Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder predominantly caused by pathogenic COL3A1 variants. Characteristic arterial and intestinal fragility and generalised severe tissue friability can lead to clinical events from childhood. We highlight a paucity of literature regarding children diagnosed with vEDS, possibly explained by a restraint in predictive testing, and present data on 63 individuals (23 index cases) with a clinical and genetic diagnosis of vEDS in childhood (<18 years) to address this.
View Article and Find Full Text PDFBackground: Merkel cell carcinoma (MCC) is a highly aggressive cutaneous malignancy for which accurate prognostication is necessary to support clinical management.
Objective: (1) To determine which survival endpoint-disease-specific death (DSD) or overall survival (OS)-was better stratified by MCC American Joint Cancer Committee eighth edition staging. (2) To develop a multivariable model for enhanced MCC survival predictions.
Introduction: the Bamenda, Santa and Tiko Health Districts are in the highest malaria transmission strata of Cameroon. The purpose of this study was to explore the indicators of ownership and utilisation as well as maintenance of Long-Lasting Insecticidal Nets (LLINs) in three health districts in Cameroon.
Methods: a cross-sectional household survey involving 1,251 households was conducted in the Tiko Health District (THD) in June and July 2017 and in Bamenda and Santa Health Districts in March to May 2018.
ACS Appl Mater Interfaces
October 2024
As the effects of climate change become more severe and widespread, maintaining personal thermal homeostasis becomes necessary for survival. In principle, advanced textiles and garments have the ability to leverage light absorption, transmission and/or reflection, in addition to straightforward convection, to heat or cool bodies in extreme temperature conditions. For cooling, in particular, surfaces adept at selectively reflecting or refracting high-energy incident light (200 nm-2.
View Article and Find Full Text PDFBackground: The cost-free increase in statistical power of using imputation to infer missing genotypes is undoubtedly appealing, but is it hazard-free? This case study of three type-2 diabetes (T2D) loci demonstrates that it is not; it sheds light on why this is so and raises concerns as to the shortcomings of imputation at disease loci, where haplotypes differ between cases and reference panel.
Results: T2D-associated variants were previously identified using targeted sequencing. We removed these significantly associated SNPs and used neighbouring SNPs to infer them by imputation.
Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis.
Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence.
Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas.
Failure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the factors that regulate the downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions to expand the pool of lineage committed progenitors allowing stem cells to preserve their self-renewal and stemness.
View Article and Find Full Text PDFACS Appl Mater Interfaces
April 2023
Humans use textiles to maintain thermal homeostasis amidst environmental extremes but known textiles have limited thermal windows. There is evidence that polar-dwelling animals have evolved a different mechanism of thermoregulation by using optical polymer materials to achieve an on-body "greenhouse" effect. Here, we design a bilayer textile to mimic these adaptations.
View Article and Find Full Text PDFMelanoma is among the most devastating human malignancies. Accurate diagnosis and prognosis are essential to offer optimal treatment. Histopathology is the gold standard for establishing melanoma diagnosis and prognostic features.
View Article and Find Full Text PDFNanobodies are single variable domain antibodies isolated from camelids and are rapidly distinguishing themselves as ideal recognition elements in biosensors due to their comparative stability, ease of production and isolation, and high binding affinities. However, transducing analyte binding by nanobodies in real time is challenging, as most nanobodies do not directly produce an optical or electrical signal upon target recognition. Here, we report a general strategy to fabricate sensitive and selective electrochemical sensors incorporating nanobodies for detecting target analytes in heterogeneous media, such as cell lysate.
View Article and Find Full Text PDFSexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice.
View Article and Find Full Text PDFReporting the activity of a specific viral protease remains an acute need for rapid point-of-care detection strategies that can distinguish active infection from a resolved infection. In this work, we present a simple colorimetric approach for reporting the activity of a specific viral protease through direct color conversion on a cotton swab, which has the potential to be extended to detect the corresponding virus. We use SARS-CoV-2 viral protease as a proof-of-concept model system.
View Article and Find Full Text PDFObjectives: To characterize the experiences of providers in completing the cause of death section on death certificates, with particular reference to deaths in people who have cancer.
Methods: Focus groups were conducted until thematic saturation was reached, resulting in four groups over three months. Participants were from a variety of specialties and levels and types of training.
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM.
View Article and Find Full Text PDFBackground: Inadequate provision of vitamin B during pregnancy is associated with a number of adverse maternal and fetal outcomes. We set out to (1) suggest pregnancy-specific reference ranges for a range of biomarkers of vitamin B; (2) assess the temporal behaviors of these markers over the course of pregnancy; and (3) test whether any biomarkers, including the genetic marker strongly associated with MMA measured early in pregnancy could reliably and significantly predict future B status within a healthy UK population of pregnant women.
Materials And Methods: We used existing biobank samples from the placebo arm of the UK Selenium in PRegnancy Intervention (SPRINT) study, to generate biochemical data for serum folate, B, holotranscobalamin (HoloTC), total homocysteine (tHcy), and MMA, calculate cB, and genotyped the polymorphism in gene on a total of =114 women across trimesters 1-3 of their pregnancy.
Objective: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations.
Research Design And Methods: To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505).
Wearable sensors allow for portable, long-term health monitoring in natural environments. Recently, there has been an increase in demand for technology that can reliably monitor respiration, which can be indicative of cardiac diseases, asthma, and infection by respiratory viruses. However, to date, the most reliable respiration monitoring system involves a tightly worn chest belt that is not conducive to longitudinal monitoring.
View Article and Find Full Text PDFBackground: Basal cell carcinoma (BCC) is the most common human cancer. Facial BCCs most commonly occur on the nose and the management of these lesions is particularly complex, given the functional and complex implications of treatment. Multidisciplinary team (MDT) meetings are routinely held to integrate expertise from dermatologists, surgeons, oncologists, radiologists, pathologists and allied health professionals.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
February 2022
This study investigated the potential genetic mechanisms which underlie adipose tissue mitochondrial dysfunction in Type 2 diabetes (T2D), by systematically identifying nuclear-encoded mitochondrial genes (NEMGs) among the genes regulated by T2D-associated genetic loci. The target genes of these 'disease loci' were identified by mapping genetic loci associated with both disease and gene expression levels (expression quantitative trait loci, eQTL) using high resolution genetic maps, with independent estimates co-locating to within a small genetic distance. These co-locating signals were defined as T2D-eQTL and the target genes as T2D genes.
View Article and Find Full Text PDFTo produce next-generation, shelf-stable biosensors for point-of-care diagnostics, a combination of rugged biomolecular recognition elements, efficient encapsulants, and innocuous deposition approaches is needed. Furthermore, to ensure that the sensitivity and specificity that are inherent to biological recognition elements are maintained in solid-state biosensing systems, site-specific immobilization chemistries must be invoked such that the function of the biomolecule remains unperturbed. In this work, we present a widely applicable strategy to develop robust solid-state biosensors using emergent nanobody (Nb) recognition elements coupled with a vapor-deposited polymer encapsulation layer.
View Article and Find Full Text PDFObjective: Gestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later in life, which might be explained by epigenetic changes in response to maternal hyperglycemic exposure.
Research Design And Methods: We explored the association between GDM exposure and maternal blood and newborn cord blood methylation in 536 mother-offspring pairs from the prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. We assessed two hypotheses.
Importance: The true incidence of sudden unexplained death in childhood (SUDC), already the fifth leading category of death among toddlers by current US Centers for Disease Control and Prevention estimates, is potentially veiled by the varied certification processes by medicolegal investigative offices across the United States.
Objective: To evaluate the frequency of SUDC incidence, understand its epidemiology, and assess the consistency of death certification among medical examiner and coroner offices in the US death investigation system.
Design, Setting, And Participants: In this case series, 2 of 13 forensic pathologists (FPs) conducted masked reviews of 100 cases enrolled in the SUDC Registry and Research Collaborative (SUDCRRC).