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2.
Reprod Biomed Online ; 49(3): 104075, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38943812

RESUMO

This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality.

3.
Clin Neurol Neurosurg ; 243: 108392, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38945118

RESUMO

OBJECTIVE: This study aimed to identify clinical and surgical features associated with poor long-term postoperative outcomes in patients diagnosed with Type I Chiari Malformation (CMI) treated with posterior fossa decompression with duroplasty (PFDD), with or without tonsillar coagulation. METHODS: This retrospective, single-center study included 107 adult patients with CMI surgically treated between 2010 and 2021. The surgical technique involved a midline suboccipital craniectomy, C1 laminectomy, durotomy, arachnoid dissection, duroplasty, and tonsillar coagulation until 2014, after which tonsillar coagulation was discontinued. Postoperative outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) at a median follow-up of 35 months. Clinical, surgical, and neuroimaging data were analyzed using the Wilcoxon signed-rank test, Cox regression analysis, and Kaplan-Meier survival curves to identify predictors of poor functional outcomes. RESULTS: Of the 107 patients (mean age 43.9 years, SD 13), 81 (75.5 %) showed functional improvement, 25 (23.4 %) remained unchanged, and 1 (0.9 %) experienced worsened outcomes. Cephalalgia, bilateral motor weakness, and bilateral paresthesia were the most frequent initial symptoms. Tonsillar coagulation was performed in 31 cases (28.9 %) but was clinically associated with higher rates of unfavorable outcomes. The Wilcoxon signed-rank test indicated that long-term follow-up CCOS was significantly higher than postoperative CCOS (Z = -7.678, p < 0.000). Multivariate Cox analysis identified preoperative bilateral motor weakness (HR 6.1, 95 % CI 1.9-18.9; p = 0.002), hydrocephalus (HR 3.01, 95 % CI 1.3-6.9; p = 0.008), and unilateral motor weakness (HR 2.99, 95 % CI 1.1-8.2; p = 0.033) as significant predictors of poor outcomes on a long-term follow-up. CONCLUSION: This study highlights the high rate of functional improvement in CMI patients following PFDD. Preoperative motor weakness and hydrocephalus were significant predictors of poor long-term outcomes. Tonsillar coagulation did not demonstrate a clear clinical benefit and may be associated with worse outcomes. Our findings suggest that careful preoperative assessment and selection of surgical techniques are crucial for optimizing patient outcomes.

4.
Acta Neurochir (Wien) ; 166(1): 243, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822878

RESUMO

BACKGROUND: Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. METHOD: We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. CONCLUSION: This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.


Assuntos
Neoplasias dos Nervos Cranianos , Neurilemoma , Humanos , Neurilemoma/cirurgia , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Doenças do Nervo Trigêmeo/cirurgia , Doenças do Nervo Trigêmeo/patologia , Maxila/cirurgia , Maxila/diagnóstico por imagem , Masculino , Feminino , Resultado do Tratamento , Endoscopia/métodos , Nervo Trigêmeo/cirurgia , Nervo Trigêmeo/patologia , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/métodos
5.
Nutrients ; 16(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38892486

RESUMO

BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.


Assuntos
Desnutrição , Músculo Quadríceps , Sarcopenia , Ultrassonografia , Humanos , Masculino , Sarcopenia/diagnóstico por imagem , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Feminino , Ultrassonografia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Músculo Quadríceps/diagnóstico por imagem , Desnutrição/diagnóstico , Estado Nutricional , Força da Mão , Avaliação Nutricional , Impedância Elétrica , Curva ROC , Sensibilidade e Especificidade , Fatores de Risco , Avaliação Geriátrica/métodos
6.
Heliyon ; 10(11): e31175, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38832259

RESUMO

Background: The vascular heterogeneity of glioblastomas (GB) remains an important area of research, since tumor progression and patient prognosis are closely tied to this feature. With this study, we aim to identify gene expression profiles associated with MRI-defined tumor vascularity and to investigate its relationship with patient prognosis. Methods: The study employed MRI parameters calculated with DSC Perfusion Quantification of ONCOhabitats glioma analysis software and RNA-seq data from the TCGA-GBM project dataset. In our study, we had a total of 147 RNA-seq samples, which 15 of them also had MRI parameter information. We analyzed the gene expression profiles associated with MRI-defined tumor vascularity using differential gene expression analysis and performed Log-rank tests to assess the correlation between the identified genes and patient prognosis. Results: The findings of our research reveal a set of 21 overexpressed genes associated with the high vascularity pattern. Notably, several of these overexpressed genes have been previously implicated in worse prognosis based on existing literature. Our log-rank test further validates that the collective upregulation of these genes is indeed correlated with an unfavorable prognosis. This set of genes includes a variety of molecules, such as cytokines, receptors, ligands, and other molecules with diverse functions. Conclusions: Our findings suggest that the set of 21 overexpressed genes in the High Vascularity group could potentially serve as prognostic markers for GB patients. These results highlight the importance of further investigating the relationship between the molecules such as cytokines or receptors underlying the vascularity in GB and its observation through MRI and developing targeted therapies for this aggressive disease.

7.
J Med Case Rep ; 18(1): 266, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822435

RESUMO

BACKGROUND: Sigmoid sinus wall dehiscence can lead to pulsatile tinnitus with a significant decrease in quality of life, occasionally leading to psychiatric disorders. Several surgical and endovascular procedures have been described for resolving dehiscence. Within endovascular procedures, the sagittal sinus approach could be a technical alternative for tracking and accurate stent positioning within the sigmoid sinus when the jugular bulb anatomy is unfavorable. CASE PRESENTATION: A retrospective case series of three patients with pulsatile tinnitus due to sigmoid sinus wall dehiscence without intracranial hypertension was reviewed from January 2018 to January 2022. From the participants enrolled, the median age was 50.3 years (range 43-63), with 67% self-identifying as female and 33% as male. They self-identified as Hispanic. Sigmoid sinus dehiscence was diagnosed using angiotomography, and contralateral transverse sinus stenosis was observed in all patients. Patients underwent surgery via a navigated endovascular sagittal sinus approach for sigmoid sinus stenting. No neurological complications were associated with the procedure. Pulsatile tinnitus improved after the procedure in all patients. CONCLUSIONS: Superior sagittal sinus resection for sigmoid sinus wall stenting is a safe and effective technique. Pulsatile tinnitus due to sigmoid sinus wall dehiscence could be treated using the endovascular resurfacing stenting technique. However, further research is needed to evaluate the potential benefit of contralateral stenting for removing sinus dehiscence when venous stenosis is detected. However, resurfacing sigmoid sinus wall dehiscence results in symptomatic improvement.


Assuntos
Procedimentos Endovasculares , Stents , Zumbido , Humanos , Feminino , Masculino , Zumbido/cirurgia , Zumbido/etiologia , Adulto , Pessoa de Meia-Idade , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Cavidades Cranianas/cirurgia , Seio Sagital Superior/cirurgia , Resultado do Tratamento , Constrição Patológica/cirurgia
8.
Sensors (Basel) ; 24(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931751

RESUMO

This work addresses the challenge of classifying multiclass visual EEG signals into 40 classes for brain-computer interface applications using deep learning architectures. The visual multiclass classification approach offers BCI applications a significant advantage since it allows the supervision of more than one BCI interaction, considering that each class label supervises a BCI task. However, because of the nonlinearity and nonstationarity of EEG signals, using multiclass classification based on EEG features remains a significant challenge for BCI systems. In the present work, mutual information-based discriminant channel selection and minimum-norm estimate algorithms were implemented to select discriminant channels and enhance the EEG data. Hence, deep EEGNet and convolutional recurrent neural networks were separately implemented to classify the EEG data for image visualization into 40 labels. Using the k-fold cross-validation approach, average classification accuracies of 94.8% and 89.8% were obtained by implementing the aforementioned network architectures. The satisfactory results obtained with this method offer a new implementation opportunity for multitask embedded BCI applications utilizing a reduced number of both channels (<50%) and network parameters (<110 K).


Assuntos
Algoritmos , Interfaces Cérebro-Computador , Aprendizado Profundo , Eletroencefalografia , Redes Neurais de Computação , Eletroencefalografia/métodos , Humanos , Processamento de Sinais Assistido por Computador
9.
Nutrients ; 16(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38931161

RESUMO

(1) Background: The aim was to validate an AI-based system compared to the classic method of reading ultrasound images of the rectus femur (RF) muscle in a real cohort of patients with disease-related malnutrition. (2) Methods: One hundred adult patients with DRM aged 18 to 85 years were enrolled. The risk of DRM was assessed by the Global Leadership Initiative on Malnutrition (GLIM). The variation, reproducibility, and reliability of measurements for the RF subcutaneous fat thickness (SFT), muscle thickness (MT), and cross-sectional area (CSA), were measured conventionally with the incorporated tools of a portable ultrasound imaging device (method A) and compared with the automated quantification of the ultrasound imaging system (method B). (3) Results: Measurements obtained using method A (i.e., conventionally) and method B (i.e., raw images analyzed by AI), showed similar values with no significant differences in absolute values and coefficients of variation, 58.39-57.68% for SFT, 30.50-28.36% for MT, and 36.50-36.91% for CSA, respectively. The Intraclass Correlation Coefficient (ICC) for reliability and consistency analysis between methods A and B showed correlations of 0.912 and 95% CI [0.872-0.940] for SFT, 0.960 and 95% CI [0.941-0.973] for MT, and 0.995 and 95% CI [0.993-0.997] for CSA; the Bland-Altman Analysis shows that the spread of points is quite uniform around the bias lines with no evidence of strong bias for any variable. (4) Conclusions: The study demonstrated the consistency and reliability of this new automatic system based on machine learning and AI for the quantification of ultrasound imaging of the muscle architecture parameters of the rectus femoris muscle compared with the conventional method of measurement.


Assuntos
Inteligência Artificial , Desnutrição , Músculo Quadríceps , Ultrassonografia , Humanos , Ultrassonografia/métodos , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Adulto , Reprodutibilidade dos Testes , Desnutrição/diagnóstico por imagem , Desnutrição/diagnóstico , Idoso de 80 Anos ou mais , Adulto Jovem , Músculo Quadríceps/diagnóstico por imagem , Adolescente
10.
J Med Internet Res ; 26: e50295, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941134

RESUMO

Artificial intelligence (AI)-based clinical decision support systems are gaining momentum by relying on a greater volume and variety of secondary use data. However, the uncertainty, variability, and biases in real-world data environments still pose significant challenges to the development of health AI, its routine clinical use, and its regulatory frameworks. Health AI should be resilient against real-world environments throughout its lifecycle, including the training and prediction phases and maintenance during production, and health AI regulations should evolve accordingly. Data quality issues, variability over time or across sites, information uncertainty, human-computer interaction, and fundamental rights assurance are among the most relevant challenges. If health AI is not designed resiliently with regard to these real-world data effects, potentially biased data-driven medical decisions can risk the safety and fundamental rights of millions of people. In this viewpoint, we review the challenges, requirements, and methods for resilient AI in health and provide a research framework to improve the trustworthiness of next-generation AI-based clinical decision support.


Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Humanos
11.
Lifestyle Genom ; 17(1): 64-71, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865975

RESUMO

INTRODUCTION: The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks. METHODS: A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT). RESULTS: These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss. CONCLUSION: Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.


Assuntos
Adiponectina , Dieta Hiperlipídica , Dieta Mediterrânea , Obesidade , Redução de Peso , Humanos , Adiponectina/sangue , Adiponectina/genética , Redução de Peso/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Obesidade/genética , Obesidade/dietoterapia , Polimorfismo de Nucleotídeo Único , Resistência à Insulina , Genótipo , Dieta Redutora , Leptina/sangue , Leptina/genética , Restrição Calórica , Frequência do Gene , Alelos , Índice de Massa Corporal
12.
Nutr Hosp ; 41(3): 712-723, 2024 Jun 27.
Artigo em Espanhol | MEDLINE | ID: mdl-38726604

RESUMO

Introduction: Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.


Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa cuya prevalencia en la actualidad está entre 3 y 6 casos/100.000. La desnutrición está íntimamente relacionada con el pronóstico en el paciente con ELA. Las implicaciones de esta enfermedad hacen que se deba recomendar al paciente la asistencia en una unidad multidisciplinar. Caso clínico: el caso presentado muestra la evolución de una paciente con esclerosis lateral amiotrófica desde el diagnóstico. Tras la valoración por parte de Neurología, se remitió a la paciente a los distintos servicios de seguimiento (Endocrinología, Rehabilitación, Neumología). No se observó deterioro nutricional al diagnóstico; no obstante, la ingesta se encontraba por debajo de los requerimientos. En la progresión de la enfermedad se observó un deterioro de la masa muscular con estabilidad ponderal y de la masa grasa, pero la paciente desarrolló disfagia, síntoma típico de la enfermedad. El planteamiento de medidas "agresivas" para controlar el estado nutricional, como la gastrostomía, fue rechazado al inicio, pero hubo que realizarlas tras la progresión de la disfagia y la desnutrición asociada. Esta situación de deterioro morfofuncional y el desarrollo de complicaciones plantearon la participación de distintos profesionales sanitarios en su control. Discusión: el manejo de la ELA de manera multidisciplinar permite mejorar la evolución de la enfermedad y la calidad de vida del paciente y sus familiares. El seguimiento se basa en el ajuste y el manejo de las complicaciones, en mantener una adecuada comunicación con el paciente y sus familiares, y en tomar de manera conjunta las decisiones sobre su patología.


Assuntos
Esclerose Lateral Amiotrófica , Desnutrição , Terapia Nutricional , Humanos , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/complicações , Desnutrição/etiologia , Desnutrição/terapia , Terapia Nutricional/métodos , Estado Nutricional
13.
Mol Ther ; 32(7): 2223-2231, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38796702

RESUMO

Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches for the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system [18F]fluoroestradiol ([18F]FES) and the estrogen receptor-based PET reporter ChRERα, to monitor expression levels of a small hairpin RNA (shRNA) designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were expressed from the same transcript via lentivirus injected into monkey striatum. In two monkeys that received injections of viral vector, [18F]FES binding increased by 70% and 86% at the target sites compared with pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Post-mortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]FES uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F]FES and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.


Assuntos
Encéfalo , Estradiol , Genes Reporter , Macaca mulatta , Tomografia por Emissão de Pósitrons , Animais , Tomografia por Emissão de Pósitrons/métodos , Estradiol/análogos & derivados , Estradiol/farmacologia , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Expressão Gênica , RNA Interferente Pequeno/genética , Lentivirus/genética , Humanos
14.
Commun Biol ; 7(1): 632, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796563

RESUMO

The stomach-derived hormone ghrelin regulates essential physiological functions. The ghrelin receptor (GHSR) has ligand-independent actions; therefore, GHSR gene deletion may be a reasonable approach to investigate the role of this system in feeding behaviors and diet-induced obesity (DIO). Here, we investigate the effects of a long-term (12-month) high-fat (HFD) versus regular diet on obesity-related measures in global GHSR-KO and wild-type (WT) Wistar male and female rats. Our main findings are that the GHSR gene deletion protects against DIO and decreases food intake during HFD in male but not in female rats. GHSR gene deletion increases thermogenesis and brain glucose uptake in male rats and modifies the effects of HFD on brain glucose metabolism in a sex-specific manner, as assessed with small animal positron emission tomography. We use RNA-sequencing to show that GHSR-KO rats have upregulated expression of genes responsible for fat oxidation in brown adipose tissue. Central administration of a novel GHSR inverse agonist, PF-5190457, attenuates ghrelin-induced food intake, but only in male, not in female mice. HFD-induced binge-like eating is reduced by inverse agonism in both sexes. Our results support GHSR as a promising target for new pharmacotherapies for obesity.


Assuntos
Dieta Hiperlipídica , Obesidade , Ratos Wistar , Receptores de Grelina , Caracteres Sexuais , Animais , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Masculino , Feminino , Ratos , Obesidade/metabolismo , Obesidade/genética , Grelina/metabolismo , Termogênese/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos
15.
Neurocrit Care ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740704

RESUMO

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

16.
Nutr Diabetes ; 14(1): 34, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816400

RESUMO

BACKGROUND/OBJECTIVES: In patients with acute stroke, the presence of hyperglycaemia has been associated with higher morbidity and less neurological recovery. The aim of the study was to evaluate the impact of a diabetes specific enteral nutrition (EN) formula on glycaemia, comorbidities and mortality in patients admitted with a first episode of stroke who received complete EN. METHODS: This was a prospective randomised controlled trial. Patients with acute stroke did not have diagnosis of diabetes mellitus and required nasogastric tube feeding. This study has been registered with code NCT03422900. The patients were randomised into two arms: an isocaloric isoprotein formula (control group (CG), 27 patients) vs a diabetes-specific formula (low glycaemic index carbohydrates, fibre (80% soluble) and higher lipid content) (experimental group (EG), 25 patients). Pre-EN blood glucose, hyperglycaemia during EN treatment, HbA1c, insulin use, oral route recovery, length of stay (LOS) and mortality at 30 days were collected. The complications of enteral nutrition during admission were collected as well. RESULTS: 52 patients were included, 50% females, with an age of 77.44(11.48) years; 34 (65.4%) had ischaemic stroke, with a Rankin score of 0(0-2), and a National Institute of Health Stroke Scale (NIHSS) of 19 (15-22). In CG, there were more cases of hyperglycaemia on the 5th day post-NE (13(65%) vs7(35%), p < 0.01). CG showed an OR of 7.58(1.49-39.16) (p = 0.02) for the development of hyperglycaemia. There were no differences in LOS between groups (12(8.5) days vs 14(23) days, p = 0.19) or in the death rate (10(37%) vs 10(40%), p = 0.8), although differences were found in terms of oral route recovery (EG: 11(44%) patients vs CG: 5(18.5%) patients, p = 0.04) (OR (EG): 5.53(1.25-24.47); p = 0.02). CONCLUSIONS: The use of a diabetes-specific enteral formula in non-diabetic patients admitted with acute stroke reduced the risk of developing hyperglycaemia and improved the rate of oral route recovery. Registered under ClinicalTrials.gov Identifier no. NCT03422900.


Assuntos
Glicemia , Nutrição Enteral , Hiperglicemia , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Nutrição Enteral/métodos , Idoso , Acidente Vascular Cerebral/terapia , Estudos Prospectivos , Glicemia/análise , Glicemia/metabolismo , Alimentos Formulados , Idoso de 80 Anos ou mais , Tempo de Internação , Insulina/uso terapêutico , Hemoglobinas Glicadas/análise , Pacientes Internados , Índice Glicêmico , Diabetes Mellitus/terapia , Resultado do Tratamento
17.
Comput Biol Med ; 175: 108548, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718666

RESUMO

The aim of this work is to develop and evaluate a deep classifier that can effectively prioritize Emergency Medical Call Incidents (EMCI) according to their life-threatening level under the presence of dataset shifts. We utilized a dataset consisting of 1982746 independent EMCI instances obtained from the Health Services Department of the Region of Valencia (Spain), with a time span from 2009 to 2019 (excluding 2013). The dataset includes free text dispatcher observations recorded during the call, as well as a binary variable indicating whether the event was life-threatening. To evaluate the presence of dataset shifts, we examined prior probability shifts, covariate shifts, and concept shifts. Subsequently, we designed and implemented four deep Continual Learning (CL) strategies-cumulative learning, continual fine-tuning, experience replay, and synaptic intelligence-alongside three deep CL baselines-joint training, static approach, and single fine-tuning-based on DistilBERT models. Our results demonstrated evidence of prior probability shifts, covariate shifts, and concept shifts in the data. Applying CL techniques had a statistically significant (α=0.05) positive impact on both backward and forward knowledge transfer, as measured by the F1-score, compared to non-continual approaches. We can argue that the utilization of CL techniques in the context of EMCI is effective in adapting deep learning classifiers to changes in data distributions, thereby maintaining the stability of model performance over time. To our knowledge, this study represents the first exploration of a CL approach using real EMCI data.


Assuntos
Aprendizado Profundo , Humanos , Bases de Dados Factuais , Espanha , Serviços Médicos de Emergência
18.
Mol Genet Genomics ; 299(1): 49, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704518

RESUMO

The main objective of this study was to determine whether the common Y-haplogroups were be associated with the risk of developing severe COVID-19 in Spanish male. We studied 479 patients who required hospitalization due to COVID-19 and 285 population controls from the region of Asturias (northern Spain), They were genotyped for several polymorphisms that define the common European Y-haplogroups. We compared the frequencies between patients and controls aged ≤ 65 and >65 years. There were no different haplogroup frequencies between the two age groups of controls. Haplogroup R1b was less common in patients aged ≤65 years. Haplogroup I was more common in the two patient´s groups compared to controls (p = 0.02). Haplogroup R1b was significantly more frequent among hypertensive patients, without difference between the hypertensive and normotensive controls. This suggested that R1b could increase the risk for severe COVID-19 among male with pre-existing hypertension. In conclusion, we described the Y-haplogroup structure among Asturians. We found an increased risk of severe COVID-19 among haplogroup I carriers, and a significantly higher frequency of R1b among hypertensive patients. These results indicate that Y-chromosome variants could serve as markers to define the risk of developing a severe form of COVID-19.


Assuntos
COVID-19 , Cromossomos Humanos Y , Haplótipos , Hipertensão , SARS-CoV-2 , Humanos , Masculino , COVID-19/genética , COVID-19/epidemiologia , Espanha/epidemiologia , Haplótipos/genética , Idoso , Pessoa de Meia-Idade , SARS-CoV-2/genética , Cromossomos Humanos Y/genética , Hipertensão/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Adulto , Feminino
19.
Int J Cardiol ; 408: 132117, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710232

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways. METHODS: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed. RESULTS: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified. CONCLUSION: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes.


Assuntos
Cardiomiopatia Hipertrófica , Testes Genéticos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/diagnóstico , Testes Genéticos/métodos , Adulto , Idoso , Análise de Sobrevida , Estudos de Coortes , Seguimentos , Taxa de Sobrevida/tendências , Encaminhamento e Consulta , Espanha/epidemiologia , Fatores Sexuais , Caracteres Sexuais
20.
Viruses ; 16(5)2024 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-38793685

RESUMO

In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA-RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA-host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV-host-cell interactions.


Assuntos
Vírus da Dengue , Genoma Viral , RNA não Traduzido , RNA Viral , Vírus da Dengue/genética , Vírus da Dengue/fisiologia , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Interações Hospedeiro-Patógeno/genética , Dengue/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Animais
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