Publications

PURPOSE

Despite concerns over risks from exposure to low-dose ionizing radiations encountered in the environment and workplace, the molecular consequences of these exposures, particularly at representative doses and dose-rates, remains poorly understood.

MATERIALS AND METHODS

Using a novel flood source construct, we performed a direct comparison of genome-wide gene expression regulations resulting from exposure of primary human prostate fibroblast cultures to acute (10 cGy and 200 cGy) and longer-term chronic (1.0-2.45 cGy cumulative over 24 h) exposures.

RESULTS

Expression profiling showed significant differential regulation of 396 genes with no measureable changes in the acute 10 cGy dose. However, there were 106 genes in common between samples given an acute 200 cGy dose compared to those given chronic doses, most of which were decreased and related to cell cycle or chromosomal movement in M-phase. Biological pathway analysis showed decreases in cell cycle, chromosomal movement, cell survival and DNA replication, recombination and repair as well as a predicted activation of transcriptional regulators TP53, RB1 and CDKN2A. In agreement with these results, prostate epithelial cells given 200 cGy or chronic doses displayed functional decreases in proliferation and mitotic cells.

CONCLUSIONS

In summary, we showed a contrast to the common observation of constant or reduced effect per unit dose as the dose (acute) was diminished, that even very low total doses delivered chronically could rival the perturbing effect of acute doses 100 times as intense. Underscored is the importance of the means of dose delivery, shown to be as important as dose size when considering biologic effect.

BACKGROUND

Multimorbidity (the presence of multiple chronic conditions) is associated with high levels of healthcare utilization and associated costs. We investigated the association between number of chronic conditions and costs of care for nonelderly and elderly Veterans Affairs (VA) patients, and estimated mean VA healthcare costs for the most prevalent and most costly combinations of 3 conditions (triads).

METHODS

We identified a cohort of 5,233,994 patients who received care within the VA system in fiscal year 2010. We estimated the costs of VA care for each patient using established methods and aggregated costs for inpatient care, outpatient care, prescription drugs, and contract care. Using ICD-9 diagnosis fields from all inpatient and outpatient records, we determined the prevalence of 28 chronic conditions and all condition triads. We then compared the condition-cost gradient, most prevalent triads, and most costly triads among nonelderly (below 65 y) and elderly (65 y and above) patients.

RESULTS

Almost one third of nonelderly and slightly more than a third of elderly VA patients had ≥3 conditions, but these patients accounted for 65% and 67% of total VA healthcare costs, respectively. The most common triad of chronic conditions for both nonelderly and elderly patients was diabetes, hyperlipidemia, and hypertension (24% and 29%, respectively). Conditions that were present in the most costly triads included spinal cord injury, heart failure, renal failure, ischemic heart disease, peripheral vascular disease, stroke, and depression. Although patients with the most costly triads had average costs that were 3 times higher than average costs among patients with ≥3 conditions, the prevalence of these costly triads was extremely low (0.1%-0.4%).

CONCLUSIONS

Patients with multiple chronic conditions account for a disproportionate share of VA healthcare expenditures. Interventions that aim to optimize care and contain costs for multimorbid patients need to incorporate strategies specific to the most prevalent and the most costly combinations of conditions.

STUDY OBJECTIVES

Cytokine activity and polymorphisms have been associated with sleep outcomes in prior animal and human research. The purpose of this study was to determine whether circulating plasma cytokines and cytokine polymorphisms are associated with the poor sleep maintenance commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).

DESIGN

Cross-sectional descriptive study.

SETTING

HIV clinics and community sites in the San Francisco Bay area.

PARTICIPANTS

A convenience sample of 289 adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS.

INTERVENTIONS

None.

MEASUREMENTS AND RESULTS

A wrist actigraph was worn for 72 h to estimate the percentage of wake after sleep onset (WASO%) and total sleep time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for demographic variables such as race and sex, and clinical variables such as CD4+ count and medications, higher WASO% was associated with single nucleotide polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also associated with short sleep duration.

CONCLUSIONS

This study strengthens the evidence for an association between inflammation and sleep maintenance problems. In this chronic illness population, cytokine polymorphisms associated with wake after sleep onset provide direction for intervention research aimed at comparing anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance and total sleep time.

SUMMARY

In this study, we present a novel technique for reduction and fixation of complex, unstable proximal humerus fractures with diaphyseal extension with the assistance of fibula allograft. We treated 14 patients using this technique since 2009 and found that it improves the reduction and enhances fixation while making the surgical procedure technically more manageable, and allows for early postoperative motion. In the first part of this study, we describe in detail the indications and surgical technique applied to these fractures. In the second part, we review the clinical and radiographic outcomes of these patients. Using this new technique, we have achieved an excellent union rate with minimal incidence of complications when treating these challenging fractures.