Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 9.740
Filter
1.
Molecules ; 29(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39125089

ABSTRACT

Nerve agents are organophosphates (OPs) that act as potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of acetylcholine. After inhibition, a dealkylation reaction of the phosphorylated serine, known as the aging of AChE, can occur. When aged, reactivators of OP-inhibited AChE are no longer effective. Therefore, the realkylation of aged AChE may offer a pathway to reverse AChE aging. In this study, molecular modeling was conducted to propose new ligands as realkylators of aged AChE. We applied a methodology involving docking and quantum mechanics/molecular mechanics (QM/MM) calculations to evaluate the resurrection kinetic constants and ligand interactions with OP-aged AChE, comparing them to data found in the literature. The results obtained confirm that this method is suitable for predicting kinetic and thermodynamic parameters of ligands, which can be useful in the design and selection of new and more effective ligands for AChE realkylation.


Subject(s)
Acetylcholinesterase , Cholinesterase Inhibitors , Indolequinones , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Kinetics , Indolequinones/chemistry , Molecular Docking Simulation , Ligands , Thermodynamics , Models, Molecular , Humans , Molecular Dynamics Simulation
2.
Hypertens Res ; 47(10): 2895-2901, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39117947

ABSTRACT

Pregnancy Hypertensive Disorders (PHD), particularly Preeclampsia (PE), are significant contributors to maternal-fetal morbidity and mortality, with chronic arterial hypertension (CH) being a major risk factor. The prevalence of CH has risen alongside obesity and advanced maternal age. While antihypertensive treatment mitigates adverse pregnancy outcomes, the duration of effective blood pressure (BP) control, termed Time in Therapeutic Range (TTR), has not been extensively studied in pregnant women. TTR, reflecting the proportion of time BP remains within target ranges, predicts long-term cardiovascular and renal events in the general population but remains unexplored in pregnancy. This study investigates the association between TTR, assessed through office BP (OBP) and ambulatory BP monitoring (ABPM), and PE development in pregnant women with CH. In a retrospective longitudinal study, data from 166 pregnant women with HA referred to our hospital analyzed. BP was measured using OBP and ABPM from 10 weeks of gestation, with TTR calculated as the percentage of visits where BP remained within target ranges. The study defined four TTR control groups: 0%, 33%, 50-66%, and 100%. Results showed that 28% of the participants developed PE, with a higher incidence correlating with lower TTR in ABPM. TTR in ABPM was a significant predictor of PE risk, with the best-controlled group (100% TTR) demonstrating a 92% reduced risk compared to those with 0% TTR. The agreement between OBP and ABPM TTR was low, emphasizing the importance of ABPM for accurate BP monitoring in pregnancy. This study indicates that integrating ABPM for TTR assessment in high-risk pregnancies has the potential to reduce maternal and fetal complications.


Subject(s)
Pre-Eclampsia , Humans , Pregnancy , Female , Pre-Eclampsia/epidemiology , Adult , Retrospective Studies , Longitudinal Studies , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Risk Factors , Hypertension, Pregnancy-Induced/drug therapy , Hypertension, Pregnancy-Induced/epidemiology , Hypertension/drug therapy , Hypertension/epidemiology , Young Adult , Blood Pressure Determination
3.
Clin Transl Oncol ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103729

ABSTRACT

BACKGROUND: In recent years, evidence has accumulated that a second method of conserving the breast from cancer with re-irradiation as part of treatment may be feasible and safe. Many oncologists are skeptical of breast re-irradiation due to concerns about late complications, so access to quantitative data on the prevalence of breast re-irradiation complications is very important. In this meta-analysis, we determine the prevalence of complications in normal tissue after breast re-irradiation. MATERIALS AND METHODS: A search was done to recognize qualified studies using EMBASE, MEDLINE, PUBMED, Google Scholar, and Cochrane Collaboration Library electronic databases from 2000 to 2023. In total, ten primary studies were applied in this meta-analysis to estimate the prevalence of complications of disorders, skin fibrosis, and chest pain. Heterogeneity was investigated using the I2 index and the meta-regression to evaluate variables suspected of causing heterogeneity. Statistical analysis and synthesis were performed using Stata 17. RESULTS: The average dose received by patients who underwent radiation therapy in two stages was 100.32 Gy, and in these patients, the prevalence of skin fibrosis and disorders was 47% (95% CI 71-22%; I2 = 96.76%, P < 0.001) and the prevalence of chest pain was 35% (95% CI 68-8%; I2 = 98.13%, P < 0.001). CONCLUSIONS: There is little clinical information about the incidence of complications in breast re-irradiation therapy. This meta-analysis presents the prevalence of complications after breast re-irradiation to help radiation oncologists and physicists make better decisions.

4.
Braz J Biol ; 84: e284361, 2024.
Article in English | MEDLINE | ID: mdl-39140507

ABSTRACT

Coronary Artery Disease (CAD) is a global health concern, with diagnostic modalities and risk factors that exhibit regional variations. This study, conducted at the Islamabad Diagnostic Center, Pakistan, aimed to provide a comprehensive assessment of CAD prevalence, severity, and associated risk factors, while also evaluating the diagnostic accuracy of Computed Tomography Coronary Test (CTT) and Exercise Treadmill Test (ETT) in a cohort of 2909 patients. Among the patients assessed via CT Coronary scans, CAD was universally observed, presenting with varying degrees of severity. Our findings indicated that 24.5% of patients had mild CAD, 28.6% exhibited mild to moderate CAD, 16.3% were diagnosed with moderate CAD, 18.4% demonstrated moderate to severe CAD, and 20.4% displayed severe CAD. This spectrum underscores the diverse nature of CAD within the study population. In addition to CTT, we conducted a detailed evaluation of ETT results in 49 patients. These results revealed that 55.1% of patients tested positive for ischemia during the exercise test, emphasizing the prevalence of cardiac stress and underlying CAD. Conversely, 32.7% of patients exhibited negative ETT results, indicating favorable cardiac tolerance during physical activity. A subset of patients yielded non-diagnostic or inconclusive results, necessitating further clinical assessment. Disease history analysis showed a dichotomy within the cohort, with 20.4% having a known medical history and 79.6% possessing an unknown disease history, highlighting the importance of comprehensive medical records in clinical practice. Hypertension, a critical cardiovascular risk factor, was identified in 87.8% of patients, underscoring its significance. Smoking history displayed notable variation, with 69.4% categorized as smokers, 14.3% as ex-smokers, and 10.2% as non-smokers. Lipid profile analysis indicated that 69.4% of patients had abnormal lipid levels. To assess the diagnostic accuracy of CTT and ETT, we calculated Positive Predictive Values (PPV) and Negative Predictive Values (NPV). CTT exhibited a PPV of approximately 5.99% and an NPV of approximately 4.40%, whereas ETT displayed a higher PPV of around 26.44% and a substantially higher NPV of about 49.24%. This study offers valuable insights into CAD prevalence, severity, and associated risk factors in a Pakistani cohort, emphasizing the importance of holistic risk assessment and tailored interventions in clinical practice. Our findings also highlight the diagnostic utility of ETT in CAD assessment.


Subject(s)
Coronary Artery Disease , Exercise Test , Humans , Exercise Test/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Pakistan/epidemiology , Male , Female , Middle Aged , Adult , Risk Factors , Aged , Prevalence , Severity of Illness Index , Tomography, X-Ray Computed , Coronary Angiography
5.
Braz J Biol ; 84: e281076, 2024.
Article in English | MEDLINE | ID: mdl-39140502

ABSTRACT

Population growth combined with the need for electrical energy resulted in the construction of hundreds of hydroelectric plants in the state of São Paulo, Brazil. The consequence of these interventions was the fragmentation of rivers, forming barriers, that hinder the mobility of migratory fish species, generating an impact on the life cycle of these species, especially about movement between breeding and feeding areas. For this reason, this article aimed to evaluate the state-of-the-art knowledge regarding dams, free stretches, and migratory species in the three main river basins of the state of São Paulo and its tributaries. Through a systematic review from 2003 to 2023, 89 articles were obtained, 48 of which were about dams, 5 which addressed fish transposition systems, and 36 portraying migratory species. In the first half, research focused more on the impacts of dams on fish fauna, while in the second half of the period studied, studies of migratory fish were dominant. Most research was conducted in the main rivers, with few in the tributaries. Finally, 16 migratory species, considered long-distance, were studied, the most studied being P. lineatus, P. maculatus, L. friderici, M. obtusidens and S. hilarri and the ones that occurred most frequently in rivers are Prochilodus lineatus, Pimelodus maculatus, Megaleporinus obtusidens and Salminus hilarii. Therefore, we recommend maintaining the natural flow regime that still exists in the main rivers and tributaries of the state of São Paulo, to maintain healthy populations of the inventoried species.


Subject(s)
Animal Migration , Fishes , Rivers , Animals , Brazil , Fishes/classification , Fishes/physiology , Animal Migration/physiology , Population Dynamics
6.
Materials (Basel) ; 17(15)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39124448

ABSTRACT

In this paper, the development of a 3D adaptive probabilistic explicit cracking model for concrete is reported. The contribution offered herein consists in a new adaptive mesh strategy designed to optimize the use of interface elements in probabilistic explicit cracking models. The proposed adaptive mesh procedure is markedly different from other strategies found in the literature, since it takes into account possible influences on the redistribution of stresses after cracking and can also be applied to purely deterministic cracking models. The process of obtaining the most appropriate adaptive mesh procedure involved the development and evaluation of three different adaptivity strategies. Two of these adaptivity strategies were shown to be inappropriate due to issues related to stress redistribution after cracking. The validation results demonstrate that the developed adaptive probabilistic model is capable of predicting the scale effect at a level similar to that experimentally observed, considering the tensile failure of plain concrete specimens. The results also show that different softening levels can be obtained. The proposed adaptive mesh strategy proved to be advantageous, being able to promote significant reductions in the simulation time in comparison with the classical strategy commonly used in probabilistic explicit cracking models.

7.
Neuroophthalmology ; 48(5): 369-372, 2024.
Article in English | MEDLINE | ID: mdl-39145320

ABSTRACT

Pelizaeus-Merzbacher-like disease (PMLD, OMIM #608804) is an autosomal recessive hypomyelinating leukodystrophy caused by homozygous variants in the GJC2 gene. It usually presents in the first months of life with nystagmus, developmental delay, and diffuse hypomyelination on brain magnetic resonance imaging (MRI). We report a case of a 3-year-old boy that presented with nystagmus and global developmental delay. MRI showed diffuse hypomyelination, including the cerebellum. Pelizaeus-Merzbacher disease (PMD) was suspected; however, no pathological variants of the PLP1 gene were found. Exome sequencing found variants in the GJC2 gene, leading to a diagnosis of PMLD. The combination of global developmental delay, hypomyelination, and nystagmus in a child should raise suspicion of PMD and PMLD. Unlike PMD, however, hypomyelination of the brainstem and cerebellum are frequently seen and brainstem auditory evoked potentials are usually normal in PMLD. The latter has an overall better prognosis than the former as well. Epidemiological studies on leukodystrophies have found conflicting results on which disease is more common. However, PMLD is a rare leukodystrophy and both PMLD and PMD should be considered in any child with developmental delay, hypomyelination, and nystagmus.

8.
Public Health ; 235: 94-101, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39084048

ABSTRACT

OBJECTIVE: The aim of this study was to analyse the attributable risk of mortality and DALYs (Disability Adjusted Life Years) due to occupational carcinogens for lung cancer between 1990 and 2019 in Brazil and federation units, as well as its relationship with the Socio-demographic Index (SDI). STUDY DESIGN: Epidemiological study. METHODS: This is an epidemiological study that used GBD 2019 (Global Burden of Disease Study) estimates of lung cancer mortality rates and DALYs attributable to occupational carcinogens. The relationship between these rates and SDI was assessed using panel data analysis. RESULTS: In Brazil, occupational exposure to asbestos, silica and diesel vapours accounted for more than 85.00% of lung cancer deaths and DALYs attributable to occupational carcinogens in both sexes between 1990 and 2019. An increase in both rates was observed in women for almost all the occupational carcinogens assessed, especially in the North and Northeast regions of the country, with diesel vapours standing out the most. CONCLUSIONS: The present study highlighted the urge to characterise exposure to occupational risks for lung cancer, especially for the female population in the North and Northeast regions of Brazil.


Subject(s)
Lung Neoplasms , Occupational Diseases , Occupational Exposure , Humans , Brazil/epidemiology , Lung Neoplasms/mortality , Lung Neoplasms/epidemiology , Female , Occupational Exposure/adverse effects , Occupational Exposure/statistics & numerical data , Male , Risk Factors , Occupational Diseases/mortality , Occupational Diseases/epidemiology , Disability-Adjusted Life Years , Middle Aged , Global Burden of Disease , Adult , Carcinogens/toxicity , Aged
9.
Acta Trop ; 258: 107333, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39067841

ABSTRACT

To evaluate the prevalence of Mycobacterium leprae and Mycobacterium lepromatosis in road killed armadillos identified along Brazilian regions, samples of liver, spleen, muscle, ear, nose and tail were collected on highways from 78 animals. The armadillos were of four different species, Cabassous tatouay, Dasypus novemcinctus, Dasypus septemcinctus and Euphractus sexcinctus. After DNA extraction from two tissues, specific primers were used for the detection of each pathogen using SYBR green qualitative Real-Time PCR, and amplicons were sequenced. The species with the highest prevalence was D. novemcinctus, mainly in the Central-West, South, and Southeast regions of Brazil. We detected M. leprae DNA in 32 (41 %) of the 78 individuals and M. lepromatosis DNA was not identified in any of the examined samples. The zoonotic component of leprosy may play a role in the transmission of the disease in endemic areas in which environmental conditions and contact with reservoirs must be investigated.


Subject(s)
Armadillos , Leprosy , Mycobacterium leprae , Armadillos/microbiology , Brazil/epidemiology , Animals , Mycobacterium leprae/genetics , Mycobacterium leprae/isolation & purification , Prevalence , Leprosy/epidemiology , Leprosy/microbiology , Mycobacterium/genetics , Mycobacterium/isolation & purification , Mycobacterium/classification , DNA, Bacterial/genetics , Real-Time Polymerase Chain Reaction
10.
Eur Arch Paediatr Dent ; 25(5): 669-676, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38969936

ABSTRACT

PURPOSE: To analyze the functions of the stomatognathic system in children with or without molar-incisor hypomineralization (MIH). METHODS: For this cross-sectional study, 72 children aged 6-12 years were recruited and divided in two groups: with MIH (G1) and without MIH (G2). T-SCAN was used to verify the distribution of occlusal contacts, gnathodynamometer to measure maximum molar bite force, and Iowa Oral Pressure Instrument (IOPI) to assess the strength of facial expression muscles. The t test and paired t test (p ≤ 0.05) were used for statistical comparisons. RESULTS: The molars affected by MIH exhibited lower distribution of occlusal forces (p < 0.001) and lower maximum molar bite force (p < 0.05) compared to the molars in the control group. However, there was no difference between the MIH-affected sides compared to the unaffected side, nor between the molars affected by MIH and their antagonists (p > 0.05). There were no differences in the forces of the facial expression muscles between the groups. CONCLUSIONS: These findings suggest that MIH significantly impacts occlusal force distribution and bite force, but not facial expression musculature.


Subject(s)
Bite Force , Masticatory Muscles , Molar , Humans , Child , Cross-Sectional Studies , Male , Female , Molar/physiopathology , Masticatory Muscles/physiopathology , Dental Enamel Hypoplasia/physiopathology , Stomatognathic System/physiopathology , Molar Hypomineralization
11.
Rev Gastroenterol Mex (Engl Ed) ; 89(3): 379-388, 2024.
Article in English | MEDLINE | ID: mdl-39025775

ABSTRACT

INTRODUCTION AND AIM: Timely detection and diagnosis of hepatitis C virus (HCV) involves identifying the population that is predisposed to treatment and prevention, thus limiting complications and preventing infection. The aim of this study was to analyze and describe risk factors associated with anti-HCV antibody detection in a population with access to public healthcare that participated in a national screening program. MATERIAL AND METHODS: An analytic cross-sectional study was conducted that utilized data related to rapid tests carried out between September 2021 and October 2022 in 26 of the 32 states of Mexico. Anti-HCV reactive tests were selected, according to age and sex, for analyzing and comparing possible risk factors through descriptive and inferential statistics. The geographic distribution and density of the screening program at the state and municipal levels was analyzed. RESULTS: There were 75,185 anti-HCV antibody detections, 2,052 reactive tests, and mean participant age was 44.3 years (±15.1). Occupation: 32.3% were employees, 19% were housewives, and 18.2% were healthcare workers. Five out of every 10 cases had no indication of risk factors, but there was a 1.4 and 5-times greater likelihood of anti-HCV detection in men with a history of sharps injury or intravenous psychoactive substance use, compared with women. Regarding place of residence, 80% of the reactive tests were concentrated in the State of Mexico, Mexico City, and Guanajuato. CONCLUSIONS: The evidence herein helps determine the population and risk factors that should be focused on in carrying out the HCV microelimination strategy of continuous screening, diagnosis, medical treatment access, and epidemiologic surveillance.


Subject(s)
Health Services Accessibility , Hepatitis C Antibodies , Hepatitis C , Humans , Mexico/epidemiology , Male , Female , Cross-Sectional Studies , Risk Factors , Adult , Middle Aged , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C Antibodies/blood , Young Adult , Aged , Adolescent , Mass Screening
12.
Braz J Biol ; 84: e271452, 2024.
Article in English | MEDLINE | ID: mdl-38985057

ABSTRACT

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Viral Load , Humans , Pakistan/epidemiology , Viral Load/drug effects , Male , Female , COVID-19 Drug Treatment , Adult , RNA, Viral/analysis , Middle Aged , Time Factors , Adrenal Cortex Hormones/therapeutic use , Young Adult , Pandemics , Adolescent , Real-Time Polymerase Chain Reaction , COVID-19 Nucleic Acid Testing
13.
Braz J Biol ; 84: e279583, 2024.
Article in English | MEDLINE | ID: mdl-38985060

ABSTRACT

We aimed to characterize the adult and regenerating tree components and their relationships with soil characteristics of a native vegetation remnant in Cuiabá, Mato Grosso, Brazil. The area of the fragment is stratified into "dry area" (lithic neosoil) and "damp area" (gleisoil). We conducted a forest inventory with a random distribution of 25 parcels. We analyzed the physical and chemical components of the soil. We evaluated the vegetation's horizontal structure, diversity, and sample sufficiency using the Bootstrap richness estimator. We classified the species according to dispersal syndrome and ecological group. Overall, we found 93 species in the adult layer and 70 species in the regenerating layer. The similarity dendrograms based on the two evaluated indices demonstrated the existence of the two initially stratified environments in both strata. The IndVal (%) indicated that the set of indicator species differed between the strata. Thereby, the fragment is in an intermediate stage of successional progression. PCA showed that plots in the wet area had higher pH values and Ca, Zn, and Fe levels, while plots in the dry area did not clearly distinguish, varying in terms of K, B, and organic matter content. In CCA, a set of species that occurred exclusively in the damp area showed a strong relationship with the analyzed variables. The area is a diverse ecosystem that efficiently provides ecosystem services to society and should be the subject of long-term conservation and research.


Subject(s)
Biodiversity , Forests , Soil , Brazil , Soil/chemistry , Trees/classification
14.
Braz J Biol ; 84: e277750, 2024.
Article in English | MEDLINE | ID: mdl-38985067

ABSTRACT

The One Health concept recognizes that human health is clearly linked to the health of animals and the environment. Infections caused by bacteria resistant to carbapenem antibiotics have become a major challenge in hospitals due to limited therapeutic options and consequent increase in mortality. In this study, we investigated the presence of carbapenem-resistant Enterobacteriaceae in 84 effluent samples (42 from hospital and 42 from non-hospital) from Campo Grande, midwest Brazil. First, sewage samples were inoculated in a selective culture medium. Bacteria with reduced susceptibility to meropenem and ertapenem were then identified and their antimicrobial susceptibility was determined using the Vitek-2 system. The blaKPC genes were detected using PCR and further confirmed by sequencing. Carbapenem-resistant Enterobacteriaceae (CRE) were identified in both hospital (n=32) and non-hospital effluent (n=16), with the most common being Klebsiella pneumoniae and of the Enterobacter cloacae complex species. This is the first study to indicate the presence of the blaKPC-2 gene in carbapenem-resistant Enterobacteriaceae, classified as a critical priority by the WHO, in hospital sewage in this region. The dissemination of carbapenem antibiotic-resistant genes may be associated with clinical pathogens. Under favorable conditions and microbial loads, resistant bacteria and antimicrobial-resistance genes found in hospital sewage can disseminate into the environment, causing health problems. Therefore, sewage treatment regulations should be implemented to minimize the transfer of antimicrobial resistance from hospitals.


Subject(s)
Anti-Bacterial Agents , Carbapenem-Resistant Enterobacteriaceae , Drug Resistance, Multiple, Bacterial , Hospitals , Microbial Sensitivity Tests , Sewage , Sewage/microbiology , Brazil , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , Polymerase Chain Reaction , Bacterial Proteins/genetics , Humans
15.
Chem Biol Drug Des ; 104(1): e14585, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39013834

ABSTRACT

Leishmaniasis is a disease caused by protozoa Leishmania spp., considered as a significant and urgent public health problem mainly in developing countries. In the absence of an effective vaccine, the treatment of infected people is one of the most commonly prophylactic measures used to control this disease. However, the therapeutic arsenal is reduced to a few drugs, with serious side effects and variability in efficacy. Attempting to this problem, in this work, a series of benzothiazole derivatives was synthetized and assayed against promastigotes and intracellular amastigotes of L. amazonensis, as well as the toxicity on macrophages. In addition, studies about the mechanism of action were also performed. Among the synthesized molecules, the substitution at position 4 of the aromatic ring appears to be critical for activity. The best compound exhibited IC50 values of 28.86 and 7.70 µM, against promastigotes and amastigotes of L. amazonensis, respectively, being more active than miltefosine, used as reference drug. The in silico analysis of physicochemical and pharmacokinetic (ADMET) properties of this compound suggested a good profile of oral bioavailability and safety. In conclusion, the strategy of using benzothiazole nucleous in the search for new antileishmanial agents was advantageous and preliminar data provide information about the mechanism of action as well as in silico parameters suggest a good profile for preclinical studies.


Subject(s)
Antiprotozoal Agents , Benzothiazoles , Hydrazones , Leishmania , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Benzothiazoles/chemical synthesis , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/chemical synthesis , Animals , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Mice , Leishmania/drug effects , Macrophages/drug effects , Macrophages/parasitology , Structure-Activity Relationship , Humans
16.
Immun Inflamm Dis ; 12(7): e1353, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39056544

ABSTRACT

BACKGROUND: SARS-CoV2 virus, responsible for the COVID-19 pandemic, has four structural proteins and 16 nonstructural proteins. S-protein is one of the structural proteins exposed on the virus surface and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry. AIMS: The goal of this study was to express in HEK293 cells a new RBD recombinant protein in a constitutive and stable manner in order to use it as an alternative immunogen and diagnostic tool for COVID-19. MATERIALS & METHODS: The protein was designed to contain an immunoglobulin signal sequence, an explanded C-terminal section of the RBD, a region responsible for the bacteriophage T4 trimerization inducer, and six histidines in the pCDNA-3.1 plasmid. Following transformation, the cells were selected with geneticin-G418 and purified from serum-fre culture supernatants using Ni2+-agarand size exclusion chromatography. The protein was structurally identified by cross-linking and circular dichroism experiments, and utilized to immunize mice in conjuction with AS03 or alum adjuvants. The mice sera were examined for antibody recognition, receptor-binding inhibition, and virus neutralization, while spleens were evaluated for γ-interferon production in the presence of RBD. RESULTS: The protein released in the culture supernatant of cells, and exhibited a molecular mass of 135 kDa with a secondary structure like the monomeric and trimeric RBD. After purification, it formed a multimeric structure comprising trimers and hexamers, which were able to bind the ACE2 receptor. It generated high antibody titers in mice when combined with AS03 adjuvant (up to 1:50,000). The sera were capable of inhibiting binding of biotin-labeled ACE2 to the virus S1 subunit and could neutralize the entry of the Wuhan virus strain into cells at dilutions up to 1:2000. It produced specific IFN-γ producing cells in immunized mouse splenocytes. DISCUSSION: Our data describe a new RBD containing protein, forming trimers and hexamers, which are able to induce a protective humoral and cellular response against SARS-CoV2. CONCLUSION: These results add a new arsenal to combat COVID-19, as an alternative immunogen or antigen for diagnosis.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Recombinant Proteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Humans , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Mice , Antibodies, Neutralizing/immunology , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , Recombinant Proteins/immunology , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , HEK293 Cells , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , Mice, Inbred BALB C , Female , Protein Multimerization , Protein Domains/immunology , Protein Binding
17.
Vaccines (Basel) ; 12(7)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39066430

ABSTRACT

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

18.
Genes (Basel) ; 15(7)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39062696

ABSTRACT

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.


Subject(s)
Polymorphism, Single Nucleotide , Self Report , Skin Pigmentation , Humans , Brazil , Skin Pigmentation/genetics , Male , Female , Adult , White People/genetics , Urban Population , Black People/genetics , Racial Groups/genetics , Middle Aged , Genetics, Population
19.
Cogent Gerontol ; 3(1)2024.
Article in English | MEDLINE | ID: mdl-39035459

ABSTRACT

Less than half of U.S. veterans meet physical activity guidelines. Even though changing physical activity can be challenging, prior studies have demonstrated that it is possible. Older adults are using technology to aid in such behavior change. However, research that explores the mechanisms of how technology can aid in behavior change is lacking, especially among older veterans. Thus, the purpose of this secondary, convergent mixed methods study was to explore how older veterans engaged with technologies that were used during a multicomponent telerehabilitation program. The study included veterans aged ≥60 years with ≥3 chronic medical conditions and physical function limitation. Quantitative data were collected during the primary randomized controlled trial, and qualitative data were collected via individual interviews following completion of the telerehabilitation program. Data were merged and then analyzed by high vs. low technology engagement groups. Key similarities and differences between groups were identified in five domains: satisfaction with the virtual environment, coping self-efficacy, perceptions of Annie (automated text messaging platform), experiences using the activity monitor, and self-management skills. Findings can help inform the successful integration of similar technologies into physical rehabilitation programs. Further study is warranted to understand additional factors and mechanisms that influence technology engagement in telerehabilitation.

20.
Article in English | MEDLINE | ID: mdl-39031814

ABSTRACT

BACKGROUND: Radiofrequency catheter ablation (RFCA) has emerged as a therapeutic option for surgical myectomy and alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM), but its efficacy remains unclear. AIM: Due to limited research on RFCA for HCM, there is an ongoing attempt to assess its efficacy and safety. METHODS: PubMed, Embase, and Scopus were systematically searched for studies assessing the efficacy outcomes for patients with HOCM who underwent RFCA. Mean differences (MDs) with 95% confidence intervals (CIs) were computed using a random-effects model and heterogeneity was assessed using I2 statistics. RESULTS: We included 11 studies comprising 470 patients, of whom 34.6% were female. The mean patient age ranged from 43.7 to 60.7 years. During the follow-up after RFCA, there was a significant decrease in the left ventricular outflow tract (LVOT) gradient at rest (MD -60.25 mmHg; 95% CI [-70.53;-59.14 mmHg]; p < 0.01) and during stimulation (MD -83.56 mmHg; 95% CI [-100.36;-66.76 mmHg]; p < 0.01). Moreover, RFCA reduced interventricular septum (IVS) thickness (MD -3.61 mm; 95% CI [-5.64; -1.59 mm]; p = 0.01) and New York Heart Association (NYHA) class (MD -1.46; 95% CI [-1.69; -1.24]; p < 0.01). CONCLUSIONS: In patients with HOCM, RFCA was associated with an improved NYHA class, reduced IVS thickness, and decreased LVOT gradient at rest and with stimulation.

SELECTION OF CITATIONS
SEARCH DETAIL