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1.
Eur Respir Rev ; 33(172)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38599674

RESUMO

Respiratory health has become a prevailing priority amid the diverse global health challenges that the 21st century brings, due to its substantial impact on individuals and communities on a global scale. Due to rapid advances in medicine, emerging knowledge gaps appear along with new challenges and ethical considerations. While breakthroughs in medical science can bring about encouraging possibilities for better treatments and interventions, they also lead to unanswered questions and areas where further research is warranted. A PubMed search on the topic "global respiratory health priorities" between the years 2000 and 2023 was conducted, which returned 236 articles. Of these, 55 were relevant and selected for inclusion in this article. The selection process took into account literature reviews, opinions from expert groups and careful analysis of existing gaps and challenges within the field; our selection encompasses specific infectious and noninfectious respiratory conditions in both adults and children. The global respiratory health priorities identified were selected on the basis that they have been recognised as critical areas of investigation and potential advancement and they span across clinical, translational, epidemiological and population health domains. Implementing these priorities will require a commitment to fostering collaboration and knowledge-sharing among experts in different fields with the ultimate aim to improve respiratory health outcomes for individuals and communities alike.


Assuntos
Saúde Global , Prioridades em Saúde , Criança , Humanos , Adulto
2.
Eur J Hum Genet ; 32(1): 117-124, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37474786

RESUMO

Thinness and anorexia nervosa are both characterised by persistent low weight. Individuals with anorexia nervosa concurrently report distorted perceptions of their body and engage in weight-loss behaviours, whereas individuals with thinness often wish to gain weight. Both conditions are heritable and share genomics with BMI, but are not genetically correlated with each other. Based on their pattern of genetic associations with other traits, we explored differences between thinness and anorexia nervosa on a genomic level. In Part 1, using publicly available data, we compared genetic correlations of persistent thinness/anorexia nervosa with eleven psychiatric disorders. In Part 2, we identified individuals with adolescent persistent thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 6594) and evaluated associations with psychiatric and anthropometric polygenic scores. In Part 1, in contrast to the positive genetic correlations of anorexia nervosa with various psychiatric disorders, persistent thinness showed negative genetic correlations with attention deficit hyperactivity disorder (rgAN = 0.08 vs. rgPT = -0.30), alcohol dependence (rgAN = 0.07 vs. rgPT = -0.44), major depressive disorder (rgAN = 0.27 vs. rgPT = -0.18) and post-traumatic stress disorder (rgAN = 0.26 vs. rgPT = -0.20). In Part 2, individuals with adolescent persistent thinness in the ALSPAC had lower borderline personality disorder polygenic scores (OR = 0.77; Q = 0.01). Overall, results suggest that genetic variants associated with thinness are negatively associated with psychiatric disorders and therefore thinness may be differentiable from anorexia nervosa on a genomic level.


Assuntos
Anorexia Nervosa , Transtorno Depressivo Maior , Adolescente , Criança , Humanos , Anorexia Nervosa/genética , Anorexia Nervosa/psicologia , Magreza/genética , Estudos Longitudinais , Genômica
3.
Health Qual Life Outcomes ; 21(1): 10, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717868

RESUMO

BACKGROUND: Childhood cancer negatively impacts a child's physical, mental, and behavioural health and significantly affects their health-related quality of life. The Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL™ 4.0 GCS) is one of the most commonly used measures of the quality of life in children. However, the Amharic version of PedsQL™ 4.0 GCS has not been validated in a paediatric oncology population. This study aimed to translate and evaluate the psychometric properties of the Amharic PedsQL™ 4.0 GCS (PedsQL™ 4.0 GCS (A)) for Ethiopian children with cancer. METHODS: A descriptive cross-sectional study was conducted among children aged 8-18 years with any type of cancer across the cancer trajectory. Cronbach's alpha and intraclass correlation coefficient were computed to determine the internal consistency and test-retest reliability of the scale. The convergent validity was established by examining the correlation of the PedsQL™ 4.0 GCS (A) with the Amharic version of the Revised Child Anxiety and Depression Scale (RCADS-25(A)). Factorial validity was evaluated by conducting a confirmatory factor analysis. RESULTS: The study included 142 participants with childhood cancer. PedsQL™ 4.0 GCS (A) had good validity and reliability. It demonstrated high internal consistency with a Cronbach's alpha of 0.96 for the scale and 0.82-0.95 for the subscales. The intraclass correlation coefficient for the scale was 0.9 and that for the subscales was 0.76-0.90. The PedsQL™ 4.0 GCS (A) was highly correlated with RCADS-25 (A) (r = - 0.97, p < 0.001), supporting its convergent validity. The four-factor structure of the model fitted the data satisfactorily (χ2/df = 1.28; CFI = 0.97; TLI = 0.97; RMSEA = 0.05; SRMR = 0.05), supporting the factorial validity of the PedsQL™ 4.0 GCS (A). CONCLUSION: The PedsQL™ 4.0 GCS (A) demonstrates desirable psychometric properties for assessing quality of life among Ethiopian children with cancer. The scale can be used in clinical settings for assessing and evaluating quality of life in children with cancer. The use of parent-report versions and studies in those with different health conditions and healthy populations are necessary to further establish the psychometric properties of the PedsQL™ 4.0 GCS (A).


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Criança , Psicometria , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e Questionários
4.
Artigo em Inglês | MEDLINE | ID: mdl-36479979

RESUMO

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases  = 612; Ncontrols  = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.


Assuntos
Tiques , Síndrome de Tourette , Gravidez , Feminino , Humanos , Criança , Masculino , Adolescente , Tiques/epidemiologia , Tiques/etiologia , Estudos Longitudinais , Síndrome de Tourette/genética , Pais/psicologia , Fatores de Risco
5.
PLoS One ; 17(11): e0276021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36355860

RESUMO

INTRODUCTION: Although the pathophysiological mechanism of hypertension is not fully elucidated yet, a large number of pieces of evidence have shown that genetic alterations in the renin-angiotensin-aldosterone system play a central role. However, the association of insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene with essential hypertension is controversial yet, and there is a limited number of publications among the Ethiopian population. Therefore, this study aimed to determine the association of ACE gene I/D polymorphism with the risk of hypertension among essential hypertension patients at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. MATERIALS AND METHODS: A case-control study was conducted from October 07, 2020, to June 02, 2021, among hypertensive patients and normotensive control groups at the University of Gondar Comprehensive Specialized Hospital. A structured questionnaire was used to collect socio-demographic data and anthropometric measurements. Five milliliters of blood were drawn from each of the randomly selected 64 hypertensive and 64 normotensive participants for molecular test analysis. Genetic polymorphism of the ACE gene was identified using polymerase chain reaction (PCR) and electrophoresis. Data analysis was done using SPSS version 25.0 software. The strength of association between the genotype and hypertension was estimated through the calculation of adjusted odds ratio and 95% confidence intervals using logistic regression. P-value < 0.05 was considered statistically significant. RESULT: The distribution of DD genotypes and D allele of the ACE gene were 48.4% and 63% in essential hypertensive patients, respectively, while it were 29.7% and 42.2% in control subjects respectively. The ACE DD genotype (p-value = 0.005) and D allele (p-value = 0.001) were more frequent among hypertensive patients as compared to controls. CONCLUSION: The present study found that the DD genotype and D allele of the ACE gene has had a strong association with a high risk of hypertension in the study population.


Assuntos
Hipertensão , Peptidil Dipeptidase A , Humanos , Etiópia/epidemiologia , Peptidil Dipeptidase A/genética , Hipertensão Essencial/genética , Estudos de Casos e Controles , Mutagênese Insercional , Hipertensão/epidemiologia , Hipertensão/genética , Polimorfismo Genético , Genótipo , Angiotensinas
6.
Am J Hum Genet ; 109(7): 1242-1254, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35705101

RESUMO

Growth deviating from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life. AN PGSs and BMI PGSs were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Female participants with AN PGSs one standard deviation (SD) higher had, on average, 0.004% slower growth in BMI between the ages 6.5 and 24 years and a 0.4% slower gain in BMD between the ages 10 and 24 years. Higher BMI PGSs were associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN PGS and a low BMI PGS showed slower growth compared to those with both a low AN PGS and a low BMI PGS. We conclude that AN PGSs and BMI PGSs have detectable sex-specific effects on growth trajectories. Female participants with a high AN PGS and low BMI PGS likely constitute a high-risk group for AN, as their growth was slower compared to their peers with high PGSs on both traits. Further research is needed to better understand how the AN PGS and the BMI PGS co-influence growth during childhood and whether a high BMI PGS can mitigate the effects of a high AN PGS.


Assuntos
Anorexia Nervosa , Adolescente , Adulto , Anorexia Nervosa/genética , Índice de Massa Corporal , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Herança Multifatorial/genética , Obesidade , Adulto Jovem
7.
BMC Cardiovasc Disord ; 22(1): 230, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35590246

RESUMO

BACKGROUND: Cardiovascular diseases are the most causes of mortality and morbidity among diabetes mellitus (DM) patients. Electrocardiographic (ECG) changes are common in the early course of the disease. Little is known about the electrocardiographic abnormalities among type 2 DM patients in Ethiopia. This study determined the overall prevalence, its patterns, and the associated factors of ECG abnormalities among people living with T2DM in Amhara National Regional State referral hospitals, Ethiopia. METHODS: A multicenter institution-based cross-sectional study was conducted from 01 April to 30 May 2021. A simple random sampling and systematic sampling techniques were employed to select the referral hospitals and study participants, respectively. A digital electrocardiograph was used to measure the ECG parameters and the other data were collected using an interviewer-administered questionnaire. Epi-data version-4.6 and Stata-14 were used for data entry and statistical analysis, respectively. The descriptive statistics were presented with tables and graphs. A binary logistic regression model was fitted to identify associated factors of ECG abnormality. In the final model, statistical significance was decided at p≤0.05, and the strength of association was indicated using an adjusted odds ratio with 95% CI. RESULTS: Two-hundred and fifty-eight participants (response rate = 99.6%) were included for the analysis. The prevalence of overall ECG abnormality was 45% (95% CI: 39, 51%). On the basis of the electrocardiographic patterns, 57 (21.1%; 95% CI: 14.6, 32.6%) were presented with T-wave abnormality, 36 (14%; 95% CI: 10.1, 18.8%) left axis deviation, and 24 (9.3% [6.3, 13.5%]) sinus tachycardia. Higher monthly income (> 90$) (AOR = 0.51 [0.31, 0.83]), over 10 years duration of DM (AOR = 4.5[1.05, 18.94]), hypertension (AOR = 3.9 [1.6, 9.40]), fasting blood sugar of ≥ 130 mg/dl (AOR = 5.01[2.13, 12.20]), and overweight (AOR = 2.65[1.17, 5.98]) were statistically significant factors of overall ECG abnormality. CONCLUSIONS: Nearly, half of the participants had at least one ECG abnormality. Higher-income, prolonged disease duration, hypertension, higher fasting blood sugar, and overweight were significantly associated with ECG abnormality. The findings of this study suggest the need to institute routine ECG screening for all T2DM patients to reduce ECG abnormalities and further complications.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Etiópia/epidemiologia , Hospitais , Humanos , Hipertensão/complicações , Sobrepeso , Encaminhamento e Consulta
8.
Infect Drug Resist ; 15: 2055-2065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480059

RESUMO

Background: Adverse events (AE) contribute to poor drug adherence and withdrawal, which contribute to a low treatment success rate. AE are commonly reported among multi-drug resistance tuberculosis (MDR-TB) patients in Ethiopia. However, predictors of AE among MDR-TB patients were limited in Ethiopia. Thus, the current study aimed to develop and validate a score to predict the risks of major AE among MDR-TB patients in Southern Ethiopia. Methods: A retrospective follow-up study design was employed among MDR-TB patients from 2014-2019 in southern Ethiopia at selected hospitals. A least absolute shrinkage and selection operator algorithm was used to select the most potent predictors of the outcome. The adverse event risk score was built based on the multivariable logistic regression analysis. Discriminatory power and calibration were checked to evaluate the performance of the model. Bootstrapping method with 100 repetitions was used for internal model validation. Results: History of baseline khat use, long-term drug regimen use, and having coexisting disorders (co-morbidity) were predictors of AEs. The score has a satisfactory discriminatory power (AUC = 0.77, 95% CI: 0.68, 0.82) and a modest calibration (Prob > chi2 = 0.2043). It was found to have the same c-statistics after validation by bootstrapping method of 100 repetitions with replacement. Conclusion: A history of baseline khat use, co-morbidity, and long-term drug regimen use are helpful to predict individual risk of major adverse events in MDR-TB patients with a satisfactory degree of accuracy (AUC = 0.77).

9.
Int J Obes (Lond) ; 46(7): 1271-1279, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35306528

RESUMO

BACKGROUND: Parental-feeding behaviors are common intervention targets for childhood obesity, but often only deliver small changes. Childhood BMI is partly driven by genetic effects, and the extent to which parental-feeding interventions can mediate child genetic liability is not known. Here we aim to examine how potential interventions on parental-feeding behaviors can mitigate some of the association between child genetic liability and BMI in early adolescence, using causal inference methods. METHODS: Data from the Avon Longitudinal Study of Parents and Children were used to estimate an interventional disparity measure for a child polygenic score for BMI (PGS-BMI) on BMI at 12 years. The approach compares counterfactual outcomes for different hypothetical interventions on parental-feeding styles applied when children are 10-11 years (n = 4248). Results are presented as adjusted total association (Adj-Ta) between genetic liability (PGS-BMI) and BMI at 12 years, versus the interventional disparity measure-direct effect (IDM-DE), which represents the association that would remain, had we intervened on parental-feeding under different scenarios. RESULTS: For children in the top quintile of genetic liability, an intervention shifting parental feeding to the levels of children with lowest genetic risk, resulted in a difference of 0.81 kg/m2 in BMI at 12 years (Adj-Ta = 3.27, 95% CI: 3.04, 3.49; versus IDM-DE = 2.46, 95% CI: 2.24, 2.67). CONCLUSIONS: Findings suggest that parental-feeding interventions have the potential to buffer some of the genetic liability for childhood obesity. Further, we highlight a novel way to analyze potential interventions for health conditions only using secondary data analyses, by combining methodology from statistical genetics and social epidemiology.


Assuntos
Obesidade Infantil , Índice de Massa Corporal , Criança , Comportamento Alimentar , Humanos , Estudos Longitudinais , Pais , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Obesidade Infantil/prevenção & controle
10.
Eur Eat Disord Rev ; 30(3): 221-236, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35178801

RESUMO

BACKGROUND: Eating disorder (ED) symptoms are prevalent in the general population, but their shared genetic underpinnings with psychiatric, metabolic, and anthropometric traits are not known. Here, we examined if polygenic scores (PGSs) of traits associated with anorexia nervosa are also associated with adolescent ED symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: A total of 8654 participants with genotype data and at least one phenotypic measure were included from the ALSPAC study. We associated PGS from 25 traits (16 psychiatric, 4 metabolic, and 5 anthropometric) with eight ED symptoms, including behaviours such as fasting for weight loss and cognitions such as body dissatisfaction. RESULTS: Higher attention deficit hyperactivity disorder PGS and lower educational attainment PGS were associated with fasting for weight loss. Higher insomnia PGS was associated with increased body dissatisfaction. We found no evidence of an association between metabolic trait PGS and any ED symptom. Fat-free mass, fat mass, and body fat percentage PGSs, were positively associated with binge eating, excessive exercise, fasting for weight loss, body dissatisfaction, and weight and shape concern. CONCLUSIONS: ED symptoms are genetically associated with psychiatric and anthropometric, but not with metabolic traits. Our findings provide insights for future genetic research investigating on why some individuals with ED symptoms progress to develop threshold EDs while others do not.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Anorexia Nervosa/genética , Criança , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Humanos , Estudos Longitudinais , Herança Multifatorial
11.
J Neural Transm (Vienna) ; 128(11): 1757-1765, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34389898

RESUMO

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Tiques , Síndrome de Tourette , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/genética , Feminino , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Gravidez , Índice de Gravidade de Doença
12.
Sci Rep ; 11(1): 12478, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127697

RESUMO

Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.


Assuntos
Doenças Cardiovasculares/epidemiologia , Fenômenos Fisiológicos da Nutrição Infantil , Comportamento Alimentar , Hiperlipidemias/epidemiologia , Hiperfagia/complicações , Adolescente , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Criança , Comportamento Infantil , Pré-Escolar , Feminino , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperfagia/epidemiologia , Hiperfagia/metabolismo , Hiperfagia/psicologia , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Metabolômica , Estudos Prospectivos , Inquéritos e Questionários/estatística & dados numéricos
13.
Infect Drug Resist ; 14: 1343-1355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854347

RESUMO

BACKGROUND: According to the 2017 global report, Ethiopia is among the top 30 high tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB) burden countries. However, studies on MDR-TB treatment outcomes in Southern Ethiopia was very limited. Therefore, the study was aimed at determining the unfavorable treatment outcome and its predictors among patients with multidrug-resistant tuberculosis in Southern Ethiopia MDR-TB treatment centers. SUBJECTS AND METHODS: A retrospective follow-up study was conducted in Southern Ethiopia MDR-TB treatment initiating centers. Three hundred sixty-three patients were included in the study. Kaplan-Meier failure curve, median time, and Log rank test were used to present the descriptive findings. Then, a Cox regression analysis was used to identify predictors of unfavorable treatment outcome. The strength of the association was reported using an adjusted hazard ratio (AHR) and a 95% confidence interval (CI). Finally, the Cox Snell residual test was used to check the goodness of fit. RESULTS: For the entire cohort, the unfavorable treatment outcome was 23.68% (19.29, 28.09). Hospitalization for care (AHR = 2.07; 95% CI = 1.21, 3.63), male sex (AHR = 1.85; 95% CI = 1.002, 3.42), attending tertiary education (AHR = 0.31; 95% CI = 0.11, 0.91), and those with low hemoglobin (AHR = 2.89; 95% CI = 1.55, 5.38) were predictors for unfavorable treatment outcome. CONCLUSION: The unfavorable treatment outcome was higher compared with the national goal of END-TB by 2020. Hospitalizations for care, male sex, and low hemoglobin level increased the hazard of the unfavorable treatment outcome. On the other hand, attending territory education decreased the hazard of the unfavorable treatment outcome.

14.
Mol Psychiatry ; 26(11): 6937-6951, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33837273

RESUMO

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.


Assuntos
Síndrome de Tourette , Proteínas Relacionadas a Caderinas , Família , Predisposição Genética para Doença/genética , Humanos , Proteínas do Tecido Nervoso/genética , Linhagem , Serina Endopeptidases , Síndrome de Tourette/genética , Sequenciamento do Exoma
15.
Int J Eat Disord ; 54(5): 785-793, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33644868

RESUMO

OBJECTIVE: Genome-wide association studies have identified multiple genomic regions associated with anorexia nervosa. No genome-wide studies of other eating disorders, such as bulimia nervosa and binge-eating disorder, have been performed, despite their substantial heritability. Exploratively, we aimed to identify traits that are genetically associated with binge-type eating disorders. METHOD: We calculated genome-wide polygenic scores for 269 trait and disease outcomes using PRSice v2.2 and their association with anorexia nervosa, bulimia nervosa, and binge-eating disorder in up to 640 cases and 17,050 controls from the UK Biobank. Significant associations were tested for replication in the Avon Longitudinal Study of Parents and Children (up to 217 cases and 3,018 controls). RESULTS: Individuals with binge-type eating disorders had higher polygenic scores than controls for other psychiatric disorders, including depression, schizophrenia, and attention deficit hyperactivity disorder, and higher polygenic scores for body mass index. DISCUSSION: Our findings replicate some of the known comorbidities of eating disorders on a genomic level and motivate a deeper investigation of shared and unique genomic factors across the three primary eating disorders.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/genética , Transtorno da Compulsão Alimentar/diagnóstico , Transtorno da Compulsão Alimentar/genética , Bulimia Nervosa/diagnóstico , Bulimia Nervosa/genética , Criança , Estudo de Associação Genômica Ampla , Genômica , Humanos , Estudos Longitudinais
16.
SAGE Open Med ; 9: 2050312121989509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552516

RESUMO

INTRODUCTION: Recently, stroke is becoming the major public health problem in developing countries including Ethiopia. Atrial fibrillation patients are the most vulnerable group for the occurrence of stroke. Knowing the predictors and being aware for it is important for preventing severe complications and death. Therefore, the aim of this study is to assess the prevalence of stroke and identifying significant predictors. METHODS: A hospital-based cross-sectional study was performed from 1 December 2018 to 30 September 2019 at University of Gondar Referral Hospital. A total of 242 patients with atrial fibrillation were included in the study. Atrial fibrillation patients were diagnosed by using 12 lead electrocardiographic tracing, in addition to thorough medical history and physical examination and analyzed by the Modular ECG Analysis System (MEANS). We used Epi info 7 and SPSS version 22 software for data entry and analysis purpose, respectively. Both bivariable and multivariable binary logistic regression model were computed to show the relationship of dependent and independent variables. RESULT: The prevalence of stroke among atrial fibrillation patients was 19.4% (95% confidence interval (CI): 14.9-25.2). Patients with heart failure (adjusted odds ratio (AOR): 5.70, 95% CI: 2.50-13.24) and thyroid disorder (AOR: 4.98, 95% CI: 1.47-16.85) are at risk of developing stroke. CONCLUSION: The prevalence of stroke was higher compared with others studies. Patients with heart failure and thyroid disorders were the risk factor for the development of stroke; therefore, physicians and cardiologists may better to consider all these two disorders when they diagnose stroke in patients with atrial fibrillation.

18.
Nat Hum Behav ; 5(5): 625-630, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33432183

RESUMO

Eating behaviours may be expressions of genetic risk for obesity and are potential antecedents of later eating disorders. However, childhood eating behaviours are heterogeneous and transient. Here we show associations between polygenic scores for body mass index (BMI-PGS) and anorexia nervosa (AN-PGS) with eating behaviour trajectories during the first 10 years of life using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), n = 7,825. Results indicated that 1 s.d. increase in the BMI-PGS was associated with a 30-37% increased risk for early- and mid-childhood overeating. In contrast, 1 s.d. increase in BMI-PGS was associated with a 20% decrease in risk of persistent high levels of undereating and a 15% decrease in risk of persistent fussy eating. There was no evidence for a significant association between AN-PGS and eating behaviour trajectories. Our results support the notion that child eating behaviours share common genetic variants associated with BMI.


Assuntos
Anorexia Nervosa/genética , Índice de Massa Corporal , Peso Corporal/genética , Comportamento Alimentar/fisiologia , Predisposição Genética para Doença , Herança Multifatorial , Criança , Genômica , Humanos
19.
BMC Cardiovasc Disord ; 20(1): 375, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807083

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the commonest clinically significant ECG-evidenced sustained cardiac arrhythmia in clinical practice. Disability and mortality attributed to AF is high in low-income regions like sub-Saharan Africa. The risk of stroke/TIA in patients with AF can be significantly reduced with anti-thrombotic therapy. Despite the existing evidence of its benefit, significant percentages of AF patients eligible for anti-thrombotic therapy are undertreated in the region. METHODS: A hospital-based cross-sectional study was conducted to determine the appropriate use of anti-thrombotic therapy in patients with AF between December 1, 2018 and September 30, 2019 at Cardiac Clinic, University of Gondar hospital, Northwest Ethiopia. Consecutive sampling method was used to recruit 210 study subjects. Patients were interviewed to obtain socio-demographic data. Relevant medical history and laboratory parameters were obtained from patients' records. Diagnosis of atrial fibrillation was based on detection of irregular arterial pulse and presence of 'f' waves on 12-lead ECG tracing. Clinical evaluation, echocardiography, chest X-ray and blood chemistry were used to diagnose underlying causes of AF. Data was entered into EPI Info version 4.4.1 and analyzed using SPSS version 20. Bi-variate and multi-variate logistic regression analyses were used to identify associated factors with appropriate use of anti-thrombotic therapy in patients with atrial fibrillation. P-values < 0.05 were used to declare significant association. RESULTS: A total of 210 patients were included in the study. The mean age of patients was 51.29 ± 17.2 years. Two-thirds (145/210) of participants were females. Seventy-four (35%) had valvular AF, while 136/210 (65%) had non-valvular AF. Sixty-six percent (139/210) of study subjects were appropriately treated with anti-thrombotic therapy. Appropriately treated subjects in valvular AF group and non-valvular AF group were 58/74 (78%) and 81/136 (60%) respectively. On multi-variate analysis, 'can afford for regular INR monitoring' (AOR = 2.60 95% CI: 1.10-6.10, P = 0.001) was significantly associated with appropriate use of anti-thrombotic therapy. CONCLUSION: Sixty-six percent of AF patients eligible for anti-thrombotic therapy were appropriately treated. Intervention program to access 'regular INR monitoring' should be practiced to escalate utilization rate of anti-thrombotic therapy (warfarin) in eligible AF patients.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Fidelidade a Diretrizes/tendências , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/tendências , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Etiópia/epidemiologia , Feminino , Pesquisas sobre Atenção à Saúde , Disparidades em Assistência à Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
20.
Int J Obes (Lond) ; 44(8): 1766-1775, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32461555

RESUMO

BACKGROUND: Child eating behaviors are highly heterogeneous and their longitudinal impact on childhood weight is unclear. The objective of this study was to characterize eating behaviors during the first 10 years of life and evaluate associations with BMI at age 11 years. METHOD: Data were parental reports of eating behaviors from 15 months to age 10 years (n = 12,048) and standardized body mass index (zBMI) at age 11 years (n = 4884) from the Avon Longitudinal Study of Parents and Children. Latent class growth analysis was used to derive latent classes of over-, under-, and fussy-eating. Linear regression models for zBMI at 11 years on each set of classes were fitted to assess associations with eating behavior trajectories. RESULTS: We identified four classes of overeating; "low stable" (70%), "low transient" (15%), "late increasing" (11%), and "early increasing" (6%). The "early increasing" class was associated with higher zBMI (boys: ß = 0.83, 95% CI: 0.65, 1.02; girls: ß = 1.1; 0.92, 1.28) compared with "low stable." Six classes were found for undereating; "low stable" (25%), "low transient" (37%), "low decreasing" (21%), "high transient" (11%), "high decreasing" (4%), and "high stable" (2%). The latter was associated with lower zBMI (boys: ß = -0.79; -1.15, -0.42; girls: ß = -0.76; -1.06, -0.45). Six classes were found for fussy eating; "low stable" (23%), "low transient" (15%), "low increasing" (28%), "high decreasing" (14%), "low increasing" (13%), and "high stable" (8%). The "high stable" class was associated with lower zBMI (boys: ß = -0.49; -0.68-0.30; girls: ß = -0.35; -0.52, -0.18). CONCLUSIONS: Early increasing overeating during childhood is associated with higher zBMI at age 11. High persistent levels of undereating and fussy eating are associated with lower zBMI. Longitudinal trajectories of eating behaviors may help identify children potentially at risk of adverse weight outcomes.


Assuntos
Índice de Massa Corporal , Comportamento Alimentar , Criança , Pré-Escolar , Feminino , Humanos , Hiperfagia , Lactente , Estudos Longitudinais , Masculino , Obesidade Infantil , Fatores de Risco
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