familial disease

Amyloid plaques composed of fibrils of misfolded Aβ peptides are pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of Aβ fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how Aβ fibril structures in situ differ in Aβ plaque of different mouse models expressing familial mutations in the AβPP gene...

INTRODUCTION: Financial toxicity is highly prevalent in patients after an orthopaedic injury. However, little is known regarding the conditions that promote and protect against this financial distress. Our objective was to understand the factors that cause and protect against financial toxicity after a lower extremity fracture. METHODS: A qualitative study was conducted using semi-structured interviews with 20 patients 3 months after surgical treatment of a lower extremity fracture...

BACKGROUND AND OBJECTIVE: Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature...

Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays...

IMPORTANCE: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. OBJECTIVES: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival...

PURPOSE: Work-related low back pain (WRLBP) is a highly prevalent health problem worldwide leading to work disability and increased healthcare utilisation. General practitioners (GPs) play an important role in the management of WRLBP. Despite this, understanding of GP service use for WRLBP is limited. This systematic review aimed to determine the prevalence, patterns and determinants of GP service use for WRLBP. METHODS: MEDLINE, Embase via Ovid, Scopus and Web of Science were searched for relevant peer-reviewed articles published in English without any restriction on time of publications...

We present a case of a young patient with chest pain. Labs and cardiac imaging were suspicious for acute myocarditis. Genetic testing revealed a diagnosis of desmoplakin cardiomyopathy. Desmoplakin cardiomyopathy may be considered in patients with recurrent acute myocarditis or a family history of cardiac disease to avoid the potential for misdiagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. AIMS: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. METHODS: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022...

PURPOSE OF REVIEW: The incorporation of genetic counseling and testing is essential to evaluation and management of thoracic aortic disease in patients under 60 years of age and those with family histories suspicious for heritable thoracic aortic disease and disorders associated with increased risk for acute type-A aortic dissection. RECENT FINDINGS: As many as 20% of individuals with thoracic aortic disease under the age of 60 years have autosomal dominant patterns of inheritance...

Angiopoietin-1 (Ang-1) and Vascular Endothelial Growth Factor (VEGF) are central regulators of angiogenesis and are often inactivated in various cardiovascular diseases. VEGF forms complexes with ETS transcription factor family and exerts its action by downregulating multiple genes. Among the target genes of the VEGF-ETS complex, there are a significant number encoding key angiogenic regulators. Phosphorylation of the VEGF-ETS complex releases transcriptional repression on these angiogenic regulators, thereby promoting their expression...

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate...

The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process...

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase β1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis...

Invertebrates constitute the majority of animal species on Earth, including most disease-causing agents or vectors, with more diverse viromes when compared to vertebrates. Recent advancements in high-throughput sequencing have significantly expanded our understanding of invertebrate viruses, yet this knowledge remains biased toward a few well-studied animal lineages. In this study, we analyze invertebrate DNA and RNA viromes for 31 phyla using 417 publicly available RNA-Seq data sets from diverse environments in the marine-terrestrial and marine-freshwater gradients...

Dear Editor, Ticks carry many diseases, bacteria, and viruses and represent a very important healthcare issue both in Croatia and globally. Although most ticks are not infected with pathogens dangerous to humans, some ticks can transmit infectious diseases with significant morbidity and mortality. This is caused by the increasing incidence of many tick-borne diseases over a growing geographical area. Many factors influence which species of ticks are present in a given geographical area, as well as the density of their population and the risk of human exposure to infected ticks...

BACKGROUND: Persons living with Alzheimer's disease and related dementia (ADRD) in nursing homes (NH) are often excluded from conversations about their health/safety. These omissions impinge on personhood and the rights to have care preferences heard and honored. While persons with ADRD maintain the ability to communicate their preferences long after their decision-making abilities are affected, little is known about how persons with ADRD understand the risks associated with their preferences...

Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease in adults. Late diagnosis points to limited knowledge among the medical community that symptoms other than typical muscular symptoms can dominate. The condition often worsens with each generation and some families are severely affected. Significantly delayed diagnosis means a risk of more serious development of the disorder and inadequate symptomatic treatment...

AIMS: Legg-Calve-Perthes disease (LCPD) is a diagnosis of exclusion. Various conditions, such as skeletal dysplasias, can closely mimic LCPD and these must be ruled out to provide appropriate treatment, prognosis, and counseling. Traditionally, genetic testing has not been readily available in pediatric orthopaedic practice. Furthermore, the clinical value of genetic testing patients with LCPD is unclear. With the advance of next-generation sequencing (NGS) technology, genetic testing has become clinically available as a lab test...

Introduction : Chronic non-communicable diseases, including diseases of mental origin such as Alzheimer's, affect all age groups and countries. These diseases have a major impact on the patient and their family environment. It is interesting that different questionnaires are measured in the same direction, given that different health questionnaires are used to measure caregiver burden. Objectives : To identify which type of intervention is the most appropriate to improve the health of the primary caregiver in patients with dementia...

In the United States and around the world, newborns are screened on a population basis for conditions benefiting from pre-symptomatic diagnosis and treatment. The number of screened conditions continues to expand as novel technologies for screening, diagnosing, treating, and managing disease are discovered. While screening all newborns facilitates early diagnosis and treatment, most screened conditions are treatable but not curable. Patients identified by newborn screening often require lifelong medical management and community support to achieve the best possible outcome...