Optimizing the impact of alcohol and drug screening and early intervention in a high-risk population receiving services in New York City sexual health clinics: A process and outcome evaluation of Project Renew.

Unhealthy substance use is associated with increased rates of STDs, including HIV. Within three high-risk New York City (NYC) sexual health clinics between 2008 and 2012 (n = 146,657), 17% of patients screened positive for a current SUD but only 5.3% ever received prior treatment. The goal of Project Renew was to expand the reach of substance use early intervention services within and across sexual health clinics citywide and decrease substance use, poor mental health, and risky sexual behavior. To accomplish this goal, Screening, Brief Intervention, and Referral to Treatment (SBIRT), an evidence-based substance use early intervention model, was implemented in all eight NYC sexual health clinics February 2012-January 2015. Clinic patients were screened for substance misuse using the AUDIT/DAST-10, and those who screened positive were eligible for on-site brief intervention. Overall, 130,597 substance misuse screenings were conducted (66,989, or 51%, positive), and 17,474 on-site brief interventions and 1238 referrals were provided (not unique to individual patients). A 10% sample of 14,709 unique patients who screened positive were interviewed using a federal data collection tool at baseline and six months later to assess changes in substance use, sexual risk behaviors, mental health, and health status (n = 1328). At six-month follow-up, patients reported reduced substance use, less sexual activity, improved overall health, and fewer days of depression and anxiety compared to measures at baseline (p < 0.05). Based on positive results, Project Renew SBIRT services have been sustained, ensuring essential care which may help prevent acquisition of HIV/STDs among a large population of high-risk New Yorkers.

Attitudes, perceptions and practice of alcohol and drug screening, brief intervention and referral to treatment: a case study of New York State primary care physicians and non-physician providers.

OBJECTIVES: Screening, Brief Intervention, and Referral to Treatment (SBIRT) has been endorsed by the United States Preventive Services Task Force as an evidence-based strategy to address risky alcohol use among adults in primary care. Nevertheless, very few healthcare professionals report using SBIRT in their practice. The purpose of this study was to explore attitudes regarding addressing substance use; perceptions of effectiveness, role responsibility, and self-efficacy; and current SBIRT practice among primary care physicians, nurse practitioners, and physician assistants to identify factors which may impact routine delivery of SBIRT in primary care. STUDY DESIGN: A cross-sectional design was used to meet study objectives. Responses of physicians and non-physician providers (nurse practitioners and physician assistants) were compared. METHODS: Primary care members of three New York State physician, nurse practitioner, and physician assistant professional organizations were surveyed between October 2013 and November 2013. RESULTS: Barely half of participants (57%) reported screening their patients for substance use, and less than half provided brief intervention (46%) or referral to treatment (47%). Using a standardized tool to screen patients for risky substance use and assessing readiness to change were practised least frequently. Compared to physicians, nurse practitioners and physician assistants felt less responsible for addressing substance use (P = 0.019), felt less comfortable discussing substance use (P = 0.004), had more negative attitudes toward addressing substance use (P = 0.015), and were less likely to conduct brief intervention (52% vs 32%; P < 0.0005) and referral to treatment (50% vs 70%; P = 0.001). CONCLUSIONS: This study identifies important attitudinal and perceptual differences between physicians and non-physician providers which may be targeted by education and training and underscores an opportunity for using non-physician providers to conduct SBIRT.

Genotype × environment interaction, environmental heterogeneity and the lek paradox.

Substantial additive genetic variance (V(A)) often exists for male signalling traits in spite of the directional selection that female choice imposes. One solution to this problem, a conundrum generally termed the 'lek paradox', is that genotype × environment interaction (GEI) occurs and generates a 'crossover' of reaction norms in which no one genotype performs in a superior manner in all environments. Theoretical work indicates that such crossover can sustain genetic variance provided that either (i) spatial heterogeneity in environmental conditions combined with limited migration among populations or (ii) temporal heterogeneity in environmental conditions combined with occasional generation overlap is present. Whereas some recent studies have revealed the intersection of reaction norms for sexually selected traits in laboratory and in natural populations, associated information on environmental heterogeneity, migration and generation overlap has not been investigated. We studied this question in an acoustic pyralid moth, Achroia grisella, in which previous work indicated GEI and crossover of reaction norms for several parameters of the male song evaluated by females. We measured reaction norms for male song as expressed when development was completed under different environmental conditions in four neighbouring, yet isolated, populations during 1 year and in one of these populations during consecutive years. Crossover occurred for the various song parameters in the several populations, but we did not observe a higher incidence of crossover between genotypes taken from two different populations than from the same population. However, for several key song parameters, crossover between genotypes taken from two different years was higher than that between genotypes from the same year. We suggest that temporal heterogeneity in the form of varying selection could potentially conserve V(A) in A. grisella, but we also note other factors that might contribute.

Corticosterone and dexamethasone potentiate cytotoxicity associated with oxygen-glucose deprivation in organotypic cerebellar slice cultures.

Many patients display elevated levels of serum cortisol following acute ischemic stroke. Given that glucocorticoids may potentiate some forms of insult, these studies examined the effects of corticosterone or dexamethasone exposure on cytotoxicity following oxygen-glucose deprivation in the cerebellum, a brain region susceptible to stroke. In organotypic cerebellar slice cultures prepared from neonatal rat pups, 90-min of oxygen-glucose deprivation at 15 days in vitro resulted in significant cytotoxicity at 24-, 48-, and 72-h post-oxygen-glucose deprivation, as measured by uptake of propidium iodide. Exposure of cultures following oxygen-glucose deprivation to the antioxidant trolox (500 microM), but not to the glucocorticoid receptor antagonist RU486 (10 microM), completely blocked oxygen-glucose deprivation-induced cytotoxicity. Corticosterone (1 microM) or dexamethasone (10 microM) exposure alone did not significantly increase propidium iodide uptake above levels observed in control cultures. However, corticosterone or dexamethasone exposure after oxygen-glucose deprivation potentiated oxygen-glucose deprivation-mediated propidium iodide uptake at each time point. Trolox, as well as RU486, co-exposure of cultures to corticosterone or dexamethasone after oxygen-glucose deprivation abolished all cytotoxicity. In conclusion, these data demonstrated that glucocorticoid exposure modulated oxygen-glucose deprivation-mediated propidium iodide uptake, which likely involved glucocorticoid receptor activation and pro-oxidant effects.

(-)-nicotine ameliorates corticosterone's potentiation of N-methyl-d-aspartate receptor-mediated cornu ammonis 1 toxicity.

Hypercortisolemia, long-term exposure of the brain to high concentrations of stress hormones (i.e. cortisol), may occur in patients suffering from depression, alcoholism, and other disorders. This has been suggested to produce neuropathological effects, in part, via increased function or sensitivity of N-methyl-d-aspartate (NMDA)-type glutamate receptors. Given that cigarette smoking is highly prevalent in some of these patient groups and nicotine has been shown to reduce toxic consequences of NMDA receptor function, it may be suggested that nicotine intake may attenuate the neurotoxic effects of hypercortisolemia. To investigate this possibility, organotypic hippocampal slice cultures derived from rat were pre-treated with corticosterone (0.001-1 microM) alone or in combination with selective glucocorticoid receptor antagonists for 72-h prior to a brief (1-h) NMDA exposure (5 microM). Pre-treatment with corticosterone (0.001-1 microM) alone did not cause hippocampal damage, while NMDA exposure produced significant cellular damage in the cornu ammonis (CA)1 subregion. No significant damage was observed in the dentate gyrus or CA3 regions following NMDA exposure. Pre-treatment of cultures with corticosterone (0.1-1 microM) markedly exacerbated NMDA-induced CA1 and dentate gyrus region damage. This effect in the CA1 region was prevented by co-administration of the glucocorticoid receptor antagonist RU486 (>or=1 microM), but not spironolactone (1-10 microM), a mineralocorticoid receptor antagonist. In a second series of studies, both acute and pre-exposure of cultures to (-)-nicotine (1-10 microM) significantly reduced NMDA toxicity in the CA1 region. Co-administration of cultures to (-)-nicotine (1-10 microM) with 100 nM corticosterone prevented corticosterone's exacerbation of subsequent CA1 insult. This protective effect of (-)-nicotine was not altered by co-exposure of cultures to 10 microM dihydro-beta-erythroidine but was blocked by co-exposure to 100 nM methyllycaconitine, suggesting the involvement of nicotinic acetylcholine receptors possessing the alpha7* subunit. The present studies suggest a role for hypercortisolemia in sensitizing the hippocampal NMDA receptor system to pathological activation and indicate that prolonged nicotine exposure attenuates this sensitization. Thus, it is possible that one consequence of heavy smoking in those suffering from hypercortisolemia may be a reduction of neuronal injury and sparing of cellular function.

Hippocampal CA1 region neurodegeneration produced by ethanol withdrawal requires activation of intrinsic polysynaptic hippocampal pathways and function of N-methyl-D-aspartate receptors.

Long-term intake of ethanol produces adaptive alterations in multiple transmitter systems in the hippocampal formation that likely contribute to ethanol withdrawal-induced seizure and excitotoxicity. The present studies were designed to examine the role of N-methyl-d-aspartate receptor activation and cytosolic Ca(2+) accumulation in the neurotoxic effects of ethanol withdrawal. Further, these studies investigated the role of hippocampal network excitation in promoting both Ca(2+) accumulation and neurotoxicity during ethanol withdrawal. Chronic, continuous (11 day) exposure to ethanol (91 mM starting concentration) did not produce neurotoxicity in any region of organotypic hippocampal explants, as measured by uptake of the non-vital fluorescent marker propidium iodide. Withdrawal from chronic (10 day) ethanol exposure was associated with rapid (30 min) and significant increases in intracellular Ca(2+), assessed by visualization of Calcium-Orange fluorescence, in each region of hippocampal explants. However, neurotoxicity was observed 24 h after initiation of withdrawal and was only seen in the cornu ammonis 1 (CA1) region. Exposure to MK-801 (20 microM) at the start of ethanol withdrawal markedly attenuated Ca(2+) entry in all regions, as well as, CA1 region neurodegeneration. Further, treatment of explants with tetrodotoxin (500 nM) as well as surgical transection of mossy fiber or Schaffer collateral projections immediately prior to ethanol withdrawal blocked both regional increases in Ca(2+) accumulation and CA1 neurotoxicity. These data suggest that neurodegeneration observed during ethanol withdrawal is dependent upon polysynaptic propagation of action potentials ("network excitation") and whole-hippocampal excitation of glutamatergic systems.

Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the alpha7 nicotinic acetylcholine receptor subunit.

BACKGROUND: Exposure to nicotine has been shown to promote neuronal survival after excitotoxic insult to the brain. The role of specific nicotinic acetylcholine receptors (nAChRs) subtypes in mediating this effect is not well understood, however. Examination of distinct receptor subtypes in promoting neuronal survival is of importance not only in understanding the regulation of necrotic cell death but potentially in the development of novel pharmacological therapies that may reduce this form of neurodegeneration. MATERIAL AND METHODS: The present studies examined the relationship between distribution of alpha7 subunit-bearing nAChRs, using autoradiographic imaging of [125I]alpha-bungarotoxin binding, and protective effects of nicotine against excitotoxic damage. Organotypic cultures of rat hippocampus were exposed to N-methyl-D-aspartate (NMDA; 200 microM) for 1 hour with or without (-)-nicotine (0.1-10 microM) and the alpha7 nAChR antagonist methyllycaconitine (MLA; 100 nM). Neuronal damage was assayed 24 hours later by observation of uptake of the non-vital fluorescent marker propidium iodide. RESULTS: NMDA exposure produced significant neurotoxicity, particularly in pyramidal cell layers of CA3 and CA1, that was prevented by co-exposure to MK-801 (10 microM). Localization of the alpha7 subunit was varied with no binding observed in the dentate gyrus, low density in the CA3 and CA1 regions, and dense binding in the hilus. In all regions, co-exposure to (-)-nicotine (0.1-10.0 microM) significantly reduced (>30%) the cytotoxic consequences of NMDA insult. This protective effect was inhibited by co-exposure to MLA in the dentate and CA3, and to a lesser extent, CA1 regions. CONCLUSIONS: The neuroprotective effect of nicotine against excitotoxicity, then, is not directly related to alpha7 subunit localization in the hippocampus.

Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28K overexpression.

Neuronal accumulation of excess Ca2+ has been implicated in cellular death following several forms of physical and chemotoxic insult. Recent studies have suggested that exposure to agonists at brain nicotinic acetylcholine receptors reduces cytotoxic consequences of increased intracellular Ca2+ following some insults. In the present study, the ability of chronic exposure to (-)-nicotine to reduce cytotoxicity and attenuate increases in intracellular Ca2+ caused by exposure to N-methyl-D-aspartate were examined in organotypic cultures of rat hippocampus. Cultures were exposed to nicotine (0.1-10.0 microM) for five days prior to excitotoxic insult with N-methyl-D-aspartate. Exposure to N-methyl-D-aspartate produced concentration-dependent increases in both accumulation of 45Ca and in early and delayed cell death in the CA1, CA3 and dentate gyrus regions of cultures. The CA1 region of the hippocampus displayed the greatest sensitivity to cytotoxic effects of N-methyl-D-aspartate exposure; however, this regional difference was not associated with increased accumulation of 45Ca. Prior exposure to nicotine markedly attenuated N-methyl-D-aspartate-induced early and delayed cell death in each hippocampal region at concentrations as low as 0.1microM. However, nicotine did not alter the initial N-methyl-D-aspartate-stimulated influx of 45Ca or enhance extrusion of accumulated 45Ca measured at several time-points after insult. Five days of exposure to nicotine markedly increased immunoreactivity of the Ca2+ binding protein calbindin-D28K in each region of hippocampal cultures, effects reduced by mecamylamine co-exposure. These findings suggest that the potent protective effects of chronic nicotine exposure against neuronal overexcitation are not likely attributable to attenuations of Ca2+ accumulation, but are likely related to increased buffering of accumulated Ca2+.

Chronic, but not acute, nicotine exposure attenuates ethanol withdrawal-induced hippocampal damage in vitro.

BACKGROUND: Long-term ethanol use and long-term tobacco use frequently occur together, which suggests concurrent dependence on ethanol and nicotine. Consequences of this form of polydrug dependence are not well understood, however. Previous evidence suggests detrimental effects of long-term ethanol and beneficial effects of nicotine exposure on neuronal viability. Thus, the present study was designed to use an organotypic hippocampal slice culture model to examine the ability of chronic and acute nicotine exposure to reduce neurotoxicity associated with withdrawal from long-term ethanol exposure. METHODS AND RESULTS: Twenty-four hours of withdrawal after continuous 10 day ethanol exposure (50 or 100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from neonatal rat, most notably in pyramidal cell layers of the CA1 region. Exposure of slices to the N-methyl-D-aspartate receptor blocker MK-801 during ethanol withdrawal significantly reduced this toxicity. Exposure of slices to nicotine (0.1-10.0 microM) during the 24 hr withdrawal period did not reduce hippocampal damage. However, treatment of slices with nicotine (0.1-10.0 microM) during 10 days of ethanol exposure was associated with significant reductions in subsequent withdrawal-induced cytotoxicity, an effect reduced by mecamylamine coexposure with nicotine and ethanol. CONCLUSIONS: These findings indicate the development of marked hippocampal neurotoxicity during withdrawal from long-term ethanol exposure that is mediated, in part, by overactivation of N-methyl-D-aspartate receptors. Furthermore, these data suggest that one consequence of concurrent dependence on ethanol and nicotine may be reduced neurological damage associated with ethanol withdrawal.

In vitro effects of ethanol withdrawal and spermidine on viability of hippocampus from male and female rat.

BACKGROUND: Long-term ethanol dependence results in neuronal adaptation that likely contributes to ethanol withdrawal-induced central nervous system excitability and, potentially, neurotoxicity. This has been suggested to result, in part, from increased release of or response to endogenous polyamines. Furthermore, it has been reported that neurological difficulties related to ethanol dependence and withdrawal may be more severe in female than in male alcoholics. Thus, we designed this study to examine effects of the polyamine spermidine on neurotoxicity associated with withdrawal from long-term ethanol exposure by using organotypic hippocampal slice cultures derived from male and female rats. METHODS AND RESULTS: Twenty-four hours of withdrawal after continuous 10 day ethanol exposure (100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from both sexes. This was most evident in pyramidal cell layers of the CA1 region, and no sex differences were observed in the severity of damage. Exposure of explants from both sexes to the NMDA blocker MK-801 during ethanol withdrawal significantly reduced this toxicity. In control cultures, exposure to spermidine (100 microM) alone produced significant and similar cytotoxicity in hippocampal explants of male and female rats. Exposure to spermidine (100 microM) during ethanol withdrawal significantly increased cytotoxicity in all regions of explants. In the CA3 region, spermidine-potentiation of ethanol withdrawal damage was significantly greater in explants from female rats compared with those from male rats. CONCLUSIONS: These data demonstrate the presence of significant hippocampal neurotoxicity during withdrawal from long-term ethanol exposure that is mediated, in part, by overactivation of NMDA receptors. Furthermore, these findings suggest that the central nervous system of females may be more susceptible than that of males to polyamine-mediated neuronal damage during withdrawal from long-term ethanol exposure.

Nonmethylated transposable elements and methylated genes in a chordate genome.

The genome of the invertebrate chordate Ciona intestinalis was found to be a stable mosaic of methylated and nonmethylated domains. Multiple copies of an apparently active long terminal repeat retrotransposon and a long interspersed element are nonmethylated and a large fraction of abundant short interspersed elements are also methylation free. Genes, by contrast, are predominantly methylated. These data are incompatible with the genome defense model, which proposes that DNA methylation in animals is primarily targeted to endogenous transposable elements. Cytosine methylation in this urochordate may be preferentially directed to genes.

Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic.

BACKGROUND: The emergence of resistance to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, in enterococci has increased the need for new antibiotics. As chemical modification of the antibiotic structure is not trivial, we have initiated studies towards enzymatic modification by sequencing the DNA coding for the biosynthesis of chloroeremomycin (also known as A82846B and LY264826). RESULTS: Analysis of 72 kilobases of genomic DNA from Amycolatopsis orientalis, the organism that produces chloroeremomycin, revealed the presence of 39 putative genes, including those coding for the biosynthesis of the antibiotic. Translation and subsequent comparison with known proteins in public databases identified enzymes responsible for the biosynthesis of the heptapeptide backbone and 4-epi-vancosamine, as well as those for chlorination and oxidation reactions involved in the biosynthesis of chloroeremomycin. CONCLUSIONS: The genes responsible for the biosynthesis of chloroeremomycin have been identified, and selective expression of these genes could lead to the synthesis of new potent glycopeptide antibiotics.

New recommendations for prophylaxis after HIV exposure.

Early prophylaxis after exposure to human immunodeficiency virus (HIV) can reduce the risk of HIV infection 10-fold and should be recommended or offered after all parenteral exposures. The current recommendations from the Centers for Disease Control and Prevention call for the use of two nucleoside antiretroviral drugs (zidovudine and lamivudine) with or without a protease inhibitor. The use of interferon alfa-2b has not been extensive but may be of benefit in cases of massive exposure. Both the HIV-source patient and the person exposed to HIV should be tested for hepatitis B and C and syphilis, as well as HIV antibody.

Tyrosine-rich crystalloids in neoplasms and tissues of the head and neck.

Tyrosine-rich crystalloids were identified in three benign mixed tumors of the parotid gland, one terminal duct adenocarcinoma of a minor salivary gland, and the fibrous connective tissue of two laryngectomy specimens. Light and electron microscopic studies showed the crystalloids to be composed of irregular deposits of amorphous electron-dense material. In the salivary gland tumors this material was commonly associated with interstitial collagen and was found in greatest abundance near myoepithelial cells. This proximity suggests that the tyrosine-rich crystalloids result from the precipitation on stromal collagen of products secreted by neoplastic myoepithelial cells.

Androgen trial in renal anaemia.

A double blind cross-over trial of Nandrolone decanoate (Decadurabolin) was carried out in 27 patients with anaemia due to end stage renal disease, stabilised on regular haemodialysis. Sixteen patients completed the study, the other patients being excluded from the final analysis for a variety of reasons including side effects related to the androgen. There was no sustained significant rise in haemoglobin concentration or in red cell mass. Erythropoietin levels did not alter, they were within or below the normal range, but were lower than would be expected for the degree of anaemia. A majority of patients reported increased well-being including exercise tolerance, appetite and libido. Voice changes and hirsutism were noted, mainly in the females. Instability of anticoagulant therapy and abnormalities in liver function were found in some patients. The benefits, though real, were restricted essentially to the improvement in subjective findings and were unrelated to laboratory measurements. These effects might be obtained with a lower dosage of the drug.