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1.
Mol Cell ; 81(16): 3323-3338.e14, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352207

RESUMO

The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m7G) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. Mechanistically, we find increased abundance of m7G-modified tRNAs, in particular Arg-TCT-4-1, and increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon. Accordingly, Arg-TCT expression is elevated in many tumor types and is associated with patient survival, and strikingly, overexpression of this individual tRNA induces oncogenic transformation. Thus, METTL1-mediated tRNA modification drives oncogenic transformation through a remodeling of the mRNA "translatome" to increase expression of growth-promoting proteins and represents a promising anti-cancer target.


Assuntos
Carcinogênese/genética , Metiltransferases/genética , Neoplasias/genética , tRNA Metiltransferases/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Metilação , Neoplasias/patologia , Oncogenes/genética , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
2.
Clin Genet ; 106(3): 347-353, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38774940

RESUMO

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.


Assuntos
Nanismo , Sequenciamento do Exoma , Mutação , Linhagem , Humanos , Feminino , Masculino , Nanismo/genética , Criança , Paquistão/epidemiologia , Predisposição Genética para Doença , Homozigoto , Fenótipo , Síndrome , Pré-Escolar , Adolescente , Estudos de Associação Genética
3.
J Gastroenterol Hepatol ; 39(8): 1500-1508, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38725188

RESUMO

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.


Assuntos
Gastroenterologia , Doenças Inflamatórias Intestinais , Humanos , Ásia/epidemiologia , Gastroenterologia/normas , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/terapia , Feminino , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Gravidez , Mesalamina/uso terapêutico , Mesalamina/administração & dosagem
4.
BMC Med Educ ; 24(1): 635, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845004

RESUMO

BACKGROUND: Curriculum integration is an important educational concept widely implemented by various educational institutions, particularly within the healthcare field. Its significance lies in enhancing the preparation of future healthcare professionals. The assessment of these integrated curricula is imperative to guarantee their effectiveness. Consequently, the aim of this systematic review is to delve into existing literature, with the goal of identifying instruments designed to assess the extent of curriculum integration in health professions' education. METHODS: A comprehensive search was conducted to identify peer-reviewed papers and grey literature describing the development, validation, or use of instruments measuring the degree of integration in a curriculum. Eight databases were searched: PubMed, Scopus, Google Scholar, CINAHL Ultimate, Web of Science, Cochrane, ProQuest Central and EMBASE. Grey literature was also included. Titles, abstracts, and full text screening was conducted. Data extraction was done using a data extraction tool developed by our research team. RESULTS: The search resulted in the identification of 2094 references. After the removal of duplicates and title and abstract screening, 16 articles were deemed suitable for inclusion in this systematic review. Twenty-two instruments were extracted from these articles. The identified instruments assessed either integration attributes, perceptions about the integrated curriculum characteristics, process and outcomes, or curriculum integration level. Two of the instruments were focused on assessing horizontal integration (Basic Science Curriculum Assessment Instrument and the integration characteristic tool). In addition, one instrument was developed to assess integration within a single session only, while other instruments assessed curriculum integration level. Two of the integration instruments (The Session Integration Tool and Integration Ladder Questionnaire) provided scales for calculating integration levels. Validation of the integration assessment instruments was infrequent, with only 9 of 22 instruments validated for their psychometric properties. CONCLUSION: Our findings reveal the existence of diverse instruments designed to assess the extent of curriculum integration within health professions' curricula. The majority of identified instruments were focused on participants' perceptions towards the attributes of the integrated curriculum, and a significant number of these tools lacked validation.


Assuntos
Currículo , Ocupações em Saúde , Humanos , Ocupações em Saúde/educação , Avaliação Educacional
5.
Gut ; 72(7): 1240-1254, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37019620

RESUMO

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.


Assuntos
Neoplasias Colorretais , Gastroenterologia , Humanos , Endoscopia Gastrointestinal , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Fezes , Biomarcadores Tumorais , Detecção Precoce de Câncer
6.
Neurogenetics ; 24(1): 55-60, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36190665

RESUMO

Cerebellar ataxias (CAs) comprise a rare group of neurological disorders characterized by extensive phenotypic and genetic heterogeneity. In the last several years, our understanding of the CA etiology has increased significantly and resulted in the discoveries of numerous ataxia-associated genes. Herein, we describe a single affected individual from a consanguineous family segregating a recessive neurodevelopmental disorder. The proband showed features such as global developmental delay, cerebellar atrophy, hypotonia, speech issues, dystonia, and profound hearing impairment. Whole-exome sequencing and Sanger sequencing revealed a biallelic nonsense variant (c.496A > T; p.Lys166*) in the exon 5 of the PRDX3 gene that segregated perfectly within the family. This is the third report that associates the PRDX3 gene variant with cerebellar ataxia. In addition, associated hearing impairment further delineates the PRDX3 associated gene phenotypes.


Assuntos
Ataxia Cerebelar , Doenças Cerebelares , Humanos , Ataxia , Ataxia Cerebelar/genética , Consanguinidade , Família , Linhagem , Peroxirredoxina III/genética
7.
Clin Gastroenterol Hepatol ; 21(9): 2211-2221, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35863682

RESUMO

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Doenças Inflamatórias Intestinais/epidemiologia , Hospitalização , Ásia/epidemiologia , Incidência
8.
Helicobacter ; 28(6): e13017, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37614081

RESUMO

BACKGROUND: Despite multiple therapy regimens, the decline in the Helicobacter pylori eradication rate poses a significant challenge to the medical community. Adding Lactobacillus reuteri probiotic as an adjunct treatment has shown some promising results. This study aims to investigate the efficacy of Lactobacillus reuteri DSM 17648 in H. pylori eradication and its effect in ameliorating gastrointestinal symptoms and adverse treatment effects. MATERIALS AND METHODS: This randomized, double-blinded, placebo-controlled trial involved treatment-naïve H. pylori-positive patients. Ninety patients received standard triple therapy for 2 weeks before receiving either a probiotic or placebo for 4 weeks. The posttreatment eradication rate was assessed via a 14 C urea breath test in Week 8. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire and an interview on treatment adverse effects were conducted during this study. RESULTS: The eradication rate was higher in the probiotic group than in the placebo group, with a 22.2% difference in the intention-to-treat analysis (91.1% vs. 68.9%; p = 0.007) and 24.3% difference in the per-protocol analysis (93.2% vs. 68.9%; p = 0.007). The probiotic group showed significant pre- to post-treatment reductions in indigestion, constipation, abdominal pain, and total GSRS scores. The probiotic group showed significantly greater reductions in GSRS scores than the placebo group: indigestion (4.34 ± 5.00 vs. 1.78 ± 5.64; p = 0.026), abdominal pain (2.64 ± 2.88 vs. 0.89 ± 3.11; p = 0.007), constipation (2.34 ± 3.91 vs. 0.64 ± 2.92; p = 0.023), and total score (12.41 ± 12.19 vs. 4.24 ± 13.72; p = 0.004). The probiotic group reported significantly fewer adverse headache (0% vs. 15.6%; p = 0.012) and abdominal pain (0% vs. 13.3%; p = 0.026) effects. CONCLUSIONS: There was a significant increase in H. pylori eradication rate and attenuation of symptoms and adverse treatment effects when L. reuteri was given as an adjunct treatment.


Assuntos
Dispepsia , Gastroenteropatias , Infecções por Helicobacter , Helicobacter pylori , Limosilactobacillus reuteri , Probióticos , Humanos , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos , Dispepsia/tratamento farmacológico , Quimioterapia Combinada , Dor Abdominal/induzido quimicamente , Dor Abdominal/tratamento farmacológico , Constipação Intestinal/tratamento farmacológico , Resultado do Tratamento
9.
BMC Med Res Methodol ; 23(1): 129, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231405

RESUMO

BACKGROUND: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. METHODS: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. RESULTS: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. CONCLUSIONS: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Colite Ulcerativa/diagnóstico , Dieta , Fatores de Risco , Progressão da Doença , Incidência
10.
J Gastroenterol Hepatol ; 38(8): 1259-1268, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36908030

RESUMO

BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Adulto , Humanos , Síndrome do Intestino Irritável/diagnóstico , Qualidade de Vida , Estudos Transversais , Etnicidade , Dieta/efeitos adversos , Fermentação
11.
BMC Public Health ; 23(1): 1386, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468880

RESUMO

BACKGROUND: Studies on the relationship between diet and colorectal cancer (CRC) risk using single food or nutrient approach are widely conducted as opposed to dietary pattern approach. Therefore, this study aimed to determine the major dietary patterns and their association with CRC risk among Malaysians. METHODS: Patients aged between 18 and 80 years old from two teaching hospitals in Peninsular Malaysia were recruited through purposive sampling. Socio-demographic information and anthropometry data were assessed before the colonoscopy procedure, and dietary intake was also recorded using a validated semi-quantitative food frequency questionnaire (FFQ). Cases were those patients having histopathologically proven CRC, while controls were those without. RESULTS: Four major dietary patterns were identified: the allergenic diet, plant-based diet, processed diet, and energy-dense diet pattern. After adjusting for potential covariates, the processed diet pattern was consistently associated with CRC (OR = 3.45; 95% CI = 1.25-9.52; P = 0.017) while the plant-based diet, energy-dense diet, and allergenic diet were not associated with CRC risk. CONCLUSIONS: The processed diet pattern attributed to a diet high in confectionaries and fast foods was associated with an increased risk of CRC in the Malaysian population. In order to give prevention measures through lifestyle change, more research could be done on the effect of food patterns on faecal microbiota associated with CRC.


Assuntos
Neoplasias Colorretais , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fatores de Risco , Neoplasias Colorretais/prevenção & controle , Dieta , Análise de Regressão
12.
Nutr Cancer ; 74(8): 2757-2768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34965818

RESUMO

Current evidence suggests that dietary and lifestyle factors may play an important role in colorectal cancer risk but there are only a few studies that investigated their relationship with colorectal adenomas (CRA), the precursors for colorectal cancer. A case-control study was conducted to determine the relationship between dietary and lifestyle factors associated with CRA risk among 125 subjects with CRA and 150 subjects without CRA at Hospital Canselor Tuanku Muhriz UKM (HCTM), Malaysia. We used dietary history questionnaire (DHQ) and International Physical Activity Questionnaire-Short Form (IPAQ) to estimate the diet and physical activity. The findings of this study showed that male gender [OR = 2.71 (95% CI= 1.01-7.27)], smoking [OR = 6.39 (95% CI= 1.04-39.30)], family history of cancer [OR = 6.39 (95% CI= 1.04-39.30)], high body fat percentage [OR = 1.25 (95% CI= 1.04-1.51)], high calorie and fat intake [OR = 1.03 (95% CI= 1.01-1.06)], [OR = 1.01 (95% CI= 0.95-1.09)] and red meat intake more than 100 g per day [OR = 1.02 (95% CI= 1.01-1.04)] increased CRA risk. High fiber [OR = 0.78 (95% CI= 0.64-0.95)] and calcium intake [OR = 0.78 (95% CI= 0.98-1.00)] was found to decrease CRA risk. Some of these modifiable risk factors could be advocated as lifestyle interventions to reduce risk of CRA.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/epidemiologia , Adenoma/etiologia , Estudos de Casos e Controles , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Humanos , Malásia/epidemiologia , Masculino , Fatores de Risco
13.
BMC Gastroenterol ; 22(1): 219, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508989

RESUMO

Gastroesophageal reflux disease (GERD) is one the most common medical complaints in pregnant women. Some women continue to experience GERD symptoms after delivery. Effective management of GERD symptoms is important to improve productivity and quality of life. Management of heartburn in pregnant and breastfeeding women involves lifestyle modifications, dietary modifications, non-pharmaceutical remedies and pharmaceutical drugs. For most patients, lifestyle/dietary modifications are helpful in reducing GERD symptoms. For patients who require a more intense intervention, various types of pharmaceutical drugs are available. However, the suitability of each treatment for use during pregnancy and lactation must be taken into consideration. This article explores the reported efficacy and safety of these treatment options in pregnant and breastfeeding women. Recommended treatment algorithm in pregnant and breastfeeding women have been developed.


Assuntos
Refluxo Gastroesofágico , Complicações na Gravidez , Aleitamento Materno , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Azia/terapia , Humanos , Preparações Farmacêuticas , Gravidez , Complicações na Gravidez/terapia , Qualidade de Vida
14.
J Gastroenterol Hepatol ; 37(5): 795-811, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35080048

RESUMO

The Malaysian Society of Gastroenterology and Hepatology saw the need for a consensus statement on metabolic dysfunction-associated fatty liver disease (MAFLD). The consensus panel consisted of experts in the field of gastroenterology/hepatology, endocrinology, bariatric surgery, family medicine, and public health. A modified Delphi process was used to prepare the consensus statements. The panel recognized the high and increasing prevalence of the disease and the consequent anticipated increase in liver-related complications and mortality. Cardiovascular disease is the leading cause of mortality in MAFLD patients; therefore, cardiovascular disease risk assessment and management is important. A simple and clear liver assessment and referral pathway was agreed upon, so that patients with more severe MAFLD can be linked to gastroenterology/hepatology care, while patients with less severe MAFLD can remain in primary care or endocrinology, where they are best managed. Lifestyle intervention is the cornerstone in the management of MAFLD. The panel provided a consensus on the use of statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1 agonist, pioglitazone, vitamin E, and metformin, as well as recommendations on bariatric surgery, screening for gastroesophageal varices and hepatocellular carcinoma, and liver transplantation in MAFLD patients. Increasing the awareness and knowledge of the various stakeholders on MAFLD and incorporating MAFLD into existing noncommunicable disease-related programs and activities are important steps to tackle the disease. These consensus statements will serve as a guide on MAFLD for clinicians and other stakeholders.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Gastroenterologia , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia
15.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232773

RESUMO

Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.


Assuntos
Colite Ulcerativa , Neoplasias Associadas a Colite , Neoplasias Colorretais , Citocinas , Fosfatidilinositol 3-Quinase , Colite Ulcerativa/genética , Neoplasias Associadas a Colite/genética , Neoplasias Colorretais/genética , Citocinas/genética , Humanos , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinase/genética , Regiões não Traduzidas
16.
Medicina (Kaunas) ; 58(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36013482

RESUMO

Background and Objectives: We aim to compare the diagnostic performance of Protein induced by vitamin K absence-II (PIVKA-II), a biomarker for hepatocellular carcinoma (HCC), and alpha-fetoprotein (AFP) in differentiating HCC and non-malignant high-risk (NMHR) groups and to determine their cut-off values. Materials and Methods: A total of 163 patients, including 40 with HCC and 123 with NMHR (100 with liver cirrhosis and 23 with non-cirrhotic high-risk patients) were prospectively enrolled. The levels of AFP and PIVKA-II were measured, and their cut-off values were determined. We calculated and compared the areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP, and their combination. Results: The levels of PIVKA-II and AFP were found to be significantly higher in the HCC compared to NMHR patients (p < 0.0001). For the differentiation of HCC from NMHR, the optimal cutoff values for PIVKA-II and AFP were 36.7 mAU/mL (90% sensitivity; 82.1% specificity) and 14.2 ng/mL (75% sensitivity; 93.5% specificity), respectively. The AUROC of PIVKA-II (0.905, p < 0.0001) was higher compared to AFP (0.869, p < 0.0001), but the combination of PIVKA−II and AFP gave the highest AUROC value (0.911, p < 0.0001). However, their differences were not statistically significant (AFP vs. PIVKA; p = 0.4775, AFP vs. Combination; p = 0.3808, PIVKA vs. Combination; p = 0.2268). Conclusions: PIVKA-II and AFP showed equal performance in detecting HCC in high-risk patients. AFP as a screening marker for HCC may be adequate, and replacing or adding the PIVKA-II test in current clinical practice may be of little value.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Protrombina , alfa-Fetoproteínas , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Precursores de Proteínas , Protrombina/metabolismo , alfa-Fetoproteínas/metabolismo
17.
Acta Med Indones ; 54(3): 456-458, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36156475

RESUMO

Obscure gastrointestinal bleeding is defined as recurrent or persistent gastrointestinal bleeding in the setting of normal upper and lower endoscopies. There are reported use of numerous pharmacological agents to halt the bleeding, including oestrogen. We report a case of middle age gentleman with multiple comorbidities, presented with life threatening gastrointestinal bleeding. He underwent bidirectional endoscopies and mesenteric angiogram, but failed to localise the bleeding. Red blood cell scintigraphy showed numerous bleeding points in small and large bowels. A 5-day oral high dose oestrogen was prescribed in view of difficulty to manage the bleeding, in which the hemostasis was ultimately achieved.


Assuntos
Angiodisplasia , Endoscopia Gastrointestinal , Estrogênios , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Clin Gastroenterol ; 55(10): 823-829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34617932

RESUMO

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.


Assuntos
Mudança Climática , Gastroenterologia , Humanos
19.
J Gastroenterol Hepatol ; 36(5): 1244-1252, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33002243

RESUMO

BACKGROUND AND AIM: Variations in the Chicago 3.0 normative metrics may exist with different postures and with different provocative swallow materials in a healthy Asian population. METHOD: Eligible healthy Malay volunteers were invited to undergo the high-resolution esophageal manometry (inSIGHT Ultima, Diversatek Healthcare, Milwaukee, WI, USA). In recumbent and standing positions, test swallows were performed using liquid, viscous, and solid materials. Metrics including integrated relaxation pressure 4 s (IRP-4 s, mmHg), distal contractile integral (DCI, mmHg s cm), distal latency (DL, s), and peristaltic break (PB, cm) were reported in median and 95th percentile. RESULTS: Fifty of 57 screened participants were recruited, and 586 saline, 265 viscous, and 261 solid swallows were analyzed. Per-patient wise, in the recumbent position, 95th percentile for IRP-4 s, DCI, DL, and PB were 16.5 mmHg, 2431 mmHg s cm, 8.5 s, and 7.2 cm, respectively. We observed that with each posture, the use of viscous swallows led to changes in DL, but the use of solid swallows led to more changes in the metrics including DCI and length of PB. Compared with a recumbent posture, anupright posture led to lower IRP-4 s and DCI values. Both per-patient analysis and per-swallow analyses yielded almost similar results when comparing the different postures and types of swallows. No major motility disorders were observed in this cohort of asymptomatic population. However, more motility disorders were reported in the upright position. CONCLUSIONS: Variations in metrics can be observed in different postures and with different provocative swallow materials in a healthy population. The normative Chicago 3.0 metrics are also determined for the Malay population.


Assuntos
Deglutição/fisiologia , Esôfago/fisiologia , Voluntários Saudáveis , Manometria/métodos , Postura/fisiologia , Adulto , Povo Asiático , Estudos de Coortes , Feminino , Humanos , Malásia , Masculino , Contração Muscular , Peristaltismo/fisiologia , Adulto Jovem
20.
BMC Med Educ ; 21(1): 562, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742275

RESUMO

BACKGROUND: The use of simulated patients (SPs) is considered a significant resource for teaching and assessing clinical and communication skills in health professional education. We conducted this study to explore pharmacy students' perspective towards the utilization of SPs in Qatar and to identify areas that require improvement. METHODS: An explanatory sequential mixed-methods design was used among students and recent graduates of the College of Pharmacy at Qatar University (QU-CPH). First, their perspectives toward the current utilization of SPs at QU-CPH was explored using a quantitative cross-sectional study design. Following this, we conducted six focus group discussions based on the analysis of the questionnaire results. The findings of the two phases were interpreted through integration of the quantitative and qualitative phases. RESULTS: The majority of the participants (> 90%) reported that interactions with SPs are important in building good communication and counseling skills during professional skills course activities. Similarly, most of the respondents (80%) indicated that interactions with SPs prepared them to apply the clinical skills gained during professional skills and patient assessment sessions in real-life. In addition, they reported that interactions with SPs during competency-based assessments were good experiences. The participants disagreed with the notion that interaction with SPs of opposite gender was uncomfortable for them. Themes identified from the focus groups include: interactions with trained SPs compared to faculty SPs, standardization and consistency of SPs' roles, communication and language barriers, simulations of real-life case scenarios, SPs' competence and preparedness, psychological impact associated with interaction with SPs, proposed strategies for improving the SP program. Identified areas for improvement include the need for strengthening the SP training and orientation program as well as the SP selection criteria. CONCLUSION: This study showed a positive impact of the utilization of SPs in this pharmacy curriculum as perceived by students and alumni. However, the SP program needs to be optimized in terms of the training and orientation of SPs.


Assuntos
Currículo , Farmácia , Estudantes de Farmácia , Comunicação , Estudos Transversais , Humanos , Aprendizagem , Ensino
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