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1.
J Gen Intern Med ; 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-38997531

RÉSUMÉ

INTRODUCTION: Although a well-established component of bone metabolism, the efficacy and safety of vitamin D supplementation for the prevention of fractures in elderly healthy individuals is still unclear. PURPOSE: To perform a meta-analysis comparing vitamin D supplementation with placebo and its contributions on fracture incidence. METHODS: This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under protocol CRD42023484979. We systematically searched PubMed, Embase, and Cochrane Central databases from inception to November 2023 for randomized controlled trials (RCTs) comparing vitamin D supplementation versus placebo in individuals with 60 years of age or more and without bone related medical conditions such as cancer and osteoporosis. RESULTS: Seven RCTs with 71,899 patients were included, of whom 36,822 (51.2%) were women. There was no significant difference in total fracture incidence (RR 1.03; 95% CI 0.93-1.14; p = 0.56; I2 = 58%) between groups or subgroups. However, women had an increased risk for hip fractures (164 vs. 121 events; RR 1.34; 95% CI 1.06-1.70; p = 0.01; I2 = 0%). There was no significant difference in non-vertebral fractures, osteoporotic fractures development, or falls (RR 1.02; 95% CI 0.94-1.12; p = 0.6; I2 = 47%; RR 0.97; 95% CI 0.87-1.08; p = 0.63; I2 = 0%; RR 1.01; 95% CI 0.97-1.04; p = 0.66; I2 = 55%, respectively). CONCLUSION: Vitamin D supplementation does not reduce the total fracture development rate in the elderly healthy population, and it may increase the incidence of hip fractures among elderly healthy women. This finding suggests refraining from prescribing high intermittent doses of vitamin D, without calcium, to individuals aged 60 or older with unknown vitamin D serum concentration or osteoporosis status and inadequate calcium intake.

2.
ChemMedChem ; : e202400293, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38924252

RÉSUMÉ

This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42 e and 49 b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.

3.
Can Geriatr J ; 27(2): 133-140, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38827426

RÉSUMÉ

Background: Resistance training with instability (REI) emerged as a promising training modality for older adults aiming to counteract age-related changes. Objectives: We compared the effects of 12 weeks of REI and traditional resistance exercise (RE) on muscle strength in older adults with cognitive impairment. We further explored if total training volume (TTV) significantly differs among training groups. Methods: This is a secondary analysis of the REI study. Participants were randomly assigned to REI (n=22) or RE (n=23). RE protocol involved moderate-intensity, free-weight, and machines-based resistance exercises (3 sets, 10-15 repetitions). REI received a similar training protocol, in which exercises were simultaneously performed with instability/unstable devices (e.g., squat exercise under a foam pad or Bosu® ball). Maximal isometric strength and isokinetic parameters were assessed at baseline and after completion of a 12-week intervention through a hydraulic handgrip and isokinetic dynamometer, respectively. TTV (sets × repetitions × load) was computed based on external training load over the 12 weeks. Results: No differences were observed between groups (p=.35) after the intervention. Over 12 weeks, REI and RE improved isometric handgrip strength (p<.001) and isokinetic performance (p=.04). We also did not find differences in the TTV between training groups (p=.28). Conclusion: We demonstrated that both REI and RE training induced similar gains in muscle strength. Combining unstable surfaces/instability devices did not hamper TTV, which may have clinical applications in the context of exercise for older adults.

4.
J Intensive Care Med ; : 8850666241255671, 2024 May 16.
Article de Anglais | MEDLINE | ID: mdl-38751353

RÉSUMÉ

Introduction: Glycemia is an important factor among critically ill patients in the intensive care unit (ICU). There is conflicting evidence on the preferred strategy of blood glucose control among patients with diabetes in the ICU. We aimed to conduct a meta-analysis comparing tight with liberal blood glucose in critically ill patients with diabetes in the ICU. Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing tight versus liberal blood glucose control in critically ill patients with diabetes from inception to December 2023. We pooled odds-ratios (OR) and 95% confidence intervals (CI) with a random-effects model for binary endpoints. We used the Review Manager 5.17 and R version 4.3.2 for statistical analyses. Risk of bias assessment was performed with the Cochrane tool for randomized trials (RoB2). Results: Eight RCTs with 4474 patients were included. There was no statistically significant difference in all-cause mortality (OR 1.11; 95% CI 0.95-1.28; P = .18; I² = 0%) between a tight and liberal blood glucose control. RoB2 identified all studies at low risk of bias and funnel plot suggested no evidence of publication bias. Conclusion: In patients with diabetes in the ICU, there was no statistically significant difference in all-cause mortality between a tight and liberal blood glucose control. PROSPERO registration: CRD42023485032.

5.
Expert Opin Drug Discov ; 19(6): 741-753, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38715393

RÉSUMÉ

INTRODUCTION: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD. AREAS COVERED: Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi, aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD. EXPERT OPINION: Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.


Sujet(s)
Maladie de Chagas , Découverte de médicament , Résistance aux substances , Nitroimidazoles , Trypanocides , Trypanosoma cruzi , Trypanosoma cruzi/effets des médicaments et des substances chimiques , Nitroimidazoles/pharmacologie , Maladie de Chagas/traitement médicamenteux , Maladie de Chagas/parasitologie , Trypanocides/pharmacologie , Humains , Animaux , Découverte de médicament/méthodes , Développement de médicament
6.
Braz J Microbiol ; 55(2): 1339-1348, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38438832

RÉSUMÉ

Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20 years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.


Sujet(s)
Infections communautaires , Méningite à pneumocoques , Récidive , Streptococcus pneumoniae , Humains , Infections communautaires/microbiologie , Infections communautaires/épidémiologie , Méningite à pneumocoques/épidémiologie , Méningite à pneumocoques/microbiologie , Adulte , Streptococcus pneumoniae/génétique , Streptococcus pneumoniae/isolement et purification , Streptococcus pneumoniae/classification , Études rétrospectives , Femelle , Mâle , Jeune adulte , Adulte d'âge moyen , Adolescent , Facteurs de risque , Sérogroupe , Antibactériens , Haemophilus influenzae/génétique , Haemophilus influenzae/isolement et purification , Haemophilus influenzae/classification
7.
Future Med Chem ; 16(3): 253-269, 2024 02.
Article de Anglais | MEDLINE | ID: mdl-38193294

RÉSUMÉ

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.


Sujet(s)
Maladie de Chagas , Trypanocides , Trypanosoma cruzi , Animaux , Souris , Trypanocides/pharmacologie , Trypanocides/composition chimique , Maladie de Chagas/traitement médicamenteux , Maladie de Chagas/parasitologie , Relation structure-activité , Parasitémie/traitement médicamenteux
8.
BMC Sports Sci Med Rehabil ; 16(1): 5, 2024 Jan 02.
Article de Anglais | MEDLINE | ID: mdl-38167062

RÉSUMÉ

BACKGROUND: Breast cancer (BC) is one of the most incident types of cancer among women in the world. Although chemotherapy is an effective way to treat several types of cancer, it may also cause serious complications, including cardiotoxicity. This study aimed to identify the impact of chemotherapy on functional capacity, muscle strength and autonomic function. METHODS: Ten breast cancer patients in therapeutic follow-up (TG) and ten women without comorbidities (CG) participated in the study (46±8.87 years old). Both groups were evaluated at two time points, before and 20 weeks after the start of chemotherapy. Functional capacity and muscle strength were assessed by 6-minute walk test (6MWT) and handgrip test, respectively. Autonomic function was assessed by heart rate variability analysis. RESULTS: TG presented greater reductions in the handgrip test for the non-dominant hand (TG ↓15.2%; CG: ↑1.1%, p<0.05) compared to GC. However, no significant differences were found regarding VO2max (p>0.05) and 6MWT total distance (p>0.05). Regarding the heart rate variability variables before and after follow-up period, rMSSD (CG= 39.15±37.66; TG= 14.89±8.28, p= 0.01) and SDNN (CG= 55.77±40.03; TG= 26.30±10.37, p= 0.02) showed effect in the group and time interaction, whereas the LF/HF ratio presented significant difference only in the time analysis (CG= 2.24±2.30; TG= 2.84±1.82, p= 0.04). CONCLUSION: Chemotherapy used in the treatment of breast cancer patients resulted in decreased muscle strength and autonomic imbalance. The data suggests that chemotherapy may carry the risk of developing cardiovascular disease. TRIAL REGISTRATION: Registration not required.

9.
Photodiagnosis Photodyn Ther ; 45: 103977, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38224724

RÉSUMÉ

To reduce the speed of selection of populations resistant to chemical insecticides, photodynamic inactivation (PDI) against Aedes aegypti is a hot-topic and promising alternative technique to vector control. Temperature is an important factor in the survival of Ae. aegypti larvae and mosquitoes as it influences physiology, behavior, and ecology. This work aimed to evaluate parameters of the biological cycle of Ae. aegypti such as: hatching rate, larval development, adult mosquito longevity, sex ratio, weight, and lethal concentration of larval mortality (LC) through the combination of PDI with different temperatures. The number of larvae found after 48 h suggests that temperature affects hatching rate. Additionally, results showed a delay in development of surviving larvae after PDI when compared to control groups, and there was a reduction in the longevity of mosquitoes that undertook photodynamic action. PDI also led to a predominance of male insects, and observed weight indicates that the inactivation method may have also interfered in mosquito size. The results point to a satisfactory performance of PDI at all tested temperatures. Experimental conditions that were not lethal to all larvae implied that PDI impacts the mosquitoes' biological cycle. Though metabolism and development are improved at higher temperatures, so is PDI action, thus maintaining the net benefit. Therefore, it is assumed that the proposed photolarvicide can be useful in reducing arbovirus transmission, and results invite for future research in different abiotic conditions.


Sujet(s)
Aedes , Photothérapie dynamique , Animaux , Mâle , Femelle , Aedes/physiologie , Température , Vecteurs moustiques/physiologie , Photothérapie dynamique/méthodes , Photosensibilisants/pharmacologie , Larve
10.
Curr Diabetes Rev ; 20(3): e220523217168, 2024.
Article de Anglais | MEDLINE | ID: mdl-37221688

RÉSUMÉ

BACKGROUND: Diabetic neuropathy (DN) causes neuropathic pain, and current treatments are unsatisfactory. Recently studies have demonstrated an assertive correlation between gut microbiota and pain modulation. OBJECTIVE: Considering the emerging search for new therapies for the control of DN and the growing commercial interest in the probiotics market, this study aimed to provide patents on the use of probiotics in the control of DN. METHODS: This is a patent prospection performed in the Espacenet Patent database, using the association of keywords and IPC related to probiotics in medical preparations and foods, from 2009 to December 2022. RESULTS: Results have shown that in 2020, there was a boom in patent filing in the area. Asian countries accounted for more than 50% of all 48 inventions (n = 48), with Japan as the only applicant in 2021. Products being developed in recent years point to effects that may represent an advancement in DN treatment, such as reduced concentration of pro-inflammatory mediators, metabolites and neurotransmitters release, and hypoglycemic potential. All effects were more related to the Lactobacillus and Bifidobacterium genera, associated with more than one property mentioned. CONCLUSION: The mechanisms attributed to the microorganisms suggest the therapeutic potential of probiotics in the non-pharmacological treatment of pain. New applications for probiotics have resulted from great research interest by academia, but also reflect commercial interests despite the paucity of clinical trials. Thus, the present work supports the evolution of research to explore the benefits of probiotics and their clinical use in DN.


Sujet(s)
Diabète , Neuropathies diabétiques , Microbiome gastro-intestinal , Probiotiques , Humains , Neuropathies diabétiques/thérapie , Probiotiques/usage thérapeutique , Lactobacillus , Douleur
11.
Diagn Microbiol Infect Dis ; 108(1): 116096, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37931387

RÉSUMÉ

This study aimed to propose and evaluate a drug susceptibility testing (DST) using the 2,3,5-triphenyl tetrazolium chloride (TTC) as a colorimetric indicator against Mycobacterium abscessus complex (MABC), M. avium complex (MAC), and M. kansasii strains, main nontuberculous mycobacteria (NTM) of clinical relevance. Our results demonstrated that the assay using TTC and the broth microdilution method recommended by the Clinical and Laboratory Standards Institute had essential agreement above 91%, 92%, and 100%, for drugs tested against MABC, MAC, and M. kansasii strains, respectively. Categorical agreement above 91% was obtained for most drugs tested against MABC, except to cefoxitin (76.5%). For drugs tested against MAC and M. kansasii, categorical agreement above 92% and 100% was observed, respectively. TTC showed to be a promising colorimetric indicator of growth to be used in DST for NTM, allowing an easier reading of results.


Sujet(s)
Infections à mycobactéries non tuberculeuses , Mycobacterium abscessus , Mycobacterium tuberculosis , Humains , Mycobactéries non tuberculeuses , Infections à mycobactéries non tuberculeuses/microbiologie , Antibactériens/usage thérapeutique , Chlorures , Colorimétrie , Tests de sensibilité microbienne
12.
Enfermeria (Montev.) ; 12(2)jul.-dez. 2023.
Article de Portugais | LILACS-Express | LILACS, BDENF - Infirmière | ID: biblio-1514109

RÉSUMÉ

Objetivo: Analisar as práticas assistenciais de saúde no processo do abortamento tipificadas como violência obstétrica. Metodologia: Estudo qualitativo e descritivo, realizado em um hospital público no Brasil com 15 profissionais de saúde de nível médio e superior. Os dados foram coletados presencialmente, através de um roteiro de entrevista semiestruturada. O perfil foi analisado pela estatística descritiva simples e as questões abertas pela técnica de conteúdo temática proposta por Bardin. Resultados: Evidenciou-se que as práticas que denotam violência obstétrica relacionam-se a alocação das mulheres em processo de abortamento no mesmo ambiente que gestantes e puérperas e ao emitirem juízos de valor no momento da assistência às mulheres. Conclusão: Há necessidade de educação permanente para que as/os profissionais possam assistir de maneira humanizada e qualificada.


Objetivo: Analizar las prácticas de atención a la salud en el proceso de aborto tipificadas como violencia obstétrica. Metodología: Estudio cualitativo y descriptivo, realizado en un hospital público en Brasil con 15 profesionales de salud de nivel medio y superior. Los datos fueron recogidos presencialmente, a través de un guion de entrevista semiestructurada. El perfil fue analizado por la estadística descriptiva simple y las cuestiones abiertas por la técnica de contenido temática propuesta por Bardin. Resultados: Se evidenció que los profesionales de salud presentaron conocimiento insuficiente sobre violencia obstétrica en el momento en que la restringieron al parto o aborto, a la tipificación física/verbal e identificaron solo a los médicos y enfermeras como los principales perpetradores. Las prácticas que denotan violencia obstétrica se relacionan a la asignación de las mujeres en proceso de aborto en el mismo ambiente que gestantes y puérperas, y al emitir juicios de valor en el momento de la asistencia. Conclusión: Hay necesidad de educación permanente para que los profesionales puedan asistir de manera humanizada y cualificada.


Objective: To analyze health care practices in the abortion process typified as obstetric violence. Methodology: Qualitative and descriptive study, conducted in a public hospital in Brazil with 15 health professionals of medium and higher education. The data were collected in person, through a semi-structured interview script. The profile was analyzed by simple descriptive statistics and the questions opened by the thematic content technique proposed by Bardin. Results: It was evidenced that health professionals had insufficient knowledge about obstetric violence at the time they restricted it to childbirth or abortion, physical/verbal typing and identified only doctors and nurses as the main perpetrators. The practices that denote obstetric violence are related to the allocation of women in the process of abortion in the same environment as pregnant women and puerperal women and when issuing value judgments at the time of care. Conclusion: There is a need for permanent education so that the professionals can assist in a humanized and qualified way.

13.
Enfermeria (Montev.) ; 12(2)jul.-dez. 2023.
Article de Portugais | LILACS-Express | LILACS, BDENF - Infirmière | ID: biblio-1520878

RÉSUMÉ

Objetivos: Traçar as características biopsicossociais das mulheres no ciclo grávido-puerperal e analisar as representações sociais dessas mulheres sobre a violência obstétrica. Metodologia: Estudo descritivo, de abordagem qualitativa, norteado pela Teoria das Representações Sociais, realizado no período de setembro de 2021 a abril de 2022, com 40 mulheres atendidas em uma maternidade de Minas Gerais, no Brasil. Os dados foram coletados por meio de um roteiro de entrevista semiestruturada e da técnica de associação livre de palavras. A caracterização foi analisada pela estatística descritiva simples, a entrevista semiestruturada pela técnica de conteúdo temática proposta por Bardin e a técnica de associação livre de palavras pelo software Iramuteq. Resultados: 82,5 % das participantes possuíam faixa de 18 e 29 anos, 77,5 % intitularam-se pardas, 25 % tinham ensino médio completo e 65 % referiram renda de 1 a 3 salários-mínimos. Quanto à história obstétrica, 52 % possuíam idade gestacional entre 37 e 41 semanas, 70 % não haviam planejado a gravidez, 42,5 % haviam sido admitidas em trabalho de parto e 87,5 % estavam acompanhadas. A violência obstétrica é representada pelas mulheres de maneira superficial com enfoque na dimensão física e emocional, sendo em alguns momentos naturalizada. Conclusão: A violência obstétrica é uma grave problemática vivenciada pelo público feminino e a falta de conhecimento pode levar à naturalização, deixando-as em posição de ampla vulnerabilidade.


Objetivos: Trazar las características biopsicosociales de mujeres en el ciclo gravídico-puerperal y analizar las representaciones sociales de estas mujeres sobre violencia obstétrica Metodología: Estudio descriptivo, de abordaje cualitativo, guiado por la teoría de las representaciones sociales, realizado en el período de septiembre de 2021 a abril de 2022, con 40 mujeres atendidas en una maternidad de Minas Gerais, en Brasil. Los datos fueron recogidos a través de un guion de entrevista semiestructurada y de la técnica de asociación libre de palabras. La caracterización fue analizada por la estadística descriptiva simple, la entrevista semiestructurada por la técnica de contenido temático propuesta por Bardin, y la técnica de asociación libre de palabras por el software Iramuteq. Resultados: 82.5 % de las participantes poseían rango de 18 y 29 años, 77.5 % se identificaron como pardas, 25 % poseían enseñanza media completa y 65 % refirieron renta de 1 a 3 salarios mínimos. En cuanto a la historia obstétrica, 52 % poseían edad gestacional entre 37 y 41 semanas, 70 % no habían planeado el embarazo, 42.5 % habían sido admitidas en trabajo de parto y 87.5 % estaban acompañadas. La violencia obstétrica es representada por las mujeres de manera superficial, con enfoque en la dimensión física y emocional, a veces naturalizada. Conclusión: La violencia obstétrica es una grave problemática vivida por el público femenino y la falta de conocimiento puede llevar a la naturalización, dejándolas en posición de amplia vulnerabilidad


Objectives: To trace the biopsychosocial characteristics of women in the pregnancy-puerperal cycle and to analyze the social representations of these women on obstetric violence. Methodology: Descriptive study, qualitative approach, guided by the Theory of Social Representations conducted in the period from September 2021 to April 2022, with 40 women assisted in a maternity hospital in Minas Gerais, Brazil. The data was collected through a script of semi-structured interview and the technique of free association of words. The characterization was analyzed by simple descriptive statistics, the semi-structured interview by the thematic content technique proposed by Bardin and the free word association technique by Iramuteq software. Results: 82.5 % of the participants had a range of 18 and 29 years, 77.5% self-identified as pardas (mixed race), 25 % had completed high school and 65 % reported income from 1 to 3 minimum wages. Regarding obstetric history, 52,0% had gestational age between 37 and 41 weeks, 70.0% had not planned pregnancy, 42.5% had been admitted for labor and 87.5% were monitored. Obstetric violence is represented by women in a superficial way with a focus on the physical and emotional dimension, being in some moments naturalized. Conclusion: Obstetric violence is a serious problem experienced by the female public and the lack of knowledge can lead to naturalization, leaving them in a position of broad vulnerability

14.
Expert Opin Ther Targets ; 27(10): 911-925, 2023.
Article de Anglais | MEDLINE | ID: mdl-37772733

RÉSUMÉ

INTRODUCTION: Chagas disease (CD) imposes social and economic burdens, yet the available treatments have limited efficacy in the disease's chronic phase and cause serious adverse effects. To address this challenge, target-based approaches are a possible strategy to develop new, safe, and active treatments for both phases of the disease. AREAS COVERED: This review delves into target-based approaches applied to CD drug discovery, emphasizing the studies from the last five years. We highlight the proteins cruzain (CZ), trypanothione reductase (TR), sterol 14 α-demethylase (CPY51), iron superoxide dismutase (Fe-SOD), proteasome, cytochrome b (Cytb), and cleavage and polyadenylation specificity factor 3 (CPSF3), chosen based on their biological and chemical validation as drug targets. For each, we discuss its biological relevance and validation as a target, currently related challenges, and the status of the most promising inhibitors. EXPERT OPINION: Target-based approaches toward developing potential CD therapeutics have yielded promising leads in recent years. We expect a significant advance in this field in the next decade, fueled by the new options for Trypanosoma cruzi genetic manipulation that arose in the past decade, combined with recent advances in computational chemistry and chemical biology.


Sujet(s)
Maladie de Chagas , Trypanosoma cruzi , Humains , Maladie de Chagas/traitement médicamenteux , Trypanosoma cruzi/génétique , Découverte de médicament
15.
Int J Biol Macromol ; 253(Pt 5): 127085, 2023 Dec 31.
Article de Anglais | MEDLINE | ID: mdl-37774819

RÉSUMÉ

This study aimed to investigate the application of biopolymeric materials (chitosan, gelatin, and pomegranate peel extract as photosensitizer) and antimicrobial photodynamic therapy (aPDT) on the physicochemical and microbial safety of strawberries. The photosensitizer potential of the materials was confirmed by a light-dose-dependent photobleaching profile. The application of light (525 nm; 50 J cm-2) decreased by >2 log CFU mL-1 the survival of Staphylococcus aureus on the surface of the photoactive-biopolymeric films. Moreover, the materials did not present in vivo cytotoxicity using Danio rerio (Zebrafish) as well as cytophytotoxic, genotoxic, or mutagenic potentials against Allium cepa plant model, which points out their safety to be used as films without posing a risk to the humans and the environment. The photoactive-polymeric coatings were able to maintain the strawberries weight, and the association with green light was 100 % effective in delaying fungal contamination. These coated-strawberries presented a significant reduction in S. aureus survival after light application (5.47-4.34 log CFU mL-1). The molecular level analysis of the photoactive compound cyanidin-3-glucoside indicates absorption on UV-Vis consistent with aPDT action. Therefore, this study showed that the antimicrobial effects of aPDT combined with photoactive-biopolymeric coatings were enhanced, while the quality of the strawberries was maintained.


Sujet(s)
Anti-infectieux , Chitosane , Fragaria , Grenadier commun , Humains , Animaux , Chitosane/pharmacologie , Chitosane/composition chimique , Grenadier commun/composition chimique , Fragaria/microbiologie , Photosensibilisants , Gélatine , Staphylococcus aureus , Danio zébré , Anti-infectieux/pharmacologie , Anti-infectieux/composition chimique , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique
16.
J Biophotonics ; 16(12): e202300168, 2023 12.
Article de Anglais | MEDLINE | ID: mdl-37679880

RÉSUMÉ

The use of artificial light sources in plants is considered a type of photobiomodulation (PBM), a trend in agriculture and food industries, aiming at decontamination, pest control, and increased production yield. However, literature lacks a broader assessment to address the effects of photon light spectra on plant characteristics. Here, we aimed to describe the effects of visible light, infrared, and ultraviolet light upon Allium cepa, a known bioindicator, under various light doses. Samples irradiated under visible and infrared light did not show cytotoxicity, genotoxicity, or mutagenicity in any of the evaluated doses. Light induction at 460 and 635 nm significantly stimulated root development of the test organism. In contrast, 254 nm irradiation proved to be cytotoxic, genotoxic, and mutagenic. This work reveals and quantifies the spectral response of A. cepa seeds, suggesting that it can be proposed as a model for future research on mechanisms of PBM in plants.


Sujet(s)
Oignons , Racines de plante , Mutagènes/toxicité , Photons , Lumière , Altération de l'ADN
17.
J Wound Care ; 32(Sup8): clxi-clxv, 2023 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-37561701

RÉSUMÉ

OBJECTIVE: To compare the predictive capacity of the current risk assessment scale for pressure ulcers in intensive care (EVARUCI), translated into Brazilian Portuguese, using the Braden scale. METHOD: This cross-sectional study collected prospective data from adult patients in three intensive care units. The receiver operating characteristic (ROC) and precision-recall curve (PR curve) were used to analyse the predictive capacity for pressure injury (PI) using both predictive values and odds ratios (ORs). RESULTS: The incidence of PIs in the study sample of 324 patients was 14.2%. The area under the ROC curve was 0.807 for EVARUCI and 0.798 for the Braden scale. At a cutoff point of 10 on the EVARUCI scale, sensitivity was 69.6%; specificity 78.4%; positive predictive value 34.8%; and OR 8.3. At a cutoff point of 11 on the Braden scale, sensitivity was 76.1%; specificity 75.9%; positive predictive value 34.3%; and OR 10. The area under the PR curve was 0.396 for the EVARUCI scale and 0.348 for the Braden scale, reflecting a smaller area for both. The F1 score value was 0.476 with 37.5% precision and 65.2% recall for the EVARUCI scale, and 0.473 with 34.3% precision and 76.1% recall for the Braden scale. CONCLUSION: The EVARUCI scale predictive capacity was similar to that of the Braden scale. However, the precision of both scales was low for the accurate prediction of patients at risk of developing PIs.


Sujet(s)
Escarre , Adulte , Humains , Escarre/diagnostic , Escarre/épidémiologie , Escarre/étiologie , Études prospectives , Études transversales , Soins de réanimation , Unités de soins intensifs , Appréciation des risques , Valeur prédictive des tests , Facteurs de risque
18.
Int J Microbiol ; 2023: 5992113, 2023.
Article de Anglais | MEDLINE | ID: mdl-37644978

RÉSUMÉ

Isoetes cangae is a native plant found only in a permanent pond in Serra dos Carajás in the Amazon region. Plant-associated microbial communities are recognized to be responsible for biological processes essential for the health, growth, and even adaptation of plants to environmental stresses. In this sense, the aims of this work were to isolate, identify, and evaluate the properties of endophytic bacteria isolated from I. cangae. The bioprospecting of potentially growth-promoting endophytes required the following steps to be taken: isolation of endophytic colonies, molecular identification by 16S rDNA sequence analysis, and evaluation of the bacterial potential for nitrogen fixation, production of indole acetic acid and siderophores, as well as phosphate solubilization and mineralization. Bacillus sp., Rhizobium sp., Priestia sp., Acinetobacter sp., Rossellomorea sp., Herbaspirillum sp., Heyndrickxia sp., and Metabacillus sp., among other bacterial species, were identified. The isolates showed to be highly promising, evidencing the physiological importance for the plant and having the potential to promote plant growth.

19.
J Basic Microbiol ; 63(6): 658-667, 2023 Jun.
Article de Anglais | MEDLINE | ID: mdl-36734187

RÉSUMÉ

Fungi, yeasts and bacteria produce volatile compounds during their metabolism. In this study, the volatile compounds produced by yeast strains (Saccharomyces cerevisiae and Rhodotorula mucilaginosa) and fungal strains (Aspergillus carbonarius and Aspergillus ochraceus) during competitive interactions were investigated by solid-phase microextraction coupled with gas chromatography-mass spectrometry. Fifty-six volatile compounds were identified representing alcohols, aldehydes, esters, ketones, aromatic compounds, acids, furans, phenols, and nitrogen compounds, being the largest amount in the class of esters and alcohols. Eight compounds were identified only in interactive culture conditions such as 2-amino-1-propanol, isopropylamine, dimethylamine, pentyl propanoate, ethyl-2-aminopropanoate, acetone, oxalic acid, and ß-elemene and five of these were produced in cocultures including A. carbonarius. These will be developed for future biotechnological applications such as in the pharmaceutical and biological industry to produce drugs. Antimicrobial and antifungal activities; Solvent and herbicide; flavoring ingredient; solvent, plastic synthesis, nail polish remover and thinner, pesticide and herbicide; important in the complexation of minerals in the soil; and plant-environment interactions, defending predators, pathogens, and competitors.


Sujet(s)
Herbicides , Composés organiques volatils , Levures/métabolisme , Alcools/analyse , Alcools/composition chimique , Alcools/métabolisme , Saccharomyces cerevisiae/métabolisme , Solvants , Esters/analyse , Herbicides/métabolisme , Composés organiques volatils/composition chimique
20.
Eur J Clin Microbiol Infect Dis ; 42(3): 255-266, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-36662376

RÉSUMÉ

Streptococcus pneumoniae causes invasive diseases of significant public health concern, such as meningitis. The culture of cerebrospinal fluid (CSF) samples, the standard technique for meningitis diagnoses, is not always positive. Consequently, meaningful information about the etiological agent is lost, which can compromise effective epidemiological surveillance and the improvement of immunization policies. This study aims to standardize a method to genotype pneumococcus in the CSF samples which could mitigate the absence of isolated strains, and also evaluate the prediction of this assay. We applied eight multiplex PCR (mPCR) assays to CSF samples paired with the Quellung reaction applied to the isolated strains. We also compared different master mix kits in the mPCR. Moreover, a retrospective study was conducted with CSF samples considered pneumococcus positive due to the presence of the lytA gene. Results showed that genotyping by the mPCR correlated 100% with the Quellung reaction, and genotyping was dependent on the master mix applied. In the retrospective study (2014-2020), 73.4% were successfully genotyped. The analyses of the receiver operating characteristic curve showed that the cycle threshold (Ct value) around 30 for the lytA gene had a 75% positive chance of successful genotyping, whereas with a Ct value > 35, the chance was 12.5%. Finally, we observed that genotype 19A was prevalent in the period (12%), information unknown until now due to the lack of isolated strains. Therefore, the mPCR of CSF samples can efficiently predict S. pneumoniae serotypes, especially in the absence of isolated strains, which can be a great tool for pneumococcal serotype surveillance.


Sujet(s)
Infections à pneumocoques , Streptococcus pneumoniae , Humains , Streptococcus pneumoniae/génétique , Réaction de polymérisation en chaine multiplex , Sérogroupe , Études rétrospectives , Sérotypie/méthodes , Infections à pneumocoques/microbiologie
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