Ronald Klein

Bio: Ronald Klein is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Population & Diabetic retinopathy. The author has an hindex of 194, co-authored 1305 publications receiving 149140 citations. Previous affiliations of Ronald Klein include Los Angeles Biomedical Research Institute & Wake Forest University.

A Novel Synaptic Vesicle-Associated Phosphoprotein: SVAPP-120

Abstract: Generation of antibodies and direct protein sequencing were used to identify and characterize proteins associated with highly purified synaptic vesicles from rat brain A protein doublet of low abundance of 119 and 124 kDa apparent molecular mass [synaptic vesicle-associated phosphoprotein with a molecular mass of 120 kDa (SVAPP-120)] was identified using polyclonal antibodies SVAPP-120 was found to copurify with synaptic vesicles and to be enriched in the purified synaptic vesicle fraction to the same extent as synapsin I Like synapsin I, SVAPP-120 is not an integral membrane protein because it was released from synaptic vesicles by high salt concentrations This protein was demonstrated to be brain specific, and its distribution in various brain regions paralleled the distribution of synapsin I and synaptophysin During the postnatal development of the rat cortex and cerebellum, its expression correlated with synaptogenesis SVAPP-120 was demonstrated to be a phosphoprotein both in vivo and in vitro It was shown to be phosphorylated on serine and to a lesser extent on threonine residues These results provide evidence that SVAPP-120 represents a novel synaptic vesicle-associated phosphoprotein In addition, aldolase, a glycolytic enzyme, and alpha c-adaptin, a clathrin assembly-promoting protein, were identified on purified synaptic vesicles by direct protein sequencing

The use of hearing protection devices by older adults during recreational noise exposure.

Abstract: A population-based study to assess the use of hearing protection devices by older adults during noisy recreational activities was performed The population-based Epidemiology of Hearing Loss Study was designed to measure the prevalence of hearing loss in adults residing in Beaver Dam, Wisconsin The use of hearing protection devices during noisy recreational activities was assessed by performing three examinations over a period of 10 years (1993-1995, no of participants (n)=3753, aged 48-92 years; 1998-2000, n=2800, aged 53-97 years; 2003-2005, n=2395, aged 58-100 years) The recreational activities included hunting, target shooting, woodworking/carpentry, metalworking, driving loud recreational vehicles, and performing yard work using either power tools or a chain saw The prevalence of using hearing protection devices during any of these activities increased with time (95%, 150%, and 199% at baseline, 5 years, and 10 years, respectively) However, the use of hearing protection devices remained low for most activities Those under the age of 65 were twice as likely to use hearing protection devices during noisy activities than were older adults Men, those with a hearing handicap, and those with significant tinnitus were more likely to use hearing protection devices Smokers and the less educated were less likely to use hearing protection devices The results demonstrated that many adults expose themselves to potentially damaging recreational noise, leaving them at risk for hearing loss

Brain Aging in Midlife: The Beaver Dam Offspring Study.

Abstract: Objectives Middle age has been identified as a critical time period for health later in life. Identifying factors associated with worse brain function in middle-aged adults may help identify ways to preserve brain function with aging. Our objective was to evaluate factors associated with a novel measure of brain aging in middle-aged and older adults. Design Longitudinal cohort study. Setting Beaver Dam Offspring Study (BOSS) baseline (2005-2008), 5-year (2010-2013), and 10-year examinations (2015-2017). Participants A total of 2285 adults, 22 to 84 years of age, with complete sensorineural and neurocognitive data at the 5-year examination. Measurements Principal component analysis (PCA) was performed combining 5-year sensorineural (hearing, vision, olfaction) and cognitive (Trail Making Test A and B, Digit Symbol Substitution Test, Verbal Fluency Test, Auditory Verbal Learning Test) test data. Participants with a standardized PCA score less than -1 were classified as having brain aging. Incident brain aging was defined as a PCA score less than -1 at 10 years among participants who had a PCA score of -1 or higher at 5 years. Logistic regression and Poisson models were used to estimate associations between baseline factors and prevalent or incident brain aging, respectively. Results Older age, being male, current smoking, larger waist circumference, not consuming alcohol, cardiovascular disease, and interleukin-6 were associated with greater odds of prevalent brain aging, whereas more education and exercise were associated with decreased odds. In addition to age and sex, less than a college education, higher levels of soluble intercellular adhesion molecule-1, diabetes, depressive symptoms, and history of head injury were associated with an increased 5-year risk of incident brain aging. Conclusion In the current study, vascular and inflammatory factors were associated with a new brain aging marker in middle-aged and older adults. Many of these factors are modifiable, highlighting the importance of addressing health and lifestyle factors in midlife to potentially preserve function for better brain health later in life. J Am Geriatr Soc 67:1610-1616, 2019.

Polygenic Effects and Cigarette Smoking Account for a Portion of the Familial Aggregation of Nuclear Sclerosis

Abstract: Cataract is the most common cause of blindness worldwide. Nuclear cataract, an advanced stage of nuclear sclerosis, is the most common type of age-related cataract. The authors assessed data from 2,089 persons within 620 extended pedigrees who participated in the 1988-1990 Beaver Dam Eye Study in Wisconsin to determine whether the observed familial aggregation of nuclear sclerosis could be explained by inheritance of a major gene. Familial correlations were examined and segregation analyses were performed on nuclear sclerosis measurements adjusted for age, sex, and pack-years of cigarette smoking. There was modest correlation among close family members after adjustment for age, sex, and pack-years of cigarette smoking: 0.084 between parents and offspring, and 0.198 between sibling pairs. Although results do not support involvement of a single major locus in the etiology of nuclear sclerosis, models that allowed for familial correlation, attributable in part to polygenic effects, did provide a better fit to the observed data than models without a polygenic effect. This finding suggests that several genes of modest effect may influence development of nuclear lens opacity, possibly in conjunction with environmental factors. Cigarette smoking was an important covariate in these analyses. Overall, results highlight the complex etiology of nuclear sclerosis.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

Abstract: Background Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. Methods A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. Results In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Conclusions Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

A New Equation to Estimate Glomerular Filtration Rate

Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

A global reference for human genetic variation.

Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.