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1.
Pak J Med Sci ; 40(6): 1083-1086, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952492

RESUMO

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic ß-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.

2.
Front Oncol ; 14: 1358804, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715785

RESUMO

Scirrhous hepatocellular carcinoma (S-HCC) represents an uncommon subtype of HCC. During radiological evaluation this unique subtype is frequently mistaken as cholangiocarcinoma, fibrolamellar HCC, or metastatic adenocarcinoma. Here, we present the case of a 50-year-old woman with a large hepatic mass. A triple-phase computed tomography of the liver revealed an arterial enhancing lesion without portovenous washout at hepatic segment 4a/8. The liver biopsy showed hepatocellular characteristics and was positive for Hep Par 1, CK7, CK19, Arginase 1 and CEA, indicating atypical S-HCC. This patient had achieved tumor control with combined treatment with atezolizumab plus bevacizumab and was then treated with lenvatinib after tumor progression. The patient died 15 months after the initial diagnosis.

3.
J Neuromuscul Dis ; 11(2): 389-410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250781

RESUMO

Background: Dysphagia is common in adults living with neuromuscular disease (NMD). Increased life expectancy, secondary to improvements in standards of care, requires the recognition and treatment of dysphagia with an increased priority. Evidence to support the establishment of healthcare pathways is, however, lacking. The experiences of people living with NMD (pplwNMD) and their caregivers are valuable to guide targeted, value-based healthcare. Objective: To generate preliminary considerations for neuromuscular dysphagia care and future research in the United Kingdom, based on the experiences of those living with, or caring for, people with NMD. Methods: Two surveys (one for adults living with NMD and dysphagia, and a second for caregivers) were co-designed with an advisory group of people living with NMD. Surveys were electronically distributed to adults living with NMD and their caregivers between 18th May and 26th July 2020. Distribution was through UK disease registries, charity websites, newsletters, and social media. Results: Adults living with NMD receive little information or education that they are likely to develop swallowing difficulties. Most respondents report wanting this information prior to developing these difficulties. Difficulties with swallowing food and medication are common in this group, and instrumental assessment is considered a helpful assessment tool. Both adults living with NMD and caregivers want earlier access to neuromuscular swallowing specialists and training in how best to manage their difficulties. Conclusions: Improvement is needed in the dysphagia healthcare pathway for adults living with NMD to help mitigate any profound physical and psychological consequences that may be caused by dysphagia. Education about swallowing difficulties and early referral to a neuromuscular swallowing specialist are important to pplwNMD and their caregivers. Further research is required to better understand the experiences of pplwNMD and their caregivers to inform the development of dysphagia healthcare pathways.


Assuntos
Transtornos de Deglutição , Doenças Neuromusculares , Adulto , Humanos , Transtornos de Deglutição/etiologia , Cuidadores , Doenças Neuromusculares/complicações , Reino Unido , Inquéritos e Questionários
4.
Mol Cell Proteomics ; 23(1): 100683, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37993104

RESUMO

Dysregulated mRNA splicing is involved in the pathogenesis of many diseases including cancer, neurodegenerative diseases, and muscular dystrophies such as myotonic dystrophy type 1 (DM1). Comprehensive assessment of dysregulated splicing on the transcriptome and proteome level has been methodologically challenging, and thus investigations have often been targeting only few genes. Here, we performed a large-scale coordinated transcriptomic and proteomic analysis to characterize a DM1 mouse model (HSALR) in comparison to wild type. Our integrative proteogenomics approach comprised gene- and splicing-level assessments for mRNAs and proteins. It recapitulated many known instances of aberrant mRNA splicing in DM1 and identified new ones. It enabled the design and targeting of splicing-specific peptides and confirmed the translation of known instances of aberrantly spliced disease-related genes (e.g., Atp2a1, Bin1, Ryr1), complemented by novel findings (Flnc and Ywhae). Comparative analysis of large-scale mRNA and protein expression data showed quantitative agreement of differentially expressed genes and splicing patterns between disease and wild type. We hence propose this work as a suitable blueprint for a robust and scalable integrative proteogenomic strategy geared toward advancing our understanding of splicing-based disorders. With such a strategy, splicing-based biomarker candidates emerge as an attractive and accessible option, as they can be efficiently asserted on the mRNA and protein level in coordinated fashion.


Assuntos
Distrofia Miotônica , Proteogenômica , Camundongos , Animais , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Distrofia Miotônica/patologia , Processamento Alternativo/genética , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Diabetes Metab Syndr Obes ; 16: 3885-3898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38054036

RESUMO

Objective: To explore lived experience of people with type 1 diabetes in North East Ethiopia; psycho-social and economical perspective. Methods: A descriptive phenomenological study was conducted to explore the lived experience of people with type 1 diabetes in North East Ethiopia; psycho-social and economical perspective from March 02 to March 25, 2020. A heterogeneous purposive sample method was used to choose the participants. The lead investigator used an in-depth interview to collect data, using an audio recorder and an interview guide. The data were analysed using the thematic analysis method. Atlas. ti software version 7 was used to facilitate the data analysis process. Results: A total of 13 participants were enrolled in this study. The participants age range were 14 to 70 years and their duration of diabetes since diagnosis were from 8 months to 16 years. The three interconnected themes that emerged from the analysis are: (1) psychological experience with two sub-themes (psychological problems due to diabetes including fear and coping strategies for psychological problems), (2) social experience, which has five categories (influence on intimate relationships, influence on social participation, disclosure status, social isolation and stigma, social support, and influence on education); and (3) economic experience. Conclusion: Fear was one of the psychological experiences felt by people with type 1 diabetes. Although type 1 diabetes is a biomedical problem, it is also accompanied by other psychological and socio-economic issues, that require a holistic approach to address it. So, health professionals should strengthen health information dissemination programs.

6.
Int J Mol Sci ; 24(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37373276

RESUMO

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disease caused by a CTG repeat expansion in the 3'-untranslated region (UTR) of DMPK gene. DM1 alleles containing non-CTG variant repeats (VRs) have been described, with uncertain molecular and clinical consequences. The expanded trinucleotide array is flanked by two CpG islands, and the presence of VRs could confer an additional level of epigenetic variability. This study aims to investigate the association between VR-containing DMPK alleles, parental inheritance and methylation pattern of the DM1 locus. The DM1 mutation has been characterized in 20 patients using a combination of SR-PCR, TP-PCR, modified TP-PCR and LR-PCR. Non-CTG motifs have been confirmed by Sanger sequencing. The methylation pattern of the DM1 locus was determined by bisulfite pyrosequencing. We characterized 7 patients with VRs within the CTG tract at 5' end and 13 patients carrying non-CTG sequences at 3' end of the DM1 expansion. DMPK alleles with VRs at 5' end or 3' end were invariably unmethylated upstream of the CTG expansion. Interestingly, DM1 patients with VRs at the 3' end showed higher methylation levels in the downstream island of the CTG repeat tract, preferentially when the disease allele was maternally inherited. Our results suggest a potential correlation between VRs, parental origin of the mutation and methylation pattern of the DMPK expanded alleles. A differential CpG methylation status could play a role in the phenotypic variability of DM1 patients, representing a potentially useful diagnostic tool.


Assuntos
Distrofia Miotônica , Humanos , Distrofia Miotônica/genética , Alelos , Miotonina Proteína Quinase/genética , Expansão das Repetições de Trinucleotídeos , Ilhas de CpG
7.
Healthcare (Basel) ; 11(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37046919

RESUMO

This study investigated factors affecting depression (CES-D) among parents of patients with type-1 diabetes mellitus (T1DM), a chronic disease that requires constant management. A complex set of factors influence depression in parents and thus requires further research. This is a cross-sectional descriptive study. A survey on related variables was conducted on 217 parents of patients with T1DM. The collected data were analyzed using the PASW Statistics program, and factors influencing participants' depression were identified through stepwise multiple regression. The results show that three variables exerted a significant effect on depression (source of information, resilience-personal competence, and Pittsburgh sleep quality index score), and all the variables explained a majority of the variance in depression. The results indicate that the parents of patients with T1DM were less depressed when the source of information was personal, when their resilience-personal competence was high, and when their Pittsburgh sleep quality index (PSQI) score was low. Interventions targeting parents of patients with T1DM should be performed with positive information on how to overcome diabetes in their children, increase resilience-personal competence, and increase sleep quality.

8.
Tohoku J Exp Med ; 259(4): 327-333, 2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-36823183

RESUMO

Gestational diabetes mellitus (GDM) is a state of pre-diabetic impaired glucose tolerance initially occurring during pregnancy. Although abnormalities in glucose metabolism normally resolve rapidly after delivery, women with GDM have a higher lifetime risk of developing diabetes mellitus than those without GDM; thus, postpartum healthcare is essential. Of all GDM patients, 5%-10% test positive for diabetes-related autoantibodies, which increase the risk of developing type 1 diabetes mellitus (T1DM). Autoantibody measurement in GDM screening remains debatable; however, it may be useful for the postnatal follow-up of GDM patients at high risk of developing T1DM. We treated a 29-year-old woman who was GDM positive for anti-glutamic acid decarboxylase antibody (GADA) requiring high-dose insulin therapy during pregnancy. As the patient tested positive for GADA, she received judicious postpartum management, allowing for early diagnosis of T1DM and resumption of treatment. Her insulin secretory capacity was preserved at 1 year after parturition, suggesting either slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults. This was a rare case of slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults in the early postpartum period, but the fact that GADA was positive during pregnancy enabled early treatment without overlooking it. Measuring diabetes-related autoantibodies in patients considered to be at a high risk for T1DM, such as those who are of slim build, young, or suffering from autoimmune thyroid disorders, may be important for appropriate individualized follow-up.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Gestacional , Intolerância à Glucose , Insulinas , Diabetes Autoimune Latente em Adultos , Humanos , Adulto , Gravidez , Feminino , Diabetes Mellitus Tipo 1/complicações , Glutamato Descarboxilase/uso terapêutico , Período Pós-Parto , Autoanticorpos , Insulinas/uso terapêutico
9.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36499107

RESUMO

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and molecular analyses of GI dysfunction in both genetic forms of DM, DM type 1 (DM1) and DM type 2 (DM2). Based on current knowledge of DM primary pathological mechanisms in other affected tissues and GI tissue studies, we suggest that misregulation of alternative splicing in smooth muscle resulting from the dysregulation of RNA binding proteins muscleblind-like and CUGBP-elav-like is likely to contribute to GI dysfunction in DM. We propose that a combinatorial approach using clinical and molecular analysis of DM GI tissues and model organisms that recapitulate DM GI manifestations will provide important insight into defects impacting DM GI motility.


Assuntos
Distrofia Miotônica , Humanos , Distrofia Miotônica/complicações , Distrofia Miotônica/genética , Processamento Alternativo , Músculo Esquelético/metabolismo , Proteínas de Ligação a RNA/metabolismo
10.
J Family Med Prim Care ; 11(9): 5676-5678, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36505621

RESUMO

Correct insulin administration technique, insulin type, and dose play a pivotal role in attaining glycemic control. An error in any of the steps may lead to poor glycaemic control, which affects the patient in the short and long term. We are presenting here unusual skin findings in children with the wrong injection technique. A 10-year-old male child already diagnosed with type 1 Diabetes Mellitus (DM), presented with poor glycemic control. On examination, we found skin rashes encircling most of his abdominal area circularly. Rashes were round to oval, well-circumscribed, hyperpigmented to hypopigmented to depigmented macules to papules surrounded by a hyperpigmented halo, 0.5 to 1 cm in diameter, painless varying in color from white to pinkish-red to light brown to brownish-black. On observing the administration technique of insulin, we found it was administered incorrectly as intradermal instead of subcutaneous. Proper Diabetes education and insulin administration techniques remain the cornerstone in the management of type 1 DM. We should ensure appropriate insulin administration on every visit.

11.
North Clin Istanb ; 9(5): 429-435, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36447574

RESUMO

OBJECTIVE: During the COVID-19 pandemic, health-care services for diseases other than COVID-19 were interrupted, and patient referrals to health institutions were postponed due to their fear of being infected with COVID-19. Under this situation, we conducted this study to evaluate the clinical and laboratory findings of COVID-19 in patients with Type 1 Diabetes Mellitus (T1DM) hospitalized in our pediatric intensive care unit (PICU) with the diagnosis of diabetic ketoacidosis (DKA) during the pandemic period, and the impact of the pandemic on these findings. METHODS: We retrospectively evaluated 55 children aged from 1 month to 18 years old, diagnosed with DKA, and followed up at Istanbul Sehit Prof. Dr. Ilhan Varank Sancaktepe Training and Research Hospital PICU between April 2020 and December 2021. RESULTS: A total of 55 patients with DKA as a complication of T1DM were admitted to the PICU during the COVID-19 pandemic. While there was no significant difference in pH and HCO3 values between those with newly diagnosed T1DM and those with previously-diagnosed T1DM, the HbA1c ratio of newly diagnosed DMs was significantly higher. Of the 55 patients, 4 were COVID-19 PCR positive, and two patients had COVID-19 antibody positivity. When COVID-19 positive patients were compared with negative patients, no significant difference was found between the hospital stay, glucose, HbA1c, lactate, pH, and HCO3 values. CONCLUSION: Higher HbA1c levels of newly diagnosed patients presenting with DKA may be associated with delayed admission to the health institutions due to COVID-19 and the length of insulin-free periods compared to pre-diagnosed patients with T1DM. In conclusion, our results, emphasize the importance of physician's and family's awareness of the symptoms of diabetes in terms of early diagnosis and prevention of DKA during public health measures due to COVID-19.

12.
J Diabetes Metab Disord ; 21(1): 689-695, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35673502

RESUMO

Aim: Vitamin D deficiency is known to be associated with metabolic bone diseases. The aim of this study is to evaluate vitamin D and calculated free and bioactive vitamin D levels of type 1 diabetic patients and to evaluate the association with bone turnover markers. Method: This cross-sectional study includes 60 patients admitted to endocrinology outpatient clinic with diagnosis of type 1 diabetes mellitus and 60 controls. Weight, height and waist circumference were recorded and blood samples were taken for measurement of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP), osteocalcin, bone alkaline phosphatase (bone-ALP), c-telopeptide. Free and bioavailable vitamin D levels were calculated with formula. Results: Vitamin D levels of type 1 diabetic patients were significantly higher (p = 0.01). Parathormone levels of the group with vitamin D level under 20 ng/ml was significantly higher (p = 0.029). VDBP levels were similar in both groups. Correlation analysis of free and bioavailable vitamin D level with osteocalcin, c-telopeptide, bone alkaline phosphatase revealed only a weak significant correlation between free vitamin D and osteocalcin (r = -0.201; p = 0.028). A negative correlation was determined between 25(OH)D and parathormone levels (r = -0.294; p < 0.005). Serum osteocalcin, bone alkaline phosphatase and c-telopeptide levels of control group were significantly higher. Conclusion: 25(OH)D levels of the study population was extremely low. The measurement of VDBP and calculated free and bioactive vitamin D levels did not show a better correlation with bone turnover markers according to 25(OH)D levels.

13.
Int J Mol Sci ; 23(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35408837

RESUMO

Among the trinucleotide repeat disorders, myotonic dystrophy type 1 (DM1) is one of the most complex neuromuscular diseases caused by an unstable CTG repeat expansion in the DMPK gene. DM1 patients exhibit high variability in the dynamics of CTG repeat instability and in the manifestations and progression of the disease. The largest expanded alleles are generally associated with the earliest and most severe clinical form. However, CTG repeat length alone is not sufficient to predict disease severity and progression, suggesting the involvement of other factors. Several data support the role of epigenetic alterations in clinical and genetic variability. By highlighting epigenetic alterations in DM1, this review provides a new avenue on how these changes can serve as biomarkers to predict clinical features and the mutation behavior.


Assuntos
Distrofia Miotônica , Alelos , Biomarcadores , Epigênese Genética , Humanos , Distrofia Miotônica/genética , Expansão das Repetições de Trinucleotídeos
14.
Int J Mol Sci ; 23(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35408941

RESUMO

Lipoprotein(a) (Lp(a)) is one of the strongest causal risk factors of atherosclerotic disease. It is rich in cholesteryl ester and composed of apolipoprotein B and apo(a). Plasma Lp(a) levels are determined by apo(a) transcriptional activity driven by a direct repeat (DR) response element in the apo(a) promoter under the control of (HNF)4α Farnesoid-X receptor (FXR) ligands play a key role in the downregulation of APOA expression. In vitro studies on the catabolism of Lp(a) have revealed that Lp(a) binds to several specific lipoprotein receptors; however, their in vivo role remains elusive. There are more than 1000 publications on the role of diabetes mellitus (DM) in Lp(a) metabolism; however, the data is often inconsistent and confusing. In patients suffering from Type-I diabetes mellitus (T1DM), provided they are metabolically well-controlled, Lp(a) plasma concentrations are directly comparable to healthy individuals. In contrast, there exists a paradox in T2DM patients, as many of these patients have reduced Lp(a) levels; however, they are still at an increased cardiovascular risk. The Lp(a) lowering mechanism observed in T2DM patients is most probably caused by mutations in the mature-onset diabetes of the young (MODY) gene and possibly other polymorphisms in key transcription factors of the apolipoprotein (a) gene (APOA).


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Apolipoproteínas A , Apoproteína(a) , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Humanos , Lipoproteína(a)/genética
15.
Int J Mol Sci ; 23(6)2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35328504

RESUMO

The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to (a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS), and (b) establish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive immunity associated with muscle-wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.


Assuntos
Distrofia Miotônica , Perfilação da Expressão Gênica , Humanos , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Qualidade de Vida , Índice de Gravidade de Doença , Transcriptoma
16.
J Family Med Prim Care ; 11(1): 27-31, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35309606

RESUMO

Type 1 Diabetes Mellitus is the most common endocrinological abnormality found in children. The incidence of T1DM has steadily increased in nearly all parts of the world. Both genetic susceptibility and environmental factors contribute to the pathogenesis. It is caused due to either decreased or absent insulin production in the body due to multiple etiologies. We have done a literature review of type 1 DM in children and a clinical audit of point prevalence of type 1 DM cases & its clinical correlates of patients presenting at the tertiary level hospital, AIIMS Rishikesh, over two years six months period (April 2015 to September 2017). We found the prevalence of diabetes mellitus (Type 1) is 2.88%. Among clinical features at presentation, 56.5% presented with polyuria, 34.8% with polydipsia, 21.7% with polyphagia, 39.1% with weight loss. 26.1% of patients had diabetic ketoacidosis at presentation. The majority of children have deranged HbA1C levels (94.4%). It is concluded that children presented with higher HbA1c levels at onset and higher duration of symptoms are at greater risk for the development of complications.

17.
Neuropathology ; 42(2): 104-116, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35199386

RESUMO

Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.0 ± 8.7 years), obtained from the NCNP Brain Bank, were compared with control cases obtained from the Brain Bank for Aging Research (BBAR) in Japan. The investigated anatomical sites followed the Dementia with Lewy Bodies Consensus Guideline, expanding to the peripheral autonomic nervous system, temporal pole, and occipital cortex, in addition to the olfactory epithelium and spinal cord. Of the 32 patients, 11 (34.4%) had Lewy pathology, with a significantly higher prevalence than that in the control cases from the BBAR (20.1%). Lewy pathology detected in DM1 was widespread, but no macroscopic depigmentation of the substantia nigra was observed in any DM1 case; this was commensurate with the microscopic paucity of Lewy pathology in the substantia nigra and amygdala. Lewy pathology in DM1 does not appear to follow either Braak's ascending paradigm or the olfactory-amygdala extension. Lewy neurites and dots in DM1 were very sparse in the cerebral cortex and distinct from those observed in BBAR control cases. This study was the first demonstration of unique Lewy pathology in DM1 and may contribute to the understanding of the protein propagation hypothesis of Lewy pathology.


Assuntos
Doença por Corpos de Lewy , Distrofia Miotônica , Doença de Parkinson , Encéfalo/patologia , Humanos , Corpos de Lewy/patologia , Doença por Corpos de Lewy/patologia , Distrofia Miotônica/patologia , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo
18.
Genes (Basel) ; 13(2)2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35205411

RESUMO

Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and gastrointestinal system. There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited with significant overlap in clinical manifestations. DM1 results from CTG repeat expansions in the 3'-untranslated region (3'UTR) of the DMPK (dystrophia myotonica protein kinase) gene on chromosome 19, while DM2 is caused by CCTG repeat expansions in intron 1 of the CNBP (cellular nucleic acid-binding protein) gene on chromosome 3. Recent advances in genetics and molecular biology, especially in the field of RNA biology, have allowed better understanding of the potential pathomechanisms involved in DM. In this review article, core clinical features and genetics of DM are presented followed by a discussion on the current postulated pathomechanisms and therapeutic approaches used in DM, including the ones currently in human clinical trial phase.


Assuntos
Distrofia Miotônica , Regiões 3' não Traduzidas , Encéfalo/metabolismo , Coração , Humanos , Distrofia Miotônica/genética
19.
Cardiol Young ; 32(10): 1677-1680, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35094738

RESUMO

Diabetic ketoacidosis is one of the most serious and common complications of diabetes, with between 15 and 70% of new-onset type 1 diabetes mellitus worldwide presented with diabetic ketoacidosis. Supraventricular tachycardia, however, is an infrequent complication of diabetic ketoacidosis. We present the case of a child with a new-onset type 1 diabetes mellitus with supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis. The patient received intravenous fluid resuscitation, insulin, and potassium supplementation and subsequently developed stable supraventricular tachycardia initially, confirmed on a 12-lead electrocardiogram despite a structurally normal heart and normal electrolytes. Vagal manoeuvers failed to achieve sinus rhythm. The patient went into respiratory distress and was intubated, for mechanical ventilation. She received one dose of adenosine with successful conversion to sinus rhythm and a heart rate decreased from 200 to 140 beats per minutes. We conclude that supraventricular tachycardia can occur as a complication of diabetic ketoacidosis, including in new-onset type 1 diabetes mellitus. Furthermore, a combination of acidosis, potassium derangement, falling magnesium, and phosphate levels may have precipitated the event. Here, we report a case of supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Taquicardia Supraventricular , Humanos , Criança , Feminino , Cetoacidose Diabética/complicações , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/terapia , Diabetes Mellitus Tipo 1/complicações , Magnésio/uso terapêutico , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/etiologia , Insulina/uso terapêutico , Adenosina , Potássio/uso terapêutico , Eletrólitos/uso terapêutico , Fosfatos
20.
Indian J Ophthalmol ; 69(11): 3178-3183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34708767

RESUMO

PURPOSE: To study the relationship between the severity of myopia and the severity of diabetic retinopathy (DR) in individuals with type 1 or type 2 diabetes mellitus (DM). METHODS: This retrospective study was conducted using data from electronic medical records from a multicentric eyecare network located in various geographic regions of India. Individuals with type 1 or type 2 DM were classified according to their refractive status. Severe nonproliferative DR (NPDR), PDR, or presence of clinically significant macular edema (CSME) with any type of DR was considered as vision-threatening diabetic retinopathy (VTDR). RESULTS: A total of 472 individuals with type-1 DM (mean age 41 ± 10 years) and 9341 individuals with type-2 DM (52 ± 9 years) were enrolled. Individuals with a hyperopic refractive error had a significant positive association with the diagnosis of VTDR (odds ratio (OR) 1.26; 95%CI 1.04-1.51, P = 0.01) and moderate nonproliferative DR (OR 1.27; 95%CI 1.02-1.59, P = 0.03) in type-2 DM; however, no significant association was found in type-1 DM. After adjusting for age, gender, anisometropia, and duration of diabetes, the presence of high myopia (< - 6 D) reduced the risk of VTDR in type 2 DM (OR 0.18; 95% CI 0.04-0.77, P = 0.02), but no association was found in type 1 DM. Mild and moderate myopia had no significant association with any forms of DR in both type-1 and type-2 DM. CONCLUSION: Hyperopic refractive error was found to increase the risk of VTDR in persons with type 2 DM. High-myopic refractive error is protective for VTDR in type 2 DM, but not in type-1 DM.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Miopia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Humanos , Pessoa de Meia-Idade , Miopia/complicações , Miopia/diagnóstico , Miopia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
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