Thirty percent of all inherited retinal disease (IRD) is accounted for by conditions with extra-ocular features. This study aimed to establish the genetic diagnostic pick-up rate for IRD patients ...with one or more extra-ocular features undergoing panel-based screening in a clinical setting. One hundred and six participants, tested on a gene panel which contained both isolated and syndromic IRD genes, were retrospectively ascertained from the Manchester Genomic Diagnostics Laboratory database spanning 6 years (2012-2017). Phenotypic features were extracted from the clinical notes and classified according to Human Phenotype Ontology; all identified genetic variants were interpreted in accordance to the American College of Medical Genetics and Genomics guidelines. Overall, 49% (n = 52) of patients received a probable genetic diagnosis. A further 6% (n = 6) had a single disease-associated variant in an autosomal recessive disease-relevant gene. Fifty-two percent (n = 55) of patients had a clinical diagnosis at the time of testing. Of these, 71% (n = 39) received a probable genetic diagnosis. By contrast, for those without a provisional clinical diagnosis (n = 51), only 25% (n = 13) received a probable genetic diagnosis. The clinical diagnosis of Usher (n = 33) and Bardet-Biedl syndrome (n = 10) was confirmed in 67% (n = 22) and 80% (n = 8), respectively. The testing diagnostic rate in patients with clinically diagnosed multisystemic IRD conditions was significantly higher than those without one (71% versus 25%; p value < 0.001). The lower pick-up rate in patients without a clinical diagnosis suggests that panel-based approaches are unlikely to be the most effective means of achieving a molecular diagnosis for this group. Here, we suggest that genome-wide approaches (whole exome or genome) are more appropriate.
An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of ...respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.
The impact of emerging infectious diseases is increasingly recognised as a major threat to wildlife. Wild populations of the endangered Tasmanian devil,
, are experiencing devastating losses from a ...novel transmissible cancer, devil facial tumour disease (DFTD); however, despite the rapid decline of this species, there is currently no information on the presence of haemoprotozoan parasites. In the present study, 95 Tasmanian devil blood samples were collected from four populations in Tasmania, Australia, which underwent molecular screening to detect four major groups of haemoprotozoa: (i) trypanosomes, (ii) piroplasms, (iii)
, and (iv) haemosporidia. Sequence results revealed
infections in 32/95 individuals.
was identified in 10 Tasmanian devils from three sites and a second
sp. was identified in 22 individuals that were grouped within the poorly described
clade. A single blood sample was positive for
sp., which most closely matched
. No other blood protozoan parasite DNA was detected. This study provides the first insight into haemoprotozoa from the Tasmanian devil and the first identification of
and
in this carnivorous marsupial.
INTRODUCTION
Recruitment of sufficient and diverse participants into clinical research for Alzheimer's disease and related dementias remains a formidable challenge. The primary goal of this ...manuscript is to provide an overview of an approach to diversifying research recruitment and to provide case examples of several methods for achieving greater diversity in clinical research enrollment.
METHODS
The University of Kansas Alzheimer's Disease Research Center (KU ADRC) developed MyAlliance for Brain Health (MyAlliance), a service‐oriented recruitment model. MyAlliance comprises a Primary Care Provider Network, a Patient and Family Network, and a Community Organization Network, each delivering tailored value to relevant parties while facilitating research referrals.
RESULTS
We review three methods for encouraging increased diversity in clinical research participation. Initial outcomes reveal an increase in underrepresented participants from 17% to 27% in a research registry. Enrollments into studies supported by the research registry experienced a 51% increase in proportion of participants from underrepresented communities.
DISCUSSION
MyAlliance shifts power, resources, and knowledge to community advocates, promoting brain health awareness and research participation, and demands substantial financial investment and administrative commitment. MyAlliance offers valuable lessons for building sustainable, community‐centered research recruitment infrastructure, emphasizing the importance of localized engagement and cultural understanding.
Highlights
MyAlliance led to a significant increase in the representation of underrepresented racial and ethnic groups and individuals from rural areas.
The service‐oriented approach facilitated long‐term community engagement and trust‐building, extending partnerships between an academic medical center and community organizations.
While effective, MyAlliance required substantial financial investment, with costs including infrastructure development, staff support, partner organization compensation, and promotional activities, underscoring the resource‐intensive nature of inclusive research recruitment efforts.
To identify the content for a vision and quality of life-related utility measure (Vision Quality of Life Index VisQoL) for the economic evaluation of eye care and rehabilitation programs.
Focus ...groups of the visually impaired elicited key concepts. Based on these and previous research, 33 items were generated. These were administered to visually impaired adults (n = 70) and a representative sample of unimpaired adults (n = 86). The item bank was reduced through examination of item properties, exploratory factor (EFA), item response theory (IRT), and structural equation modeling (SEM) analyses. The resultant model was confirmed through administration to a second sample of participants.
Focus group themes included physical well-being, social well-being, independence, self-actualization, emotional well-being, and planning and organization. Poorly performing items were eliminated on basic psychometric properties, including failure to discriminate. Next, EFA loadings were used to select items. Twelve items survived. To minimize redundancy, IRT analysis and SEM reduced the VisQoL item pool to six items (Cronbach alpha = 0.88). To confirm this model, these items were then administered to an additional 218 participants; 35% with a vision impairment. A pooled SEM analysis showed the model to have very good fit properties (root mean square error of approximation RMSEA = 0.000). A preliminary test of the model against visual acuity showed a significant monotonic relationship.
The short 6-item VisQoL has excellent psychometric properties as a simple summative instrument. It can be used in its present state as a condition-specific outcome measure for the evaluation of healthcare interventions for the visually impaired. The descriptive model is also suitable for generating utility values for the economic evaluation of vision-related programs and services.
Insulin production in pancreatic β cells is predominantly regulated through glucose control of proinsulin translation. Previously, this was shown to require sequences within the untranslated regions ...(UTRs) of the preproinsulin (
ppI) mRNA. Here, those sequences were found to be sufficient for specific glucose-regulated proinsulin translation. Furthermore, an element 40–48 bp from the 5′ end of the
ppI mRNA specifically bound a factor present in islets of Langerhans. Glucose-responsive factor binding to this
cis-element exhibited temporal and glucose-concentration-dependent patterns that paralleled proinsulin biosynthesis. Mutating this
cis-element abolished the ability of
ppI mRNA UTRs to confer glucose regulation upon translation. Like the rat 5′UTR, the human
ppI 5′UTR conferred glucose regulation of translation. However alternative splicing of the human 5′UTR that disrupts the
cis-element abolished glucose-regulated translation. These data indicate that glucose regulation of
cis-element/
trans-acting factor interaction is a key component of the mechanism by which glucose regulates insulin production.
The iron‐y of fate: Isobole analyses of fluorescently labeled antimalarial endoperoxides with chelators selective for non‐heme iron, and laser confocal microscopy studies within living malaria ...parasites have shown that the semisynthetic analogues of artemisinin and synthetic endoperoxides (see example) share a common mechanism of action involving chelatable‐iron‐mediated bioactivation (see images) and irreversible alkylation of parasite targets.
This study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer based on personal health and family history information. The ...software is compatible with the US Surgeon General's My Family Health Portrait (MFHP).
An algorithm for risk assessment was created using accepted colorectal risk assessment guidelines and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared with "gold standard" risk assessments developed by three expert cancer genetic counselors.
Genetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for colorectal cancer yielded a sensitivity for colorectal cancer risk of 81% (95% confidence interval: 54-96%) and specificity of 90% (95% confidence interval: 83-94%), as compared with genetic counselor pedigree review. The positive predictive value for risk for MFHP was 48% (95% confidence interval: 29-68%), whereas the negative predictive value was 98% (95% confidence interval: 93-99%). Agreement between MFHP and genetic counselor pedigree review was moderate (κ = 0.54).
The analytic validity of the MFHP colorectal cancer risk assessment software is similar to those of other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups.Genet Med 17 9, 753-756.
Abstract Objective To assess the feasibility of a lifestyle intervention, focusing on diet and activity, in adults participating in cardiovascular screening. Methods The 12-week lifestyle ...intervention comprised three personalised counselling sessions plus telephone contact. Outcome data were collected by anthropometry, activity monitoring and lifestyle questionnaires. Acceptability of study measures was assessed by questionnaire and the intervention delivery by in-depth interviews. Results Between June 2008 and March 2009, 75 (62%) of 121 eligible individuals were recruited from Tayside, Scotland. Randomisation was to intervention (IV) ( n = 55) or comparison group (CG) ( n = 20). Retention was 99% across both groups. In the IV group, 63% increased moderate-vigorous activity by ≥ 30 minutes/week, 82% successfully maintained or lost weight (mean loss 1.1 kg, and 2.6 cm waist circumference) and 85% reported eating five portions of fruit and vegetables compared with 56% at baseline. No behaviour changes were detected in the CG. Feedback highlighted the value of lifestyle “checks,” realising that current habits were sub-optimal, receiving personalised advice on specific behaviours, and feeling “healthier” through participation. Conclusions HealthForce was feasible to deliver and implement, acceptable to participants, and associated with reported changes in health behaviours over a 12-week period. International Standard Randomised Controlled Trial Number: 38976321.
Insulin receptor substrate 2 (IRS-2) plays a critical role in pancreatic β-cells. Increased IRS-2 expression promotes β-cell growth and survival, whereas decreased IRS-2 levels lead to apoptosis. It ...was found that IRS-2 turnover in rat islet β-cells was rapid, with mRNA and protein half-lives of ∼90 min and ∼2 h, respectively. However, this was countered by specific glucose-regulated IRS-2 expression mediated at the transcriptional level. Glucose (≥6 mm) increased IRS-2 mRNA and protein levels in a dose-dependent manner, reaching a maximum 4-fold increase in IRS-2 mRNA and a 5–6-fold increase in IRS-2 protein levels at ≥12 mm glucose (p ≤ 0.01). Glucose (15 mm) regulation of islet β-cell IRS-2 gene expression was rapid, with a significant increase in IRS-2 mRNA levels within 2 h that reached a maximum 4-fold increase by 4 h. IRS-2 protein expression in β-cells followed that of IRS-2 mRNA. Glucose metabolism was necessary for increased IRS-2 expression in β-cells. Moreover, inhibition of a glucose-induced rise in islet β-cell cytosolic Ca2+i prevented an increase in IRS-2 expression, indicating this was Ca2+-dependent. The glucose-induced rise in IRS-2 levels correlated with increased IRS-2 tyrosine phosphorylation and downstream activation of protein kinase B. These data indicate that fluctuations of glucose in the normal physiological range (5–15 mm) promote β-cell survival via regulation of IRS-2 expression and a subsequent parallel protein kinase B activation. Given that the onset of type-2 diabetes is marked by loss of β-cells, these data further the idea that controlled IRS-2 expression in β-cells could be a therapeutic means to promote β-cell survival and delay the onset of the disease.
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