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1.
BMC Psychiatry ; 22(1): 164, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248015

RESUMO

BACKGROUND: CUIDA-TE is an APP that offers transdiagnostic cognitive behavioral therapy focused on enhancing emotion regulation. As a novelty, it incorporates ecological momentary interventions (EMI), which can provide psychological support in real time, when suffering arises. The main goal of the study is to evaluate the efficacy of CUIDA-TE to improve emotion regulation in healthcare workers, a population that has been particularly emotionally impacted by the COVID-19 pandemic. METHODS: In this three-arm, randomized controlled trial (RCT) the study sample will be composed of a minimum of 174 healthcare workers. They will be randomly assigned to a 2-month EMI group (CUIDA-TE APP, n ≥ 58), a 2-month ecological momentary assessment (EMA) only group (MONITOR EMOCIONAL APP, n ≥ 58), or a wait-list control group (no daily monitoring nor intervention, n ≥ 58). CUIDA-TE will provide EMI if EMA reveals emotional problems, poor sleep quality/quantity, burnout, stress, or low perceived self-efficacy when regulating emotions. Depression will be the primary outcome. Secondary outcomes will include emotion regulation, quality of life, and resilience. Treatment acceptance and usability will also be measured. Primary and secondary outcomes will be obtained at pre- and post-intervention measurements, and at the 3-month follow-up for all groups. DISCUSSION: To our knowledge, this is the first RCT that evaluates the efficacy of an APP-based EMI to improve emotion regulation skills in healthcare workers. This type of intervention might ultimately help disseminate treatments and reach a larger number of individuals than traditional face-to-face individual therapies. TRIAL REGISTRATION: ClinicalTrial.gov : NCT04958941 Registered 7 Jun 2021. STUDY STATUS: Participant recruitment has not started.


Assuntos
COVID-19 , Regulação Emocional , Pessoal de Saúde , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Smartphone , Resultado do Tratamento
2.
Hum Mol Genet ; 28(12): 2014-2029, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30753434

RESUMO

An early hallmark of Alzheimer's disease is the accumulation of amyloid-ß (Aß), inspiring numerous therapeutic strategies targeting this peptide. An alternative approach is to destabilize the amyloid beta precursor protein (APP) from which Aß is derived. We interrogated innate pathways governing APP stability using a siRNA screen for modifiers whose own reduction diminished APP in human cell lines and transgenic Drosophila. As proof of principle, we validated PKCß-a known modifier identified by the screen-in an APP transgenic mouse model. PKCß was genetically targeted using a novel adeno-associated virus shuttle vector to deliver microRNA-adapted shRNA via intracranial injection. In vivo reduction of PKCß initially diminished APP and delayed plaque formation. Despite persistent PKCß suppression, the effect on APP and amyloid diminished over time. Our study advances this approach for mining druggable modifiers of disease-associated proteins, while cautioning that prolonged in vivo validation may be needed to reveal emergent limitations on efficacy.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Amiloidose/metabolismo , Proteína Quinase C beta/antagonistas & inibidores , Doença de Alzheimer/genética , Amiloidose/terapia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Drosophila , Testes Genéticos , Terapia Genética , Humanos , Camundongos , Camundongos Transgênicos , Células NIH 3T3 , Fosforilação , Placa Amiloide/patologia , Proteína Quinase C beta/genética , Proteína Quinase C beta/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
3.
Telemed J E Health ; 27(8): 919-928, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34182825

RESUMO

Background: Social distancing restrictions imposed due to the Novel Coronavirus 2019 (COVID-19) pandemic resulted in a rapid shift in the delivery of psychological interventions from in-person to telehealth. Much of the research on this transition has been conducted with English-speaking mental health providers, leaving a gap in understanding related to how this shift has impacted Spanish-speaking treatment providers. Methods: Fifty non-U.S. Spanish-speaking therapists completed a survey related to their use of telecommunication modalities; client population characteristics; professional, ethical, and legal/regulatory issues; and telehealth training and practice. Participants completed the survey at one time point and retrospectively described their use of telehealth both pre-pandemic and during the pandemic. Results: Most of the 50 Spanish-speaking therapists surveyed reported using telepsychology 58% before COVID-19 versus 84% during the COVID-19 pandemic (χ2 = 5.76, p < 0.05). Compared with pre-pandemic, the number of hours therapists spent using telepsychology per week increased significantly for early adopter therapists (those who began using telehealth before the pandemic began) (Z = -3.18, p = 0.001) and also for late adopter therapists who only began using telehealth during the pandemic (Z = -3.74, p < 0.001). Many therapists reported equity issues. Most participants also reported ethical and regulatory concerns regarding security/confidentiality or Health Insurance Porability and Accountability Act. Conclusions: The rapid adoption of technology to deliver therapy during COVID-19 has spurred growing pains for Spanish-speaking therapists and their underserved clients, and more research is needed to better understand and improve the therapists' adoption of these technologies with diverse patient populations.


Assuntos
COVID-19 , Telemedicina , Realidade Virtual , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206170

RESUMO

Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson's disease. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) ß/ζ, which is abundantly expressed in the CNS. Using a specific inhibitor of RPTPß/ζ (MY10), we aimed to assess whether the PTN/RPTPß/ζ axis is involved in neuronal and glial injury induced by the toxin MPP+. Treatment with the RPTPß/ζ inhibitor MY10 alone decreased the viability of both SH-SY5Y neuroblastoma cells and BV2 microglial cultures, suggesting that normal RPTPß/ζ function is involved in neuronal and microglial viability. We observed that PTN partially decreased the cytotoxicity induced by MPP+ in SH-SY5Y cells underpinning the neuroprotective function of PTN. However, MY10 did not seem to modulate the SH-SY5Y cell loss induced by MPP+. Interestingly, we observed that media from SH-SY5Y cells treated with MPP+ and MY10 decreases microglial viability but may elicit a neuroprotective response of microglia by upregulating Ptn expression. The data suggest a neurotrophic role of microglia in response to neuronal injury through upregulation of Ptn levels.


Assuntos
Proteínas de Transporte/metabolismo , Comunicação Celular , Citocinas/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Animais , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Camundongos , Microglia/fisiologia , Modelos Biológicos , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/fisiologia , Transdução de Sinais
5.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502170

RESUMO

(1) Background: Pleiotrophin preserves insulin sensitivity, regulates adipose tissue lipid turnover and plasticity, energy metabolism and thermogenesis. The aim of this study was to determine the role of pleiotrophin in hepatic lipid metabolism and in the metabolic crosstalk between the liver and brown and white adipose tissue (AT) in a high-fat diet-induced (HFD) obesity mice model. (2) Methods: We analyzed circulating variables, lipid metabolism (hepatic lipid content and mRNA expression), brown AT thermogenesis (UCP-1 expression) and periovarian AT browning (brown adipocyte markers mRNA and immunodetection) in Ptn-/- mice either fed with standard-chow diet or with HFD and in their corresponding Ptn+/+ counterparts. (3) Results: HFD-Ptn-/- mice are protected against the development of HFD-induced insulin resistance, had lower liver lipid content and lower expression of the key enzymes involved in triacylglycerides and fatty acid synthesis in liver. HFD-Ptn-/- mice showed higher UCP-1 expression in brown AT. Moreover, Ptn deletion increased the expression of specific markers of brown/beige adipocytes and was associated with the immunodetection of UCP-1 enriched multilocular adipocytes in periovarian AT. (4) Conclusions: Ptn deletion protects against the development of HFD-induced insulin resistance and liver steatosis, by increasing UCP-1 expression in brown AT and promoting periovarian AT browning.


Assuntos
Tecido Adiposo Marrom/metabolismo , Citocinas/deficiência , Dieta Hiperlipídica/efeitos adversos , Suscetibilidade a Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores , Proteínas de Transporte , Modelos Animais de Doenças , Metabolismo Energético , Fígado Gorduroso/patologia , Expressão Gênica , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Tamanho do Órgão , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
6.
Community Ment Health J ; 55(1): 100-111, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29508180

RESUMO

Dialectical behavior therapy (DBT) is an evidence-based treatment for borderline personality disorder. The DBT Intensive Training™ is widely used to train community clinicians to deliver DBT, but little is known about its effectiveness. This study prospectively evaluated predictors of adoption and reach of DBT among 52 community teams (212 clinicians) after DBT Intensive Training™. Pre-post training questionnaires were completed by trainees and a follow-up survey by team leaders approximately 8 months later. Overall, 75% of teams adopted all DBT modes and delivered DBT to an average of 118 clients. Lower training and program needs, fewer bachelor's-level clinicians, and greater prior DBT experience predicted adoption of more DBT modes. More prior DBT experience, smaller team size, more negative team functioning, and staff with lower job satisfaction, growth, efficacy, and influence predicted greater DBT reach. DBT Intensive Training™ appears effective in promoting DBT adoption and reach in routine clinical practice settings.


Assuntos
Atitude do Pessoal de Saúde , Transtorno da Personalidade Borderline/terapia , Terapia do Comportamento Dialético/estatística & dados numéricos , Pessoal de Saúde/psicologia , Transtorno da Personalidade Borderline/psicologia , Conselheiros , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Psicologia , Assistentes Sociais , Inquéritos e Questionários , Estados Unidos
7.
BMC Psychiatry ; 18(1): 364, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424750

RESUMO

INTRODUCTION: Orthorexia nervosa (ON) is characterized by an obsession with healthy eating, which may lead to severe physical, psychological and social disorders. It is particularly important to research this problem in populations that do not receive clinical care in order to improve early detection and treatment. OBJECTIVE: The aim of this study was to research the prevalence of ON in a population of Spanish university students and to analyze the possible associations between ON and psychological traits and behaviors that are common to ED. METHOD: A cross-sectional study with 454 students from the University of Castilla La Mancha, Spain. In total, 295 women and 159 men participated, aged between 18 and 41 years. The ORTO-11-ES questionnaire and the Eating Disorder Inventory (EDI-2) were used for this study. The chi squared test was used to compare the homogeneity among the different groups. RESULTS: The scores on the ORTO-11-ES suggested that 17% of students were at risk of ON. The scores on the EDI-2 for the group at risk of ON were significant, compared to the remaining individuals, regarding their drive for thinness (17.1% vs 2.1%), bulimia (2.6% vs 0%), body dissatisfaction (26.3% vs. 12.4%), perfectionism (14.5% vs 4.8%), interoceptive awareness (13.2% vs 1.3%), asceticism (15.8% vs 3.7%) and impulsiveness (9.2% vs 1.9%). DISCUSSION AND CONCLUSION: These findings suggest that many of the psychological and behavioral aspects of ED are shared by people who are at risk of ON. Future research should use longitudinal data, examining the temporal relationship among these variables or other underlying variables that may contribute to the concurrence of ED and ON.


Assuntos
Dieta Saudável/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Estudantes/psicologia , Universidades , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Autorrelato , Espanha/epidemiologia , Inquéritos e Questionários , Adulto Jovem
8.
Eat Weight Disord ; 23(6): 745-752, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30196527

RESUMO

PURPOSE: The ORTO-11-ES questionnaire is a tool to assess the pathological obsession displayed by some individuals regarding healthy eating. The aims of this study were (1) to confirm the factor structure of the Spanish version of ORTO-11-ES using confirmatory factor analysis (CFA) and (2) to examine the possible association between the ORTO-11-ES score, gender and body mass index (BMI). METHODS: The sample comprised 492 students from the University of Castilla la Mancha, Spain. Of these, 280 were women (56.9%). Participants were surveyed using the ORTO-11-ES questionnaire. RESULTS: The confirmatory factor analysis (CFA) supported the 11 elements and 3 domains of this tool as the better fitting model; for the Comparative Fit Index (CFI) and the Tucker-Lewis Index (TLI), the values were 0.94 and 0.91, respectively, and the Root Mean-Square Error of Approximation (RMSEA) was 0.058. The tendency towards orthorexic behavior is more associated with the female gender. The BMI had no influence on the tendency for ON. CONCLUSIONS: This study is the first attempt to confirm the three-factor structure of a Spanish version of the ORTO-15 questionnaire. These findings suggest that the ORTO-11-ES may be a valuable tool for identifying subjects with specific eating behavior patterns. This information may be useful for health professionals involved in the research, development and implementation of interventions catered to individuals suffering from this eating disorder. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional study.


Assuntos
Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Comportamento Obsessivo/diagnóstico , Adolescente , Índice de Massa Corporal , Estudos Transversais , Análise Fatorial , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Comportamento Obsessivo/psicologia , Espanha , Estudantes , Inquéritos e Questionários , Traduções , Adulto Jovem
9.
PLoS Genet ; 9(4): e1003445, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23637619

RESUMO

We report the identification and characterization of a previously unknown suppressor of myopathy caused by expansion of CUG repeats, the mutation that triggers Myotonic Dystrophy Type 1 (DM1). We screened a collection of genes encoding RNA-binding proteins as candidates to modify DM1 pathogenesis using a well established Drosophila model of the disease. The screen revealed smaug as a powerful modulator of CUG-induced toxicity. Increasing smaug levels prevents muscle wasting and restores muscle function, while reducing its function exacerbates CUG-induced phenotypes. Using human myoblasts, we show physical interactions between human Smaug (SMAUG1/SMAD4A) and CUGBP1. Increased levels of SMAUG1 correct the abnormally high nuclear accumulation of CUGBP1 in myoblasts from DM1 patients. In addition, augmenting SMAUG1 levels leads to a reduction of inactive CUGBP1-eIF2α translational complexes and to a correction of translation of MRG15, a downstream target of CUGBP1. Therefore, Smaug suppresses CUG-mediated muscle wasting at least in part via restoration of translational activity of CUGBP1.


Assuntos
Distrofia Miotônica , Proteínas de Ligação a RNA , Regulação da Expressão Gênica , Humanos , Mioblastos/metabolismo , Distrofia Miotônica/genética , Proteínas de Ligação a RNA/genética
10.
Compr Psychiatry ; 63: 123-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26555500

RESUMO

Different dysfunctional emotion regulation strategies are observed in patients with borderline personality disorder (BPD) and comorbid eating disorders (EDs) who report non-suicidal self-injury (NSSI). The objective of this study was to investigate the relationship of two well-defined emotion regulation strategies (i.e. expressive suppression and cognitive reappraisal) and dissociation with NSSI. The participants were sixty-eight women diagnosed with BPD and comorbid ED. A cross-sectional research design was used, and clinical interviews and self-report questionnaires were administered to collect data. Multiple regression was conducted to analyze the relationship of two emotion regulation strategies and dissociation with NSSI. According to the results, for low cognitive reappraisal scores, an increase in dissociation leads to an increase in NSSI; however, as cognitive reappraisal increases, higher dissociation is associated with fewer NSSI. When expressive suppression is low, an increase in cognitive reappraisal is associated with a decrease in NSSI; however, as suppression increases, a higher cognitive reappraisal has less effect on decreasing NSSI. These findings indicate that cognitive reappraisal reduces the harmful effects that dissociation has on NSSI, and that expressive suppression interferes with the beneficial effects of cognitive reappraisal on NSSI. Therefore, targeting expressive suppression before cognitive reappraisal is conducted may enhance treatment outcomes for patients with BPD and comorbid ED.


Assuntos
Transtorno da Personalidade Borderline/psicologia , Transtornos Dissociativos/psicologia , Emoções , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Comportamento Autodestrutivo/psicologia , Adulto , Transtorno da Personalidade Borderline/diagnóstico , Transtorno da Personalidade Borderline/epidemiologia , Comorbidade , Estudos Transversais , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Autorrelato , Comportamento Autodestrutivo/diagnóstico , Comportamento Autodestrutivo/epidemiologia , Ideação Suicida , Inquéritos e Questionários , Resultado do Tratamento
11.
PLoS Genet ; 8(11): e1003042, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23209424

RESUMO

A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity. Ontology analysis of suppressor data identified processes previously implicated in Huntington's disease, including proteolysis, glutamate excitotoxicity, and mitochondrial dysfunction. In addition to established mechanisms, the screen identified multiple components of the RRAS signaling pathway as loss-of-function suppressors of mutant huntingtin toxicity in human and mouse cell models. Loss-of-function in orthologous RRAS pathway members also suppressed motor dysfunction in a Drosophila model of Huntington's disease. Abnormal activation of RRAS and a down-stream effector, RAF1, was observed in cellular models and a mouse model of Huntington's disease. We also observe co-localization of RRAS and mutant huntingtin in cells and in mouse striatum, suggesting that activation of R-Ras may occur through protein interaction. These data indicate that mutant huntingtin exerts a pathogenic effect on this pathway that can be corrected at multiple intervention points including RRAS, FNTA/B, PIN1, and PLK1. Consistent with these results, chemical inhibition of farnesyltransferase can also suppress mutant huntingtin toxicity. These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease.


Assuntos
Doença de Huntington , Proteínas do Tecido Nervoso , Interferência de RNA , Proteínas ras , Animais , Corpo Estriado/ultraestrutura , Modelos Animais de Doenças , Drosophila melanogaster/genética , Farnesiltranstransferase/antagonistas & inibidores , Farnesiltranstransferase/metabolismo , Genoma Humano , Células HEK293 , Humanos , Proteína Huntingtina , Doença de Huntington/genética , Doença de Huntington/metabolismo , Redes e Vias Metabólicas , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/toxicidade , Proteínas do Tecido Nervoso/ultraestrutura , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triazóis/farmacologia , Proteínas ras/antagonistas & inibidores , Proteínas ras/genética , Proteínas ras/metabolismo
12.
FASEB J ; 27(10): 3928-37, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23825226

RESUMO

In developed societies, high-sugar and high-fat (HSHF) diets are now the norm and are increasing the rates of maternal obesity during pregnancy. In pregnant rodents, these diets lead to cardiovascular and metabolic dysfunction in their adult offspring, but the intrauterine mechanisms involved remain unknown. This study shows that, relative to standard chow, HSHF feeding throughout mouse pregnancy increases maternal adiposity (+30%, P<0.05) and reduces fetoplacental growth at d 16 (-10%, P<0.001). At d 19, however, HSHF diet group pup weight had normalized, despite the HSHF diet group placenta remaining small and morphologically compromised. This altered fetal growth trajectory was associated with enhanced placental glucose and amino acid transfer (+35%, P<0.001) and expression of their transporters (+40%, P<0.024). HSHF feeding also up-regulated placental expression of fatty acid transporter protein, metabolic signaling pathways (phosphoinositol 3-kinase and mitogen-activated protein kinase), and several growth regulatory imprinted genes (Igf2, Dlk1, Snrpn, Grb10, and H19) independently of changes in DNA methylation. Obesogenic diets during pregnancy, therefore, alter maternal nutrient partitioning, partly through changes in the placental phenotype, which helps to meet fetal nutrient demands for growth near term. However, by altering provision of specific nutrients, dietary-induced placental adaptations have important roles in programming development with health implications for the offspring in later life.


Assuntos
Gorduras na Dieta/farmacologia , Desenvolvimento Fetal/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Placenta/metabolismo , Gravidez
13.
Nat Rev Nephrol ; 20(4): 218-232, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38168662

RESUMO

Antibody-mediated rejection (AMR), including chronic AMR (cAMR), causes ~50% of kidney allograft losses each year. Despite attempts to develop well-tolerated and effective therapeutics for the management of AMR, to date, none has obtained FDA approval, thereby highlighting an urgent unmet medical need. Discoveries over the past decade from basic, translational and clinical studies of transplant recipients have provided a foundation for developing novel therapeutic approaches to preventing and treating AMR and cAMR. These interventions are aimed at reducing donor-specific antibody levels, decreasing graft injury and fibrosis, and preserving kidney function. Innovative approaches emerging from basic science findings include targeting interactions between alloreactive T cells and B cells, and depleting alloreactive memory B cells, as well as donor-specific antibody-producing plasmablasts and plasma cells. Therapies aimed at reducing the cytotoxic antibody effector functions mediated by natural killer cells and the complement system, and their associated pro-inflammatory cytokines, are also undergoing evaluation. The complexity of the pathogenesis of AMR and cAMR suggest that multiple approaches will probably be required to treat these disease processes effectively. Definitive answers await results from large, double-blind, multicentre, randomized controlled clinical trials.


Assuntos
Transplante de Rim , Humanos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Transplante Homólogo , Imunoglobulinas , Aloenxertos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
J Nutr ; 143(2): 221-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23256139

RESUMO

Vitamin A (VA) deficiency (VAD) continues to be a major nutritional problem in developing countries, including Central America. In Mexico, milk is a well-accepted vehicle for the administration of micronutrients, including VA, to preschoolers. Thus, we conducted a randomized, controlled, clinical trial to investigate the efficacy of daily consumption of 250 mL of VA-fortified milk (which provided 196 retinol equivalents/d) for 3 mo on VA stores in mildly to moderately VAD (serum retinol concentration 0.35-0.7 µmol/L) preschoolers who were not enrolled in a food assistance program. Twenty-seven mildly to moderately VAD children were randomly assigned based on screening measurements to either the intervention (n = 14) or control group (n = 13) (children in the control group did not receive placebo). All children in the control group and 79% (n = 11) of the children in the intervention group completed the study. The total body VA (TBVA) pool size was estimated using the deuterated retinol dilution technique before and after the intervention. After 3 mo, median changes in the serum retinol concentration for the intervention and control groups were 0.13 and -0.21 µmol/L, respectively (P = 0.009). Median changes in the TBVA stores were 0.06 and 0.01 mmol, respectively (P = 0.006) and estimated median changes in the liver VA concentration were 0.09 and 0.01 µmol/g, respectively (P = 0.002). The VA-fortified milk was well accepted among preschoolers and significantly increased TBVA stores, liver VA stores, and serum retinol concentration, indicating that it may be an effective means to ameliorate VAD in young Mexican children.


Assuntos
Alimentos Fortificados , Leite , Deficiência de Vitamina A/dietoterapia , Vitamina A/metabolismo , Vitamina A/uso terapêutico , Animais , Criança , Pré-Escolar , Deutério , Países em Desenvolvimento , Dieta/efeitos adversos , Feminino , Preferências Alimentares , Alimentos em Conserva , Humanos , Técnicas de Diluição do Indicador , Fígado/metabolismo , Masculino , México , Pacientes Desistentes do Tratamento , Índice de Gravidade de Doença , Vitamina A/administração & dosagem , Vitamina A/sangue , Deficiência de Vitamina A/sangue , Deficiência de Vitamina A/etiologia , Deficiência de Vitamina A/fisiopatologia
15.
Nutrients ; 15(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37764661

RESUMO

Mitochondrial fatty acid oxidation (FAO) is lower in placentas with pre-eclampsia. The aim of our study was to compare the placental mRNA expression of FAO enzymes in healthy pregnancies vs. different subgroups of pre-eclampsia according to the severity, time of onset, and the presence of intrauterine growth restriction (IUGR). By using real-time qPCR, we measured the mRNA levels of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), medium-chain acyl-CoA dehydrogenase (MCAD), and carnitine palmitoyltransferases 1A and 2 (CPT1A, CPT2) on the maternal side (anchoring villi in the basal decidua) and on the fetal side (chorionic plate) of the placenta (n = 56). When compared to the controls, LCHAD, MCAD, and CPT2 mRNA had decreased in all pre-eclampsia subgroups globally and on the fetal side. On the maternal side, LCHAD mRNA was also lower in all pre-eclampsia subgroups; however, MCAD and CPT2 mRNA were only reduced in severe and early-onset disease, as well as CPT2 in IUGR (p < 0.05). There were no differences in CPT1A mRNA expression. We conclude that the FAO enzymes mRNA in the placenta was lower in pre-eclampsia, with higher reductions observed in severe, early-onset, and IUGR cases and more striking reductions on the fetal side.


Assuntos
Retardo do Crescimento Fetal , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Retardo do Crescimento Fetal/genética , Pré-Eclâmpsia/genética , Placenta , Acil-CoA Desidrogenase , Expressão Gênica , Ácidos Graxos
16.
Neuron ; 111(6): 824-838.e7, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36610398

RESUMO

Tauopathies are neurodegenerative diseases that involve the pathological accumulation of tau proteins; in this family are Alzheimer disease, corticobasal degeneration, and chronic traumatic encephalopathy, among others. Hypothesizing that reducing this accumulation could mitigate pathogenesis, we performed a cross-species genetic screen targeting 6,600 potentially druggable genes in human cells and Drosophila. We found and validated 83 hits in cells and further validated 11 hits in the mouse brain. Three of these hits (USP7, RNF130, and RNF149) converge on the C terminus of Hsc70-interacting protein (CHIP) to regulate tau levels, highlighting the role of CHIP in maintaining tau proteostasis in the brain. Knockdown of each of these three genes in adult tauopathy mice reduced tau levels and rescued the disease phenotypes. This study thus identifies several points of intervention to reduce tau levels and demonstrates that reduction of tau levels via regulation of this pathway is a viable therapeutic strategy for Alzheimer disease and other tauopathies.


Assuntos
Tauopatias , Proteínas tau , Adulto , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Drosophila/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Tauopatias/tratamento farmacológico , Tauopatias/genética , Tauopatias/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo
17.
Mult Scler Relat Disord ; 78: 104909, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603928

RESUMO

BACKGROUND AND PURPOSE: disease-modifying treatments (DMT) for Multiple Sclerosis (MS) have expanded in recent years making the shared-decision process challenging. Moreover, no head-to-head studies are available within the first-line options. Our aim is to compare therapeutic persistence within first-line DMT: teriflunomide (TER), dimethyl fumarate (DMF), and injectable drugs (INJ) in a real-world setting. METHODS: Retrospective observational study analyzing diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) who started DMT between January 2015 and April 2022 (TER=117, DMF=117, INJ=123). Clinical, radiological, and demographic variables were collected. The primary outcome was the median time to discontinuation of any DMT. Dropout was defined as discontinuation for 6 months for any reason. RESULTS: Of the total of 357 patients, 155 withdraw with a median time-to-discontinuation of 1.427 years (IQR 2.410). The discontinuation rate was higher in the injectable group, 49.6%; compared to teriflunomide 40.2%, and dimethyl fumarate 39.8% (p = 0.201). The most frequent reason of discontinuation differs within groups (lack of efficacy in TER, 63.8%, and adverse effects in DMF and INJ (40.4% and 40.9% respectively). No difference in persistence was observed between DMT (p = 0.30). After 2018 there has been a tendency to treat in a quick and early manner (lower EDSS; relapse rate and number of naïve patients), statistically significant for TER (p = 0.005, p = 0.010, and p = 0.045). CONCLUSIONS: Our study demonstrated no differences in persistence between the actual first-line DMT in a real-world setting, although a trend to favor oral-DMT was seen. Reasons for discontinuation differs within groups.

18.
Healthcare (Basel) ; 11(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37830734

RESUMO

Presurgical anxiety is very common and is often treated with sedatives. Minimizing or avoiding sedation reduces the risk of sedation-related adverse events. Reducing sedation can increase early cognitive recovery and reduce time to discharge after surgery. The current case study is the first to explore the use of interactive eye-tracked VR as a nonpharmacologic anxiolytic customized for physically immobilized presurgery patients. Method: A 44-year-old female patient presenting for gallbladder surgery participated. Using a within-subject repeated measures design (treatment order randomized), the participant received no VR during one portion of her preoperative wait and interactive eye-tracked virtual reality during an equivalent portion of time in the presurgery room. After each condition (no VR vs. VR), the participant provided subjective 0-10 ratings and state-trait short form Y anxiety measures of the amount of anxiety and fear she experienced during that condition. Results: As predicted, compared to treatment as usual (no VR), the patient reported having 67% lower presurgical anxiety during VR. She also experienced "strong fear" (8 out of 10) during no VR vs. "no fear" (0 out of 10) during VR. She reported a strong sense of presence during VR and zero nausea. She liked VR, she had fun during VR, and she recommended VR to future patients during pre-op. Interactive VR distraction with eye tracking was an effective nonpharmacologic technique for reducing anticipatory fear and anxiety prior to surgery. The results add to existing evidence that supports the use of VR in perioperative settings. VR technology has recently become affordable and more user friendly, increasing the potential for widespread dissemination into medical practice. Although case studies are scientifically inconclusive by nature, they help identify new directions for future larger, carefully controlled studies. VR sedation is a promising non-drug fear and anxiety management technique meriting further investigation.

19.
Psicothema ; 34(1): 25-34, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35048892

RESUMO

BACKGROUND: The Unified Protocol (UP) for the transdiagnostic treatment of emotional disorders (EDs) has demonstrated its efficacy in improving dimensions shared by EDs, but there is insufficient evidence regarding the specific symptoms of each ED. The main objective of the study was to evaluate the efficacy of the UP applied in a group format compared with individual Treatment as Usual (TAU), in improving specific ED symptoms. METHODS: The study sample (n=243) was a subset of participants of a randomized controlled trial conducted in the Spanish public health system. Specific symptoms assessed from pre-treatment to the six-month follow-up were: depressive, agoraphobic, generalized anxiety, panic, and obsessive-compulsive symptoms. Personality dimensions and quality of life were also measured. RESULTS: There were statistically significant changes after the UP in all the study variables (0.44 = d = 1.35). Changes in depressive symptoms, obsessive-compulsive disorder, and perceived quality of life were superior in the UP. CONCLUSIONS: The results support the efficacy of group UP for improving both transdiagnostic dimensions and specific ED symptoms, as well as quality of life, through the public health-care system.


Assuntos
Terapia Cognitivo-Comportamental , Qualidade de Vida , Transtornos de Ansiedade , Humanos , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Nutrients ; 14(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35631313

RESUMO

Antiangiogenic factors are currently used for the prediction of preeclampsia. The present study aimed to evaluate the relationship between antiangiogenic factors and lipid and carbohydrate metabolism in maternal plasma and placenta. We analyzed 56 pregnant women, 30 healthy and 26 with preeclampsia (including early and late onset). We compared antiangiogenic factors soluble Fms-like Tyrosine Kinase-1 (sfLt-1), placental growth factor (PlGF), and soluble endoglin (sEng)), lipid and carbohydrate metabolism in maternal plasma, and lipid metabolism in the placenta from assays of fatty acid oxidation, fatty acid esterification, and triglyceride levels in all groups. Antiangiogenic factors sFlt-1, sFlt-1/PlGF ratio, and sEng showed a positive correlation with triglyceride, free fatty acid, and C-peptide maternal serum levels. However, there was no relationship between angiogenic factors and placental lipid metabolism parameters. Free fatty acids were predictive of elevated sFlt-1 and sEng, while C-peptide was predictive of an elevated sFlt1/PlGF ratio. The findings in this study generate a model to predict elevated antiangiogenic factor values and the relationship between them with different products of lipid and carbohydrate metabolism in maternal serum and placenta in preeclampsia.


Assuntos
Pré-Eclâmpsia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Indutores da Angiogênese/metabolismo , Peptídeo C/metabolismo , Endoglina/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Feminino , Humanos , Lipídeos , Placenta/metabolismo , Fator de Crescimento Placentário/metabolismo , Gravidez , Triglicerídeos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
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