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Acta Diabetologica Mar 2023
Topics: Female; Humans; Donohue Syndrome; Insulin Resistance; Receptor, Insulin; Mutation
PubMed: 36331627
DOI: 10.1007/s00592-022-01971-3 -
Neurotherapeutics : the Journal of the... Oct 2023Patients with Lafora disease have a mutation in EPM2A or EPM2B, resulting in dysregulation of glycogen metabolism throughout the body and aberrant glycogen molecules...
Patients with Lafora disease have a mutation in EPM2A or EPM2B, resulting in dysregulation of glycogen metabolism throughout the body and aberrant glycogen molecules that aggregate into Lafora bodies. Lafora bodies are particularly damaging in the brain, where the aggregation drives seizures with increasing severity and frequency, coupled with neurodegeneration. Previous work employed mouse genetic models to reduce glycogen synthesis by approximately 50%, and this strategy significantly reduced Lafora body formation and disease phenotypes. Therefore, an antisense oligonucleotide (ASO) was developed to reduce glycogen synthesis in the brain by targeting glycogen synthase 1 (Gys1). To test the distribution and efficacy of this drug, the Gys1-ASO was administered to Epm2b-/- mice via intracerebroventricular administration at 4, 7, and 10 months. The mice were then sacrificed at 13 months and their brains analyzed for Gys1 expression, glycogen aggregation, and neuronal excitability. The mice treated with Gys1-ASO exhibited decreased Gys1 protein levels, decreased glycogen aggregation, and reduced epileptiform discharges compared to untreated Epm2b-/- mice. This work provides proof of concept that a Gys1-ASO halts disease progression of EPM2B mutations of Lafora disease.
Topics: Humans; Mice; Animals; Lafora Disease; Glycogen Synthase; Disease Models, Animal; Mutation; Oligonucleotides, Antisense; Glycogen; Ubiquitin-Protein Ligases
PubMed: 37700152
DOI: 10.1007/s13311-023-01434-9 -
The American Journal of Tropical... Aug 2021Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome...
Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty cases of reinfection with viral sequencing were identified in PubMed, Embase, Web of Science, and medRxiv before May 1, 2021.Episodes of infection were separated by a median of 116 days. Severity of illness was greater among individuals reinfected within 90 days of initial infection, no asymptomatic initial cases developed severe reinfection, nearly half of cases had suspected escape variants, and nearly all individuals tested following reinfection were found to have detectable levels of anti-SARS-CoV-2 antibodies. This analysis is limited by the heterogeneous methods used among reports. Reinfection continues to be relatively rare. As the case rate presumably increases over time, this review will inform measurements to determine the natural history and causal determinants of reinfection in more rigorous observational cohort studies and other standardized surveillance approaches.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Viral; COVID-19; COVID-19 Nucleic Acid Testing; Female; Humans; Male; Middle Aged; Reinfection; SARS-CoV-2; Sequence Analysis
PubMed: 34370705
DOI: 10.4269/ajtmh.21-0365 -
Indian Journal of Pediatrics Feb 2021
Topics: Abnormalities, Multiple; Donohue Syndrome; Face; Humans; Insulin Resistance
PubMed: 32623589
DOI: 10.1007/s12098-020-03433-6 -
Echocardiography (Mount Kisco, N.Y.) Mar 2008Cardiac tamponade is usually a consequence of increased pericardial pressure with accumulation of pericardial effusion. Pericardial effusion may be caused by acute... (Review)
Review
Cardiac tamponade is usually a consequence of increased pericardial pressure with accumulation of pericardial effusion. Pericardial effusion may be caused by acute pericarditis, tumor, uremia, hypothyroidism, trauma, cardiac surgery, or other inflammatory/noninflammatory conditions. In this article we describe four scenarios illustrated by case reports where a small or apparently small pericardial effusion may produce cardiac tamponade. The first scenario illustrates how a small pericardial effusion can cause clinically significant cardiac tamponade when it accumulates rapidly. The second scenario exhibits how an apparently small pericardial effusion on transthoracic echocardiogram (TTE) turned out to be a small amount of unclotted blood and an echogenic hematoma. The third scenario details how an apparently small pericardial effusion on TTE was actually a large loculated effusion in an unusual location seen only by transesophageal echocardiogram (TEE). The fourth scenario demonstrates how the combination of a large pleural effusion and a small pericardial effusion can result in cardiac tamponade. The role of echocardiography in the diagnosis and management of these scenarios is discussed here. Although many clinicians depend on the amount of pericardial effusion to suspect cardiac tamponade, it is important to suspect cardiac tamponade when patients have hemodynamic compromise regardless of the amount of pericardial effusion.
Topics: Adult; Cardiac Tamponade; Echocardiography; Echocardiography, Transesophageal; Humans; Male; Middle Aged; Pericardial Effusion
PubMed: 18307446
DOI: 10.1111/j.1540-8175.2007.00567.x -
Pediatrics Sep 2023Neurodevelopmental evaluation of toddlers with complex congenital heart disease is recommended but reported frequency is low. Data on barriers to attending...
BACKGROUND AND OBJECTIVES
Neurodevelopmental evaluation of toddlers with complex congenital heart disease is recommended but reported frequency is low. Data on barriers to attending neurodevelopmental follow-up are limited. This study aims to estimate the attendance rate for a toddler neurodevelopmental evaluation in a contemporary multicenter cohort and to assess patient and center level factors associated with attending this evaluation.
METHODS
This is a retrospective cohort study of children born between September 2017 and September 2018 who underwent cardiopulmonary bypass in their first year of life at a center contributing data to the Cardiac Neurodevelopmental Outcome Collaborative and Pediatric Cardiac Critical Care Consortium clinical registries. The primary outcome was attendance for a neurodevelopmental evaluation between 11 and 30 months of age. Sociodemographic and medical characteristics and center factors specific to neurodevelopmental program design were considered as predictors for attendance.
RESULTS
Among 2385 patients eligible from 16 cardiac centers, the attendance rate was 29.0% (692 of 2385), with a range of 7.8% to 54.3% across individual centers. In multivariable logistic regression models, hospital-initiated (versus family-initiated) scheduling for neurodevelopmental evaluation had the largest odds ratio in predicting attendance (odds ratio = 4.24, 95% confidence interval, 2.74-6.55). Other predictors of attendance included antenatal diagnosis, absence of Trisomy 21, higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, longer postoperative length of stay, private insurance, and residing a shorter distance from the hospital.
CONCLUSIONS
Attendance rates reflect some improvement but remain low. Changes to program infrastructure and design and minimizing barriers affecting access to care are essential components for improving neurodevelopmental care and outcomes for children with congenital heart disease.
Topics: Pregnancy; Humans; Female; Child; Retrospective Studies; Heart; Cardiopulmonary Bypass; Critical Care; Down Syndrome
PubMed: 37593818
DOI: 10.1542/peds.2022-060995 -
Biology Oct 2023The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary... (Review)
Review
The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed "metabolic-dysfunction-associated steatotic liver disease" (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.
PubMed: 37887021
DOI: 10.3390/biology12101311 -
The Journal of Pediatrics Jan 1949
Topics: Child; Cushing Syndrome; Humans; Infant; Neoplasms
PubMed: 18127157
DOI: 10.1016/s0022-3476(49)80195-8 -
Clinical Pediatric Endocrinology : Case... Apr 2013Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and...
Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth. However, there are few reports on the long-term course of leprechaunism. We reported the long-term clinical course and rh-IGF-1 treatment in a patient with leprechaunism. During follow-up her diabetes gradually deteriorated despite of treatment of rh-IGF-1. Furthermore, she developed endometrioid adenocarcinoma at the age of 24 yr. The development of endometrial disease must be carefully followed up in this disease.
PubMed: 23990696
DOI: 10.1292/cpe.22.33 -
Journal of Diabetes Investigation May 2020Insulin resistance syndrome (IRS) of type A or B is triggered by gene abnormalities of or autoantibodies to the insulin receptor, respectively....
AIMS/INTRODUCTION
Insulin resistance syndrome (IRS) of type A or B is triggered by gene abnormalities of or autoantibodies to the insulin receptor, respectively. Rabson-Mendenhall/Donohue syndrome is also caused by defects of the insulin receptor gene (INSR), but is more serious than type A IRS. Here, we carried out a nationwide survey of these syndromes in Japan.
MATERIALS AND METHODS
We sent questionnaires to a total of 1,957 academic councilors or responsible individuals at certified facilities of the Japan Diabetes Society, as well as at the department pediatrics or neonatology in medical centers with >300 beds.
RESULTS
We received 904 responses with information on 23, 30 and 10 cases of type A or B IRS and Rabson-Mendenhall/Donohue syndrome, respectively. Eight cases with type A IRS-like clinical features, but without an abnormality of INSR, were tentatively designated type X IRS, with five of these cases testing positive for PIK3R1 mutations. Fasting serum insulin levels at diagnosis (mean ± standard deviation) were 132.0 ± 112.4, 1122.1 ± 3292.5, 2895.5 ± 3181.5 and 145.0 ± 141.4 μU/mL for type A IRS, type B IRS, Rabson-Mendenhall/Donohue syndrome and type X IRS, respectively. Type A and type X IRS, as well as Rabson-Mendenhall/Donohue syndrome were associated with low birthweight. Type B IRS was diagnosed most frequently in older individuals, and was often associated with concurrent autoimmune conditions and hypoglycemia.
CONCLUSIONS
Information yielded by this first nationwide survey should provide epidemiological insight into these rare conditions and inform better healthcare for affected patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Asian People; Child; Child, Preschool; Donohue Syndrome; Female; Health Surveys; Humans; Infant; Infant, Newborn; Japan; Male; Metabolic Syndrome; Middle Aged; Receptor, Insulin; Young Adult
PubMed: 31677333
DOI: 10.1111/jdi.13171