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1.
J Hepatol ; 80(3): 419-430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37984709

RESUMO

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.


Assuntos
Gastroenterologistas , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Transversais , Comorbidade , Obesidade/metabolismo , Doenças Metabólicas/complicações
2.
Phys Rev Lett ; 132(11): 117102, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563945

RESUMO

Many systems, when initially placed far from equilibrium, exhibit surprising behavior in their attempt to equilibrate. Striking examples are the Mpemba effect and the cooling-heating asymmetry. These anomalous behaviors can be exploited to shorten the time needed to cool down (or heat up) a system. Though, a strategy to design these effects in mesoscopic systems is missing. We bring forward a description that allows us to formulate such strategies, and, along the way, makes natural these paradoxical behaviors. In particular, we study the evolution of macroscopic physical observables of systems freely relaxing under the influence of one or two instantaneous thermal quenches. The two crucial ingredients in our approach are timescale separation and a nonmonotonic temperature evolution of an important state function. We argue that both are generic features near a first-order transition. Our theory is exemplified with the one-dimensional Ising model in a magnetic field using analytic results and numerical experiments.

3.
J Stroke Cerebrovasc Dis ; 33(11): 107894, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39106921

RESUMO

OBJECTIVES: SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data. MATERIALS AND METHODS: Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system. RESULTS: Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA. CONCLUSIONS: Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.

4.
BMC Gastroenterol ; 20(1): 282, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838747

RESUMO

BACKGROUND: Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior. CASE PRESENTATION: A 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum. Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident. CONCLUSION: Inflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.


Assuntos
Neoplasias da Vesícula Biliar , Granuloma de Células Plasmáticas , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Granuloma de Células Plasmáticas/diagnóstico por imagem , Granuloma de Células Plasmáticas/cirurgia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
5.
Genet Med ; 19(2): 144-156, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27467453

RESUMO

PURPOSE: EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. METHODS: We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1-/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. RESULTS: Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. CONCLUSIONS: NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Epilepsia Mioclônica Juvenil/genética , Convulsões/genética , Animais , Dendritos/patologia , Exoma , Frequência do Gene , Humanos , Camundongos , Camundongos Knockout , Mutação , Epilepsia Mioclônica Juvenil/fisiopatologia , National Human Genome Research Institute (U.S.) , Neurônios/patologia , Linhagem , Polimorfismo de Nucleotídeo Único , Convulsões/fisiopatologia , Sinapses/patologia , Estados Unidos
6.
Cureus ; 16(6): e61601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38962621

RESUMO

Longitudinally extensive transverse myelitis (LETM) is traditionally classified as an inflammatory disorder of the spinal cord spanning three or more vertebral segments. The differential diagnosis for TM is vast and can include infectious, nutritional, and can even be idiopathic in some reported cases. However, autoimmune etiologies such as systemic lupus erythematosus (SLE) can rarely present with neurological manifestations such as LETM. In this case report, we present a 33-year-old female with a prior history of SLE who developed an LETM in the setting of possible provoking factors such as nutritional deficiencies and a recent viral illness. In this case report, we highlight her clinical course, recovery, and working differential diagnosis after laboratory testing and neurological imaging. Finally, we discuss the different treatments that ultimately lead to her successful recovery after her prolonged clinical course.

7.
PLoS One ; 19(5): e0300362, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709751

RESUMO

BACKGROUND: It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities. METHODS: HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohorts of patients with NAFLD in this cross-sectional study. For each cohort, participant data were recorded on histological grade of steatohepatitis, stage of fibrosis and biopsychosocial variables. Regression analysis was used to explore which of these variables predicted HRQoL. Moderated mediation models were conducted using SPSS PROCESS v3.5 macro. RESULTS: Participants with severe fibrosis reported more fatigue, systemic symptoms and worry, and lower HRQoL than those with none/mild fibrosis, regardless of place of origin. In addition, body mass index (BMI) and gender were found to be significant predictors of HRQoL in both Spanish and UK participants. Female gender was associated with worse emotional function, higher BMI and more fatigue, which predicted lower participants' HRQoL. UK participants showed more systemic symptoms and worry than Spanish participants, regardless of liver severity. The negative effects of gender on HRQoL through emotional function, BMI and fatigue were reported to a greater degree in UK than in Spanish participants. CONCLUSIONS: UK participants showed a greater impairment in HRQoL as compared to Spanish participants. Higher fibrosis stage predicted lower HRQoL, mainly in the Spanish cohort. Factors such as female gender or higher BMI contributed to the impact on HRQoL in both cohorts of patients and should be considered in future multinational intervention studies in NAFLD.


Assuntos
Comparação Transcultural , Hepatopatia Gordurosa não Alcoólica , Qualidade de Vida , Humanos , Hepatopatia Gordurosa não Alcoólica/psicologia , Masculino , Reino Unido/epidemiologia , Feminino , Espanha/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Índice de Massa Corporal , Fadiga/psicologia
8.
Sci Rep ; 14(1): 21650, 2024 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289410

RESUMO

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (ß: - 0.247; 95% CI - 0.419, - 0.077) and AF (ß: - 0.222; 95% CI - 0.383, - 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Cirrose Hepática , Qualidade de Vida , Humanos , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cirrose Hepática/psicologia , Cirrose Hepática/patologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Técnicas de Imagem por Elasticidade , Inquéritos e Questionários , Prevalência , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Comorbidade
9.
JHEP Rep ; 6(7): 101066, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39022387

RESUMO

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

10.
BMC Res Notes ; 16(1): 375, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115153

RESUMO

OBJECTIVE: The centrosome is universally recognized as the microtubule organizing center of animal cells, but emerging evidence suggests that it has other important functions including primary cilia formation, DNA damage checkpoints, and cell cycle progression. Despite this, the role of individual components of the centrosome remains unclear. Previous studies suggest that one component, centriolin, has an important function in cytokinesis and cell cycle progression, although its exact role in these processes is not known. To determine how centriolin influences the progression through the cell cycle, we sought to identify interacting partners that may be involved in regulating its function. RESULTS: This study provides evidence that the ubiquitin E3 ligase HectD1 binds to centriolin and that this association likely accounts for our observation that HectD1 co-localizes with centriolin at the centrosome during mitosis. In addition to its centrosomal localization, we also show that the expression of HectD1 fluctuates throughout the cell cycle, with the highest levels during mitosis, coinciding with a marked reduction in centriolin expression. We propose that the interaction between HectD1 and centriolin may be necessary for normal cell cycle progression and we speculate that this function may involve HectD1-mediated degradation of centriolin.


Assuntos
Ubiquitina-Proteína Ligases , Animais , Ciclo Celular , Ubiquitina-Proteína Ligases/genética
11.
Healthcare (Basel) ; 11(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37239676

RESUMO

We investigated the influence of post-traumatic growth (PTG) and mental health (MH) on multiple sclerosis (MS) caregivers' uses of coping strategies and identified biopsychosocial predictors of proactive or reactive coping. The Short Form Health Survey (SF-12), General Health Questionnaire (GHQ-28), Post-Traumatic Growth Inventory (PGI-21), Brief COPE Questionnaire (COPE-28), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to evaluate 209 caregivers. Higher PTG was related to greater use of emotional support, positive reframing, religion, active coping, instrumental support, planning, denial, self-distraction, self-blaming, and venting. Better MH was associated with greater use of acceptance, while behavioral disengagement and self-distraction were associated with poorer MH. The PTG dimensions relating to others and new possibilities, SF-12 dimensions of physical and emotional roles as well as partnership, not living with the patient, and significant others' social support were predictors of proactive coping. Reactive coping was positively predicted by the PTG dimension relating to others, depression, vitality, other than partner relation, and physical role, and negatively predicted by mental health level and emotional role. In summary, higher MH was associated with proactive coping strategies, whereas post-traumatic growth was related to the use of a wide range of proactive coping as well as reactive coping strategies.

12.
Aliment Pharmacol Ther ; 58(4): 395-403, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37328931

RESUMO

BACKGROUND: Non-alcoholic steatohepatitis (NASH) can adversely affect health-related quality of life (HRQoL). AIMS: This double-blind, placebo-controlled, phase 2 trial aimed to report the effects of the glucagon-like peptide-1 receptor agonist, semaglutide, on HRQoL in patients with NASH as a secondary endpoint. METHODS: Adults with biopsy-proven NASH and stage 1-3 fibrosis were randomised (3:3:3:1:1:1) to once-daily subcutaneous semaglutide 0.1, 0.2 or 0.4 mg, or placebo, for 72 weeks. Patients were invited to complete the Short Form-36 version 2.0 questionnaire at weeks 0, 28, 52 and 72. RESULTS: Between January 2017 and September 2018, 320 patients were enrolled. At 72 weeks, semaglutide was associated with significant improvements in physical component summary (PCS) score (estimated treatment difference [ETD] 4.26; 95% confidence interval [CI]: 1.96-6.55; p = 0.0003); bodily pain (ETD 5.07; 95% CI: 2.15-7.99; p = 0.0007); physical functioning (ETD 3.51; 95% CI: 1.16-5.86; p = 0.0034); role limitations due to physical health problems (ETD 2.80; 95% CI: 0.28-5.33; p = 0.0294); social functioning (ETD 3.16; 95% CI: 0.53-5.78; p = 0.0183) and vitality (ETD 4.47; 95% CI: 1.63-7.32; p = 0.0021). There was no significant difference in the mental component summary score (ETD 1.02; 95% CI: -1.59 to 3.62; p = 0.4441). After 72 weeks, improvements in PCS scores were significantly greater in patients (pooled semaglutide and placebo) with NASH resolution than without (p = 0.014). CONCLUSIONS: Treatment with semaglutide is associated with improvements in the physical components of HRQoL in patients with biopsy-proven NASH and fibrosis compared with placebo. CLINICALTRIALS: gov: NCT02970942.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Método Duplo-Cego
13.
J Psychosom Res ; 162: 111045, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36174369

RESUMO

OBJECTIVE: Our aim was to determine whether the association between active coping and depressive symptoms in patients with non-alcoholic fatty liver disease (NAFLD) was mediated by vitality, and whether diabetes and obesity could impact on this relationship. We also wanted to find out whether mental health and role-physical modulated the relationship between passive/avoidance coping and self-efficacy, and the role of liver fibrosis. METHODS: Depressive symptoms (BDI-II), self-efficacy (GSE), coping (COPE-28) and quality of life (SF-12) were evaluated in 509 biopsy-proven NAFLD patients in this cross-sectional study. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. RESULTS: Vitality mediated the relationship between active coping and depressive symptoms (-2.254, CI = -2.792 to -1.765), with diabetes (-0.043, p = 0.017) and body mass index (BMI) (-0.005, p = 0.009) moderating the association. In addition, mental health (-6.435, CI = -8.399 to -4.542) and role-physical (-1.137, CI = -2.141 to -0.315) mediated the relationship between passive/avoidance coping and self-efficacy, with fibrosis stage (0.367, p < 0.001) moderating this association. Specifically, the presence of diabetes and significant fibrosis, and a higher BMI, were associated with greater negative impact on participant depressive symptoms or self-efficacy. CONCLUSION: A maladaptive coping style was associated with poorer vitality, mental health and role-physical in NAFLD patients, which along with the presence of metabolic comorbidity (diabetes and obesity) and significant fibrosis predicted more depressive symptoms or poorer self-efficacy in these patients. These results suggested incorporating emotional and cognitive evaluation and treatment in patients with NAFLD.


Assuntos
Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Adaptação Psicológica , Estudos Transversais , Depressão/psicologia , Fibrose , Humanos , Saúde Mental , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , Qualidade de Vida , Autoeficácia
14.
Am J Hum Genet ; 82(6): 1249-61, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18514161

RESUMO

Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents.


Assuntos
Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/fisiopatologia , Mutação de Sentido Incorreto , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Criança , Pré-Escolar , Análise Mutacional de DNA , DNA Complementar/genética , Eletroencefalografia , Feminino , Ligação Genética , Genótipo , Glicosilação , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Receptores de GABA-A/química , Homologia de Sequência de Aminoácidos , Transfecção
15.
Phys Rev Lett ; 107(15): 150601, 2011 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-22107278

RESUMO

We argue that the four-state Potts antiferromagnet has a finite-temperature phase transition on any Eulerian plane triangulation in which one sublattice consists of vertices of degree 4. We furthermore predict the universality class of this transition. We then present transfer-matrix and Monte Carlo data confirming these predictions for the cases of the Union Jack and bisected hexagonal lattices.

16.
Phys Rev E ; 104(4-1): 044114, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781476

RESUMO

Cooling and heating faster a system is a crucial problem in science, technology, and industry. Indeed, choosing the best thermal protocol to reach a desired temperature or energy is not a trivial task. Noticeably, we find that the phase transitions may speed up thermalization in systems where there are no conserved quantities. In particular, we show that the slow growth of magnetic domains shortens the overall time that the system takes to reach a final desired state. To prove that statement, we use intensive numerical simulations of a prototypical many-body system, namely, the two-dimensional Ising model.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33800585

RESUMO

Our aim was to analyze how type 2 diabetes and obesity influence quality of life (QoL) and coping in patients with nonalcoholic fatty liver disease (NAFLD), and which coping strategies predict diabetic or obese participants' QoL. QoL (SF-12, CLDQ-NAFLD) and coping strategies (COPE-28) were evaluated in 307 biopsy-proven NAFLD patients with absence or presence of diabetes or obesity. QoL was compared with normality tables for the general Spanish population. Interactive effects were found in physical functioning (p = 0.008), role-physical (p = 0.016) and activity (p = 0.014). Diabetic patients reported worse scores when they were also obese and vice versa, that is, obese patients scored worse when they were also diabetic. Both diabetic and obese patients had lower QoL than those without metabolic pathology or the general population, and obese patients also reported more passive/avoidance coping. Active coping, positive reframing and acceptance predicted better QoL, while denial, self-blame, self-distraction, disengagement and religion predicted lower QoL. In conclusion, diabetes and obesity were associated with lower QoL in patients with NAFLD. Obesity was also associated with more passive/avoidance coping. Furthermore, passive/avoidance coping strategies predicted lower QoL than active, recommending modification of maladaptive coping strategies in future multidisciplinary NAFLD treatments.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adaptação Psicológica , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Obesidade/epidemiologia , Qualidade de Vida
18.
J Clin Med ; 10(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065216

RESUMO

Our aim was to analyze whether depressive symptoms mediated the association between physical quality of life (QoL) and adherence to physical activity in patients with non-alcoholic fatty liver disease (NAFLD), as well as the association between social support and adherence to diet. We also examined whether self-efficacy exerted a moderating role in these associations. QoL (SF-12), social support (MSPSS), depressive symptoms (HADS), self-efficacy (GSE), physical activity (IPAQ) and diet (MEDAS) were evaluated in 413 biopsy-proven NAFLD patients. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. Results showed that depressive symptoms mediated the relationship between physical QoL and adherence to physical activity (indirect effect = 6.248, CI = 1.917-10.727), as well as the relationship between social support and adherence to diet (indirect effect = 0.148, CI = 0.035-0.275). Self-efficacy also moderated the indirect effects of QoL and social support on therapeutic adherence through depressive symptoms. Specifically, the higher self-efficacy was, the lower the negative impact on the NAFLD patient's mental health. In conclusion, self-efficacy is defined as a protective factor for therapeutic adherence by NAFLD patients with a psychosocial risk profile. Self-efficacy should, therefore, be a main psychological target in future multidisciplinary NAFLD approaches.

19.
Phys Rev E ; 102(3-1): 032124, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33076030

RESUMO

In this paper we study the phase diagram of the five-state Potts antiferromagnet on the bisected-hexagonal lattice. This question is important since Delfino and Tartaglia recently showed that a second-order transition in a five-state Potts antiferromagnet is allowed, and the bisected-hexagonal lattice had emerged as a candidate for such a transition on numerical grounds. By using high-precision Monte Carlo simulations and two complementary analysis methods, we conclude that there is a finite-temperature first-order transition point. This one separates a paramagnetic high-temperature phase, and a low-temperature phase where five phases coexist. This phase transition is very weak in the sense that its latent heat (per edge) is two orders of magnitude smaller than that of other well-known weak first-order phase transitions.

20.
Front Med (Lausanne) ; 7: 585425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195340

RESUMO

Background: It is unknown how perceived social support and the progression of liver damage influence the psychosocial profile of patients with non-alcoholic fatty liver disease (NAFLD). In the present study, we therefore investigated which biomarkers influence the quality of life, mental health, and coping strategies of NAFLD patients. Methods: Quality of life (SF-12 and CLDQ-NAFLD), mental health (HADS and BDI-II), and coping strategies (COPE-28) were evaluated by high or low perceived social support (MSPSS) and the presence of non-alcoholic steatohepatitis (NASH) and significant fibrosis in 492 biopsy-proven NAFLD patients. The results were compared with quality of life normality tables for the general Spanish population. We also determined whether liver histology and biopsychosocial variables predicted participants' quality of life. Results: Interactive effects were found in vitality (p = 0.05), activity (p = 0.005), anxiety (p = 0.04), and denial (p = 0.04), with NASH patients showing a higher-risk biopsychosocial profile when they perceived less social support. Furthermore, patients with low perceived social support showed lower quality of life, worse mental health, and more maladaptive coping than those with high perceived social support, regardless of NASH presence. Patients with significant fibrosis showed lower quality of life compared to those without or the general Spanish population. Patients with significant fibrosis also reported worse mental health and more maladaptive coping. Lastly, significant fibrosis, female sex, greater anxiety and depressive symptoms, and worse physical and mental health-related quality of life were found to be independent determinants of worse disease-specific quality of life in these patients. Conclusions: Low perceived social support, significant fibrosis, and female sex were independently associated with a higher-risk psychosocial profile in NAFLD. These findings support the role of psychological biomarkers based on quality of life, mental health, and coping strategies in the management of these patients and suggest the potential benefits of a psychological intervention.

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