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1.
Proc Natl Acad Sci U S A ; 119(35): e2200960119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35951647

RESUMO

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.


Assuntos
Encéfalo , COVID-19 , Viroses do Sistema Nervoso Central , SARS-CoV-2 , Astrócitos/patologia , Astrócitos/virologia , Encéfalo/patologia , Encéfalo/virologia , COVID-19/complicações , COVID-19/patologia , Viroses do Sistema Nervoso Central/etiologia , Viroses do Sistema Nervoso Central/patologia , Humanos , Síndrome de COVID-19 Pós-Aguda
2.
Echocardiography ; 41(1): e15726, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38078698

RESUMO

BACKGROUND: Iron deficiency correction with ferric carboxymaltose improves symptoms and reduces rehospitalization in patients with reduced left ventricular ejection fraction. The mechanisms underlying these improvements are poorly understood. This study aimed to determine changes in left ventricular contractility after iron treatment as reflected in global longitudinal strain. METHODS: Prospective single-center study including 43 adults with reduced ejection fraction, non-anemic iron deficiency, and functional class II-III heart failure despite optimal medical treatment. Global longitudinal strain through speckle-tracking echocardiography was measured at baseline and 4 weeks after ferric carboxymaltose. RESULTS: A significant improvement in global longitudinal strain was detected (from -12.3% ± 4.0% at baseline to -15.6% ± 4.1%, p < .001); ferritin and transferrin saturation index had increased, but ejection fraction presented no significant changes (baseline 35.7% ± 4.6%, follow-up 37.2% ± 6.6%, p = .073). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, the correction of iron deficiency with ferric carboxymaltose is associated with an early improvement in global longitudinal strain, possibly suggesting a direct effect of iron correction on myocardial contractility.


Assuntos
Anemia Ferropriva , Insuficiência Cardíaca , Deficiências de Ferro , Maltose/análogos & derivados , Disfunção Ventricular Esquerda , Adulto , Humanos , Volume Sistólico , Estudos Prospectivos , Deformação Longitudinal Global , Função Ventricular Esquerda , Compostos Férricos/uso terapêutico , Compostos Férricos/farmacologia , Ferro/farmacologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico
3.
J Integr Neurosci ; 23(3): 51, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38538228

RESUMO

BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated. METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance. RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine. CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.


Assuntos
Fluoxetina , Receptores de GABA-A , Ratos , Masculino , Animais , Fluoxetina/farmacologia , Pregnanolona , Ratos Wistar , Receptores de GABA , Picrotoxina , Estudos Longitudinais , Antidepressivos/farmacologia , Flavonoides/farmacologia , Ácido gama-Aminobutírico
4.
Proc Natl Acad Sci U S A ; 117(38): 23932-23941, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900951

RESUMO

DICER is a key enzyme in microRNA (miRNA) biogenesis. Here we show that aerobic exercise training up-regulates DICER in adipose tissue of mice and humans. This can be mimicked by infusion of serum from exercised mice into sedentary mice and depends on AMPK-mediated signaling in both muscle and adipocytes. Adipocyte DICER is required for whole-body metabolic adaptations to aerobic exercise training, in part, by allowing controlled substrate utilization in adipose tissue, which, in turn, supports skeletal muscle function. Exercise training increases overall miRNA expression in adipose tissue, and up-regulation of miR-203-3p limits glycolysis in adipose under conditions of metabolic stress. We propose that exercise training-induced DICER-miR-203-3p up-regulation in adipocytes is a key adaptive response that coordinates signals from working muscle to promote whole-body metabolic adaptations.


Assuntos
Tecido Adiposo/metabolismo , RNA Helicases DEAD-box/metabolismo , Exercício Físico/fisiologia , Ribonuclease III/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adaptação Fisiológica/fisiologia , Adipócitos/metabolismo , Animais , Células Cultivadas , RNA Helicases DEAD-box/deficiência , RNA Helicases DEAD-box/genética , Feminino , Glicólise , Humanos , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , Condicionamento Físico Animal , Ribonuclease III/deficiência , Ribonuclease III/genética
5.
Clin Gerontol ; : 1-11, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37921425

RESUMO

BACKGROUND: Many older adults in Colombia have lived through violent and stressful life events, particularly in areas of poverty. The aim of this qualitative study was to understand the impact of stressful life events on the mental health and wellbeing of older Colombians living in areas of relative poverty. METHODS: Older adults (aged 60+) living in the Turbo region in Colombia were interviewed face-to-face between August and December 2021. Transcripts were coded in Spanish and English by at least two researchers, using inductive thematic analysis. RESULTS: Twenty-six older adults participated in the study. Four overarching themes were generated: Living in violent and dangerous communities; Disturbing gender violence and gender roles; Lack of mental health awareness; Coping mechanisms. Older adults experienced a long narrative of stressful life events. Younger generations appeared to disrespect older members of Society. Without any mental health support, older adults coped by accepting the extreme situations or seeking solace in their faith. CONCLUSIONS: The health system and Government need to build up trust and generate an awareness of mental health, as older Colombians will not approach psychological support otherwise. Intergenerational community-based interventions may provide a first avenue of mental health support.

6.
Ear Hear ; 43(3): 1079-1085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34799494

RESUMO

OBJECTIVES: Meniere disease (MD) is defined by a clinical syndrome of recurrent attacks of spontaneous vertigo associated with tinnitus, aural fullness, and sensorineural hearing loss (SNHL). Most patients have unilateral SNHL, but some of them will develop contralateral SNHL during the course of the disease. Several studies have reported a frequency of 2 to 73% SNHL in the second ear, according to the duration of disease and the period of follow-up. We hypothesize that unilateral and bilateral MD are different conditions, the first would initially involve the apical turn of the cochlea, while bilateral MD would affect the entire length of the cochlea. The aim of the study is to search for clinical predictors of bilateral SNHL in MD to build a predictive model of bilateral involvement. DESIGN: A retrospective, longitudinal study including two cohorts with a total of 400 patients with definite MD was carried out. The inception cohort consisted of 150 patients with MD and the validation cohort included 250 cases. All of the cases were diagnosed of unilateral MD according to their hearing loss thresholds. The following variables were assessed as predictors of bilateral SNHL for the two cohorts: sex, age of onset, familiar history of MD, migraine and high-frequency hearing loss (HFHL, defined if hearing threshold >20 dB in two or more consecutive frequencies from 2 to 8 KHz). A descriptive analysis was carried out according to the presence of HFHL in the first audiogram for the main variables. By using multiple logistic regression, we built-up several predictive models for the inception cohort and validated it with the replication cohort and merged dataset. RESULTS: Twenty-three (19.3%) and 78 (41%) of patients with HFHL developed contralateral SNHL during the follow-up, in the inception and validation cohorts, respectively. In the inception cohort, the best predictive model included HFHL in the first audiogram (OR = 6.985, p = 0.063) and the absence of migraine (OR = 0.215, p = 0.144) as clinical predictors for bilateral SNHL [area under the curve (AUC) = 0.641, p = 0.002]. The model was validated in the second cohort (AUC = 0.621, p < 0.001). Finally, we merged both datasets to improve the precision of the model including HFHL in the first audiogram (OR = 3.168, p = 0.001), migraine (OR = 0.482, p = 0.036) and age of onset >35 years old (OR = 2.422, p = 0.006) as clinical predictors (AUC = 0.639, p < 0.001). CONCLUSIONS: A predictive model including the age of onset, HFHL in the first audiogram and migraine can help to assess the risk of bilateral SNHL in MD. This model may have significant implications for clinical management of patients with MD.


Assuntos
Perda Auditiva Neurossensorial , Doença de Meniere , Transtornos de Enxaqueca , Adulto , Perda Auditiva Bilateral , Humanos , Estudos Longitudinais , Doença de Meniere/complicações , Transtornos de Enxaqueca/complicações , Estudos Retrospectivos
7.
Int J Mol Sci ; 23(18)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36142808

RESUMO

Depressive disorders are among the most disabling diseases experienced around the world, and their incidence has significantly increased over the last few decades due to multiple environmental, social, and biological factors. The search for new pharmacological alternatives to treat depression is a global priority. In preclinical research, molecules obtained from plants, such as flavonoids, have shown promising antidepressant-like properties through several mechanisms of action that have not been fully elucidated, including crossing of the blood brain barrier (BBB). This review will focus on discussing the main findings related to the participation of the serotonergic system and brain-derived neurotrophic factor (BDNF) on the antidepressant-like effect of some flavonoids reported by behavioral, neurochemical, and molecular studies. In this sense, evidence shows that depressive individuals have low levels of serotonin and BDNF, while flavonoids can reverse it. Finally, the elucidation of the mechanism used by flavonoids to modulate serotonin and BDNF will contribute to our understanding of the neurobiological bases underlying the antidepressant-like effects produced by these natural compounds.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Serotonina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Hipocampo/metabolismo , Humanos , Serotonina/farmacologia
8.
Ear Hear ; 41(5): 1397-1406, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32058350

RESUMO

OBJECTIVE: To evaluate the effect of artifacts on the impulse and response recordings with the video head impulse test (VHIT) and determine how many stimuli are necessary for obtaining acceptably efficient measurements. METHODS: One hundred fifty patients were examined using VHIT and their registries searched for artifacts. We compared several variations of the dataset. The first variation used only samples without artifacts, the second used all samples (with and without artifacts), and the rest used only samples with each type of artifact. We calculated the relative efficiency (RE) of evaluating an increasingly large number of samples (3 to 19 per side) when compared with the complete sample (20 impulses per side). RESULTS: Overshoot was associated with significantly higher speed (p = 0.005), higher duration (p < 0.001) and lower amplitude of the impulses (p = 0.002), and consequent higher saccades' latency (p = 0.035) and lower amplitude (p = 0.025). Loss of track was associated with lower gain (p = 0.035). Blink was associated with a higher number of saccades (p < 0.001), and wrong way was associated with lower saccade latency (p = 0.012). The coefficient of quartile deviation escalated as the number of artifacts of any type rose, indicating an increment of variability. Overshoot increased the probability of the impulse to lay on the outlier range for gain and peak speed. Blink did so for the number of saccades, and wrong way for the saccade amplitude and speed. RE reached a tolerable level of 1.1 at 7 to 10 impulses for all measurements except the PR score. CONCLUSIONS: Our results suggest the necessity of removing artifacts after collecting VHIT samples to improve the accuracy and precision of results. Ten impulses are sufficient for achieving acceptable RE for all measurements except the PR score.


Assuntos
Artefatos , Teste do Impulso da Cabeça , Humanos , Reflexo Vestíbulo-Ocular , Movimentos Sacádicos
9.
Ear Hear ; 41(2): 323-329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31517671

RESUMO

OBJECTIVES: Oscillopsia is a disabling condition for patients with bilateral vestibular hypofunction (BVH). When the vestibulo-ocular reflex is bilaterally impaired, its ability to compensate for rapid head movements must be supported by refixation saccades. The objective of this study is to assess the relationship between saccadic strategies and perceived oscillopsia. DESIGN: To avoid the possibility of bias due to remaining vestibular function, we classified patients into two groups according to their gain values in the video head impulse test. One group comprised patients with extremely low gain (0.2 or below) in both sides, and a control group contained BVH patients with gain between 0.2 and 0.6 bilaterally. Binary logistic regression (BLR) was used to determine the variables predicting oscillopsia. RESULTS: Twenty-nine patients were assigned to the extremely low gain group and 23 to the control group. The BLR model revealed the PR score (saccades synchrony measurement) to be the best predictor of oscillopsia. Receiver operating characteristic analysis determined that the most efficient cutoff point for the probabilities saved with the BLR was 0.518, yielding a sensitivity of 86.6% and specificity of 84.2%. CONCLUSIONS: BVH patients with higher PR values (nonsynchronized saccades) were more prone to oscillopsia independent of their gain values. We suggest that the PR score can be considered a useful measurement of compensation.


Assuntos
Movimentos Sacádicos , Vestíbulo do Labirinto , Teste do Impulso da Cabeça , Humanos , Reflexo Vestíbulo-Ocular , Transtornos da Visão
10.
Am J Otolaryngol ; 41(4): 102557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497952

RESUMO

PURPOSE: To evaluate the prophylactic, protocolized, and standardized use of a Montgomery tube in preventing pharyngocutaneous fistulas after total laryngectomy and neck dissection. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral centre. SUBJECT AND METHODS: A Montgomery salivary bypass tube was placed in 44 patients undergoing total laryngectomy and neck dissection, observing the percentage of fistula appearance and the time of start of deglutition. Comparison was made with a group of 28 patients prior to the implantation of the protocol in whom the tube was not used. RESULTS: There was a statistically significant decrease in the percentage of fistulas and an earlier onset of deglutition in the salivary bypass tube patients compared to those in whom the tube had not been used. CONCLUSION: Prophylactic and standardized use of the Montgomery salivary bypass tube in patients undergoing total laryngectomy and neck dissection might decrease the incidence of pharyngocutaneous fistula and improve the course of one that is already established.


Assuntos
Fístula Cutânea/prevenção & controle , Drenagem/instrumentação , Fístula/prevenção & controle , Intubação/instrumentação , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Doenças Faríngeas/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Saliva , Idoso , Estudos de Coortes , Fístula Cutânea/etiologia , Deglutição , Feminino , Fístula/etiologia , Humanos , Neoplasias Laríngeas/fisiopatologia , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Doenças Faríngeas/etiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
11.
Eur Arch Otorhinolaryngol ; 276(1): 41-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327905

RESUMO

PURPOSE: Computerized posturography is the gold standard for balance assessment. Because of the great cost and dimensions of commercial equipments, low-cost and portable devices have been developed and validated, such as RombergLab, a software in open source term which works connected with a low-cost force platform. The objective of this study was to obtain normative posturography data using this software. METHODS: A multicentric prospective and descriptive study, with 350 healthy participants, was designed. Static postural stability (measured using the modified clinical test of sensory interaction on balance) was evaluated using the software connected to the force platform. Using the confidence ellipse area (CEA) in each condition, global equilibrium score (GES) was calculated and adjusted for significant variable factors using cluster analysis. RESULTS: Mean (SD) GES was 0.72 (0.22). Age (p < 0.01), height (p < 0.01) and recruitment center (p < 0.05) were found as influence factors for GES. Cluster analysis obtained 16 groups stratified by age and height. GES decreases with age and height (p < 0.005). No significant interaction of age nor height was found with GES in these clusters (p > 0.05). After correction for height and age, GES was no longer influenced by the recruitment center (p > 0.05). CONCLUSIONS: With the introduction of the global equilibrium score values of the present study into the software, we consider RombergLab v1.3 a reference posturography tool for healthy individuals. Further studies are needed for validating it as a suitable instrumented test for screening between healthy and pathologic subjects and its reliability over time for the follow-up of patients.


Assuntos
Diagnóstico por Computador/métodos , Técnicas de Diagnóstico Neurológico , Equilíbrio Postural/fisiologia , Software , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Adulto Jovem
12.
Genet Epidemiol ; 41(8): 726-743, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28913944

RESUMO

The increasing accessibility of data to researchers makes it possible to conduct massive amounts of statistical testing. Rather than follow specific scientific hypotheses with statistical analysis, researchers can now test many possible relationships and let statistics generate hypotheses for them. The field of genetic epidemiology is an illustrative case, where testing of candidate genetic variants for association with an outcome has been replaced by agnostic screening of the entire genome. Poor replication rates of candidate gene studies have improved dramatically with the increase in genomic coverage, due to factors such as adoption of better statistical practices and availability of larger sample sizes. Here, we suggest that another important factor behind the improved replicability of genome-wide scans is an increase in the amount of statistical testing itself. We show that an increase in the number of tested hypotheses increases the proportion of true associations among the variants with the smallest P-values. We develop statistical theory to quantify how the expected proportion of genuine signals (EPGS) among top hits depends on the number of tests. This enrichment of top hits by real findings holds regardless of whether genome-wide statistical significance has been reached in a study. Moreover, if we consider only those "failed" studies that produce no statistically significant results, the same enrichment phenomenon takes place: the proportion of true associations among top hits grows with the number of tests. The enrichment occurs even if the true signals are encountered at the logarithmically decreasing rate with the additional testing.


Assuntos
Modelos Genéticos , Teorema de Bayes , Estudo de Associação Genômica Ampla , Humanos , Modelos Estatísticos
13.
Ear Hear ; 39(6): 1176-1186, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29578887

RESUMO

OBJECTIVES: To evaluate the ability of saccadic strategies developed during vestibular compensation to reduce the effect of an impaired vestibulo-ocular reflex (VOR) on a retinal smear and image motion sensation. DESIGN: Twenty patients with unilateral vestibular loss were examined with a video head impulse test before and after vestibular rehabilitation (VR) with the use of gaze stabilization and refixation saccades training. Head and eye velocity functions were processed to infer the retinal eccentricity, and through its correlation with visual acuity (VA), several measurements are proposed to evaluate the influence of VR on saccades behavior and visual performance. To isolate the effect of saccades on the findings and avoid bias because of gain differences, only patients whose VOR gain values remained unchanged after VR were included. RESULTS: Improved contribution of covert saccades and reduction of overt saccades latency were measured after VR. We found significant differences when assessing both the interval less than 70% VA (50.25 ms), which is considered the limit of a moderate low vision, and less than 50% VA (39.515 ms), which is the limit for severe low vision. Time to recover a VA of 75% (near normal) was reduced in all the patients (median: 56.472 ms). CONCLUSION: Despite the absence of VOR gain improvement, patients with unilateral vestibular loss are able to develop saccadic strategies that allow the shortening of the interval of retinal smear and image motion. The proposed measurements might be of use to evaluate VR outcomes and visually induced impairment.


Assuntos
Movimentos Sacádicos , Doenças Vestibulares/reabilitação , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Teste do Impulso da Cabeça , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Estudos Prospectivos , Acompanhamento Ocular Uniforme/fisiologia , Reflexo Vestíbulo-Ocular , Retina/fisiologia , Doenças Vestibulares/patologia , Doenças Vestibulares/fisiopatologia
14.
Semin Thromb Hemost ; 41(1): 43-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25590525

RESUMO

To our knowledge, this is the first comprehensive review on the subject of venous thromboembolism (VTE) and hypercoagulability in burn patients. Specific changes in coagulability are reviewed using data from thromboelastography and other techniques. Disseminated intravascular coagulation in burn patients is discussed. The incidence and risk factors associated with VTE in burn patients are then examined, followed by the use of low-molecular-weight heparin thromboprophylaxis and monitoring techniques using antifactor Xa levels. The need for large, prospective trials in burn patients is highlighted, especially in the areas of VTE incidence and safe, effective thromboprophylaxis.


Assuntos
Queimaduras/sangue , Trombofilia/sangue , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Humanos , Fatores de Risco , Tromboelastografia/métodos
15.
Cardiooncology ; 10(1): 37, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886852

RESUMO

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer may precipitate cardiotoxic events. We aimed to perform a meta-analysis to evaluate the cardiotoxicity associated with ICIs in patients with lung cancer. METHODS: A literature search was conducted across four electronic databases (Cochrane CENTRAL, MEDLINE, OVID EMBASE and Google Scholar) from inception through 31st May 2023. Randomized controlled trials (RCTs) assessing the impact of ICIs on cardiac outcomes in lung cancer patients were considered for inclusion. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled and analysis was performed using a random-effects model. The Grading of Recommendations Assessment, Development and Evaluation approach was followed to assess confidence in the estimates of effect (i.e., the quality of evidence). RESULTS: A total of 30 studies including 16,331 patients, were included in the analysis. Pooled results showed that single ICI (RR: 2.15; 95% CI: 1.13-4.12; p = 0.02; I2 = 0%) or a combination of single ICI plus chemotherapy (RR: 1.38 [1.05-1.82]; p = 0.02) significantly increased the risk of cardiac adverse events when compared with chemotherapy alone. No significant difference was noted when a dual ICI (RR: 0.48 [0.13-1.80]; p = 0.27) was compared with single ICI. In addition, there was no significant association between the use of ICIs and incidence of cardiac failure (RR: 1.11 [0.48-2.58]; p = 0.80), or arrhythmia (RR: 1.87; [0.69-5.08]; p = 0.22). CONCLUSION: Compared with chemotherapy alone, use of a single ICI or a combination of single ICI plus chemotherapy significantly increased the risk of cardiotoxicity. However, employing dual immunotherapy did not result in a significant increase in the risk of cardiotoxicity when compared to the use of a single ICI.

16.
Cell Rep ; 43(7): 114491, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002127

RESUMO

Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin's regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.

17.
Nat Commun ; 15(1): 3070, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594249

RESUMO

Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. ALG-1, the C. elegans ortholog of human AGO2, plays an essential role in microRNA processing and function. Here we investigated the mechanisms governing ALG-1 expression in C. elegans and the players controlling lifespan and stress resistance downstream of ALG-1. We show that upregulation of ALG-1 is a shared feature in conditions linked to increased longevity (e.g., germline-deficient glp-1 mutants). ALG-1 knockdown reduces lifespan and oxidative stress resistance, while overexpression enhances survival against pro-oxidant agents but not heat or reductive stress. R02D3.7 represses alg-1 expression, impacting oxidative stress resistance at least in part via ALG-1. microRNAs upregulated in glp-1 mutants (miR-87-3p, miR-230-3p, and miR-235-3p) can target genes in the protein disulfide isomerase pathway and protect against oxidative stress. This study unveils a tightly regulated network involving transcription factors and microRNAs which controls organisms' ability to withstand oxidative stress.


Assuntos
Proteínas de Caenorhabditis elegans , MicroRNAs , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
18.
Behav Pharmacol ; 24(8): 693-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24196028

RESUMO

The defensive burying test is an experimental model that is used to explore anxiety-like behavior in adult rats. Because the expression of anxiety-like behavior may differ between infant and adult rats, we tested the impact of chambers with different sizes and shapes on defensive burying in 28-day-old Wistar rats. The first two chambers had base areas of 560 cm, but one was rectangular and the other round. The base areas of the other two chambers were 282 cm, also with one rectangular and one round. We examined the effects of vehicle and 1 mg/kg diazepam on defensive burying in the various chambers. Locomotor activity was also measured to identify or exclude any sedative effects. Independent of the treatments used, the infant rats showed a shorter burying latency in the three modified chambers and a longer cumulative burying time compared with the original apparatus. The effects of diazepam (i.e. increased latency and decreased burying time) were only significant in the small round chamber, without significant effects on general motor activity. These results suggest that a small round chamber that is used to test burying behavior is sensitive to the anxiolytic actions of diazepam when the experimental subjects are very young rats.


Assuntos
Envelhecimento/fisiologia , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiedade/psicologia , Modelos Animais de Doenças , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Desmame
19.
Gerontology ; 59(5): 408-12, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23689314

RESUMO

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most frequent peripheral vertigo in the elderly. It is a well-characterized entity and generally easy to treat. OBJECTIVE: To evaluate the main symptoms, time to consult for the problem, vertigo characteristics, treatment and follow-up in patients over 70 with BPPV. METHODS: This was a retrospective cohort study. Four hundred and four patients were diagnosed to have BPPV (between January 2006 and December 2012); 211 of them were ≥70 years old (mean 77.7 years) and 193 <70 years old (mean 53.82 years). RESULTS: Patients over 70 with BPPV took longer to consult for the problem (Spearman rho, p = 0.01). The frequency of a clinical presentation consisting of unsteadiness or imbalance without vertigo sensation is higher among elderly patients (χ(2), p = 10(-6)). The effectiveness of the repositioning maneuver is lower than in patients under 70 (χ(2), p = 0.002), and the recurrences are more frequent (χ(2), p = 0.04). CONCLUSION: BPPV is a frequent entity in the elderly, and it is necessary to take it into account when older patients complain about imbalance. An appropriate treatment with repositioning maneuvers and prolonged follow-up are required in order to detect recurrences.


Assuntos
Vertigem/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Vertigem Posicional Paroxística Benigna , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Canais Semicirculares/fisiopatologia , Resultado do Tratamento , Vertigem/fisiopatologia , Vertigem/terapia
20.
Laryngoscope ; 133(12): 3554-3563, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37114648

RESUMO

OBJECTIVE: To develop a new method to quantify visually-enhanced vestibulo-ocular reflex (VVOR) gain, in patients with vestibular function loss, that is mathematically suitable given the nature of the test, and determine the reliability of the method by comparing results with those of the gold standard, the video head impulse test (vHIT). MATERIALS AND METHODS: We developed a new method for VVOR gain quantification and conducted a cross-sectional study in patients diagnosed with vestibular function loss and controls, all participants undergoing both a VVOR test and a vHIT. We measured VVOR gain with three different methods: area under the curve (AUC), slope regression, and a Fourier method (VVORAUC , VVORSP , and VVORFR , respectively); and compared these gain values with vHIT gain calculated using the AUC method. RESULTS: Overall, 111 patients were included: 29 healthy subjects and 82 patients with vestibular function loss. Intraclass correlation coefficients (ICC(1,1)) between gain from the gold standard and each of the VVOR gain methods were: 0.68 (CI: 0.61-0.75) for VVORAUC , 0.66 (CI: 0.58-0.73) for VVORSP and 0.71 (CI: 0.64-0.77) for VVORFR . No interference was found between VVOR gain calculation methods and potentially influential variables considered (p ≥ 0.98). CONCLUSION: The new method for quantifying VVOR gain showed good concordance with the vHIT method. LEVEL OF EVIDENCE: 2: Individual cross-sectional studies with consistently applied reference standard and blinding (Diagnosis) Laryngoscope, 133:3554-3563, 2023.


Assuntos
Reflexo Vestíbulo-Ocular , Vestíbulo do Labirinto , Humanos , Estudos Transversais , Reprodutibilidade dos Testes , Teste do Impulso da Cabeça/métodos
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