Chromogenic detection of yam mosaic virus by closed-tube reverse transcription loop-mediated isothermal amplification (CT-RT-LAMP)

A closed-tube reverse transcription loop-mediated isothermal amplification (CT-RT-LAMP) assay was developed for the detection of yam mosaic virus (YMV, genus Potyvirus) infecting yam (Dioscorea spp.). The assay uses a set of six oligonucleotide primers targeting the YMV coat protein region, and the amplification products in YMV-positive samples are visualized by chromogenic detection with SYBR Green I dye. The CT-RT-LAMP assay detected YMV in leaf and tuber tissues of infected plants. The assay is 100 times more sensitive in detecting YMV than standard RT-PCR, while maintaining the same specificity

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Distribution and relative abundance of bean leaf beetles (Ootheca spp.) (Insecta: Coleoptera: Chrysomelidae) in Uganda

Bean leaf beetles (Ootheca spp.) (Insecta: Coleoptera: Chrysomelidae) are one of Africa’s most destructive pests of common bean and other leguminous crops. The beetles are widely distributed in Africa where they are estimated to cause annual crop yield losses of 116,400 tons of crop yields in sub-Saharan Africa. Despite their importance, little is known about the distribution, relative abundance and damage caused by bean leaf beetles in Uganda. As a result, the development of effective management methods has been hampered. We conducted surveys in six key Ugandan agro-ecological zones to determine the species distribution and relative abundance of bean leaf beetles. Findings indicate that leaf beetles belonging to 12 genera are present, including members of the genera Afrophthalma Medvedev, 1980, Buphonella Jacoby, 1903, Chrysochrus Chevrolat in Dejean, 1836, Diacantha Dejean, 1845, Exosoma Jacoby, 1903, Lamprocopa Hincks, 1949, Lema Fabricius, 1798, Nisotra Baly, 1864, Neobarombiella Bolz and Wagner, 2012, Ootheca Dejean, 1935, Parasbecesta Laboissière, 1940, and Plagiodera Dejean, 1835. We identified only three species belonging to the genus Ootheca: O. mutabilis, O. proteus, and O. orientalis. Seventy percent of all the beetles collected were O. mutabilis and these were present in all agro-ecological zones studied. The Northern Moist Farmlands (21.9%), West Nile Farmlands (12.9%), Central Wooded Savanna (4.4%) and Southern and Eastern Lake Kyoga Basin (1.4%) were the only agro-ecological zones where O. proteus was found. Only one specimen of O. orientalis was found at a single site in the Central Wooded Savanna. The Northern Moist Farmlands had a significantly (p < 0.05) higher bean leaf beetle density than the West Nile Farmlands and Southwestern Highlands. Similarly, the Northern Moist Farmlands had the highest beetle foliar damage per plant (1.15 - 0.05), while the Southwestern Highlands had the lowest (0.03 - 0.02). We provide the first information on Ootheca species distribution, abundance and damage in Uganda. Our findings provide a foundation for assessing the importance of Ootheca spp. as common bean pests in Uganda

Global COVID-19 childhood disability data coordination: A collaborative initiative of the international alliance of academies of childhood disability

Purpose: The International Alliance of Academies of Childhood Disability created a COVID-19 Task Force with the goal of understanding the global impact of COVID-19 on children with disabilities and their families. The aim of this paper is to synthesize existing evidence describing the impact of COVID-19 on people with disabilities, derived from surveys conducted across the globe. Methods: A descriptive environmental scan of surveys was conducted. From June to November 2020, a global call for surveys addressing the impact of COVID-19 on disability was launched. To identify gaps and overlaps, the content of the surveys was compared to the Convention of the Rights of the Child and the International Classification of Functioning, Disability and Health. Results: Forty-nine surveys, involving information from more than 17,230 participants around the world were collected. Overall, surveys identified that COVID-19 has negatively impacted several areas of functioning - including mental health, and human rights of people with disabilities and their families worldwide. Conclusion: Globally, the surveys highlight that impact of COVID-19 on mental health of people with disabilities, caregivers, and professionals continues to be a major issue. Rapid dissemination of collected information is essential for ameliorating the impact of COVID-19 across the globe

Ramadan and Diabetes: A Narrative Review and Practice Update.

Fasting in the Islamic month of Ramadan is obligatory for all sane, healthy adult Muslims. The length of the day varies significantly in temperate regions-typically lasting ≥ 18 h during peak summer in the UK. The synodic nature of the Islamic calendar means that Ramadan migrates across all four seasons over an approximately 33-year cycle. Despite valid exemptions, there is an intense desire to fast during this month, even among those who are considered to be at high risk, including many individuals with diabetes mellitus. In this review we explore the current scientific and clinical evidence on fasting in patients with diabetes mellitus, focussing on type 2 diabetes mellitus and type 1 diabetes mellitus, with brief reviews on pregnancy, pancreatic diabetes, bariatric surgery, the elderly population and current practice guidelines. We also make recommendations on the management of diabetes patients during the month of Ramadan. Many patients admit to a do-it-yourself approach to diabetes mellitus management during Ramadan, largely due to an under-appreciation of the risks and implications of the rigors of fasting on their health. Part of the issue may also lie with a healthcare professional's perceived inability to grasp the religious sensitivities of Muslims in relation to disease management. Thus, the pre-Ramadan assessment is crucial to ensure a safe Ramadan experience. Diabetes patients can be risk-stratified from low, medium to high or very high risk during the pre-Ramadan assessment and counselled accordingly. Those who are assessed to be at high to very high risk are advised not to fast. The current COVID-19 pandemic upgrades those in the high-risk category to very high risk; hence a significant number of diabetes patients may fall under the penumbra of the 'not to fast' advisory. We recognize that fasting is a personal choice and if a person chooses to fast despite advice to the contrary, he/she should be adequately supported and monitored closely during Ramadan and for a brief period thereafter. Current advancements in insulin delivery and glucose monitoring technologies are useful adjuncts to strategies for supporting type 1 diabetes patients considered to be high risk as well as 'high-risk' type 2 patients manage their diabetes during Ramadan. Although there is a lack of formal trial data, there is sufficient evidence across the different classes of therapeutic hypoglycaemic agents in terms of safety and efficacy to enable informed decision-making and provide a breadth of therapeutic options for the patient and the healthcare professional, even if the professional advice is to abstain. Thus, Ramadan provides an excellent opportunity for patient engagement to discuss important aspects of management, to improve control in the short term during Ramadan and to help the observants understand that the metabolic gains achieved during Ramadan are also sustainable in the other months of the year by maintaining a dietary and behavioural discipline. The application of this understanding can potentially prevent long-term complications. Electronic Supplementary Material The online version of this article (10.1007/s13300-020-00886-y) contains supplementary material, which is available to authorized users