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1.
Arq. bras. oftalmol ; Arq. bras. oftalmol;88(1): e2022, 2025. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1574008

ABSTRACT

ABSTRACT Purpose: This study aimed to examine the prevalence of myopic eyes over 11 years (2008-2018) in a private clinic and a public assistance service. Methods: We retrospectively evaluated 6332 individuals (12,664 eyes) between 5 and 25 years old, seen at a private clinic-CEMO (2,663 individuals) and a public service-HOIP (3,669 individuals) from 2008 to 2018. We evaluated the prevalence of myopic eyes (EE ≤-0.50) and high myopic eyes (EE ≤-6.00). Results: Sex and services did not show statistical differences. The variation in the prevalence of myopic and high myopic eyes showed a random pattern during the study period (this prevalence could not be increased). Prevalences ranged from 20.7% (in 2017) to 32.4% (in 2015) for myopic eyes and from 1.6% (in 2009 and 2016) to 3.3% (in 2015) for eyes with high myopia. The prevalence of myopia showed a statistically significant increase based on the age group. Conclusion: The prevalence of myopic eyes did not increase in our study. The mean prevalence of myopic eyes was similar in the private clinic and public service.

2.
Arq Bras Oftalmol ; 88(1): e20220367, 2024.
Article in English | MEDLINE | ID: mdl-39319840

ABSTRACT

PURPOSE: This study aimed to examine the prevalence of myopic eyes over 11 years (2008-2018) in a private clinic and a public assistance service. METHODS: We retrospectively evaluated 6332 individuals (12,664 eyes) between 5 and 25 years old, seen at a private clinic-CEMO (2,663 individuals) and a public service-HOIP (3,669 individuals) from 2008 to 2018. We evaluated the prevalence of myopic eyes (EE ≤-0.50) and high myopic eyes (EE ≤-6.00). RESULTS: Sex and services did not show statistical differences. The variation in the prevalence of myopic and high myopic eyes showed a random pattern during the study period (this prevalence could not be increased). Prevalences ranged from 20.7% (in 2017) to 32.4% (in 2015) for myopic eyes and from 1.6% (in 2009 and 2016) to 3.3% (in 2015) for eyes with high myopia. The prevalence of myopia showed a statistically significant increase based on the age group. CONCLUSION: The prevalence of myopic eyes did not increase in our study. The mean prevalence of myopic eyes was similar in the private clinic and public service.


Subject(s)
Myopia , Private Practice , Humans , Brazil/epidemiology , Retrospective Studies , Male , Female , Adult , Prevalence , Myopia/epidemiology , Adolescent , Child , Young Adult , Private Practice/statistics & numerical data , Child, Preschool , Age Distribution , Sex Distribution , Public Sector/statistics & numerical data
3.
Immunobiology ; 229(6): 152853, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39303324

ABSTRACT

Laboratorial diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests, which are still hampered by blood́ invasive collection. In this context, in the present study, we develop a serum- and urine-based ELISA to TL diagnoses. A recombinant protein (rLiHyA), which was previously showed to be antigenic for the disease, as well as a B-cell epitope produced as synthetic peptide and a Leishmania antigenic extract (SLA), were used as antigens. A total of paired 205 urine and serum samples were used, which were comprised by samples from cutaneous (n = 30) and mucosal (n = 30) leishmaniasis patients, as well as from healthy individuals living in endemic region of disease (n = 45), of patients with Chagas disease (n = 30), leprosy (n = 35), malaria (n = 15) or HIV-infected (n = 20). Results showed that serum-based ELISA presented sensitivity of 24.0 %, 100 % and 41.0 %, when SLA, rLiHyA and synthetic peptide were used as antigens, and specificity of 98.4 %, 98.4 % and 98.4 %, respectively. The area under the curve (AUC) was calculated and results were 0.74, 1.0, and 0.71, respectively, when SLA, rLiHyA and synthetic peptide were used as antigens. Performing an urine-based ELISA, sensitivity was 28.0 %, 100 % and 75.0 %, respectively, when SLA, rLiHyA, and synthetic peptide were used, while specificity values were of 98.4 %, 98.4 % and 98.4 %, respectively. In addition, the AUC values were 0.82, 1.0, and 0.94, respectively. A significant drop in specific antibodies levels in both patients serum and urine samples was found six months after treatment, suggesting a prognostic role of rLiHyA for TL. In conclusion, preliminary data suggest the potential of use patient urine to TL diagnoses.

4.
Biomed Pharmacother ; 179: 117291, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146766

ABSTRACT

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Cell Membrane Permeability , Microbial Sensitivity Tests , Molecular Docking Simulation , Staphylococcus aureus , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cell Membrane Permeability/drug effects , Gene Expression Regulation, Bacterial/drug effects , Thiazines/pharmacology , Membrane Transport Proteins/metabolism , Membrane Transport Proteins/genetics
5.
Acta Trop ; 258: 107326, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39029609

ABSTRACT

The diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests. Serological assays are suitable to diagnose visceral leishmaniasis (VL); however, they present low performance for the detection of TL cases. Additionally, blood collection to obtain patient serum represents a challenge, as it is an invasive and uncomfortable procedure, requiring laboratorial infrastructure and trained professionals. In this context, the present study proposed to evaluate patient urine to detect TL, given that this analyte has proven to be effective in ELISA experiments for the detection of VL cases. For this, a Leishmania protein called LiHyV, two specific B-cell epitopes derived from protein amino acid sequence, and a Leishmania antigenic extract (SLA) were used as antigens. A total of 215 paired urine and serum samples were evaluated, and results showed that, when serum was employed as an analyte, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 85 %, 29 %, 58 %, and 31 %, respectively, and a specificity of 97.5 %, 98 %, 100 %, and 97.5 %, respectively, in the diagnosis of TL. When urine was used, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 95 %, 74 %, 67 %, and 52 %, respectively, and a specificity of 100 %, 99 %, 98 %, and 86 %, respectively. In conclusion, preliminary data suggest that urine could be considered as an alternative biological sample for the detection of TL cases.


Subject(s)
Antibodies, Protozoan , Antigens, Protozoan , Enzyme-Linked Immunosorbent Assay , Leishmania , Leishmaniasis, Cutaneous , Protozoan Proteins , Recombinant Proteins , Sensitivity and Specificity , Humans , Enzyme-Linked Immunosorbent Assay/methods , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/urine , Protozoan Proteins/urine , Protozoan Proteins/immunology , Antigens, Protozoan/urine , Antigens, Protozoan/immunology , Leishmania/immunology , Recombinant Proteins/immunology , Recombinant Proteins/urine , Adult , Female , Antibodies, Protozoan/blood , Antibodies, Protozoan/urine , Male , Middle Aged , Young Adult , Adolescent , Aged , Urine/chemistry , Urine/parasitology , Child , Child, Preschool , Epitopes, B-Lymphocyte/immunology
6.
Front Artif Intell ; 7: 1343447, 2024.
Article in English | MEDLINE | ID: mdl-38510471

ABSTRACT

Introduction: Acute Myeloid Leukemia (AML) is one of the most aggressive hematological neoplasms, emphasizing the critical need for early detection and strategic treatment planning. The association between prompt intervention and enhanced patient survival rates underscores the pivotal role of therapy decisions. To determine the treatment protocol, specialists heavily rely on prognostic predictions that consider the response to treatment and clinical outcomes. The existing risk classification system categorizes patients into favorable, intermediate, and adverse groups, forming the basis for personalized therapeutic choices. However, accurately assessing the intermediate-risk group poses significant challenges, potentially resulting in treatment delays and deterioration of patient conditions. Methods: This study introduces a decision support system leveraging cutting-edge machine learning techniques to address these issues. The system automatically recommends tailored oncology therapy protocols based on outcome predictions. Results: The proposed approach achieved a high performance close to 0.9 in F1-Score and AUC. The model generated with gene expression data exhibited superior performance. Discussion: Our system can effectively support specialists in making well-informed decisions regarding the most suitable and safe therapy for individual patients. The proposed decision support system has the potential to not only streamline treatment initiation but also contribute to prolonged survival and improved quality of life for individuals diagnosed with AML. This marks a significant stride toward optimizing therapeutic interventions and patient outcomes.

7.
PLoS One ; 19(2): e0298762, 2024.
Article in English | MEDLINE | ID: mdl-38416729

ABSTRACT

Epilepsy affects millions of people worldwide every year and remains an open subject for research. Current development on this field has focused on obtaining computational models to better understand its triggering mechanisms, attain realistic descriptions and study seizure suppression. Controllers have been successfully applied to mitigate epileptiform activity in dynamic models written in state-space notation, whose applicability is, however, restricted to signatures that are accurately described by them. Alternatively, autoregressive modeling (AR), a typical data-driven tool related to system identification (SI), can be directly applied to signals to generate more realistic models, and since it is inherently convertible into state-space representation, it can thus be used for the artificial reconstruction and attenuation of seizures as well. Considering this, the first objective of this work is to propose an SI approach using AR models to describe real epileptiform activity. The second objective is to provide a strategy for reconstructing and mitigating such activity artificially, considering non-hybrid and hybrid controllers - designed from ictal and interictal events, respectively. The results show that AR models of relatively low order represent epileptiform activities fairly well and both controllers are effective in attenuating the undesired activity while simultaneously driving the signal to an interictal condition. These findings may lead to customized models based on each signal, brain region or patient, from which it is possible to better define shape, frequency and duration of external stimuli that are necessary to attenuate seizures.


Subject(s)
Electroencephalography , Epilepsy , Humans , Electroencephalography/methods , Seizures , Brain , Writing
8.
Foods ; 13(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38338594

ABSTRACT

This study aimed to investigate the incorporation of micronized salt (MS) to reduce sodium content in fresh sausages while preserving technological, chemical, textural, and sensory characteristics. Four treatments were prepared: control (C) with 2.0% regular salt; M2.0% with 2.0% micronized salt; M1.5% with 1.5% micronized salt; and M1.0% with 1.0% micronized salt, containing 1004, 1133, 860, and 525 mg of sodium/100 g of product, respectively. To characterize the samples, analyses of sodium content, cooking loss, relative myoglobin content, and instrumental color were carried out. The sensory analysis was performed using the Temporal-Check-All-That-Apply (TCATA) method. Half of the micronized salt treatment was mixed with the fat during the processing of the fresh sausages. It was possible to achieve a 50% reduction in sodium (M1.0%) in the fresh sausages without negative effects on most technological, chemical, and textural parameters, which did not differ from the control treatment (C). Conversely, "chewiness" decreased in M2.0% compared to the control (C) due to mixing micronized salt with the fat. The sodium reduction did not impact the temporal sensory profile and overall liking. Therefore, using micronized salt in fresh sausages reduces sodium content without affecting sensory traits and product stability.

9.
Curr Probl Cardiol ; 49(3): 102340, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38103813

ABSTRACT

Schistosomiasis is a prevalent disease in Brazil whose etiological agent is Schistosoma mansoni, the main species associated with pulmonary arterial hypertension (PAH), a serious complication. It is estimated that this complication affects up to 15% of patients with the hepatosplenic form of the disease. Despite being an endemic country, Brazil does not have a screening scheme for cases of PAH associated with schistosomiasis (PAH-Sch), nor protocols for notification and treatment of this vascular complication. The objectives of this literature review are to gather knowledge about the pathophysiology, clinical manifestations, diagnosis and treatment of PAH-Sch and to highlight relevant aspects for the Brazilian reality. The pathophysiology, although lacking information, has proliferative vasculopathy as a central element. The clinical presentation of this disease can be asymptomatic or with nonspecific manifestations. Thus, complementary exams are essential for a confirmatory diagnosis, the gold standard being right heart catheterization, a scarce resource in endemic regions of the country. The treatment of PAH-Sch is similar to that performed for other causes of PAH, but the impact of anthelmintic therapy on the evolution of the vascular pathology is unknown. Therefore, Brazil needs to develop a screening plan for early diagnosis of PAH-Sch and new studies should be carried out to determine a more specific treatment.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Schistosomiasis , Humans , Brazil/epidemiology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/etiology , Schistosomiasis/complications , Schistosomiasis/diagnosis , Schistosomiasis/drug therapy , Familial Primary Pulmonary Hypertension/complications
10.
Mar Environ Res ; 194: 106304, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38142582

ABSTRACT

The rapid decline of coral reefs calls for cost-effective benthic cover data to improve reef health forecasts, policy building, management responses and evaluation. Reef monitoring has been largely based on divers' observations along transects, and secondarily on quadrat-based protocols, video and photographic records. However, the accuracy and precision of the most common sampling approaches are not yet fully understood. Here, we compared benthic cover estimates from three common sampling protocols: Reef Check (RC), Atlantic and Gulf Rapid Reef Assessment (AGRRA) and photoquadrats (PQ). The reef cover of two contrasting sites was reconstructed with ∼450 m2 orthomosaics built with high resolution Structure-from-Motion (SfM) photogrammetry, which were used as references for comparisons among protocols. In addition, we explored sample size requirements for each protocol and provided cost-effectiveness comparisons. Our results evidenced between-reef differences in the accuracy and precision of estimates with the different protocols. The three protocols performed similarly in the reef with low macroalgal cover (<0.5%), but PQ were more accurate and precise in the reef with relatively high (∼20%) macroalgal cover. The sample size for estimating coral cover with a 20% error margin and a 0.05 significance level was lower for PQ, followed by AGRRA and RC. Considering performance, cost surrogates and equipment needs, cost-effectiveness was higher for PQ. We also discuss costs, limitations and advantages/disadvantages of SfM photogrammetry as a sampling approach for coral reef monitoring.


Subject(s)
Anthozoa , Coral Reefs , Animals , Photogrammetry
11.
Eur J Med Chem ; 263: 115935, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37989057

ABSTRACT

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Janus Kinases , Purines/pharmacology , Cell Line, Tumor , Cell Proliferation
12.
Entropy (Basel) ; 25(12)2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38136545

ABSTRACT

The spin-1/2 quantum transverse Ising model, defined on a ladder structure, with nearest-neighbor and four-spin interaction on a plaquette, was studied by using exact diagonalization on finite ladders together with finite-size-scaling procedures. The quantum phase transition between the ferromagnetic and paramagnetic phases has then been obtained by extrapolating the data to the thermodynamic limit. The critical transverse field decreases as the antiferromagnetic four-spin interaction increases and reaches a multicritical point. However, the exact diagonalization approach was not able to capture the essence of the dimer phase beyond the multicritical transition.

13.
PLoS One ; 18(10): e0293581, 2023.
Article in English | MEDLINE | ID: mdl-37903131

ABSTRACT

Social media platforms are a valuable source of data for investigating cultural and political trends related to public interest in nature and conservation. Here, we use the micro-blogging social network Twitter to explore trends in public interest in Brazilian protected areas (PAs). We identified ~400,000 Portuguese language tweets pertaining to all categories of Brazilian PAs over a ten-year period (1 January 2011-31 December 2020). We analysed the content of these tweets and calculated metrics of user engagement (likes and retweets) to uncover patterns and drivers of public interest in Brazilian PAs. Our results indicate that users / tweets mentioning PAs remained stable throughout the sample period. However, engagement with tweets grew steeply, particularly from 2018 onward and coinciding with a change in the Brazilian federal government. Furthermore, public interest was not evenly distributed across PAs; while national parks were the subject of the most tweets, mainly related to tourism activities, tweets related to conflicts among park users and managers were more likely to engage Twitter users. Our study highlights that automatic or semi-automatic monitoring of social media content and engagement has great potential as an early warning system to identify emerging conflicts and to generate data and metrics to support PA policy, governance and management.


Subject(s)
Social Media , Humans , Brazil , Blogging , Language
14.
J Anim Sci ; 1012023 Jan 03.
Article in English | MEDLINE | ID: mdl-37681983

ABSTRACT

The objective of the present study was to verify the effect of handling in corrals on the stress of beef cattle of Nelore, Caracu, and Guzerá breeds through the analysis of the relationship between behavioral traits, growth, and blood parameters. A total of 778 records of entry scores, chute scores, exit scores, flight speed, cortisol, glucose, lactate, live weight, and body condition scores were collected on steers and heifers of the three breeds, born between September and December. The animals came from the Advanced Beef Cattle Research Center of the Animal Science Institute. The variance analyses were performed using the GENMOD procedure. The PROC CORR estimated Spearman correlation coefficients for all traits studied, and the principal components analysis was performed according to the procedure PRINCOMP. Heifers had higher reactivity than steers, with higher behavioral scores and blood parameters. Overall, Caracu individuals demonstrated lower reactivity in comparison to Nelore and Guzerá. However, they presented high stress when they were restrained. The principal component analysis highlighted that behavioral traits and blood parameters were contrasted with growth traits; thus, this analysis can help selectors (livestock farmers) understand the importance of selecting less reactive animals and more easily choose the animals they want to select for breeding. Our results indicate that handling in corrals could be considered a stressful event for bovines. For this reason, measuring blood parameters and behavioral traits can compose necessary decision-making tools regarding changes and adequacies while handling events to reduce stress and consequently improve the herd's reactivity.


Some scientific studies have shown the negative effect of poor handling on the welfare and temperament of animals. Furthermore, there is evidence that more reactive cattle present the highest blood cortisol concentrations indicative of stress. In our study, the objective was to evaluate and quantify the temperament of animals from three different breeds of beef cattle in a stressful situation handled in the corrals. Differences in behavior between breeds and sexes were also analyzed. Through a statistical method, such as principal component analysis, we verified that exit and chute scores are better behavioral indicators of animal stress, allowing the development of sound management practices, especially when passing through the corrals.


Subject(s)
Parturition , Temperament , Humans , Pregnancy , Cattle , Animals , Female , Brazil , Breeding , Lactic Acid
15.
Viruses ; 15(9)2023 09 05.
Article in English | MEDLINE | ID: mdl-37766284

ABSTRACT

The impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus underscored the crucial role of laboratorial tests as a strategy to control the disease, mainly to indicate the presence of specific antibodies in human samples from infected patients. Therefore, suitable recombinant antigens are relevant for the development of reliable tests, and so far, single recombinant proteins have been used. In this context, B-cell epitopes-based chimeric proteins can be an alternative to obtain tests with high accuracy through easier and cheaper production. The present study used bioinformatics tools to select specific B-cell epitopes from the spike (S) and the nucleocapsid (N) proteins from the SARS-CoV-2 virus, aiming to produce a novel recombinant chimeric antigen (N4S11-SC2). Eleven S and four N-derived B-cell epitopes were predicted and used to construct the N4S11-SC2 protein, which was analyzed in a recombinant format against serum and urine samples, by means of an in house-ELISA. Specific antibodies were detected in the serum and urine samples of COVID-19 patients, which were previously confirmed by qRT-PCR. Results showed that N4S11-SC2 presented 83.7% sensitivity and 100% specificity when using sera samples, and 91.1% sensitivity and 100% specificity using urine samples. Comparable findings were achieved with paired urine samples when compared to N and S recombinant proteins expressed in prokaryotic systems. However, better results were reached for N4S11-SC2 in comparison to the S recombinant protein when using paired serum samples. Anti-N4S11-SC2 antibodies were not clearly identified in Janssen Ad26.COV2.S COVID-19-vaccinated subjects, using serum or paired urine samples. In conclusion, this study presents a new chimeric recombinant antigen expressed in a prokaryotic system that could be considered as an alternative diagnostic marker for the SARS-CoV-2 infection, with the potential benefits to be used on serum or urine from infected patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Epitopes, B-Lymphocyte , Ad26COVS1 , Pandemics , COVID-19/diagnosis , Recombinant Proteins/genetics , Recombinant Fusion Proteins/genetics
16.
Int J Mol Sci ; 24(14)2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37511073

ABSTRACT

The endogenous estradiol derivative 2-Methoxyestradiol (2-ME) has shown good and wide anticancer activity but suffers from poor oral bioavailability and extensive metabolic conjugation. However, its sulfamoylated derivative, 2-methoxyestradiol-3,17-O,O-bis-sulfamate (STX140), has superior potential as a therapeutic agent, acts by disrupting microtubule polymerization, leading to cell cycle arrest and apoptosis in cancer cells and possesses much better pharmaceutical properties. This study investigated the antiproliferative and anti-invasive activities of STX140 in both SKMEL-28 naïve melanoma (SKMEL28-P) cells and resistant melanoma cells (SKMEL-28R). STX140 inhibited cell proliferation in the nanomolar range while having a less pronounced effect on human melanocytes. Additionally, STX140 induced cell cycle arrest in the G2/M phase and sub-G1, reduced migration, and clonogenic potential in monolayer models, and inhibited invasion in a 3D human skin model with melanoma cells. Furthermore, STX140 induced senescence features in melanoma and activated the senescence machinery by upregulating the expression of senescence genes and proteins related to senescence signaling. These findings suggest that STX140 may hold potential as a therapeutic agent for melanoma treatment.


Subject(s)
Estrenes , Melanoma , Humans , 2-Methoxyestradiol/pharmacology , Estrenes/pharmacology , Cell Proliferation , Melanoma/drug therapy , Cell Line, Tumor , Apoptosis
17.
J Pediatr (Rio J) ; 99(6): 641-647, 2023.
Article in English | MEDLINE | ID: mdl-37478896

ABSTRACT

OBJECTIVE: To verify the association between nutritional risk on admission and clinical outcomes of COVID-19 in hospitalized children and adolescents. METHODS: Multicenter cohort study was conducted in two cities in the northeastern region of Brazil, with children under 18 years of age laboratory diagnosed with COVID-19. Sociodemographic data and nutritional risk screening by STRONGKids (low, medium and high risk) were collected remotely and in hospital records, respectively. The outcomes assessed were the need for ICU admission, length of stay (< 10 days or ≥ 10 days), critical cases, and death. Multivariable logistic regression models were used to evaluate the effects of high nutritional risk on COVID-19 clinical outcomes. RESULTS: 103 individuals were evaluated, of these 35 (34.0%) had low risk, 44 (42.7%) medium risk, and 24 (23.3%) had high risk of malnutrition. In multivariate analysis, ICU bed admission (OR: 4.57; 95%CI, 1.39-4.97; p = 0.01), hospitalization longer than or equal to ten days (OR: 3.96; 95%CI, 1.22-2.83; p = 0.02) and critical cases (OR: 4.35; 95%CI, 1.08-7.55; p = 0.04) were associated with high nutritional risk. Death was not associated with high nutritional risk. CONCLUSIONS: Children and adolescents with high nutritional risk by STRONGkids at hospital admission were more likely to be admitted to the ICU, have hospitalization longer than or equal to ten days, and have critical cases when infected with SARS-CoV-2.


Subject(s)
COVID-19 , Malnutrition , Child , Humans , Adolescent , Child, Hospitalized , Nutritional Status , Nutrition Assessment , Cohort Studies , SARS-CoV-2 , Hospitalization , Malnutrition/epidemiology , Malnutrition/diagnosis
18.
Temperature (Austin) ; 10(2): 159-165, 2023.
Article in English | MEDLINE | ID: mdl-37332302

ABSTRACT

Among the vital signs collected during hospital triage, respiratory rate is an important parameter associated with physiological, pathophysiological, and emotional changes. In recent years, the importance of its verification in emergency centers due to the severe acute respiratory syndrome 2 (SARS2) pandemic has become very clear, although it is still one of the least evaluated and collected vital signs. In this context, infrared imaging has been shown to be a reliable estimator of respiratory rate, with the advantage of not requiring physical contact with patients. The objective of this study was to evaluate the potential of analyzing a sequence of thermal images as an estimator of respiratory rate in the clinical routine of an emergency room. We used an infrared thermal camera (T540, Flir Systems) to obtain the respiratory rate data of 136 patients, based on nostrils' temperature fluctuation, during the peak of the COVID-19 pandemic in Brazil and compared it with the chest incursion count method, commonly employed in the emergency screening procedures. We found a good agreement between both methods, with Bland-Altman limits of agreement ranging from -4 to 4 min-1, no proportional bias (R2 = 0.021, p = 0.095), and a strong correlation between them (r = 0.95, p < 0.001). Our results suggest that infrared thermography has potential to be a good estimator of respiratory rate in the routine of an emergency room.

19.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-37259357

ABSTRACT

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib (4). This inhibitor was elected as a prototype and molecular modifications were planned to design a new series of simplified gedatolisib analogues (5a-f). The analogues were synthesised, and the comparative cytotoxic activity profile was studied in phenotypic models employing solid and nonadherent tumour cell lines. Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 µM (pH = 7.4); 39.33 µM (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t1/2 = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.

20.
Physiol Int ; 110(2): 121-134, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37235453

ABSTRACT

Cellular senescence is a defense mechanism to arrest proliferation of damaged cells. The number of senescent cells increases with age in different tissues and contributes to the development of age-related diseases. Old mice treated with senolytics drugs, dasatinib and quercetin (D+Q), have reduced senescent cells burden. The aim of this study was to evaluate the effects of D+Q on testicular function and fertility of male mice. Mice (n = 9/group) received D (5 mg kg-1) and Q (50 mg kg-1) via gavage every moth for three consecutive days from 3 to 8 months of age. At 8 months mice were breed with young non-treated females and euthanized. The treatment of male mice with D+Q increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology. Sperm motility, seminiferous tubule morphometry, testicular gene expression and fertility were not affected by treatment. There was no effect of D+Q treatment in ß-galactosidase activity and in lipofuscin staining in testes. D+Q treatment also did not affect body mass gain and testes mass. In conclusion, D+Q treatment increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology, however did not affect fertility. Further studies with older mice and different senolytics are necessary to elucidate the effects in the decline of sperm output (quality and quantity) associated with aging.


Subject(s)
Quercetin , Testosterone , Female , Male , Animals , Mice , Quercetin/pharmacology , Dasatinib/pharmacology , Senotherapeutics , Sperm Motility , Semen/metabolism , Spermatozoa
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