A Peer-Educator Network HIV Prevention Intervention Among Injection Drug Users: Results of a Randomized Controlled Trial in St. Petersburg, Russia

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74–35.65) and 7.76 (95 % CI 3.51–17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15–1.08) without a statistically significant difference between the two groups (log rank test statistic X² = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.     

Are we there yet? Assessing achievement of vaccine-preventable disease goals in WHO's Western Pacific Region

Accelerated disease control goals have long been appreciated for their role in galvanizing commitment and bringing a sense of urgency for disease prevention. WHO's Western Pacific Region has 14 on-going communicable disease reduction goals including 1 targeting eradication, 10 targeting elimination, and 3 control initiatives. These goals cover mother-to-child transmission of HIV, congenital syphilis, tuberculosis, leprosy, five parasitic diseases and four vaccine-preventable diseases (VPD). The initiatives have distinct objectives, approaches, and means in which to measure achievement of the goals.     

In Vivo Toxicity of Intravenously Administered Silica and Silicon Nanoparticles

Both silicon and silica nanoparticles (SiNPs and SiO₂NPs, respectively) are currently considered to be promising carriers for targeted drug delivery. However, the available data on their in vivo toxicity are limited. The present study was aimed at investigation of SiNP and SiO₂NP (mean diameter 10 and 13 nm, respectively) toxicity using both morphological and functional criteria. Hematological and biochemical parameters were assessed in Sprague-Dawley rats 5, 21 and 60 days after administration of NPs. Inner ear function was determined using otoacoustic emission testing at 21 and 60 days after infusion of NPs. Furthermore, the histological structure of liver, spleen and kidney samples was analyzed. Intravenous infusion of SiNPs or SiO₂NPs (7 mg/kg) was not associated with significant changes in hemodynamic parameters. Hearing function remained unchanged over the entire observation period. Both inter- and intragroup changes in blood counts and biochemical markers were non-significant. Histological findings included the appearance of foreign body-type granulomas in the liver and spleen as well as microgranulation in the liver after administration of NPs. The number of granulomas was significantly lower after administration of SiNPs compared with SiO₂NPs. In conclusion, both tested types of NPs are relatively biocompatible nanomaterials, at least when considering acute toxicity.     

Augmenting Regional Cerebral Blood Flow Using External-to-Internal Carotid Artery Flow Diversion Method

The objective of this study was to assess the effect of flow diversion by external carotid artery (ECA) occlusion on ipsilateral regional cerebral blood flow (rCBF). Local cerebral hyperperfusion in rats (n = 12) was induced by ligating the right ECA. Ipsilateral rCBF was determined pre- and post-ligation for 120 min using a laser Doppler flow meter. Sham animals (n = 6) were subjected to the craniotomy without ligation of the right ECA. In a separate series of rats (n = 5), brain tissue oxygen levels (pO₂) in the right and left brain hemispheres were determined before and 90 min after ligation of the right ECA using a tissue oxygenation monitoring unit. We investigated the effect of ECA occlusion hemispheric changes in rCBF in one clinical case as a proof of concept. Ligation of ECA resulted in a statistically significant increase in rCBF on the ipsilateral side compared to the sham-operated rats (p < 0.0001). On average we observed a 34% increase (95% CI: 24–45%) in rCBF in the ipsilateral territory in the treated group compared with sham-operated rats. There was no significant variation in MAP for the treated animals. Vascular permeability and cerebral water content in the right hemisphere after ligation of ECA did not significantly differ from the contralateral hemisphere. Ipsilateral hemisphere tissue pO₂ was significantly higher compared to the contralateral area (p < 0.002) post-ligation or to the ipsilateral area (p < 0.001) prior to ligation. In the clinical case, occlusion of ECA resulted in 3.6% and 12.1% increase in peak value and rise-time of the time-density curves. Flow diversion by temporary occlusion of the ECA can result in increased rCBF and cerebral pO₂ on the ipsilateral side. The strategy may represent a viable option to augment rCBF in focal cerebral ischemia.     

miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance.     

Heparanase Levels Are Elevated in the Plasma of Pediatric Cancer Patients and Correlate with Response to Anticancer Treatment

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans, the major proteoglycan in the extracellular matrix (ECM) and cell surfaces. Heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. The purpose of the current study was to determine heparanase levels in blood samples collected from pediatric cancer patients using an ELISA method. Heparanase levels were elevated four-fold in the plasma of cancer patients compared with healthy controls (664 ± 143 vs 163 ± 18 pg/ml, respectively). Evaluating plasma samples following anticancer therapy revealed reduced heparanase levels (664 ± 143 vs 429 ± 82 pg/ml), differences that are statistically highly significant (P = .0048). Of the 55 patients with complete remission (CR) or very good partial remission (VGPR) at restaging, 41 (74.5%) had lower heparanase amounts, whereas 14 patients (25.5%) had similar or higher amounts of plasma heparanase. All nine patients with stable or advancing disease had similar or elevated levels of heparanase on restaging. The results show that heparanase levels are elevated in the plasma of pediatric cancer patients and closely correlate with treatment responsiveness, indicating that heparanase levels can be used to diagnose and monitor patient''s response to anticancer treatment.     

Chronic hepatitis B: current and future treatment options

Hepatitis B, a major viral infection that can lead to cirrhosis and hepatocellular carcinoma, is the ninth most common cause of death worldwide. Prevention of hepatitis B virus transmission is key to reducing the spread of this serious condition. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Today, agents approved by the Food and Drug Administration for this infection are interferon-alpha-2b and lamivudine. Newer agents are being developed and hold promise: adefovir, famciclovir, ganciclovir, lobucavir, entecavir, emtricitabine, L-deoxythymidine, clevudine, a therapeutic vaccine, and thymosin alpha-1. Therapeutic options for managing hepatitis infection after liver transplantation are also evolving. These include hepatitis B immunoglobulin and nucleoside analogues.     

Relationship between lead levels on painted surfaces and percent lead in the particles aerosolized during lead abatement

Quantifying airborne lead on lead abatement work sites is critical in assessing worker lead exposures. Airborne lead levels depend on both the concentration of aerosolized particles and the percent lead in those particles. The lead level on the painted surface being abated may affect the percent lead in aerosolized particles. Experiments were performed in the University of Cincinnati Environmental Test Chamber (volume approximately 24.3 m3) using wood doors painted with lead-based paint. Three methods were used for paint removal: dry scraping, wet scraping, and dry machine sanding. Particles aerosolized during lead abatement activities were collected on filters using the Button Personal Inhalable Aerosol Samplers (SKC Inc., Eighty Four, PA) mounted in the workers' breathing zone. The filters were subsequently analyzed for percent lead in the particles. A portable X-ray fluorescence (XRF) instrument (NITON-700, NITON Inc., Bedford, MA) was used to measure surface lead levels of the doors. The accuracy of the XRF instrument was verified by testing standard reference materials prepared by the National Institute of Standards and Technology (NIST) and by Princeton Gamma Tech Inc. It was also verified by relating XRF results from painted door surfaces to laboratory lead analysis data obtained from paint chip samples taken from the same painted surfaces (r2 = 0.81, p < 0.001). A highly significant relationship (r2 = 0.83, p < 0.001) was found between the XRF readings and the percent lead in the particles aerosolized during dry scraping. No significant relationship was found for wet scraping (r2 = 0.09, p = 0.56) or dry machine sanding (r2 = 0.002, p = 0.92). The relationship between surface lead levels and percent lead in particles was found to be dependent on the paint removal method. This variation was attributed to the difference in water absorption property of the paint layers and the different particle aerosolization mechanisms inherent in each paint removal method.     

More severe neurologic deficits in SJL/J male than female mice following Theiler's virus-induced CNS demyelination

Although multiple sclerosis (MS) is more prevalent in women than men, male MS patients develop more severe clinical symptoms and deteriorate faster than female patients. We investigated the differences in CNS demyelinating disease between SJL/J male and female mice following Theiler's murine encephalomyelitis virus (TMEV) infection. Infected female mice had consistently higher serum levels of virus-specific IgG at 14 and 21 days and and 7 months postinfection, which resulted in less infectious virus in CNS. All male mice infected for 6 to 7 months developed paralysis, with 50% displaying bilateral posterior limb paralysis, whereas 77% of age-matched female mice were paralyzed, all displaying unilateral posterior limb paralysis. Male mice infected for 6 to 7 months performed up to threefold fewer spontaneous horizontal and vertical movements (activity box test) compared to infected age-matched females. In addition, infected male mice performed the coordination and balance (Rotarod) test at 27 +/- 4% of the expected level (expressed as a percentage of that of uninfected age-matched mice), whereas infected female mice performed at 41 +/- 5% of the expected level. Male mice had a small increase in the extent of spinal cord white matter demyelination analyzed at both 45 days and between 6 and 7 months postinfection. For individual male and female mice, the extent of demyelination had a negative linear relationship with the neurologic performances. The emergence of a disease paradigm similar to MS supports using the TMEV model to investigate molecular and genetic factors responsible for the gender dimorphism in MS and other autoimmune diseases.