Sea surface temperature and the subsequent freshwater survival rate of some salmon stocks: a surprising link between the climate of land and sea

Previous consideration of the relationship between climate and the survival rate of Pacific salmon eggs and fry has been confined to effects of large variation in the ambient freshwater environment; e.g., stream discharge, temperature, turbidity. This analysis shows sea surface temperatures during the last year of life of maturing adult salmon are also strongly associated with the subsequent survival rate of salmon eggs and fry is fresh water, presumably through development of the future eggs or sperm. In several stocks of three species of North American salmon, the association between the "marine" climate and egg survival is stronger than, or additive to, any estimated climatic association in fresh water. This apparent and surprising link between fresh water and the distant ocean has some interesting and complex implications for management of future salmon production

Very high prevalence of 25-hydroxyvitamin D deficiency in 6433 UK South Asian adults : Analysis of the UK Biobank Cohort

Acknowledgements This research has been conducted using the UK Biobank Resource under application number 15168. This work was supported by in-house funds from the University of Surrey for payment of the UK Biobank access fee. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. UK Biobank is hosted by the University of Manchester and supported by the National Health Service (NHS). All the above funders had no role in the design, analysis or writing of the present study. Author contributions were as follows: Formulating the research question(s) (A. L. D., D. J. B., K. R. A., S. L. N.), designing the study (A. L. D., D. J. B., K. R. A., S. A. L.-N.), data collection (not applicable), analysing the data (A. L. D., D. J. B., K. R. A., S. A. L.-N.) and writing the article (A. L. D., D. J. B., K. R. A., S. L. N.). S. A. L.-N. discloses that she is Research Director of D3-TEX limited which holds the UK and Gulf Corporation Council (GCC) patents for the use of UVB transparent clothing to prevent vitamin D deficiency. S. A. L.-N.’s husband William Lanham-New is Managing Director of D3-TEX limited. S. A. L.-N. has received grants from (1) The UK Biotechnology and Biological Sciences Research Council (BBSRC) (project: Ergocalciferol (D2) v. Cholecalciferol (D3) Food Fortification: Comparative Efficiency in Raising 25OHD Status & Mechanisms of Action (D2–D3 Study), BB/I006192/1, £516 823); (2) The UK Food Standards Agency (Project: Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England (D-FINES) Study, N05064, £600 000); (3) The European Union (Project: Food Based Solutions for optimal vitamin D nutrition and health through the life cycle, Lead Work Package; (4) nutritional requirements for vitamin D during pregnancy, childhood and adolescence using RCTs, FP7-613977-ODIN, Euro 6·2 million) and (5) The UK Ministry of Defence (MoD, £2·4 million). S. L. N. is a current member of the Scientific Advisory Committee for Nutrition (SACN) and a member of the panel who was responsible for the most recent revision of vitamin D recommended nutritional intake guidelines in the UK. She is a board member for the UK Royal Osteoporosis Society and the British Nutrition Foundation. She is Secretary of the Nutrition Society as well as Editor in Chief of the Nutrition Society textbook series. All other authors have no conflict of interest.Peer reviewedPublisher PD

Vitamin D Status of the British African-Caribbean Residents : Analysis of the UK Biobank Cohort

Funding: This work is part of the PhD of R.M.V., which is funded by the Universities Global Part‐ nership Network, co‐supervised by the Universities of Surrey and Wollongong. Funders did not have a role in the study. The researchers are independent to the funders. All authors take responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPublisher PD

Infection and transmission dynamics of rKSHV.219 in primary endothelial cells

Kaposi's sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of Kaposi's sarcoma (KS), a tumour of endothelial cell origin. The study of KS development was aided by the generation of a recombinant GFP (latent)/RFP (lytic)-expressing KSHV (rKSHV.219) by Vieira and O’Hearn (2004). In this study the first data characterising primary endothelial cell infection and transmission with this virus is presented. Infection was predominantly latent and the percentage of GFP-positive cells increased over time. Neither horizontal transmission of infection, nor cellular proliferation, explained this increase. Analysis of latency-associated nuclear antigen (LANA-1) expression revealed that a threshold level of infection was required for GFP expression early post infection. At later time points GFP correlated more closely with LANA-1 expression, likely due to the accumulation of GFP over time. This study provides methodological guidance for the use of rKSHV.21. In addition, it highlights potential problems associated with the use of fluorescent proteins as markers of viral infection

Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II.

Bone morphogenetic proteins (BMPs) are critically involved in early development and cell differentiation. In humans, dysfunction of the bone morphogenetic protein type II receptor (BMPR-II) is associated with pulmonary arterial hypertension (PAH) and neoplasia. The ability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma and primary effusion lymphoma, to down-regulate cell surface receptor expression is well documented. Here we show that KSHV infection reduces cell surface BMPR-II. We propose that this occurs through the expression of the viral lytic gene, K5, a ubiquitin E3 ligase. Ectopic expression of K5 leads to BMPR-II ubiquitination and lysosomal degradation with a consequent decrease in BMP signaling. The down-regulation by K5 is dependent on both its RING domain and a membrane-proximal lysine in the cytoplasmic domain of BMPR-II. We demonstrate that expression of BMPR-II protein is constitutively regulated by lysosomal degradation in vascular cells and provide preliminary evidence for the involvement of the mammalian E3 ligase, Itch, in the constitutive degradation of BMPR-II. Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease

Prescribing paradigm shift? Applying the 2019 European Society of Cardiology-led guidelines on ‘diabetes, pre-diabetes, and cardiovascular disease’ to assess eligibility for sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists as first-line monotherapy (or add-on to metformin monotherapy) in type 2 diabetes in Scotland

Objective: In 2019, the European Society of Cardiology led and released new guidelines for diabetes cardiovascular risk management, reflecting recent evidence of cardiovascular disease (CVD) reduction with sodium–glucose cotransporter 2 inhibitors (SGLT-2is) and some glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D). A key recommendation is that all those with T2D who are (antihyperglycemic) drug naïve or on metformin monotherapy should be CVD risk stratified and an SGLT-2i or a GLP-1RA initiated in all those at high or very high risk, irrespective of glycated hemoglobin. We assessed the impact of these guidelines in Scotland were they introduced as is.Research design and methods: Using a nationwide diabetes register in Scotland, we did a cross-sectional analysis, using variables in our register for risk stratification at 1 January 2019. We were conservative in our definitions, assuming the absence of a risk factor where data were not available. The risk classifications were applied to people who were drug naïve or on metformin monotherapy and the anticipated prescribing change calculated.Results: Of the 265,774 people with T2D in Scotland, 53,194 (20.0% of those with T2D) were drug naïve, and56,906(21.4%) were on metformin monotherapy. Of these, 74.5%and72.4%, respectively, were estimated as at least high risk given the guideline risk definitions.Conclusions: Thus, 80,830 (30.4%) of all those with T2D (n 5 265,774) would start one of these drug classes according to table 7 and figure 3 of the guideline. The sizeable impact on drug budgets, enhanced clinical monitoring, and the trade-off with reduced CVD-related health care costs will need careful consideration.</p

Effect of serum sample storage temperature on metabolomic and proteomic biomarkers

Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at - 20 degrees C vs - 80 degrees C. Our objectives were to document analytes affected by storage of serum samples at - 20 degrees C vs - 80 degrees C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at - 80 degrees C and - 20 degrees C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at -20 degrees C and at - 80 degrees C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at - 20 degrees C vs - 80 degrees C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at - 20 degrees C vs - 80 degrees C. The results provide a catalogue of analytes unaffected and affected by storage at - 20 degrees C vs - 80 degrees C and biomarkers indicative of suboptimal storage.Peer reviewe

KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection

Funding Information: This research was supported in part by Cancer Research Switzerland , Switzerland ( KFS-4091-02-2017 ); KFSP-PrecisionMS and HMZ ImmunoTargET of the University of Zurich , Switzerland; the Cancer Research Center Zurich , Switzerland; the Vontobel Foundation , Switzerland; the Baugarten Foundation , Switzerland; the Sobek Foundation , Germany; the Swiss Vaccine Research Institute , Switzerland; Roche , Switzerland; Novartis , Switzerland; and the Swiss National Science Foundation , Switzerland ( 310030B_182827 and CRSII5_180323 ). A.M.M. was funded by a National Institutes of Health , United States, grant ( R01 CA189806 ). N.C. was supported by a career advancement grant from the University of Zurich , Switzerland ( FK-18-026 ). D.M. and M.B. were supported by MD-PhD fellowships from the Swiss National Science Foundation , Switzerland, and the Swiss Academy of Medical Sciences , Switzerland ( 323530_145247 and 323630_19938 ).Peer reviewedPublisher PD

Cohort profile : the Scottish Diabetes Research Network national diabetes cohort - a population-based cohort of people with diabetes in Scotland

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

Calibrating a network meta-analysis of diabetes trials of sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors to a representative routine population : a systematic review protocol

Introduction: Participants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register. Methods and analysis: Medline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded. We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin. Ethics and dissemination: Ethical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147). PROSPERO registration number: CRD42020184174