Spin-Orbit Coupling Controlled J=3/2 Electronic Ground State in 5d

Entanglement of spin and orbital degrees of freedom drives the formation of novel quantum and topological physical states. Here we report resonant inelastic x-ray scattering measurements of the transition metal oxides Ca_{3}LiOsO_{6} and Ba_{2}YOsO_{6}, which reveals a dramatic spitting of the t_{2g} manifold. We invoke an intermediate coupling approach that incorporates both spin-orbit coupling and electron-electron interactions on an even footing and reveal that the ground state of 5d^{3}-based compounds, which has remained elusive in previously applied models, is a novel spin-orbit entangled J=3/2 electronic ground state. This work reveals the hidden diversity of spin-orbit controlled ground states in 5d systems and introduces a new arena in the search for spin-orbit controlled phases of matter.

A Novel Mental Health Crisis Service - Outcomes of Inpatient Data.

INTRODUCTION: Northern Ireland has high mental health needs and a rising suicide rate. Our area has suffered a 32% reduction of inpatient beds consistent with the national drive towards community based treatment. Taking these factors into account, a new Mental Health Crisis Service was developed incorporating a high fidelity Crisis Response Home Treatment Team (CRHTT), Acute Day Care facility and two inpatient wards. The aim was to provide alternatives to inpatient admission. The new service would facilitate transition between inpatient and community care while decreasing bed occupancy and increasing treatment in the community. METHODS: All services and processes were reviewed to assess deficiencies in current care. There was extensive consultation with internal and external stakeholders and process mapping using the COBRAs framework as a basis for the service improvement model. The project team set the service criteria and reviewed progress. RESULTS: In the original service model, the average inpatient occupancy rate was 106.6%, admission rate was 48 patients per month and total length of stay was 23.4 days. After introducing the inpatient consultant hospital model, the average occupancy rate decreased to 90%, admissions to 43 per month and total length of stay to 22 days. The results further decreased to 83% occupancy, 32 admissions per month and total length of stay 12 days after CRHTT initiation. DISCUSSION: The Crisis Service is still being evaluated but currently the model has provided safe alternatives to inpatient care. Involvement with patients, carers and all multidisciplinary teams is maximised to improve the quality and safety of care. Innovative ideas including structured weekly timetable and regular interface meetings have improved communication and allowed additional time for patient care.

Epitaxial growth of iridate pyrochlore Nd2Ir2O7 films.

Epitaxial films of the pyrochlore Nd2Ir2O7 have been grown on (111)-oriented yttria-stabilized zirconia (YSZ) substrates by off-axis sputtering followed by post-growth annealing. X-ray diffraction (XRD) results demonstrate phase-pure epitaxial growth of the pyrochlore films on YSZ. Scanning transmission electron microscopy (STEM) investigation of an Nd2Ir2O7 film with a short post-annealing provides insight into the mechanism for crystallization of Nd2Ir2O7 during the post-annealing process. STEM images reveal clear pyrochlore ordering of Nd and Ir in the films. The epitaxial relationship between the YSZ and Nd2Ir2O7 is observed clearly while some interfacial regions show a thin region with polycrystalline Ir nanocrystals.

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya.

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.

Performance of the Euroline Western blot assay in the detection of herpes simplex virus type 2 antibody in Uganda, China and the USA.

Herpes simplex virus type 2 (HSV-2) infection is one of the most common sexually transmitted infections (STIs) worldwide. While glycoprotein G-2 enzyme-linked immunosorbent assays are commonly used for the serological detection of HSV-2 antibodies, they have low specificity in developing countries. The Euroline Western blot (WB) is a commercially available assay that is easy to perform; however, little is known about its performance characteristics. This study evaluated Euroline WB for the detection of HSV-2 antibodies compared with University of Washington Western blot in three geographically different regions: Baltimore, MD, USA; Rakai, Uganda; and Kunming, China. Among the 135 American men attending a STI clinic in Baltimore, MD, 72% (n = 97) were HSV-2-positive by Euroline WB, showing a sensitivity of 97.8% and a specificity of 81.8%. Among the 273 commercial sex workers in Kunming, 62.3% were HSV-2-positive by Euroline WB (sensitivity 96.9%, specificity 89.1%). Among the 437 Ugandans in Rakai, 67.3% were HSV-2-positive by Euroline WB (sensitivity 98.7%, specificity 65.4%). The Euroline WB has a consistently high sensitivity, but specificity varied significantly among the different locations.

Fear of movement, quality of life, and self-reported disability in obese patients with chronic lumbar pain.

OBJECTIVE: To compare fear of movement between obese and non-obese individuals seeking therapy for chronic low back pain and to examine whether fear of movement predicted disability due to back pain, self-reported walking disability, and flexibility. DESIGN: This was a cross-sectional study. SETTING: Outpatient physical therapy clinic associated with a tertiary care hospital. PATIENTS: Patients with chronic low back pain (N=192; 48.2±18.8 years) were stratified into obese (average body mass index [BMI] 36.9±7.1 kg/m(2) ) or non-obese status (average BMI 24.5±3.4 kg/m(2) ). OUTCOME MEASURES: The Tampa Scale of Kinesiophobia (TSK), Short-Form 8 (SF-8), and Oswestry Disability Survey results were main outcome measures. METHODS: Retrospective review of medical charts was performed. Hierarchical regression modeling determined the contribution of TSK scores to the variance of self-reported disability with walking, overall Oswestry score, and flexibility. RESULTS: TSK scores were higher in obese than non-obese patients (26.2±7.5 vs 23.9±6.8 points; P=0.032). The SF-8 physical and mental subscores were 6-10% lower in the obese than non-obese patients. Oswestry survey scores were higher in the obese patients (40.6 vs 31.6 points; P<0.001). TSK scores contributed to self-reported disability with walking and Oswestry disability score (both P<0.001), but not flexibility. CONCLUSIONS: Among obese patients with chronic lumbar pain, pain-related fear of movement enhanced prediction of self-reported disability with walking and overall Oswestry scores. The TSK might be a useful clinical assessment to identify obese patients at higher risk for future low back disability.

Sensitivity and specificity of herpes simplex virus-2 serological assays among HIV-infected and uninfected urban Ugandans.

Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We characterized HSV-2 serology assay performance in HIV-positive and HIV-negative Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2 serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was compared with HSV-2 Western blot (WB) according to HIV-1 serostatus. Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and 97.5%/96.2% for Kalon. Focus with Biokit confirmation improved sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%. Kalon had higher specificity than Focus (P < 0.001). Of commercially available HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1 public health activities in Africa.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Absence of combined effects of anemia and bilateral surgical status on inpatient rehabilitation outcomes following total knee arthroplasty.

PURPOSE: To examine the effects of anemia on inpatient rehabilitation outcomes following unilateral and bilateral total knee arthroplasty (TKA). METHOD: This was a multicenter, retrospective study from 15 inpatient rehabilitation facilities. Patients (N = 5421) with very low hematocrit (Hct <30%), low Hct (30-36% women, 30-41% men), or normal Hct (>36% women, 41% men) were included. Inpatient rehabilitation occurred following TKA. Functional independence measure (FIM) scores, length of stay (LOS), itemized hospital charges, discharge destination were main outcomes. RESULTS: LOS was 13% longer and hospital charges were 12.5-18.0% higher in the very low Hct than remaining groups (p = 0.0001). The FIM score and subscores for walking, stair climbing, bathing, transfers, and dressing changes were comparable for all Hct groups for the overall score. Hct <30% did not correspond to worse outcomes in patients with bilateral surgeries compared with unilateral surgeries; total FIM scores improved 47-53% across all Hct groups, regardless of bilateral surgical status. Discharge to home ranged 92.6-94.7% across all Hct groups (p > 0.05). CONCLUSIONS: Rehabilitation teams can expect comparable functional improvements and discharge to home in anemic and non-anemic patients with either unilateral or bilateral surgeries without hematologic correction in the rehabilitation setting, but might need an additional day to accomplish these outcomes.

Bimodal effect of humic acids on the LPS-induced TNF-alpha release from differentiated U937 cells.

Humic substances (HS) have been reported to possess anti-inflammatory as well as pro-inflammatory properties. The anti-inflammatory activity was demonstrated in the rat paw edema model and we found a preliminary explanation in the 5-lipoxygenase inhibitory effect of humic acids (HA). The pro-inflammatory activity is reflected by the production and release of pro-inflammatory cytokines in HA-treated neutrophilic granulocytes. With regard to the potential use of HA as antiviral and UV-protective agents it appears advisable to investigate the role of HS in the inflammation process in more detail. Hence we tested four different HS preparations - two naturally occurring HA from the Altteich peatland in Germany, one fulvic acid (FA) preparation from a Finnish spruce forest and a synthetic HA-like polymer (caffeic acid oxidation product, KOP) for their influence on the lipopolysaccharide (LPS)-induced TNF-alpha release in human U937 cells. In addition, the cytotoxicity of HS was determined. The results demonstrate a concentration-dependent bimodal effect of HA on the TNF-alpha release of differentiated LPS-stimulated U937 cells for both the natural black peat HA from the Altteich peatland and the HA-like polymer KOP. Low HA concentrations (10-80 microg/ml) enhanced the TNF-alpha release by up to threefold (pro-inflammatory activity), while HA concentrations >100 microg/ml reduced it about 10-fold (anti-inflammatory activity). FA failed to enhance TNF-alpha release, but reduced it at higher concentrations (>200 microg/ml) by the half. Brown water HA did not exert any significant effect on TNF-alpha release. No HS-stimulated TNF-alpha release was also observed in the absence of exogenously supplied LPS. This means that HS, unlike endotoxin, are no inflammation-causing agents for LPS-untreated cells. Differences in the effect of individual HS on TNF-alpha release are discussed in connection with the polyanionic character of HS, their molecular mass distribution and the hitherto imperfectly known chemical structure.

Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing.

BACKGROUND: In certain parts of Africa, type-specific herpes simplex virus type 2 (HSV-2) ELISAs may have limited specificity. To date, no study has been conducted to validate HerpeSelect and Kalon type-specific HSV-2 ELISAs using both the Western blot and recombinant gG ELISA inhibition testing as reference standards. METHODS: A total of 120 men who were HIV seronegative (aged 18-24 years) provided blood samples. HSV-2 IgG serum antibodies were detected using four different methods: HerpeSelect HSV-2 ELISA (n = 120), Kalon HSV-2 ELISA (n = 120), University of Washington Western blot (n = 101) and a recombinant inhibition test (n = 93). RESULTS: HSV-2 seroprevalence differed significantly by HSV-2 detection method, ranging from 24.8% with the Western blot to 69.8% with the HerpeSelect ELISA. Using the Western blot as the reference standard, the HerpesSelect had the highest sensitivity for HSV-2 antibody detection (100%) yet lowest specificity (40%). Similar results were obtained using the inhibition test as the reference standard. The sensitivity and specificity of the Kalon test versus the Western blot were 92% and 79%, respectively, and 80% and 82% versus the inhibition test. Using the inhibition test as the reference standard, the sensitivity of the Western blot appeared low (49%). CONCLUSIONS: In men in western Kenya who were HIV seronegative, the HerpeSelect and Kalon type-specific ELISAs had high sensitivities yet limited specificities using the Western blot as reference standard. Overall, the Kalon ELISA performed better than the HerpeSelect ELISA in these young men from Kisumu. Further understanding is needed for the interpretation of HSV-2 inhibition or ELISA test positive/ Western blot seronegative results. Before HSV-2 seropositivity may be reliably reported in selected areas of Africa, performance studies of HSV-2 serological assays in individual geographical areas are recommended.

The negative consequences of other students' drinking: inventory development and assessment of differences by student characteristics and risk behaviors.

UNLABELLED: College students continue to report being disrupted by other students' alcohol use. OBJECTIVE: This study was designed to develop measures to document the consequences resulting from other students' drinking and identify differences in experiencing these consequences by student characteristics and drinking behaviors. STUDY GROUP: A stratified random sample of undergraduate students (N = 3,908) from ten universities in North Carolina, USA, completed a web-based assessment. METHODS: Exploratory factor analysis (EFA) was performed on the random first split-half sample (n = 1,954) to identify factor structure. Confirmatory factor analysis (CFA) was performed on the remaining half sample (n = 1,954) using structural equation modeling. RESULTS: EFA revealed two inventories: interpersonal and community consequences of others' drinking inventories. CFA on the second split-half sample identified model fits for the two factor structure suggested by EFA. Of 3,908 participants, 78% reported experiencing one or more consequences due to others' drinking during the past 30 days. Multivariable generalized linear mixed modeling further validated the inventories and resulted in several associations. Male students who reported getting drunk experienced significantly more interpersonal consequences from others' drinking (p < .001). Minority students, students who lived on campus and students who reported getting drunk experienced significantly more community consequences from others' drinking (p < .01). CONCLUSIONS: These findings demonstrate that 4 out of 5 college students experience consequences from others' drinking, and consequences vary for different subgroups of students. Although these inventories should be tested further, these findings propose standardized measures that may be useful to assess the consequences of others' drinking among college students.

Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia.

Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.

Sexual and demographic determinants for herpes simplex virus type 2 among fishermen along Lake Victoria, Kenya.

OBJECTIVES: To determine the prevalence and correlates of herpes simplex virus type 2 (HSV-2) seropositivity among fishermen along the shores of Lake Victoria in Kisumu district, Kenya. METHODS: Sera from a random sample of 250 fishermen from 18 beaches were collected after a detailed sociodemographic interview. HSV-2 infection was tested by Kalon HSV-2 ELISA. RESULTS: The HSV-2 seroprevalence was 63.9%. In multivariate analysis, fishermen were more likely to be infected with HSV-2 if they were HIV positive (prevalence ratio (PR) 1.27; 95% CI 1.06 to 1.52) compared with those testing HIV negative, were aged 18-20 (PR 0.49; 95% CI 0.24 to 0.99) and older than 40 (PR 1.66; 95% CI 1.30 to 2.14) years compared with those aged 21-25 years, perceived their last two sexual partners to have a sexually transmitted infection (STI; PR 1.27; 95% CI 1.06 to 1.52) compared with those who did not and were more likely to be circumcised (PR 1.49; 95% CI 1.19 to 1.86). CONCLUSIONS: HSV-2 seroprevalence is high among this population and is associated with HIV serostatus, age, perception about partner's STI status and circumcision.

Drink specials and the intoxication levels of patrons exiting college bars.

OBJECTIVES: To determine whether drink specials independently increase patrons' risk of achieving a high level of intoxication upon exiting drinking establishments. METHODS: In a campus community, data were collected from exiting patrons (N=291) via sidewalk interviews and breath tests on 6 nights of 2 consecutive semesters. RESULTS: A multivariate model revealed that taking advantage of a drink special was associated with a fourfold increase in risk of achieving a BAC >or= 80 mg/dl. CONCLUSIONS: These findings are the first to document that the drink discounting practices of college bars can be linked to higher intoxication levels among exiting patrons.

Type-specific seroprevalence of herpes simplex virus type 2 and associated risk factors in middle-aged women from 6 countries: the IARC multicentric study.

GOAL: To determine type-specific seroprevalence of herpes simplex viruses (HSV-1 and HSV-2) and HSV-2 risk factors. STUDY DESIGN: Six-hundred fifty eight middle-aged control women (hospital-based in 4 of 6 countries) from a multicenter cervical cancer case-control study participated from 1985 to 1997. Type-specific serum IgG antibodies against HSV-1 and HSV-2 were detected with Western Blot. RESULTS: HSV-1 seroprevalence was 89% to 100% everywhere except Thailand (51%). HSV-2 seroprevalence ranged from 9% (Spain) to 57% (Colombia), and was independently associated with having >or=2 lifetime sexual partners overall [Odds ratio (OR), 2.1; 95% confidence interval (CI) 2.5-3.1], and in Morocco (OR, 2.7; 95% CI, 1.2-6.1) and Thailand (OR, 4.4; 95% CI, 1.3-15.4), and with being unmarried in Colombia, Peru, Spain, but not significantly in Mali. Women whose male partner's sexual debut was

Exploring the health behavior disparities of gay men in the United States: comparing gay male university students to their heterosexual peers.

Little is known about the health disparities that affect gay men in the United States. Using data collected from an online Internet-based assessment, we sought to compare health-compromising behaviors of gay male university students to their heterosexual peers. Participants included 1,014 self-reported males. Mean age was 20 years (+/-2.5; range 17-30). Of these men, 43 (4.2%) self identified as gay and 971 (95.8%) self identified as heterosexual. After adjusting for age, race, academic classification, residence type, and clustering within university, gay men had higher odds of reporting inconsistent condom use; reporting multiple partners within the past 30 days; reporting a lifetime history of illicit drug use. Understanding the health behavior disparities between gay and heterosexual men is crucial to identifying associated factors and intervening upon them using appropriate and meaningful tailored strategies to reduce these disparities and improve health outcomes.

Characteristics of a sample of men who have sex with men, recruited from gay bars and Internet chat rooms, who report methamphetamine use.

Crystal methamphetamine is a highly addictive stimulant that initially gained popularity in the western region of the United States and has spread to all regions of the country. This study was designed to identify factors associated with methamphetamine use among men who have sex with men (MSM) in North Carolina. Participants were recruited in five gay bars and in five geographically defined Internet chat rooms concurrently in 2005 to complete a brief assessment of drug use and other risk behaviors. Of the 1189 MSM who completed the assessment, mean age was 29 years. Two thirds self-identified as black/African American or other minorities, and 25% as bisexual. Nearly 6% reported using methamphetamines during the past 30 days. In multivariable analysis, MSM who reported using methamphetamines were more likely to report higher education; health insurance coverage; inconsistent condom use during anal sex within the past 3 months; a history of sexually transmitted disease (STD) infection; positive HIV serostatus; and use of medications designed to treat erectile dysfunction. A lack of data exists on methamphetamine use among MSM in the southeastern United States, particularly in nonurban regions. Because the southeastern United States carries a disproportionate HIV, AIDS, and STD burden, our findings underscore the need for further research and intervention.

Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation.

BACKGROUND AND PURPOSE: The neuromedin U (NMU) receptors, NMU1 and NMU2, are expressed in the gut but their functions are unclear. This study explores the role of NMU in gastrointestinal motility. EXPERIMENTAL APPROACH: The effects of NMU were examined in the forestomach and colon isolated from NMU2R wild-type and NMU2R-/- (knockout) mice, looking for changes in muscle tension and in nerve-mediated responses evoked by electrical field stimulation (EFS), and in models of peristalsis in mouse colon and faecal pellet transit in guinea-pig colon. KEY RESULTS: In the mouse forestomach, NMU (1 nM-10 microM) concentration-dependently induced muscle contraction, in the presence of tetrodotoxin and atropine, in preparations from both wild-type and NMU2R-/- mice (pEC50: 7.9, 7.6, Emax: 0.26, 0.20g tension, respectively, n=8 each concentration). The same concentrations of NMU had no consistent effects on the responses to EFS (n=8). In the mouse colon, NMU (0.1 nM-1 microM) had no significant effect on baseline muscle tension (n=8), but concentration-dependently potentiated EFS-evoked contractions in preparations from both wild-type and NMU2R-/- mice, pEC50: 8.1, 7.8, Emax: 24%, 21%, respectively, n=6-11. NMU (0.01 nM-0.1 microM, n=5-7) concentration-dependently decreased the interval between waves of peristalsis in the mouse colon (pEC50: 8.8) and increased the rate at which a faecal pellet moved along the guinea-pig colon. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that NMU exerts colon-specific, nerve-mediated, prokinetic activity, via a pathway involving activation of NMU1 receptors. This suggests that this receptor may represent a molecular target for the treatment of intestinal motility disorders.

High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study.

The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioral intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003. Sexual behavior data were obtained by computer-assisted self-interview, and sera were collected semiannually for HIV and HSV-2 serology. HSV-2 infection was classified as "recent incident" (at the first HSV-2 seropositive visit), "remote incident" (within 24 months of the first positive visit), and "prevalent" (for visits >24 months after the first HSV-2 positive visit). Baseline HSV-2 prevalence was 20.3%. HSV-2 incidence was 1.9 (95% confidence interval (CI): 1.6, 2.2) per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months. The behavioral intervention did not reduce HSV-2 acquisition (adjusted hazard ratio (HR) = 1.2, 95% CI: 0.9, 1.6). Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years. HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants. HIV intervention strategies targeting HSV-2 prevention and suppression among men who have sex with men should be evaluated.