreatic lipase. The rhizome extracts exhibited potent cytotoxic activity against HCT-116 and HepG2 with IC50 values of 30 and 54 µg/mL after 48 h of treatment. The present study demonstrated that A. stipularis can be used as a new source of natural antioxidants and potential anticancer and antiobesity compounds.

Identification of key neuronal mechanisms triggered by dimethyl fumarate in SH-SY5Y human neuroblastoma cells through a metabolomic approach.

Dimethyl fumarate (DMF) is an old drug used for psoriasis treatment that has recently been repurposed to treat relapse-remitting multiple sclerosis, mostly due to its neuro- and immunomodulatory actions. However, mining of a pharmacovigilance database recently ranked DMF as the second pharmaceutical most associated with cognitive adverse events. To our best knowledge, the signaling mechanisms underlying its therapeutic and neurotoxic outcomes remain mostly undisclosed. This work thus represents the first-hand assessment of DMF-induced metabolic changes in undifferentiated SH-SY5Y human neuroblastoma cells, through an untargeted metabolomic approach using gas chromatography-mass spectrometry (GC-MS). The endometabolome was analyzed following 24 h and 96 h of exposure to two pharmacologically relevant DMF concentrations (0.1 and 10 µM). None of these conditions significantly reduced metabolic activity (MTT reduction assay). Our data showed that 24 h-exposure to DMF at both concentrations tested mainly affected metabolic pathways involved in mitochondrial activity (e.g., citric acid cycle, de novo triacylglycerol biosynthesis), and the synthesis of catecholamines and serotonin by changing the levels of their respective precursors, namely phenylalanine (0.68-fold decrease for 10 µM DMF vs vehicle), and tryptophan (1.36-fold increase for 0.1 µM DMF vs vehicle). Interestingly, taurine, whose levels can be modulated via Nrf2 signaling (DMF's primary target), emerged as a key mediator of DMF's neuronal action, displaying a 3.86-fold increase and 0.27-fold decrease for 10 µM DMF at 24 h and 96 h, respectively. A 96 h-exposure to DMF seemed to mainly trigger pathways associated with glucose production (e.g., gluconeogenesis, glucose-alanine cycle, malate-aspartate shuttle), possibly related to the metabolism of DMF into monomethyl fumarate and its further conversion into glucose via activation of the citric acid cycle. Overall, our data contribute to improving the understanding of the events associated with neuronal exposure to DMF.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

BACKGROUND: Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management. METHODS: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported. RESULTS: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died. CONCLUSIONS: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Applications of Saponin Extract from Asparagus Roots as Functional Ingredient.

When replanting an asparagus field, the roots of the previous crop are crushed and incorporated into the soil, creating problems of autotoxicity and fungal infections. Asparagus roots can be considered as a valuable byproduct, since they are very rich in saponins (3-6%), compounds currently considered as bio-emulsifiers. The objective is to evaluate the emulsifying and foaming capacity of a saponin extract from asparagus roots (ARS) and compare it with other commercial extracts. ARS was obtained using a process patented by our research group. The results have shown that ARS has activity similar to Quillaja extract. Its critical micellar concentration falls between that of Quillaja and Tribulus extracts (0.064, 0.043, and 0.094 g/100 mL, respectively). Both emulsifying and foaming activities are affected by pH, salt, and sucrose to a similar extent as the other extracts. Additionally, it has demonstrated an inhibitory effect on pancreatic lipase, which is even better than the other two studied extracts, as indicated by its IC50 value (0.7887, 1.6366, and 2.0107 mg/mL for asparagus, Quillaja, and Tribulus, respectively). These results suggest that ARS could serve as a natural emulsifying/foaming agent for healthier and safer food products and as a potential aid in treatments for obesity and hyperlipidemia.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Audiometric evaluation in different clinical presentations of otitis media.

OBJECTIVES: To assess the hearing thresholds in acute otitis media, otitis media with effusion and chronic otitis media (non-suppurative, non-cholesteatomatous suppurative and cholesteatomatous) and to compare the hearing outcomes with non-diseased ears (in bilateral cases) or contralateral healthy ears (in unilateral cases), since hearing loss is the most frequent sequel of otitis media and there is no previous study comparing the audiometric thresholds among the different forms of otitis media. METHODS: Cross sectional, controlled study. We performed conventional audiometry (500-8000Hz) and tympanometry in patients with otitis media and healthy individuals (control group). Hearing loss was considered when the hearing thresholds were > 25 dBHL. RESULTS: Of the 112 patients diagnosed with otitis media (151 ears), 48 were men (42.86%) and 64 were women (57.14%). The average age was 42.72 years. Of those, 25 (22.32%) were diagnosed as AOM, 15 (13.39%) were diagnosed with OME and the remaining 72 (63.28%) were diagnosed with COM (non-suppurative COM, n=31; suppurative COM, n=18; cholesteatomatous COM, n=23). As compared with controls, all forms of otitis media had significantly higher bone-conduction thresholds (500-4000Hz). Conductive hearing loss was the most frequent type of hearing loss (58.94%). However, the number of patients with mixed hearing loss was also relevant (39.07%). We noted that the presence of sensorioneural component occurred more frequently in 1) Higher frequencies; and 2) In groups of otitis media that were more active or severe in the inflammatory/infective standpoint (AOM, suppurative COM and cholesteatomatous COM). CONCLUSION: All types of otitis media, even those with infrequent episodes of inflammation and otorrhea, had worse bone conduction thresholds as compared with nondiseased ears (p<0.01). We observed worse hearing outcomes in ears with recurrent episodes of otorrhea and in ears with AOM, especially in high frequencies.

Evaluation of the effects of COVID-19 on semen parameters and male infertility.

The new coronavirus pandemic resulted in millions of deaths in Brazil and around the world, and presented substantial challenges to society. The shortand long-term clinical manifestations tied to COVID-19 are still poorly understood, and may involve several organs and systems, including the male genital tract, which may lead to impaired fertility. The present study aimed to analyze, through an integrative literature review of articles available in databases, the effects of COVID-19 on parameters related to human semen quality. The analyzed studies reported significant decreases in sperm motility and morphology related to COVID-19. Reductions in concentration and volume were also observed. Inflammatory response is one of the leading mechanisms that may potentially explain the observed changes, although others may also be involved. More studies are needed to better understand the effects, modes of action, as well as other aspects involved in this complex phenomenon.

Stigma and knowledge about autism in Brazil: A psychometric and intervention study.

LAY ABSTRACT: To promote the full inclusion of autistic people, we must change the knowledge and attitudes of non-autistic individuals. Unfortunately, access to autism information and support remains limited in Brazil, and stigma is also common. Brazilian researchers reached out to a researcher in the United States to co-develop Brazilian surveys to measure autism stigma and knowledge. Together, they made Brazilian versions of stigma and knowledge surveys which autistic people in the United States had helped make. They also adapted an online autism training used in other countries with help from three Brazilian autistic people and the mother of an autistic child. They used the new measures to see if the autism training improved autism stigma and knowledge among Brazilians. The surveys, called EARPA and ECAT in Brazil, were translated into Portuguese in a previous study. In the first study in this article, 532 Brazilians completed the stigma measure and 510 completed the knowledge measure. The researchers used exploratory graph analysis, which uses the connections between items in a survey to understand which items belong together. Seventy-nine Brazilians participated in the training. They were mostly white, female university students. The EGA showed that the stigma survey measured one big idea while the knowledge survey measured four ideas: diagnosis/cause; socio-communicative development; stimming and special interests; and autism in adulthood. Both scales are promising and may be helpful in future Brazilian and cross-cultural studies about autism. Participants reported more knowledge and less stigma after the autism training, which has been found in other countries too.

Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and ß-lactamase.

BACKGROUND: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity. OBJECTIVES: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties. METHODS: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of ß-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100. RESULTS: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 µg/mL, or on the enzymatic mechanism of ß-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 µg/mL. CONCLUSION: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.

Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

BACKGROUND: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. OBJECTIVES: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. METHODS: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi-drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. RESULTS: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti-inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi-drug resistant strains, indicating a possible synergistic action. CONCLUSIONS: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti-inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out.

Estratégia do Ministério da Saúde do Brasil para aumento das coberturas vacinais nas fronteiras / Brazilian Ministry of Health strategy to increase vaccination coverage at borders / Estrategia del Ministerio de Salud de Brasil para aumentar las tasas de cobertura de vacunación en las fronteras

[RESUMO]. Objetivo. Avaliar a implementação de estratégia do “Plano de Ação: Estratégia de Vacinação nas Fronteiras – Agenda 2022” do Ministério da Saúde nas 33 cidades gêmeas e avaliar o incremento das coberturas vacinais (CV) brasileiras. Métodos. Ensaio clínico comunitário, do tipo antes e depois. Analisou-se a realização da estratégia, bem como comparadas as CV pré e pós-intervenção em dois tempos: P1 (pré-intervenção) e P2 (pós-intervenção). Análises estatísticas sobre a CV, no P1 e P2, foram calculados os valores de média entres os municípios, desvio padrão e diferença entre as coberturas dos dois períodos. Resultados. Observou-se integração entre as equipes de Atenção Primária à Saúde (APS), Vigilância, Imunização e Distrito Sanitário Especial Indígena (DSEI), porém com dificuldades, como aquelas inerentes ao fluxo migratório. Ressalta-se que o fluxo imigratório é um dos desafios no contexto da imunização, APS e DSEI, entretanto, a esta dificuldade soma-se a polarização entre os serviços (imunização, APS e DISEI), ocasionando um desafio para a integração dos setores. Em relação à análise das CV, após a realização das oficinas, foram totalizadas 50 977 doses aplicadas na população geral nas 33 cidades-gêmeas do Brasil. Houve incremento das coberturas vacinais de crianças de até um ano de idade nos locais avaliados após a intervenção, o que pode ser importante para aumentar as CV no Brasil. Conclusão. Houve incremento das coberturas vacinais das crianças até um ano de idade nos locais avalia- dos após a intervenção e isso influenciou no aumento das CV no Brasil.

[ABSTRACT]. Objective. Evaluate the implementation of the Ministry of Health’s “Action Plan: Border Vaccination Strategy – Agenda 2022” in the Brazil’s 33 twin cities and evaluate the increase in the country’s vaccination coverage (VC). Methodology. Pre-post community clinical trial. Implementation of the strategy was analyzed, and pre- and post-intervention VC were compared in two stages: P1 (pre-intervention) and P2 (post-intervention). Based on statistical analyses of P1 and P2 coverage, calculations were made of municipal averages, standard deviation, and difference in VC between the two periods. Results. Integration was observed between the primary health care (PHC), surveillance, immunization, and special indigenous health district (DSEI) teams, although there were difficulties, for example, in relation to migratory flows. While immigration flows present challenges in the areas of immunization, PHC, and DSEI, the difficulties are compounded by the polarization of these services, which hinders intersectoral integration. After carrying out the workshops, a total of 50 977 doses were administered in the general population in the 33 twin cities. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, which may be relevant in terms of increasing VC in Brazil. Conclusion. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, helping to increase VC in Brazil.

[RESUMEN]. Objetivo. Evaluar la aplicación de la Estrategia de Vacunación en las Fronteras - Agenda 2022, que forma parte del Plan de Acción del Ministerio de Salud en las 33 ciudades hermanas y evaluar el aumento de las tasas de cobertura de vacunación en Brasil. Métodos. Ensayo clínico comunitario realizado antes y después de la intervención correspondiente. Se analizó la aplicación de la estrategia y se compararon las tasas de cobertura de vacunación antes y después de la intervención en dos periodos: P1 (pre-intervención) y P2 (post-intervención). En los análisis estadísticos de la tasa de cobertura de vacunación en P1 y P2 se calcularon los valores de media y desviación estándar de los municipios y la diferencia entre las tasas de cobertura de los dos periodos. Resultados. Se observó una integración entre los equipos de Atención Primaria de Salud, Vigilancia, Inmu- nización y el Distrito Especial de Salud Indígena (DISEI), pero con dificultades, como las inherentes al flujo migratorio. Cabe destacar que el flujo migratorio es uno de los desafíos en el contexto de la inmunización, la atención primaria de salud y el DISEI, dificultad que se ve agravada por la polarización entre los servicios (inmunización, atención primaria de salud y el DISEI), lo que supone un reto para la integración de los sectores. Por lo que respecta al análisis de las tasas de cobertura de vacunación llevado a cabo después de realizar los talleres, se administró un total de 50 977 dosis a la población general en las 33 ciudades hermanas de Brasil. Hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados después de la intervención, lo que puede ser importante para aumentar las tasas de cobertura de Brasil. Conclusión. Después de la intervención hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados, lo cual influyó en el incremento de las tasas de cobertura de Brasil.