Publications

OBJECTIVES

Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya.

DESIGN

This is a pilot cluster randomized controlled trial.

METHODS

The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years' old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for 1 year. Data were collected on nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms.

RESULTS

We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/μl, P < 0.001) and proportion virologically suppressed in the intervention arm compared with the control arm (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95% confidence interval: 2.2-26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, P < 0.001) and frequency of food consumption (9.4 times per week greater frequency, P = 0.013) compared to controls.

CONCLUSION

Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity.

During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum sexual and asexual blood stage (ABS) development. Using liquid chromatography-mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum, and 70%-75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts.

BACKGROUND

Isocyanates remain a leading cause of work-related asthma (WRA).

METHODS

Two independent data systems were analyzed for the period 1993-2008: (1) State-based WRA case surveillance data on persons with isocyanate-induced WRA from four states, and (2) Occupational Safety and Health Administration (OSHA) Integrated Management Information System (IMIS) isocyanate air sampling results.

RESULTS

We identified 368 cases of isocyanate-induced WRA from 32 industries and 678 OSHA isocyanate air samples with detectable levels from 31 industries. Seventeen industries were unique to one or the other dataset.

CONCLUSION

Isocyanate-induced WRA continues to occur in a wide variety of industries. Two data systems uncovered industries with isocyanate exposures and/or illness. Improved control measures and standards, including medical surveillance, are needed. More emphasis is needed on task-specific guidance, spill clean-up procedures, skin and respiratory protection, and targeted medical monitoring to mitigate the hazards of isocyanate use.

The primary afferent nociceptor was used as a model system to study mechanisms of pain induced by chronic opioid administration. Repeated intradermal injection of the selective mu-opioid receptor (MOR) agonist DAMGO induced mechanical hyperalgesia and marked prolongation of prostaglandin E2 (PGE2) hyperalgesia, a key feature of hyperalgesic priming. However, in contrast to prior studies of priming induced by receptor-mediated (i.e., TNFα, NGF, or IL-6 receptor) or direct activation of protein kinase Cε (PKCε), the pronociceptive effects of PGE2 in DAMGO-treated rats demonstrated the following: (1) rapid induction (4 h compared with 3 d); (2) protein kinase A (PKA), rather than PKCε, dependence; (3) prolongation of hyperalgesia induced by an activator of PKA, 8-bromo cAMP; (4) failure to be reversed by a protein translation inhibitor; (5) priming in females as well as in males; and (6) lack of dependence on the isolectin B4-positive nociceptor. These studies demonstrate a novel form of hyperalgesic priming induced by repeated administration of an agonist at the Gi-protein-coupled MOR to the peripheral terminal of the nociceptor. Significance statement: The current study demonstrates the molecular mechanisms involved in the sensitization of nociceptors produced by repeated activation of mu-opioid receptors and contributes to our understanding of the painful condition observed in patients submitted to chronic use of opioids.

Novel targeted cancer therapies, especially kinase inhibitors, have revolutionized the treatment of many cancers and have dramatically improved the survival of several types of malignancies. Because kinases not only are important in cancer development and progression, but also play a critical role in the cardiovascular (CV) system and metabolic homeostasis, important CV and metabolic sequelae have been associated with several types of kinase inhibitors. This paper reviews the incidences and highlights potential mechanisms of vascular and metabolic perturbations associated with 3 classes of commonly used kinase inhibitors that target the vascular endothelial growth factor signaling pathway, the ABL kinase, and the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathway. We propose preventive, screening, monitoring, and management strategies for CV care of patients treated with these novel agents.