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.     

Kin KeeperSM: Design and baseline characteristics of a community-based randomized controlled trial promoting cancer screening in Black,Latina, and Arab women

BackgroundAlthough breast and cervical cancer deaths have declined due to early screening, detection, and more effective treatment, racial and ethnic disparities persist. This paper describes the study design and baseline characteristics of a randomized controlled trial (RCT) evaluating the effectiveness of the Kin Keeper^SM Cancer Prevention Intervention, a family-focused educational intervention for underserved women applied in a community-based setting to promote health literacy and screening adherence to address cancer disparities.MethodsFemale public health community health workers (CHWs) were trained to administer the intervention. They recruited female clients from their public health program caseload and asked each to assemble two to four adult female family members for the breast and cervical cancer home-based education sessions the CHWs would deliver in English, Spanish or Arabic. We randomized the clients into the kin keeper group (treatment) or the participant client group (control).ResultsComplete data were obtained on 514 Black, Latina, and Arab women. Close to half were unemployed and had yearly family income below $20,000. Thirty-four percent had no medical insurance, and 21% had diabetes. Almost 40% had no mammography in the last year. Treatment and control groups were similar on most sociodemographics but showed differences in breast and cervical screening history.ConclusionsThis innovative study demonstrates the implementation of an RCT using community-based participatory research, while delivering cancer prevention education across woman's life span with women not connected to the health care system.     

Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation: The Strong Heart Study

OBJECTIVE

To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.

RESEARCH DESIGN AND METHODS

We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m² (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).

RESULTS

BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m^2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.

CONCLUSIONS

Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).Diabetes increases the risk of cardiovascular (CV) disease and mortality (1), an association that is independent of other CV risk factors (2). Evidence has also emerged of an increased CV risk in individuals with abnormal glucose regulation (3,4). Both states of abnormal glucose regulation (i.e., impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) are reported to be associated with excess body weight and increased levels of CV risk factors, morbidity, and mortality (5–7), although these associations are not universally recognized (8,9).Whether increased plasma glucose above the normal range but below that of clinical diabetes has an impact on cardiac geometry and function is little explored. Cohort studies in communities have shown increased left ventricular (LV) mass and remodeling in individuals with prediabetes (10–12), which appear to be mediated by insulin resistance and body fat distribution (11). However, there are limited clinical or population studies examining CV phenotype in individuals with IGT (13,14), and they included participants with hypertension and/or CV disease, making it difficult to evaluate the role of abnormal glucose levels.Glucose dysregulation is a continuum from elevation of either fasting or postprandial glucose concentration to impairment of both and, eventually, to type 2 diabetes. This progression is associated with worsening CV risk profile, and individuals with both IFG and IGT have more severe metabolic abnormalities and a greater risk of conversion to type 2 diabetes than those with isolated IFG or IGT (5). Thus, it is plausible that CV phenotype also may worsen in parallel with more severe glucose impairment. Accordingly, in the population of the Strong Heart Study (SHS), we compared the metabolic and echocardiographic features of nondiabetic participants who had either IFG or IFG and IGT combined from the second exam; we hypothesized that the combination of IFG and IGT is associated with more severe abnormalities of cardiac geometry and function than isolated IFG.     

Electrophysiologically identified subpopulations of taste bud cells

The heterogeneous population of mammalian taste cells includes several cellular subtypes specializing in distinct physiological functions. They are poorly understood at the single cell level because the available physiological data have generally been obtained from unidentified taste cells. We recorded them from individual taste cells isolated from circumvallate, foliate, and fungiform papilla of the mouse, employing the patch clamp technique, and tried to elucidate whether universal electrophysiological criteria may be established for the identification of functionally different cellular subpopulations. It was found that irrespective of the papillae type, most ( approximately 96%) of robust taste cells could be categorized into three distinct subgroups on the basis of families of whole-cell (WC) currents exhibited in response to membrane polarization. The validity of this quite simple criterion was further confirmed by using different voltage clamp protocols, ion substitutions, and channel blockers to record different ionic currents, including voltage-gated (VG) Ca(2+), inward-rectifying K(+), and hyperpolarization-activated currents. Given that our findings are based on the statistically significant number of recordings, we believe that the electrophysiological identification of taste cells presented here may be effective for further studies on single taste cell physiology, including taste transduction.     

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children

Background and aims

Polyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica.

Interactions of the cellular CCAAT displacement protein and human papillomavirus E2 protein with the viral origin of replication can regulate DNA replication

Previously, we and others have shown that CCAAT displacement protein (CDP) negatively regulates the papillomavirus promoters. Overexpression of CDP has been shown to inhibit high-risk human papillomavirus virus (HPV) and bovine papillomavirus DNA replication in vivo presumably through reduction in expression of viral replication proteins, E1 and E2. Sequence analysis of the HPV origin indicates several potential CDP-binding sites with one site overlapping the E1-binding site. Therefore, CDP could also negatively regulate papillomavirus replication directly by preventing the loading of the initiation complex. We show here that purified CDP inhibits in vitro HPV DNA replication. Footprint analysis demonstrated that CDP binds the E1-binding site and the TATA box, and that the binding of purified CDP to the E1-binding site is decreased by the addition of purified E2 protein. Consistent with this, E2-independent in vitro HPV replication is inhibited by CDP to a greater extent than E2-dependent replication. These results suggest that binding of E2 at the E2-binding site may play an important role in overcoming the inhibition of E1 initiation complex formation caused by the binding of negative regulators like CDP to the origin of replication.     

Lysophosphatidic acid modulates the activation of human monocyte-derived dendritic cells

Lysophosphatidic acid (LPA) is a biologically active lysophospholipid that can regulate immune activation. LPA can activate T cells and dendritic cells (DCs), but the effects of LPA on the ability of DCs to influence T cell polarization are not well understood. Human monocyte-derived DCs were differentiated in vitro in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colonystimulating factor (GM-CSF), and matured with LPA and lipopolysaccharide (LPS) alone or in combination. DC activation was monitored by analyzing cell-surface expression of co-stimulatory receptors and cytokine production. The ability of DCs to influence T cell activation was determined using two models of DC:T cell co-culture. Maturation with LPS induced dose-dependent DC activation characterized by enhanced expression of co-stimulatory molecules (e.g., CD86) and production of cytokines including IL-6 and IL-10. Co-incubation with LPA attenuated the LPS-induced production of IL-6, without significantly affecting IL-10 secretion or the ability of DC to promote T cell proliferation. DCs matured in the presence of both LPA and LPS enhanced the production of interferon-gamma (IFN-gamma) when co-cultured with allogeneic T cells, compared with DC matured by LPS alone. Similar results were found using a model of allogeneic na?ve T cell differentiation, where LPA- plus LPS-matured DC enhanced IFN-gamma as well as IL-4 secretion after restimulation. Lysophosphatidic acid fine-tunes the effects of LPS on human myeloid DC maturation, but does not exert a dominant effect on the ability of DC to influence Th cell polarization.     

Cannabinoid agonists attenuate capsaicin-induced responses in human skin

The induction of hyperalgesia upon capsaicin administration requires activation of specific sub-classes of nociceptive afferent C-fibres providing nociceptive input to the central nervous system.It has been demonstrated in animal models that the endocannabinoid anandamide has anti-hyperalgesic properties upon capsaicin stimulation, albeit it also binds to vanilloid receptors. In the present study we topically administered the cannabinoid receptor ligand HU210 to human skin and investigated its effects on capsaicin-induced pain and hyperalgesia.We demonstrated that pre-treatment with HU210 significantly reduced the perception of pain following the administration of capsaicin. Heat pain thresholds were significantly reduced by capsaicin application measured 5 and 30min after administration. In contrast, at the HU210 pre-treated skin sites capsaicin failed to induce heat hyperalgesia during the fifth minute of administration. Secondary mechanical hyperalgesia to touch (allodynia) was measured during the fifth, 15th and 30th minute after capsaicin administration. In comparison to the ethanol control site, the area of touch-evoked allodynia was significantly reduced at the HU210 skin site during the first two measures. However, 30min after the administration of capsaicin no significant differences of allodynia were observed between the HU210 and ethanol pre-treated skin.The present study provided evidence for analgesic and anti-hyperalgesic properties of a topically applied cannabinoid receptor ligand, which might have important therapeutic implications in humans.     

Economic consequences of severe bleeding in patients with acute coronary syndrome in the USA

Introduction  

Previous studies have demonstrated increased costs associated with bleeding in clinical trials, but none have yet examined the association of bleeding with costs/charges in a real-world setting. This study examines the association between health care charges and severe bleeding events among patients with acute coronary syndrome (ACS) in a real-world US setting.