https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61728-0.pdf

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010

https://hull-repository.worktribe.com/preview/1797952/1-s2.0-S0140673618322797-main.pdf

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61766-8.pdf

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010

ABI
: ankle–brachial index
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
AGREE
: Appraisal of Guidelines Research and Evaluation
AHA
: American Heart Association
apoA1
: apolipoprotein A1
apoB
: apolipoprotein B
CABG
: coronary artery bypass graft surgery
CARDS
: Collaborative AtoRvastatin Diabetes Study
CCNAP
: Council on Cardiovascular Nursing and Allied Professions
CHARISMA
: Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance
CHD
: coronary heart disease
CKD
: chronic kidney disease
COMMIT
: Clopidogrel and Metoprolol in Myocardial Infarction Trial
CRP
: C-reactive protein
CURE
: Clopidogrel in Unstable Angina to Prevent Recurrent Events
CVD
: cardiovascular disease
DALYs
: disability-adjusted life years
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Trial
ED
: erectile dysfunction
eGFR
: estimated glomerular filtration rate
EHN
: European Heart Network
EPIC
: European Prospective Investigation into Cancer and Nutrition
EUROASPIRE
: European Action on Secondary and Primary Prevention through Intervention to Reduce Events
GFR
: glomerular filtration rate
GOSPEL
: Global Secondary Prevention Strategies to Limit Event Recurrence After MI
GRADE
: Grading of Recommendations Assessment, Development and Evaluation
HbA1c
: glycated haemoglobin
HDL
: high-density lipoprotein
HF-ACTION
: Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing
HOT
: Hypertension Optimal Treatment Study
HPS
: Heart Protection Study
HR
: hazard ratio
hsCRP
: high-sensitivity C-reactive protein
HYVET
: Hypertension in the Very Elderly Trial
ICD
: International Classification of Diseases
IMT
: intima-media thickness
INVEST
: International Verapamil SR/Trandolapril
JTF
: Joint Task Force
LDL
: low-density lipoprotein
Lp(a)
: lipoprotein(a)
LpPLA2
: lipoprotein-associated phospholipase 2
LVH
: left ventricular hypertrophy
MATCH
: Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke
MDRD
: Modification of Diet in Renal Disease
MET
: metabolic equivalent
MONICA
: Multinational MONItoring of trends and determinants in CArdiovascular disease
NICE
: National Institute of Health and Clinical Excellence
NRT
: nicotine replacement therapy
NSTEMI
: non-ST elevation myocardial infarction
ONTARGET
: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
OSA
: obstructive sleep apnoea
PAD
: peripheral artery disease
PCI
: percutaneous coronary intervention
PROactive
: Prospective Pioglitazone Clinical Trial in Macrovascular Events
PWV
: pulse wave velocity
QOF
: Quality and Outcomes Framework
RCT
: randomized clinical trial
RR
: relative risk
SBP
: systolic blood pressure
SCORE
: Systematic Coronary Risk Evaluation Project
SEARCH
: Study of the Effectiveness of Additional Reductions in Cholesterol and
SHEP
: Systolic Hypertension in the Elderly Program
STEMI
: ST-elevation myocardial infarction
SU.FOL.OM3
: SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids
Syst-Eur
: Systolic Hypertension in Europe
TNT
: Treating to New Targets
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use
VITATOPS
: VITAmins TO Prevent Stroke
VLDL
: very low-density lipoprotein
WHO
: World Health Organization

### 1.1 Introduction

Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

/pdf/european-guidelines-on-cardiovascular-disease-prevention-in-4z4nw4311i.pdf

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

https://openresearch-repository.anu.edu.au/bitstream/1885/164632/2/01_Bin%2bSayeed_Global%252C_regional%252C_and_national_2018.pdf

Global, regional, and national incidence, prevalence, andyears lived with disability for 354 diseases and injuries for195 countries and territories, 1990–2017: a systematicanalysis for the Global Burden of Disease Study 2017

Optogenetic modulation of neural circuits has opened new avenues into neuroscience research, allowing the control of cellular activity of genetically specified cell types. Optogenetics is still underdeveloped in the peripheral nervous system, yet there are many applications related to sensorimotor function, pain and nerve injury that would be of great benefit. We recently established a method for non-invasive, transdermal optogenetic stimulation of the facial muscles that control whisker movements in mice (Park et al., 2016, eLife, e14140)1. Here we present results comparing the effects of optogenetic stimulation of whisker movements in mice that express channelrhodopsin-2 (ChR2) selectively in either the facial motor nerve (ChAT-ChR2 mice) or muscle (Emx1-ChR2 or ACTA1-ChR2 mice). We tracked changes in nerve and muscle function before and up to 14 days after nerve transection. Optogenetic 460 nm transdermal stimulation of the distal cut nerve showed that nerve degeneration progresses rapidly over 24 hours. In contrast, the whisker movements evoked by optogenetic muscle stimulation were up-regulated after denervation, including increased maximum protraction amplitude, increased sensitivity to low-intensity stimuli, and more sustained muscle contractions (reduced adaptation). Our results indicate that peripheral optogenetic stimulation is a promising technique for probing the timecourse of functional changes of both nerve and muscle, and holds potential for restoring movement after paralysis induced by nerve damage or motoneuron degeneration.

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

Venous leg ulcer risk factors: who will study the problem?

Abstract Natural killer cells (NK) have been associated with the pathophysiology of atopic dermatitis (AD). NK function is regulated by killer cell Ig-like receptor family (KIR) receptors that interact with HLA ligands. The study goal was to focus on allelic variation in genes KIR2DL5 , KIR2DS5 , and KIR2DS1 with respect to AD. This was a case–control study of individuals with (n = 313) and without (n = 176) AD. Associations were estimated using logistic regression. The prevalence of KIR2DL5 was 52.5% (95% CI 48.0,57.0), KIR2DS5 was 33.0% (28.8,37.3), and KIR2DS1 was 33.6% (29.4,38.0). The presence of the KIR2DL5*001:01 increased the odds of having AD by about 86% (odds ratio (OR): 1.86(1.23,2.82) p = 0.003). The risk for individuals homozygous for KIR2DL5*001:01 was even greater (OR: 2.16 (95% CI 1.31,3.53) p = 0.0023). The odds of having AD with KIR2DL5*001:01 was similar in Whites and Blacks. Allelic variation in KIR2DS5 and KIR2DS1 was not associated with AD. There is no known HLA binding ligand for KIR2DL5 . The effect of KIR2DL5*001:01 increased in the presence of HLA-B*-21TT leader sequence (2.46(1.37,4.41) p = 0.0025) and the HLA-C2 ligand (2.07 (1.37,4.41, p = 0.000002). Our study shows an independent association of the KIR2DL5*001:01 with AD and is the first study to associate AD with KIR allelic variation. 

https://www.nature.com/articles/s41598-023-28847-y.pdf

Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis

Diabetes is the major risk factor for nontraumatic lower extremity amputation (LEA). The role of genetic polymorphisms in predisposing diabetics to impaired wound healing leading to LEA has not been sufficiently explored. We investigated the association between a set of genes belonging to the angiogenesis/wound repair pathway with LEA in the Chronic Renal Insufficiency Cohort, a study of adults with chronic kidney disease (CKD) that includes a subgroup with diabetes. This study was performed on 3,772 Chronic Renal Insufficiency Cohort participants who were genotyped on the ITMAT-Broad-CARe array chip. A total of 1,017 single-nucleotide polymorphisms (SNPs) in 22 genes belonging to the angiogenesis/would repair pathway were investigated. LEA was determined from patient self-report. The association between genetic variants and LEA status was examined using logistic regression and additive genetic models after stratifying the cohort by race/ethnicity and diabetic status. Unadjusted analyses as well as analyses adjusted for age, sex, estimated glomerular filtration rate, body mass index, peripheral vascular disease, hemoglobin A1c, and population stratification were performed. In non-Hispanic white participants with diabetes, rs11938826 and rs1960669, both intronic SNPs in the gene basic fibroblast growth factor-2 (FGF2), were significantly associated with LEA in covariate-adjusted analysis (OR: 2.83 (95% CI: 1.73, 4.62); p-value: 0.000034; Bonferroni adjusted p-value: 0.0006) and (OR: 2.61 (95% CI: 1.48, 4.61); p-value: 0.00095; Bonferroni adjusted p-value: 0.02). In the same subgroup, rs10883688, an FGF8 SNP of unknown functional effect, was also associated with LEA (OR: 1.72 (95% Confidence Interval: 1.14, 2.6); p-value: 0.00999; Bonferroni adjusted p-value: 0.04). No statistically significant associations were identified in the other ethnic groups. In conclusion, variant/s in FGF2 and FGF8 may predispose diabetics with CKD to LEA. Dysregulation of the FGF2 gene represents an opportunity to understand further, and possibly intervene upon, mechanisms of wound healing in diabetics with CKD.

/pdf/variants-in-genes-belonging-to-the-fibroblast-growth-factor-29qsobb32k.pdf

Variants in genes belonging to the fibroblast growth factor family are associated with lower extremity amputation in non‐Hispanic whites: Findings from the chronic renal insufficiency cohort study

NK cell function has been shown to be associated with atopic dermatitis (AD), with patients with AD usually having decreased circulating numbers of NK cells but increasing lesional skin numbers of NK cells (Kabashima and Weidinger, 2020; Mack et al., 2020; Möbus et al., 2021; Sun et al., 2021). An important regulator of NK cell function are KIR genes, which can have either inhibitory or activating effects on NK cells (Pende et al., 2019). In addition to having a potential role in the pathogenesis of AD, NK cells have also been implicated in the development of preeclampsia and endometriosis. 

http://www.jidinnovations.org/article/S2667026722000315/pdf

David J. Margolis

Papers

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

Venous leg ulcer risk factors: who will study the problem?

Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis

Variants in genes belonging to the fibroblast growth factor family are associated with lower extremity amputation in non‐Hispanic whites: Findings from the chronic renal insufficiency cohort study

Atopic Dermatitis Is Associated with Preeclampsia and Endometriosis