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1.
Nucleic Acids Res ; 50(D1): D1468-D1474, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34747486

RESUMO

PLAZA is a platform for comparative, evolutionary, and functional plant genomics. It makes a broad set of genomes, data types and analysis tools available to researchers through a user-friendly website, an API, and bulk downloads. In this latest release of the PLAZA platform, we are integrating a record number of 134 high-quality plant genomes, split up over two instances: PLAZA Dicots 5.0 and PLAZA Monocots 5.0. This number of genomes corresponds with a massive expansion in the number of available species when compared to PLAZA 4.0, which offered access to 71 species, a 89% overall increase. The PLAZA 5.0 release contains information for 5 882 730 genes, and offers pre-computed gene families and phylogenetic trees for 5 274 684 protein-coding genes. This latest release also comes with a set of new and updated features: a new BED import functionality for the workbench, improved interactive visualizations for functional enrichments and genome-wide mapping of gene sets, and a fully redesigned and extended API. Taken together, this new version offers extended support for plant biologists working on different families within the green plant lineage and provides an efficient and versatile toolbox for plant genomics. All PLAZA releases are accessible from the portal website: https://bioinformatics.psb.ugent.be/plaza/.


Assuntos
Evolução Biológica , Bases de Dados Genéticas , Plantas/classificação , Software , Genoma de Planta/genética , Genômica/normas , Anotação de Sequência Molecular , Família Multigênica/genética , Filogenia , Plantas/genética
2.
BMC Med Educ ; 24(1): 323, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515122

RESUMO

BACKGROUND: Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care. METHODS: Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons. RESULTS: The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories. CONCLUSIONS: The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.


Assuntos
Clínica Dirigida por Estudantes , Estudantes de Medicina , Humanos , Feminino , Idoso , Estados Unidos , Pessoa de Meia-Idade , Masculino , Medicare , Instituições de Assistência Ambulatorial , Avaliação de Resultados em Cuidados de Saúde
3.
Sex Transm Infect ; 99(5): 348-350, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37015803

RESUMO

OBJECTIVE: We aimed to evaluate the efficacy of PrEP (pre-exposure prophylaxis) training sessions for OBGYN (obstetrician gynaecologist) providers given underutilisation of PrEP among women despite a high HIV burden. METHODS: Three separate training sessions were held for providers in the OBGYN department at an academic medical centre in New York City from 2019 to 2021. The 1-hour training sessions were conducted by HIV specialists as in-person lectures or online live lectures. Participants were surveyed after the training on metrics of PrEP awareness, knowledge and comfort with management. Two-sample t-tests were used to compare difference in proportions of binomial variables and difference in means of Likert-scored answers pretraining and post-training events. RESULTS: 63 respondents completed the surveys. There were low rates (13%) of past PrEP prescription among the respondents, while awareness of PrEP as an HIV prevention strategy was high before (95%) and after (98%) the training. After the training, there was an increase in understanding the epidemiology of HIV transmission (40% to 97%, p<0.00), familiarity with the PrEP clinical trials (18% to 97%, p<0.00), comfort in determining PrEP candidacy (mean score 2.3 to 4.1, p<0.00) and comfort prescribing PrEP (mean score 2.0 to 3.6, p<0.00). After the trainings, the majority of participants reported feeling 'comfortable' or 'very comfortable' in determining candidacy for PrEP and prescribing PrEP with follow-up. CONCLUSION: Implementation of PrEP training courses for OBGYN providers increased knowledge and comfort in identifying and managing patients who may benefit from PrEP services. Increasing training among OBGYN providers serving women at risk for HIV infection is an effective tool to narrow gaps in PrEP access.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Obstetra , Conhecimentos, Atitudes e Prática em Saúde , Fármacos Anti-HIV/uso terapêutico , Inquéritos e Questionários
4.
AIDS Behav ; 27(2): 496-505, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35831493

RESUMO

Urban Black men who have sex with men (MSM) bear a disproportionate burden of HIV and syphilis in the U.S. Experiences of enacted sexual minority stigma and psychological distress among these men may be associated with HIV/STI sexual and drug risk behaviors. The objective was to determine the associations between enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. In an urban prospective cohort study, survey measures assessed past 3-month exposure to enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. Multivariable logistic regression models were utilized for hypothesis testing. The Black MSM (N = 140) reported the following: 22.1% experiences of enacted sexual minority stigma, 39% high levels of psychological distress, 48.6% > 1 sex partner, 8.6% transactional sex, and 6% injection drug use (IDU). In models adjusted for age and education, enacted sexual minority stigma significantly increased the odds of reporting > 1 sex partner, transactional sex, and IDU. Adjusting additionally for homelessness, the association between enacted sexual minority stigma and transactional sex remained significant. Adding psychological distress to this model showed a significant association between psychological distress and transactional sex, while the association was no longer significant for transactional sex. These findings highlight some of the complex psycho-social relationships that may be associated with sexual and drug risk behaviors among Black MSM placing them at increased risk for HIV and syphilis.


RESUMEN: Hombres urbanos de raza Negra que tienen sexo con hombres (HSH) sobrellevan una carga desproporcionada de VIH y sífilis en los EE.UU. Experiencias de estigma efectivo de minoría sexual y angustia psicológica entre estos hombres pudiese ser asociado con conductas sexuales de riesgo VIH/ITS y drogas. El objetivo era determinar las asociaciones entre un estigma efectivo de minoría sexual, angustia psicológica, y comportamientos sexuales y de riesgo de drogas. En un estudio de cohortes prospectivo urbano, las medidas de la encuesta evaluada en los últimos tres meses de exposición al estigma efectivo, angustia psicológica, y sus conductas sexuales y comportamientos riesgoso de drogas. Modelos de regresión logística multivariante se utilizaron para la prueba de hipótesis. Los HSH de raza negra (N = 140) reportaron lo siguiente: 22.1% experiencias de estigma efectivo, 39% niveles altos de angustia psicológica, 48.6% y > 1 pareja sexual, 8.6% sexo transaccional, y 6% uso de drogas inyectables (UDI). En modelos ajustados a edad y educación, un estigma efectivo de minoría sexual aumentó de manera significante las probabilidades de reportar y > 1 pareja sexual, sexo transaccional, y UDI. Ajustando adicionalmente para personas sin vivienda, la asociación entre estigma efectivo de minoría sexual y sexo transaccional permaneció significante. La adición de angustia psicológica al modelo mostró una asociación significativa entre angustia psicológica y sexo transaccional, mientras que la asociación ya no era significativa para el sexo transaccional. Estos resultados destacan algunas de las complejas relaciones psicosociales que pudiesen estar asociadas con conductas sexuales y de riesgo de drogas entre HSH de raza negra, poniéndolos a mayor riesgo de contraer VIH y sífilis.


Assuntos
Infecções por HIV , Angústia Psicológica , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Homossexualidade Masculina/psicologia , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Estudos Prospectivos , Comportamento Sexual , Estigma Social , Assunção de Riscos
5.
Teach Learn Med ; : 1-13, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37571960

RESUMO

Phenomenon: Student-run free clinics (SRFCs) serve an integral role in most United States (US) medical schools and contribute substantially to literature on the quality of care to uninsured persons. There has been substantial growth over the past decade of scholarly work produced by SRFCs as they have increased in size and number. Research on patient care outcomes informs better care structures for patients, however there is no current synthesis of patient care outcomes research among SRFCs. This article provides an overview of SRFC research on patient outcomes to understand current research domains and to identify gaps in the literature. Approach: We completed a scoping review by searching Scopus, PubMed, and Journal of Student Run Clinics in June 2021. All peer-reviewed, English-language articles focused on patient-centered outcomes at SRFCs in the US were included. Two independent reviewers performed title, abstract, and full-text screening of relevant works, and eight reviewers conducted data extraction. Descriptive data analysis was performed along with relevant content analysis of patient-centered outcomes. Findings: The search strategy identified 784 studies, of which 87 met inclusion criteria. Most studies were published within the last six years (81.6%), located in California, New York, or Florida (43.7%), and intervention based (33.3%). Many studies (46.0%) had a specific disease of focus of which diabetes was the most researched(19.5%). Patient-centered studies were the leading focus of the study aims (40.2%), where key findings demonstrated primarily improved outcomes in clinic metrics post-intervention (36.8%) or equivalent/better clinical performance than national metrics (20.7%). Insights: This review brings to light gaps in the literature reporting research in SRFCs and can be applied to other low-resource settings. Future efforts to expand SRFC outcomes research should focus on community relationship building, understanding institutional support, and ensuring education on best practices for research within SRFCs. Doing so informs patient care improvement as SRFCs continue to operate as safety net clinics for marginalized populations.

6.
New Microbiol ; 44(4): 241-244, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34942009

RESUMO

Type 1 diabetes (T1DM) ethiopathogenesis is still being studied, since the role of environmental factors , especially viruses, is not yet clear. This study was conducted on 31 paediatric patients with T1DM at onset. We analysed: Coxsackieviruses A (CoxA), Coxsackieviruses B (CoxB), Echoviruses (Echo); Influenzavirus A and B (IV-A and IV-B); Adenovirus (AdV); Parainfluenza viruses 1-2 and 3 (PiV 1-2-3); Cytomegalovirus (CMV) and Respiratory Syncytial Virus (RSV). Enteroviruses, especially CoxB and Echo, are most represented. Unexpectedly, Parainfluenza viruses were detected in seasonal subgroups, with peaks in autumn and spring, and spread homogeneously in different age groups.


Assuntos
Diabetes Mellitus Tipo 1 , Infecções por Enterovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Vírus , Criança , Humanos , Lactente , Estações do Ano
9.
Res Sq ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38947074

RESUMO

Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue culture of primary breast epithelial cells, breast organoids preserve the epithelial lineages and architecture of the normal tissue. However, existing organoid culture methods are tedious, difficult to scale, and do not robustly retain estrogen receptor (ER) expression and responsiveness in long-term culture. Here, we describe a modified culture method to generate and maintain organoids as suspension cultures in reconstituted basement membrane (™Matrigel). This method improves organoid growth and uniformity compared to the conventional Matrigel dome embedding method, while maintaining the fidelity of the three major epithelial lineages. Using this adopted method, we are able to culture and passage purified hormone sensing (HS) cells that retain ER responsiveness upon estrogen stimulation in long-term culture. This culture system presents a valuable platform to study the events involved in initiation and evolution of ER-positive breast cancer.

10.
Minerva Pediatr (Torino) ; 75(6): 822-827, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-31729208

RESUMO

BACKGROUND: Hepatitis B virus (HBV) vaccine reduced the incidence of Hepatitis B worldwide. Genetic variability, by the presence of specific haplotypes of HLA system (HLA-DR3, HLA-DR4), influences the response to the vaccination. Subjects affected by type 1 diabetes (T1D), contrary to non-diabetics, have a high prevalence of Hepatitis B. METHODS: The objective of the study was to evaluate anti-HBs antigen (anti-HBsAg) antibody (Ab) in a group of 201 children (age range: 2-18 years), regularly vaccinated against HBV according to the national vaccination schedule. Patients with anti-HBs Ab≥10 mIU/mL have been defined "responders" and those with anti-HBs Ab<10mIU/mL have been defined "non-responders." The possible association between the T1D and a low immune response to the vaccine has been subsequently valued. Besides the presence of T1D, other possible influential variables have been studied: sex, age, presence of celiac disease and Hashimoto's thyroiditis, intervening years from the diagnosis of diabetes and presence/absence of diabetic ketoacidosis at time of diagnosis. RESULTS: Among the 201 subjects with T1D, 90 (44.8%) were responders, while 111 (55.2%) were non-responders; among the 145 subjects without T1D, 86 (59.3%) were responders and 59 (40.7%) non-responders. We invited "Subjects with T1D non-responders" to undergo a booster dose of the same vaccine. Of these, 21 refused the booster, reducing the sample to 90 patients. After 4 weeks from the booster dose 81 patients showed seroconversion ("false non-responders"), and 9 did not ("true non-responders"). CONCLUSIONS: After the booster dose, immune response in our cross-section has been similar to general population. Given the high frequency of "false non-responders" anti-HBsAg Ab should be tested in T1D patients and a booster dose should be administrated in non-responders.


Assuntos
Diabetes Mellitus Tipo 1 , Hepatite B , Humanos , Criança , Pré-Escolar , Adolescente , Vírus da Hepatite B , Imunização Secundária , Vacinas contra Hepatite B/uso terapêutico , Antígenos de Superfície da Hepatite B , Anticorpos Anti-Hepatite B , Hepatite B/prevenção & controle , Imunidade
11.
Acta Diabetol ; 60(10): 1301-1307, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37171699

RESUMO

AIMS: To evaluate the relationship between SARS-CoV-2 infection and autoimmunity in type 1 diabetes (T1D) and SARS-CoV-2 antibodies frequency at diagnosis of T1D during pandemic. METHODS: The presence of T1D-specific autoimmunity was evaluated in a cohort of 99 children and adolescents without diabetes that contracted SARS-CoV-2 infection. Moreover, the frequency of IgM- and IgG-SARS-CoV-2 antibodies was evaluated in 41 newly diagnosed T1D patients not yet vaccinated against SARS-CoV-2 disease, collected during the pandemic, compared to healthy subjects (CTRL). RESULTS: None of the 99 patients that contracted SARS-CoV-2 infection during the pandemic period was found positive for T1D autoantibodies. The frequency of SARS-CoV-2 antibodies was not significantly different in patients newly diagnosed with T1D (12.2%), compared with CTRL (8.4%). Among SARS-CoV-2 antibody positive T1D patients, 80% were target of diabetes autoantibodies and 60% had another concomitant autoimmune disease. Among the CTRL subjects positive for SARS-CoV-2Abs (n = 10), none was found positive for T1D autoantibodies. CONCLUSIONS: The results of the present study do not confirm, at least in the short term, a role of COVID-19 as a potential trigger of T1D autoimmunity and do not provide evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed T1D patients in comparison with healthy population.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Criança , Adolescente , Humanos , Diabetes Mellitus Tipo 1/epidemiologia , Autoimunidade , SARS-CoV-2 , COVID-19/epidemiologia , Voluntários Saudáveis , Autoanticorpos
12.
Cell Rep ; 42(11): 113354, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37917586

RESUMO

The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/ß-catenin signaling and engineer endogenous WNT/ß-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/ß-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.


Assuntos
Tubas Uterinas , beta Catenina , Feminino , Humanos , beta Catenina/metabolismo , Tubas Uterinas/metabolismo , Transcriptoma/genética , Células-Tronco/metabolismo , Via de Sinalização Wnt , Organoides/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Receptores Frizzled/metabolismo
13.
AACE Clin Case Rep ; 8(3): 128-130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602877

RESUMO

Objective: Early diagnosis of syndromic monogenic diabetes allows for proper management and can lead to improved quality of life in the long term. This report aimed to describe 2 genetically confirmed cases of Wolfram syndrome, a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Case Report: A 16-year-old Caucasian male patient and a 25-year-old Caucasian female patient with a history of diabetes mellitus and optic nerve atrophy presented at our medical center. Both patients were initially diagnosed with type 1 diabetes but negative for islet autoantibodies. Their body mass indexes were under 25 at the diagnosis. Their history and presentation were highly suspicious for Wolfram syndrome. Discussion: The genetic tests revealed a known Wolfram syndrome 1 (WFS1) pathogenic variant (homozygous) in the 16-year-old male patient and 2 known WFS1 pathogenic variants (compound heterozygous) in the 25-year-old female patient with diabetes mellitus and optic nerve atrophy, confirming the diagnosis of Wolfram syndrome. The first patient had a moderate form, and the second patient had a milder form of Wolfram syndrome. Conclusion: Providers should consider monogenic diabetes genetic testing, including WFS1 gene, for patients with early-onset diabetes who are negative for islet autoantibodies and lean. Two patients described in this article could have been diagnosed with Wolfram syndrome before they developed optic nerve atrophy. Genetic testing is a valuable tool for the early detection of Wolfram syndrome, which leads to proper management and improved quality of life in patients with this rare medical condition.

14.
Eval Program Plann ; 90: 101978, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34275640

RESUMO

Etiologies of HIV disparities are multifaceted; anti-LGBTQ stigma and social marginalization are contributory factors. A city health department developed a program, #ProjectPresence, exhibiting professional photos of Black LGBTQ persons in public spaces. An academic partner explored the relationship of the program to visibility, anti-LGBTQ stigma and social marginalization of Black LGBTQ persons, i.e. models, directly involved in the program and their perceptions of these relationships more broadly for community members. Brief self-administered surveys and semi-structured, in-depth interviews with #ProjectPresence models (n = 15) were conducted after the program to gather their experiences before, during and after the program. Descriptive analyses of survey responses were conducted using Stata 15.1. Interviews were audio-recorded, transcribed and analyzed in NVivo10 using categorical analysis. Surveys indicated prevalent experiences of enacted stigma (73 %) and perceptions of poor local acceptance of LGBTQ people (53 %). Interviews suggested that the program may have influenced positive individual- and community-level changes by increasing visibility of LGBTQ communities and improving acceptance among non-LGBTQ persons, inspiring personal growth and self-acceptance among models, and providing opportunities to foster new connections among LGBTQ subpopulations. Our findings suggest similar programs may present promising approaches for the reduction of stigma and social marginalization affecting LGBTQ persons and communities.


Assuntos
Minorias Sexuais e de Gênero , Humanos , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Estigma Social
15.
Pediatr Endocrinol Diabetes Metab ; 28(3): 197-206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36134673

RESUMO

INTRODUCTION: Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. MATERIAL AND METHODS: We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual ß-cell function. RESULTS: 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of ß-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. CONCLUSIONS: Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual ß-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.


Assuntos
Diabetes Mellitus Tipo 1 , Falanges dos Dedos da Mão , Absorciometria de Fóton , Adolescente , Fosfatase Alcalina , Glicemia , Densidade Óssea/fisiologia , Peptídeo C , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Feminino , Hemoglobinas Glicadas , Humanos , Osteocalcina , Estudos Retrospectivos
16.
Metabol Open ; 11: 100099, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34159308

RESUMO

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by an absolute deficiency of insulin secretion. T1D management rests on three pillars: insulin therapy, correct diet and physical exercise. The aim is to focus the attention on diet and mainly on vegetarian diet, in order to evaluate if this kind of food style can offer the correct supply of nutrients, necessary for growth and well control glycaemic management. This paper is a short commentary on vegetarianism in the pediatric and adolescent population with Type 1 Diabetes. In all non-omnivorous diets there is a risk of a lack of some nutrients, as B12 vitamin and n 3 fatty acids which must therefore be measured. It is also important to monitor eating disorders especially in adolescent girls. About vegan diet, attention must be paid to the possible injury on growth brain already at risk, in diabetic children compared to the general population, due to insults related to frequent glucose variability (periods of prolonged hyperglycaemia alternating with hypoglycaemic episodes). In conclusion, vegetarian diet could be suitable for children with type 1 diabetes; vegan diet could be too restrictive but with appropriate additions can be followed by these patients.

17.
Eur J Endocrinol ; 184(4): 575-585, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33606663

RESUMO

OBJECTIVE: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. DESIGN: Retrospective analysis of the Italian data set of patients with TNDM. METHODS: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. RESULTS: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. CONCLUSIONS: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.


Assuntos
Diabetes Mellitus , Doenças do Recém-Nascido , Conjuntos de Dados como Assunto , Diabetes Mellitus/classificação , Diabetes Mellitus/congênito , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/classificação , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/terapia , Itália , Masculino , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Indução de Remissão/métodos , Estudos Retrospectivos , Receptores de Sulfonilureias/genética
18.
Eur J Paediatr Neurol ; 23(2): 240-247, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30600130

RESUMO

We provide an overview on the current knowledge about the association between epilepsy and type 1 diabetes mellitus (T1DM). People with T1DM have a 2-6-fold higher risk of epilepsy than the general population. The onset of T1DM anticipates the onset of epilepsy by a mean period between 1,5 and 2,8 years. These two disorders share four potential distinct pathogenic factors: a) genetic predisposition; b) factors involved in autoimmune responses (i.e. anti-glutamic acid decarboxylase antibodies-GADAbs); c) effects of hypo/hyperglycaemia; d) cerebrovascular damages resulting in ischaemic processes. Seizures semiology prominently includes focal (up to patterns of epilepsia partialis continua) or secondarily generalized seizures but also reflex seizures and various forms of generalized seizures. EEG abnormalities are more common in people with an inappropriate metabolic control with a prominent involvement of fronto-temporal regions. Epilepsy management does not differ between patients with and without diabetes and insulin, nutritional recommendations and physical activity may also produce significant benefits on seizures control. Possible therapeutic alternatives in selected cases include immunosuppressive drugs (in patients with GADAbs) and ketogenic diet.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino
20.
Sci Rep ; 8(1): 13308, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30190542

RESUMO

This study assessed whether cytoskeletal protein alpha-II spectrin breakdown products (SBDP150, SBDP145, and SBDP120) would identify the presence of aSAH and be associated with severity (GCS score, WFNS grade and survival to hospital discharge). This prospective case-control study, conducted at a tertiary care Level I trauma center, enrolled adult patients with angiography confirmed aSAH who underwent ventriculostomy placement for cerebrospinal fluid (CSF) drainage. There were 40 patients enrolled in the study, 20 with aSAH and 20 control subjects. Patients with aSAH were a mean age of 54 (SD15) and 75% were female. There were significant differences in SBDP150, SBDP145, and SBDP120 CSF levels between patients with and without aSAH (p < 0.001), even in those presenting with a GCS Score of 15 and a WFNS Grade 1. The AUC for distinguishing aSAH from control subjects was 1.0 for SBDP150 and SBDP145, and 0.95 for SBDP120. SBDP150 and SBDP145 both yielded sensitivities and specificities of 100% and SBDP120 was 90% and 100% respectively. Moreover, there were significantly higher levels of SBDP150 and SBDP145 in the non-survivors than in the survivors (p < 0.001). This study demonstrates the potential that SBDP's have as biomarkers for recognition and severity of aSAH. A larger prospective study is warranted.


Assuntos
Espectrina/sangue , Hemorragia Subaracnóidea/sangue , Adulto , Idoso , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Hemorragia Subaracnóidea/mortalidade , Taxa de Sobrevida
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