Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease.

Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity.

Prognostic stratification in older adults commencing dialysis.

Background: Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.

Methods: In a cohort of patients aged ≥ 67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age.

Thematic synthesis of qualitative studies on patient and caregiver perspectives on end-of-life care in CKD.

Background: Although dialysis prolongs life for patients with end-stage kidney disease, 20% of deaths in this population are preceded by dialysis therapy withdrawal. Recently, there has been more focus on conservative (nondialytic) care as a legitimate option, particularly for elderly patients. This study aims to describe patients' and caregivers' perspectives on conservative treatment and end-of-life care in chronic kidney disease (CKD).

Clinical impact of recent genetic discoveries in osteoporosis.

Osteoporotic fracture carries an enormous public health burden in terms of mortality and morbidity. Current approaches to identify individuals at high risk for fracture are based on assessment of bone mineral density and presence of other osteoporosis risk factors. Bone mineral density and susceptibility to osteoporotic fractures are highly heritable, and over 60 loci have been robustly associated with one or both traits through genome-wide association studies carried out over the past 7 years.

Discovery and refinement of loci associated with lipid levels.

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans.

Longitudinal diffusion tensor imaging and neuropsychological correlates in traumatic brain injury patients.

Traumatic brain injury (TBI) often involves focal cortical injury and white matter (WM) damage that can be measured shortly after injury. Additionally, slowly evolving WM change can be observed but there is a paucity of research on the duration and spatial pattern of long-term changes several years post-injury. The current study utilized diffusion tensor imaging to identify regional WM changes in 12 TBI patients and nine healthy controls at three time points over a four year period.

The evaluation of rapidly progressive dementia.

Background: Rapidly progressive dementia (RPD) is a unique set of disorders resulting in cognitive, behavioral, and motor decline within 2 years. A variety of etiologies may contribute to RPD including neurodegenerative, inflammatory, infectious, and toxic-metabolic conditions. Jakob-Creutzfeldt disease (CJD) is frequently the most concerning diagnosis on the differential.

Should there be an expanded role for palliative care in end-stage renal disease?

Purpose Of Review: In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation.

Recent Findings: Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently.

Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women.

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women.

Exercise can increase small heat shock proteins (sHSP) and pre- and post-synaptic proteins in the hippocampus.

The molecular events mediating the complex interaction between exercise and cognition are not well-understood. Although many aspects of the signal transduction pathways mediate exercise induced improvement in cognition are elucidated, little is known about the molecular events interrelating physiological stress with synaptic proteins, following physical exercise. Small heat shock proteins (sHSP), HSP27 and alpha-B-crystallin are co-localized to synapses and astrocytes, but their role in the brain is not well-understood.

Molecular pathology of aging and its implications for senescent coronary atherosclerosis.

Purpose Of Review: This review highlights common mechanisms of organismal aging and inflammatory coronary atherosclerosis.

Recent Findings: A substantial body of evidence now indicates that aging is largely due to molecular damage inflicted by reactive oxygen species, electrophiles, and other reactive endobiotic and xenobiotic metabolites. Our understanding of genetic pathways regulating longevity began 12 years ago with the discovery that a developmental-arrest program in the nematode Caenorhabditis elegans also has marked effects on adult lifespan.

Are all pressure ulcers avoidable?

A quality of care debate centers on whether pressure ulcers result from factors largely dependent on caregivers, or whether pressure ulcers result from factors associated with patient morbidity. A reduction in incidence, defined as the development of a new pressure ulcer, is the focus of prevention strategies. Yet epidemiological data demonstrates a stability in the incidence of pressure ulcers despite drastic improvements in understanding of pressure ulcers, increased regulatory oversight, and improvements in technologies available for prevention of pressure ulcers.

Are all pressure ulcers avoidable?

A quality of care debate centers on whether pressure ulcers result from factors largely dependent on caregivers, or whether pressure ulcers result from factors associated with patient morbidity. A reduction in incidence, defined as the development of a new pressure ulcer, is the focus of prevention strategies. Yet epidemiological data demonstrates a stability in the incidence of pressure ulcers despite drastic improvements in understanding of pressure ulcers, increased regulatory oversight, and improvements in technologies available for prevention of pressure ulcers.

Optimizing aptamer activity for gene therapy applications using expression cassette SELEX.

RNA aptamers against a variety of clinically relevant target proteins have been generated. For example, we previously isolated an RNA aptamer that inhibits the function of the E2F family of transcription factors that play a critical role in the control of cell proliferation. However, the development of this and other aptamers for gene therapy applications has been complicated by the fact that expression of RNA aptamers in the context of flanking sequences can inhibit the ability of an aptamer to fold into its functional conformation.

Reconstitution of dna synthetic capacity in senescent normal human fibroblasts by expressing cellular factors E2F and Mdm2.

Unraveling the mechanisms underlying cellular senescence will contribute to the understanding of processes involved in aging and cancer. We sought to determine whether expression of cellular factors in senescent WI-38 human fibroblasts was sufficient to induce nuclear DNA synthesis. Expression by recombinant adenovirus of E2F1, E2F2, E2F3, cyclin E/cdk2, and Mdm2 individually resulted in DNA synthesis in 10-30% of cells.

Cholinergic control of cerebral blood flow in stroke, trauma and aging.

Enhancing the availability of endogenous acetylcholine by inhibition of cholinesterase with physostigmine, eptastigmine or soman at sub-toxic doses increases cerebral blood flow (CBF) and the response of this variable to changes in PaCO2. These effects are not correlated with metabolic activation, suggesting that the function of the cholinergic vasodilation is not merely to supply metabolic substrates. Since choline (Ch) can exchange between blood and the brain extracellular milieu the stage is set for possible feedback interactions between ACh synthesis and CBF.