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1.
J Clin Pediatr Dent ; 48(3): 146-155, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38755993

RESUMO

The objective of this work was to estimate the prevalence and severity of erosive tooth wear (ETW), and to identify risk indicators of deciduous dentition of a group of schoolchildren from public schools in Tlalnepantla de Baz, State of Mexico. A cross-sectional study was carried out in 352 schoolchildren from 5 to 7 years old. The severity of the ETW was evaluated using the Basic Erosive Wear Examination (BEWE). Risk indicators were evaluated through a survey which included food and beverage consumption, consumption habits, vitamin C consumption, gastroesophageal reflux, heartburn, belching, xerostomia, vomiting and teeth grinding. Multinomial logistic regression models were fitted. The prevalence of ETW was 99.7% (n = 351). Regarding severity, 46.6% were at a null/mild level, 27.3% moderate, and 26.1% severe. Males were more likely to present severe ETW (odds ratio (OR) = 2.23, 95% confidence interval (CI), 1.27-3.93; p = 0.005). The risk indicators for the severity of ETW were the frequent consumption of citrus fruits (OR = 2.09, 95% CI, 1.12-3.89; p = 0.021), fruit juice (OR = 1.99, 95% CI, 1.06-3.75; p = 0.033), processed beverages (OR = 2.15, 95% CI, 1.23-3.78; p = 0.008) and hot sauce (OR = 1.82, 95% CI, 1.03-3.20; p = 0.036). The prevalence of ETW in the deciduous dentition was very high (99.7%) and ~1/3 for severe ETW. The dietary factors associated with severe ETW are part of the regular consumption of Mexican school-age children, which impact their oral health condition. It is important to establish intervention strategies from the infant stage, focused on both children and their caregivers.


Assuntos
Erosão Dentária , Dente Decíduo , Humanos , Dente Decíduo/patologia , México/epidemiologia , Masculino , Erosão Dentária/epidemiologia , Estudos Transversais , Feminino , Pré-Escolar , Criança , Fatores de Risco , Prevalência , Índice de Gravidade de Doença , Comportamento Alimentar , Ácido Ascórbico , Refluxo Gastroesofágico/epidemiologia , Citrus , Dieta , Bebidas
2.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38675459

RESUMO

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, Tubastraea coccinea, Mussismilia hispida, Madracis decactis, and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus, and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. The crude extracts showed IC50 values ranging from 15 to 51 µg/mL against the trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 µg/mL and 23.8 µg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against T. cruzi.

3.
bioRxiv ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38045341

RESUMO

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

4.
Sci Rep ; 13(1): 9760, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328506

RESUMO

Ephyrae, the early stages of scyphozoan jellyfish, possess a conserved morphology among species. However, ontogenetic transitions lead to morphologically different shapes among scyphozoan lineages, with important consequences for swimming biomechanics, bioenergetics and ecology. We used high-speed imaging to analyse biomechanical and kinematic variables of swimming in 17 species of Scyphozoa (1 Coronatae, 8 "Semaeostomeae" and 8 Rhizostomeae) at different developmental stages. Swimming kinematics of early ephyrae were similar, in general, but differences related to major lineages emerged through development. Rhizostomeae medusae have more prolate bells, shorter pulse cycles and higher swimming performances. Medusae of "Semaeostomeae", in turn, have more variable bell shapes and most species had lower swimming performances. Despite these differences, both groups travelled the same distance per pulse suggesting that each pulse is hydrodynamically similar. Therefore, higher swimming velocities are achieved in species with higher pulsation frequencies. Our results suggest that medusae of Rhizostomeae and "Semaeostomeae" have evolved bell kinematics with different optimized traits, rhizostomes optimize rapid fluid processing, through faster pulsations, while "semaeostomes" optimize swimming efficiency, through longer interpulse intervals that enhance mechanisms of passive energy recapture.


Assuntos
Hidrozoários , Cifozoários , Animais , Natação , Fenômenos Biomecânicos , Metabolismo Energético
5.
Children (Basel) ; 10(2)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36832478

RESUMO

Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020-March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2-<6, 27.9% 6-<12, 39.5% 12-<19, and 23.3% > 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6-<12, 53.8% 12-<19, and 25.0% > 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.

6.
Malar J ; 22(1): 43, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739391

RESUMO

BACKGROUND: Early-evening and outdoor-biting mosquitoes may compromise the effectiveness of frontline malaria interventions, notably insecticide-treated nets (ITNs). This study aimed to evaluate the efficacy of low-cost insecticide-treated eave ribbons and sandals as supplementary interventions against indoor-biting and outdoor-biting mosquitoes in south-eastern Tanzania, where ITNs are already widely used. METHODS: This study was conducted in three villages, with 72 households participating (24 households per village). The households were divided into four study arms and assigned: transfluthrin-treated sandals (TS), transfluthrin-treated eave ribbons (TER), a combination of TER and TS, or experimental controls. Each arm had 18 households, and all households received new ITNs. Mosquitoes were collected using double net traps (to assess outdoor biting), CDC light traps (to assess indoor biting), and Prokopack aspirators (to assess indoor resting). Protection provided by the interventions was evaluated by comparing mosquito densities between the treatment and control arms. Additional tests were done in experimental huts to assess the mortality of wild mosquitoes exposed to the treatments or controls. RESULTS: TERs reduced indoor-biting, indoor-resting and outdoor-biting Anopheles arabiensis by 60%, 73% and 41%, respectively, while TS reduced the densities by 18%, 40% and 42%, respectively. When used together, TER & TS reduced indoor-biting, indoor-resting and outdoor-biting An. arabiensis by 53%, 67% and 57%, respectively. Protection against Anopheles funestus ranged from 42 to 69% with TER and from 57 to 74% with TER & TS combined. Mortality of field-collected mosquitoes exposed to TER, TS or both interventions was 56-78% for An. arabiensis and 47-74% for An. funestus. CONCLUSION: Transfluthrin-treated eave ribbons and sandals or their combination can offer significant household-level protection against malaria vectors. Their efficacy is magnified by the transfluthrin-induced mortality, which was observed despite the prevailing pyrethroid resistance in the study area. These results suggest that TER and TS could be useful supplementary tools against residual malaria transmission in areas where ITN coverage is high but additional protection is needed against early-evening and outdoor-biting mosquitoes. Further research is needed to validate the performance of these tools in different settings, and assess their long-term effectiveness and feasibility for malaria control.


Assuntos
Anopheles , Repelentes de Insetos , Inseticidas , Malária , Animais , Humanos , Mosquitos Vetores , Tanzânia , Malária/prevenção & controle , Repelentes de Insetos/farmacologia , Controle de Mosquitos/métodos
7.
J Electrocardiol ; 76: 61-65, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36436476

RESUMO

BACKGROUND: Several large trials have employed age or clinical features to select patients for atrial fibrillation (AF) screening to reduce strokes. We hypothesized that a machine learning (ML) model trained to predict AF risk from 12­lead electrocardiogram (ECG) would be more efficient than criteria based on clinical variables in indicating a population for AF screening to potentially prevent AF-related stroke. METHODS: We retrospectively included all patients with clinical encounters in Geisinger without a prior history of AF. Incidence of AF within 1 year and AF-related strokes within 3 years of the encounter were identified. AF-related stroke was defined as a stroke where AF was diagnosed at the time of stroke or within a year after the stroke. The efficiency of five methods was evaluated for selecting a cohort for AF screening. The methods were selected from four clinical trials (mSToPS, GUARD-AF, SCREEN-AF and STROKESTOP) and the ECG-based ML model. We simulated patient selection for the five methods between the years 2011 and 2014 and evaluated outcomes for 1 year intervals between 2012 and 2015, resulting in a total of twenty 1-year periods. Patients were considered eligible if they met the criteria before the start of the given 1-year period or within that period. The primary outcomes were numbers needed to screen (NNS) for AF and AF-associated stroke. RESULTS: The clinical trial models indicated large proportions of the population with a prior ECG for AF screening (up to 31%), coinciding with NNS ranging from 14 to 18 for AF and 249-359 for AF-associated stroke. At comparable sensitivity, the ECG ML model indicated a modest number of patients for screening (14%) and had the highest efficiency in NNS for AF (7.3; up to 60% reduction) and AF-associated stroke (223; up to 38% reduction). CONCLUSIONS: An ECG-based ML risk prediction model is more efficient than contemporary AF-screening criteria based on age alone or age and clinical features at indicating a population for AF screening to potentially prevent AF-related strokes.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Eletrocardiografia , Estudos Retrospectivos , Programas de Rastreamento , Acidente Vascular Cerebral/diagnóstico
8.
Sci Data ; 9(1): 778, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566260

RESUMO

Automatic speech emotion recognition is an important research topic for human-computer interaction and affective computing. Over ten million people speak the Quechua language throughout South America, and one of the most known variants is the Quechua Collao one. However, this language can be considered a low resource for machine emotion recognition, creating a barrier for Quechua speakers who want to use this technology. Therefore, the contribution of this work is a 15 hours speech corpus in Quechua Collao, which is made publicly available to the research community. The corpus was created from a set of words and sentences explicitly collected for this task, divided into nine categorical emotions: happy, sad, bored, fear, sleepy, calm, excited, angry, and neutral. The annotation was performed on a 5-value discrete scale according to 3 dimensions: valence, arousal, and dominance. To demonstrate the usefulness of the corpus, we have performed speech emotion recognition using machine learning methods and neural networks.


Assuntos
Emoções , Fala , Humanos , Ira , Idioma , Peru
9.
Rev. Fac. Med. Hum ; 22(4): 682-688, octubre-diciembre 2022.
Artigo em Inglês, Espanhol | LILACS-Express | LILACS | ID: biblio-1401381

RESUMO

Introduction: Hip fractures are a pathology of traumatic origin that generates a high impact on public health. The objective is to evaluate the interobserver reproducibility of the Tronzo classification for intertrochanteric fractures. Methods: Observational, analytical and retrospective study carried out in Ibagué - Colombia, 48 hip radiographs were analyzed, classified by 10 observed among specialists and training personnel, using the Tronzo classification. Interobserver reproducibility is assessed using the kappa concordance coefficient. Results: Among all those observed in the study, there is greater agreement in the identification of intertrochanteric fractures of lesser and greater severity (Tronzo I and V), the main exponents of this agreement are the most experienced staff, the staff in training, with intermediate experience they agree when identifying those of intermediate severity and for those with less experience the concordance becomes evident when evaluating the intermediate grades. Conclusion: The concordance increases with the experience for the identification of the types with high complexity. This classification is not suitable for clinical practice, another system is necessary for this type of fracture in clinical conduct.


Introducción: Las fracturas de cadera son una patología de origen traumático que genera un alto impacto en la salud pública. El objetivo es evaluar la reproducibilidad interobservador de la clasificación de Tronzo para fracturas intertrocantéricas. Métodos: Estudio observacional, analítico y retrospectivo realizado en Ibagué ­ Colombia, se analizaron 48 radiografías de cadera, clasificadas por 10 observado entre especialistas y personal en formación, utilizando la clasificación de Tronzo. La reproducibilidad interobservador se evalúa mediante el coeficiente de concordancia kappa. Resultados: Entre todos los observados del estudio existe mayor acuerdo en la identificación de fracturas intertrocantéricas de menor y mayor gravedad (Tronzo I y V), los principales exponentes de este acuerdo son el personal de mayor experiencia, el personal en formación, con experiencia intermedia están de acuerdo al identificar a los de gravedad intermedia y para los que tienen menos experiencia la concordancia se hace evidente a la hora de evaluar los grados intermedios. Conclusión: La concordancia aumenta con la experiencia para la identificación de los tipos con alta complejidad. No es adecuado para la práctica clínica esta clasificación, es necesario otro sistema para este tipo de fracturas en las conductas clínicas.

10.
ACS Omega ; 7(32): 28561-28570, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35990437

RESUMO

Chagas disease, caused by Trypanosoma cruzi, affects seven million people worldwide and lacks effective treatments. Using bioactivity-guided fractionation, NMR, and electrospray ionization-high resolution mass spectrometry (ESI-HRMS) spectral analysis, the indole alkaloid 6-bromo-2'-de-N-methylaplysinopsin (BMA) was isolated and chemically characterized from the marine coral Tubastraea tagusensis. BMA was tested against trypomastigotes and intracellular amastigotes of T. cruzi, resulting in IC50 values of 62 and 5.7 µM, respectively, with no mammalian cytotoxicity. The mechanism of action studies showed that BMA induced no alterations in the plasma membrane permeability but caused depolarization of the mitochondrial membrane potential, reducing ATP levels. Intracellular calcium levels were also reduced after the treatment, which was associated with pH alteration of acidocalcisomes. Using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)/MS analysis, alterations of mass spectral signals were observed after treatment with BMA, suggesting a different mechanism from benznidazole. In silico pharmacokinetic-pharmacodynamic (PKPD) parameters suggested a drug-likeness property, supporting the promising usefulness of this compound as a new hit for optimizations.

11.
PLoS One ; 17(7): e0271833, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35877666

RESUMO

BACKGROUND: Understanding mosquito biting behaviours is important for designing and evaluating protection methods against nuisance biting and mosquito-borne diseases (e.g. dengue, malaria and zika). We investigated the preferred biting sites by Aedes aegypti and Anopheles arabiensis on adult volunteers in standing or sleeping positions; and estimated the theoretical protection limits affordable from protective clothing or repellent-treated footwear. METHODS: Adult volunteers dressed in shorts and t-shirts were exposed to infection-free laboratory-reared mosquitoes inside screened chambers from 6am to noon (for day-biting Ae. aegypti) or 6pm to midnight (night-biting An. arabiensis). Attempted bites on different body parts were recorded. Comparative observations were made on same volunteers while wearing sandals treated with transfluthrin, a vapour-phase pyrethroid that kills and repels mosquitoes. RESULTS: An. arabiensis bites were mainly on the lower limbs of standing volunteers (95.9% of bites below the knees) but evenly-distributed over all exposed body surfaces when the volunteers were on sleeping positions (only 28.8% bites below knees). Ae. aegypti bites were slightly concentrated on lower limbs of standing volunteers (47.7% below knees), but evenly-distributed on sleeping volunteers (23.3% below knees). Wearing protective clothing that leave only hands and head uncovered (e.g. socks + trousers + long-sleeved shirts) could theoretically prevent 78-83% of bites during sleeping, and at least 90% of bites during non-sleeping hours. If the feet are also exposed, protection declines to as low as 36.3% against Anopheles. The experiments showed that transfluthrin-treated sandals reduced An. arabiensis by 54-86% and Ae. aegypti by 32-39%, but did not change overall distributions of bites. CONCLUSION: Biting by An. arabiensis and Ae. aegypti occur mainly on the lower limbs, though this proclivity is less pronounced in the Aedes species. However, when hosts are on sleeping positions, biting by both species is more evenly-distributed over the exposed body surfaces. High personal protection might be achieved by simply wearing long-sleeved clothing, though protection against Anopheles particularly requires covering of feet and lower legs. The transfluthrin-treated footwear can reduce biting risk, especially by An. arabiensis. These findings could inform the design and use of personal protection tools (both insecticidal and non-insecticidal) against mosquitoes and mosquito-borne diseases.


Assuntos
Aedes , Anopheles , Dengue , Mordeduras e Picadas de Insetos , Repelentes de Insetos , Malária , Infecção por Zika virus , Zika virus , Adulto , Animais , Dengue/prevenção & controle , Humanos , Mordeduras e Picadas de Insetos/prevenção & controle , Repelentes de Insetos/farmacologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores
12.
Circulation ; 146(1): 36-47, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35533093

RESUMO

BACKGROUND: Timely diagnosis of structural heart disease improves patient outcomes, yet many remain underdiagnosed. While population screening with echocardiography is impractical, ECG-based prediction models can help target high-risk patients. We developed a novel ECG-based machine learning approach to predict multiple structural heart conditions, hypothesizing that a composite model would yield higher prevalence and positive predictive values to facilitate meaningful recommendations for echocardiography. METHODS: Using 2 232 130 ECGs linked to electronic health records and echocardiography reports from 484 765 adults between 1984 to 2021, we trained machine learning models to predict the presence or absence of any of 7 echocardiography-confirmed diseases within 1 year. This composite label included the following: moderate or severe valvular disease (aortic/mitral stenosis or regurgitation, tricuspid regurgitation), reduced ejection fraction <50%, or interventricular septal thickness >15 mm. We tested various combinations of input features (demographics, laboratory values, structured ECG data, ECG traces) and evaluated model performance using 5-fold cross-validation, multisite validation trained on 1 site and tested on 10 independent sites, and simulated retrospective deployment trained on pre-2010 data and deployed in 2010. RESULTS: Our composite rECHOmmend model used age, sex, and ECG traces and had a 0.91 area under the receiver operating characteristic curve and a 42% positive predictive value at 90% sensitivity, with a composite label prevalence of 17.9%. Individual disease models had area under the receiver operating characteristic curves from 0.86 to 0.93 and lower positive predictive values from 1% to 31%. Area under the receiver operating characteristic curves for models using different input features ranged from 0.80 to 0.93, increasing with additional features. Multisite validation showed similar results to cross-validation, with an aggregate area under the receiver operating characteristic curve of 0.91 across our independent test set of 10 clinical sites after training on a separate site. Our simulated retrospective deployment showed that for ECGs acquired in patients without preexisting structural heart disease in the year 2010, 11% were classified as high risk and 41% (4.5% of total patients) developed true echocardiography-confirmed disease within 1 year. CONCLUSIONS: An ECG-based machine learning model using a composite end point can identify a high-risk population for having undiagnosed, clinically significant structural heart disease while outperforming single-disease models and improving practical utility with higher positive predictive values. This approach can facilitate targeted screening with echocardiography to improve underdiagnosis of structural heart disease.


Assuntos
Cardiopatias , Aprendizado de Máquina , Adulto , Ecocardiografia , Eletrocardiografia , Cardiopatias/diagnóstico por imagem , Cardiopatias/epidemiologia , Humanos , Estudos Retrospectivos
13.
Genes (Basel) ; 13(3)2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35328049

RESUMO

While Inherited Retinal Diseases (IRDs) are typically considered rare diseases, Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie Disease (ND) are more rare than retinitis pigmentosa. We wanted to determine if multigenic protein-altering variants are common in FEVR subjects within a set of FEVR-related genes. The potential occurrence of protein-altering variants in two different genes has been documented in a very small percentage of patients, but potential multigenic contributions to FEVR remain unclear. Genes involved in these orphan pediatric retinal diseases are not universally included in available IRD targeted-sequencing panels, and cost is also a factor limiting multigenic-sequence-based testing for these rare conditions. To provide an accurate solution at lower cost, we developed a targeted-sequencing protocol that includes seven genes involved in Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie disease. Seventy-six DNA samples from persons refered to clinic with possible FEVR and some close relatives were sequenced using a novel Oakland-ERI orphan pediatric retinal disease panel (version 2) providing 900 times average read coverage. The seven genes involved in FEVR/ND were: NDP (ChrX), CTNNB1 (Chr3); TSPAN12 (Chr7); KIF11 (Chr10), FZD4 (Chr11), LRP5 (Chr11), ZNF408 (Chr11). A total of 33 variants were found that alter protein sequence, with the following relative distribution: LRP5 13/33 (40%), FZD4 9/33 (27%), ZNF408 6/33 (18%), (KIF11 3/33 (9%), NDP 1/33 (3%), CTNNB1 1/33 (3%). Most protein-altering variants, 85%, were found in three genes: FZD4, LRP5, and ZNF408. Four previously known pathogenic variants were detected in five families and two unrelated individuals. Two novel, likely pathogenic variants were detected in one family (FZD4: Cys450ter), and a likely pathogenic frame shift termination variant was detected in one unrelated individual (LRP5: Ala919CysfsTer67). The average number of genes with protein-altering variants was greater in subjects with confirmed FEVR (1.46, n = 30) compared to subjects confirmed unaffected by FEVR (0.95, n = 20), (p = 0.009). Thirty-four percent of persons sequenced had digenic and trigenic protein-altering variants within this set of FEVR genes, which was much greater than expected in the general population (3.6%), as derived from GnomAD data. While the potential contributions to FEVR are not known for most of the variants in a multigenic context, the high multigenic frequency suggests that potential multigenic contributions to FEVR severity warrant future investigation. The targeted-sequencing format developed will support such exploration by reducing the testing cost to $250 (US) for seven genes and facilitating greater access to genetic testing for families with this very rare inherited retinal disease.


Assuntos
Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Doenças Retinianas , Cegueira/congênito , Criança , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Vitreorretinopatias Exsudativas Familiares/genética , Receptores Frizzled/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Mutação , Doenças do Sistema Nervoso , Degeneração Retiniana , Doenças Retinianas/metabolismo , Espasmos Infantis , Tetraspaninas/genética , Tetraspaninas/metabolismo , Fatores de Transcrição/genética
14.
Int J Cardiovasc Imaging ; 38(8): 1685-1697, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35201510

RESUMO

Use of machine learning (ML) for automated annotation of heart structures from echocardiographic videos is an active research area, but understanding of comparative, generalizable performance among models is lacking. This study aimed to (1) assess the generalizability of five state-of-the-art ML-based echocardiography segmentation models within a large Geisinger clinical dataset, and (2) test the hypothesis that a quality control (QC) method based on segmentation uncertainty can further improve segmentation results. Five models were applied to 47,431 echocardiography studies that were independent from any training samples. Chamber volume and mass from model segmentations were compared to clinically-reported values. The median absolute errors (MAE) in left ventricular (LV) volumes and ejection fraction exhibited by all five models were comparable to reported inter-observer errors (IOE). MAE for left atrial volume and LV mass were similarly favorable to respective IOE for models trained for those tasks. A single model consistently exhibited the lowest MAE in all five clinically-reported measures. We leveraged the tenfold cross-validation training scheme of this best-performing model to quantify segmentation uncertainty. We observed that removing segmentations with high uncertainty from 14 to 71% studies reduced volume/mass MAE by 6-10%. The addition of convexity filters improved specificity, efficiently removing < 10% studies with large MAE (16-40%). In conclusion, five previously published echocardiography segmentation models generalized to a large, independent clinical dataset-segmenting one or multiple cardiac structures with overall accuracy comparable to manual analyses-with variable performance. Convexity-reinforced uncertainty QC efficiently improved segmentation performance and may further facilitate the translation of such models.


Assuntos
Aprendizado Profundo , Humanos , Valor Preditivo dos Testes , Ecocardiografia/métodos , Aprendizado de Máquina , Átrios do Coração , Processamento de Imagem Assistida por Computador/métodos
15.
Biota Neotrop. (Online, Ed. ingl.) ; 22(spe): e20221385, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403637

RESUMO

Abstract In this study we survey and analyze 300 projects related to marine biodiversity funded by FAPESP from 1972 to 2021, of which 46 were nested in the BIOTA Program. From a unique project in the 1970's, the number gradually increased until 2009, when BIOTA promoted a call on marine biodiversity, which led to a boost in the number of funded projects in the subsequent years. The geographical range of the projects expanded over the years and, from studies based on the coast of São Paulo State, the focus gradually shifted to broader areas of the Brazilian coast, then to other areas of the Atlantic, and eventually became global. The majority of projects focused on coastal benthic organisms living on hard-bottom. In terms of taxa, six groups accounted for about 60% of the projects (viz. Crustacea, Actinopterygii, Mollusca, Chondrichthyes, Cnidaria, and Rhodophyta), but it is observed an increase in the number of groups studied over the decades. The 300 projects refer to a set of 82 different topics, of which the top five are taxonomy, phylogeny, community, "omics", and pollution. The analyses show a long-standing effort in marine biodiversity surveys, with ongoing updated approaches regarding scope and methods. Research on strategic areas is discussed, including deep-sea and marine microbiota. Climate change and the increasing pressure of human activity on the ocean, including pollution, acidification and invasive species, are among the main challenges for the future. Projects producing and using basic research data in an integrative and transdisciplinary way offer multiple perspectives in understanding changes in ecosystem functioning and, consequently, are essential to support public policies for the conservation and sustainable use of marine biodiversity at different scales. UNESCO's Decade of Ocean (starting 2021) is a window of opportunity to strengthen marine research, to promote national and international collaboration, to build up networks involving the public and private sector, but particularly to draw society's attention to the importance of knowing marine environments and using ocean resources in a sustainable way. The advancement of ocean literacy is one of the main legacies for future generations promoted by integrated research programs such as BIOTA-FAPESP.


Resumo Neste estudo levantamos e analisamos 300 projetos relacionados à biodiversidade marinha financiados pela FAPESP entre 1972 a 2021, dos quais 46 foram realizados no Programa BIOTA. De um projeto único na década de 1970, o número foi aumentando gradativamente até 2009, quando o BIOTA promoveu uma chamada sobre biodiversidade marinha, o que impulsionou o número de projetos financiados nos anos seguintes. A abrangência geográfica dos projetos se expandiu ao longo dos anos e, a partir de estudos baseados no litoral do Estado de São Paulo, o foco gradualmente se deslocou para áreas mais amplas da costa brasileira, depois para outras áreas do Atlântico, e acabou se tornando global. A maioria dos projetos se concentrou em organismos costeiros, bentônicos, em substrato consolidado. Em termos de táxons, seis grupos responderam por cerca de 60% dos projetos (Crustacea, Actinopterygii, Mollusca, Chondrichthyes, Cnidaria e Rhodophyta), mas observa-se um aumento no número de grupos estudados ao longo das décadas. Os 300 projetos referem-se a um conjunto de 82 temas diferentes, dos quais os cinco principais são taxonomia, filogenia, comunidade, "ômicas" e poluição. As análises mostram um esforço de longa data em pesquisas de biodiversidade marinha, com abordagens atualizadas em relação ao escopo e métodos. A pesquisa em áreas estratégicas é discutida, incluindo os estudos sobre a microbiota marinha e em águas profundas. As mudanças climáticas e a crescente pressão da atividade humana sobre o oceano, incluindo poluição, acidificação e espécies invasoras, estão entre os principais desafios para o futuro. Projetos de produção e uso de dados de pesquisa básica de forma integrada e transdisciplinar oferecem múltiplas perspectivas de compreensão das mudanças no funcionamento dos ecossistemas e, consequentemente, são essenciais para subsidiar políticas públicas de conservação e uso sustentável da biodiversidade marinha em diferentes escalas. A Década do Oceano da UNESCO (a partir de 2021) é uma janela de oportunidade para fortalecer a pesquisa marinha, promover a colaboração nacional e internacional, construir redes envolvendo os setores público e privado, mas principalmente para chamar a atenção da sociedade para a importância de conhecer os ambientes marinhos e utilizar os recursos oceânicos de forma sustentável. O avanço da "alfabetização" oceânica é um dos principais legados para as gerações futuras promovidos por programas integrados de pesquisa como o BIOTA-FAPESP.

16.
JMIR Ment Health ; 8(12): e26814, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34927594

RESUMO

BACKGROUND: Internet-based interventions promise to enhance the accessibility of mental health care for a greater number of people and in more remote places. Their effectiveness has been shown for the prevention and treatment of various mental disorders. However, their potential when delivered as add-on to conventional treatment (ie, blended care) is less clear. OBJECTIVE: The aim of this study is to study the effectiveness of an internet intervention (ASCENSO) implemented in addition to face-to-face treatment as usual (TAU) for depression. METHODS: A 2-arm, parallel-group, randomized controlled trial was conducted in an outpatient private mental health care center in Chile. In all, 167 adults, diagnosed with major depressive disorder, without severe comorbidities, and with internet access, were included. Eighty-four participants were assigned to the intervention group and received medical and psychological TAU from the mental health center plus access to the ASCENSO online platform. The control group (n=83) received only TAU. The ASCENSO platform includes psycho-educational information, depressive symptom monitoring and feedback, and managing emergencies based on the principles of cognitive behavioral therapy. Emergency management was mental health provider-assisted. TAU includes access to primary care physicians and psychiatrists, to a brief individual psychotherapy, and to medication when needed. The baseline questionnaires were administered in person, and 6- and 9-months assessments were conducted online. Depression symptoms and quality of life were measured by self-administered questionnaires, and treatment adherence was determined via the Mental Health Center's internal records. The usage of ASCENSO was assessed by server logs. Reduction on depressive symptomatology was considered as the primary outcome of the intervention and quality of life as a secondary outcome. RESULTS: Of the 84 participants in the intervention group, 5 participants (6%) never accessed the online platform. Of the remaining 79 participants who accessed ASCENSO, 1 (1%, 1/79) did not answer any of the symptom questionnaire, and most participants (72/79, 91%) answered the monitoring questionnaires irregularly. The ASCENSO intervention implemented in addition to face-to-face care did not improve the outcome of the usual care delivered at the mental health center, either in terms of reduction of depressive symptoms (F2,6087= 0.48; P=.62) or in the improvement of quality of life (EQ-5D-3L: F2,7678=0.24; P=.79 and EQ-VAS: F2,6670= 0.13; P=.88). In contrast, for the primary (F2,850=78.25; P<.001) and secondary outcomes (EQ-5D-3L: F2,1067=37.87; EQ-VAS: F2,4390= 51.69; P<.001) in both groups, there was an improvement from baseline to 6 months (P<.001), but there was no change at 9 months. In addition, no effects on adherence to or use of TAU were found. Finally, the dropout rate for the face-to-face treatment component was 54% (45/84) for the intervention group versus 39% (32/83) for the control group (P=.07). CONCLUSIONS: The fact that the adjunctive access to ASCENSO did not improve outcome could be due to both the rather high effectiveness of TAU and to patients' limited use of the online platform. TRIAL REGISTRATION: ClinicalTrials.gov NCT03093467; https://clinicaltrials.gov/ct2/show/NCT03093467.

17.
Cir Cir ; 89(6): 822-826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34851592

RESUMO

Blunt abdominal trauma occurs in 20% of polytraumatized patients, of which approximately 5% may have mesenteric lesions. We present a case of a woman suffering from a blunt abdominal trauma, who underwent computed tomography with evidence of hematoma on the right flank, which was controlled by angioembolization of the superior mesenteric artery. Treatment of mesenteric lesions will be determined according to the hemodynamic status of the patient, since in view of stability, a choice can be made between open surgery and embolization, but in case of instability, laparotomy is recommended.


El trauma abdominal cerrado se presenta en el 20% de los pacientes politraumatizados, de los cuales aproximadamente el 5% pueden llegar a tener lesiones mesentéricas. Presentamos el caso de una mujer que sufre un traumatismo abdominal cerrado a la cual se le realizó tomografía computarizada con evidencia de un hematoma en el flanco derecho, que se logra controlar por angioembolización de la arteria mesentérica superior. El tratamiento de las lesiones mesentéricas se determinará según el estado hemodinámico del paciente, pues ante la estabilidad se puede escoger entre cirugía abierta y embolización, pero en caso de inestabilidad se recomienda la laparotomía.


Assuntos
Traumatismos Abdominais , Embolização Terapêutica , Ferimentos não Penetrantes , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/terapia , Feminino , Humanos , Mesentério/diagnóstico por imagem , Mesentério/lesões , Estudos Retrospectivos , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia
18.
J Am Mosq Control Assoc ; 37(4): 224-241, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34817602

RESUMO

Mosquito surveillance is an essential component of mosquito control and mosquito traps are a universally employed tool to monitor adult populations. The objective of this paper was to evaluate the new modular Biogents BG-Pro mosquito trap (BGP) and compare its performance to 4 widely used traps for adult mosquitoes: the BG-Sentinel (BGS), the BG Mosquitaire (BGM), the CDC miniature light trap (CDC), and the encephalitis vector survey trap (EVS). One semi-field and 9 field Latin square trials were performed in 7 countries. Results showed that the collection performance of the BGP was equivalent to or exceeded that of the BGS, BGM, CDC, and EVS traps in head-to-head comparisons. The BGP uses 35% less power than the CDC and 75% less than the BGS and BGM. This lower power consumption allows it to run at 5 V for 2 days using a small lightweight 10,000-mAh rechargeable power bank. The BG-Pro is an excellent alternative for the surveillance of mosquito species that are usually monitored with BG-Sentinel, CDC, or EVS traps.


Assuntos
Aedes , Encefalite , Animais , Centers for Disease Control and Prevention, U.S. , Controle de Mosquitos , Inquéritos e Questionários , Estados Unidos
19.
Semin Pediatr Surg ; 30(3): 151054, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34172211

RESUMO

Over the last few decades, tracheostomy has been increasingly performed in children with various complex and chronic conditions. We have seen a dramatic change in indications for tracheostomy in pediatric patients due to better survival of premature infants and those suffering from severe congenital anomalies. There is no consensus about the timing of tracheostomy in pediatric patients. Although percutaneous tracheostomy has become the standard of care for adults, there is not sufficient evidence to start performing it routinely in pediatric patients. The indications, preoperative considerations, and different procedures for tracheostomy in children are reviewed. Surgical tracheostomy is described step by step placing an emphasis on safety measures to minimize complications. There is also a great variability in tracheostomy care protocols in the literature. Post-operative tracheostomy care is discussed for the early and late post-operative periods. There is no general consensus on decannulation protocols, but prevailing expert opinion is presented. There is growing evidence in support for an interdisciplinary approach to pediatric tracheostomized patients. The focus of this paper is the review of the literature regarding safety improvement strategies from the surgical and post-operative point of view.


Assuntos
Traqueostomia , Criança , Remoção de Dispositivo , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro , Traqueostomia/efeitos adversos , Traqueostomia/normas
20.
Rev. invest. clín ; 73(3): 145-153, May.-Jun. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1280451

RESUMO

ABSTRACT Background: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incomplete penetrance and variable expression that result in a challenging diagnosis. Objective: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. Methods: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. Results: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier’s scale. Conclusions: Extra-cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

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