Review of the effects of self-stigma and perceived social stigma on the treatment-seeking decisions of individuals with drug- and alcohol-use disorders.

Substance-use disorders are a public health crisis globally and carry with them significant morbidity and mortality. Stigma toward people who abuse these substances, as well as the internalization of that stigma by substance users, is widespread. In this review, we synthesized the available evidence for the role of perceived social stigma and self-stigma in people's willingness to seek treatment. While stigma may be frequently cited as a barrier to treatment in some samples, the degree of its impact on decision-making regarding treatment varied widely. More research needs to be done to standardize the definition and measurement of self- and perceived social stigma to fully determine the magnitude of their effect on treatment-seeking decisions.

Wilt, Crown, and Root Rot of Common Rose Mallow (Hibiscus moscheutos) Caused by a Novel Fusarium sp.

A new crown and root rot disease of landscape plantings of the malvaceous ornamental common rose mallow (Hibiscus moscheutos) was first detected in Washington State in 2012. The main objectives of this study were to complete Koch's postulates, document the disease symptoms photographically, and identify the causal agent using multilocus molecular phylogenetics. Results of the pathogenicity experiments demonstrated that the Fusarium sp. could induce vascular wilt and root and crown rot symptoms on H. moscheutos 'Luna Rose'. Maximum-likelihood and maximum-parsimony phylogenetic analyses of portions of translation elongation factor 1-α and DNA-directed RNA polymerase II largest and second-largest subunit indicated that the Hibiscus pathogen represents a novel, undescribed Fusarium sp. nested within the Fusarium buharicum species complex.

Growth, morphometrics, and nutrient content of farmed eastern oysters, Crassostrea virginica (Gmelin), in New Hampshire, USA.

When harvested, oysters represent a removal from the ecosystem of nutrients such as nitrogen (N) and carbon (C). A number of factors potentially affect nutrient content, but a quantitative understanding across the geographic range of the eastern oysters is lacking. The present study was designed to quantify the relationships among various metrics of farmed eastern oysters near its northern geographic range focusing on nutrient content. Hatchery-reared oysters were deployed in polyethylene bags at six sites, and were measured on multiple occasions from 2010-2012. A quadratic polynomial fit to the combined datasets for shell height indicated that on average a 'cocktail' size oyster (63 mm shell height) would be reached after 2 yr, and 'regular' size (76 mm) would require 3 yr. There were significant differences in growth rates and oyster nutrient content among the sites; means for %N in soft tissue ranged from 6.9 to 8.6, and 0.07 to 0.18 in shell. Percent N in soft tissue and shell were highest at two sites at the mouths of rivers with elevated dissolved inorganic N concentrations in the water. Grand means (all sites, seasons and years combined) of soft tissue N and C for regular size oysters were 7.3% and 38.5%, respectively; and for shell N and C were 0.13% and 12.0%, respectively. Our study extends the range of data on nutrient content of the eastern oyster to northern New England, and indicates that oyster size, seasonality, and nutrient concentration in ambient water potentially affect %N and %C content of oysters.

Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence.

BACKGROUND AND PURPOSE: Smoking cessation trials with three high-affinity partial agonists of alpha4beta2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human alpha4beta2 nAChRs. EXPERIMENTAL APPROACH: Rat plasma and brain pharmacokinetics were characterized and used to predict human steady-state plasma and brain concentrations following recommended doses of each of the three compounds. The pharmacological characterization included in vitro affinities at different nAChR subtypes, functional efficacies and potencies at the human alpha4beta2 nAChR, as well as in vivo effects on rat mesolimbic dopamine turn-over. KEY RESULTS: A comparison of predicted human brain concentrations following therapeutic doses demonstrated that varenicline and nicotine, but not dianicline and cytisine, can extensively desensitize and, to a lesser extent, activate alpha4beta2 nAChRs. The limited clinical efficacy of dianicline may be accounted for by a combination of weak functional potency at alpha4beta2 nAChRs and moderate brain penetration, while recommended doses of cytisine, despite its high in vitro potency, are predicted to result in brain concentrations that are insufficient to affect alpha4beta2 nAChRs. CONCLUSIONS AND IMPLICATIONS: The data provide a plausible explanation for the higher abstinence rate in smoking cessation trials following treatment with varenicline than with the two other alpha4beta2 nAChR partial agonists. In addition, this retrospective analysis demonstrates the usefulness of combining in vitro and in vivo parameters with estimated therapeutic human brain concentrations for translation to clinical efficacy.

Evaluation of germline CDKN2A, ARF, CDK4, PTEN, and BRAF alterations in atypical mole syndrome.

Atypical mole syndrome is a sporadic or an inherited condition with an increased risk of melanoma. Germline mutations in the CDKN2A, ARF, CDK4 and somatic mutations in the PTEN and BRAF genes have been associated with melanoma. In this study, we evaluated genes associated with familial and sporadic melanoma for mutations in 28 probands with the atypical mole syndrome. No sequence alterations in the coding regions or in the splice junctions of CDKN2A, ARF, CDK4, PTEN or BRAF were identified. These data suggest that genes evaluated in this study are unlikely to be candidate genes for atypical mole syndrome and support the notion that unknown susceptibility gene/s for this disease exist.

Identification of a recurrent mutation in keratin 6a in a patient with overlapping clinical features of pachyonychia congenita types 1 and 2.

Pachyonychia congenita is characterized by hypertrophic nail dystrophy and associated ectodermal features. PC-1 subtype is associated with mutations in keratins 6a or 16, whereas PC-2 subtype is linked to mutations in keratins 6b or 17. The correlation between the mutated gene and the type of PC has generally been consistent. In this report, we describe a case with overlapping clinical features of PC-1 and PC-2 in which a mutation in K6a was identified.

A near-fatal hypersensitivity reaction to abacavir: case report and literature review.

A near-fatal hypersensitivity reaction to abacavir developed in a 62-year-old HIV-seropositive man who had been sensitized 17 months before presentation. Six days after he was rechallenged, acute respiratory distress developed, requiring mechanical ventilation for 2 weeks. Four days after extubation, he was again rechallenged. Hours later, the patient experienced anaphylactic shock, requiring mechanical ventilation for 3 weeks, aggressive volume resuscitation, and vasopressor support. Recovery was complicated by acute tubular necrosis, digital necrosis, and a GI bleed. This report reviews the mechanisms of action, efficacy, and adverse reactions of abacavir and illustrates the danger of serially rechallenging patients with this agent.

Community services, issues, and service gaps for individuals with developmental disabilities who exhibit inappropriate sexual behaviors.

Inappropriate sexual behaviors represent the most challenging behaviors for community service providers. A national survey of 243 community agencies was conducted to describe services provided for individuals with developmental disabilities who exhibit high-risk sexual behaviors and to identify issues and service gaps. The most common types of offenses were sexual behavior (a) in public situations, (b) that inappropriately involved others, and (c) involved minors. Community agencies used multifaceted approaches to serve these individuals. The major issues and problems were systemic, specifically staff issues and service gaps, followed by funding. Implications of this study are that increased knowledge and skills related to sexuality and inappropriate sexual behavior and mental health resources are needed to build community capacity to serve this population.

Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST).

Solution pH was measured using water proton NMR via chemical exchange dependent saturation transfer (CEST) with selected chemical exchange sites. Several useful pH-sensitive proton chemical exchange agents were found: 5,6-dihydrouracil, 5-hydroxytryptophan, and a combination of 5-hydroxytryptophan and 2-imidazolidinethione. A ratiometric approach was developed that permitted pH determinations that were independent of water T(1) or exchange site concentration.

A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST).

It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.

University-community partnerships for health: a model interdisciplinary service-learning project.

This project is an example of a successful service-learning experiment at a major university. The program was successful in providing service-learning experiences for an interdisciplinary group of health-professions students, delivering essential health services to a community at risk, providing health-risk and demographic data, and offering opportunities for scholarly productivity for faculty. This was accomplished with a modest investment of internal start-up funding. Goals of the project were achieved, and the program and course were viewed as successful by students, faculty, and community partners.

Phosphorus nuclear magnetic resonance spectroscopy: in vivo magnesium measurements in the skeletal muscle of normal subjects.

31P nuclear magnetic resonance spectroscopy was used to study the skeletal muscle of 33 normal males and 32 females. Free intracellular magnesium levels and the ratios of the phosphorus metabolites were determined. Males had significantly lower free magnesium levels (499.8 microM +/- 26.3 microM vs. 530.7 microM +/- 36.0 microM, P = 0.001, d.f. = 63, analysis of variance). The free magnesium level (rs = -0.5431, P = 0.001) and the phosphocreatin/Inorganic phosphate ratio in males (rs = -0.4102, P = 0.018), and the phosphocreatine/Inorganic phosphate ratio in females (rn = -0.4759, P = 0.009) fell with the increasing Minnesota Heart Health Program Questionnaire score.

Association between mild, routine exercise and improved insulin dynamics and glucose control in obese adolescents.

The association between mild routine exercise and glucose homeostasis, insulin dynamics, and risk factors for coronary artery disease was investigated in obese adolescent males. Subjects (n = 7; mean +/- SD age 13.3 +/- 1.4 yr) were tested before and after 15 wk of supervised mild intensity exercise. Serum glucose (GLU), insulin (IN), and C-peptide (CP) were measured in response to a mixed meal before and after the 15 wk period. Weight, body composition, peak oxygen uptake (peak VO2), resting blood pressure (BP), and blood lipid levels were also assessed pre- and post-training. After training, percent fat and body weight were not decreased compared to the initial values. Relative changes (p < or = 0.02) in mean values for GLU and peptides after training were: fasting GLU, -15%; total GLU response, -15%; peak IN response, -51%; total IN response, -46%; peak CP response, +55%; and total CP response, +53%. Following training, the subjects did not have an increased peak VO2, but showed consistent reductions in systolic BP and LDL-cholesterol (p < 0.05). Increases in hepatic insulin clearance (decreased insulin levels but increased CP levels) might be training adaptations unique to low intensity exercise or to obese youth. Decreased insulin levels with concurrent decreases in resting blood pressure and the LDL-cholesterol levels suggest that mild exercise training may reduce health risk factors without weight loss in the obese adolescent male.

Diabetic nephropathy in an aerobically trained rat model of diabetes.

The purpose of this study was to determine the effects of aerobic training on indices of glycemic control, blood pressure, serum lipids, and diabetic nephropathy (DN) in an animal model of insulin deficient diabetes mellitus. Thirty-four male Sprague-Dawley rats made diabetic with streptozocin were randomly assigned to a trained group or a sedentary group. Fifteen sedentary-nondiabetic rats served as a control group. The animals were trained on a treadmill at 18 m.min-1, 8 degrees incline for 120 min.d-1, 5 d.wk-1. Blood and 24 h urine collections were obtained at various intervals throughout the study. At 21 wk of age systolic blood pressure was measured and kidney tissue was obtained for light and electron microscopy. Analysis of variance was used to detect differences among the groups (P < or = 0.05). The diabetes produced in this investigation resulted in hyperglycemia, increased urine albumin and total protein excretion, elevated systolic blood pressure, increased fractional volume of the mesangium, and widening of the glomerular basement membrane in the sedentary-diabetic animals. Aerobic training significantly reduced the increase in fractional volume of the mesangium and fructosamine. Most importantly, aerobic training did not augment the renal damage seen in DN.

Clozapine is a potent and selective muscarinic M4 receptor agonist.

Clozapine was studied in functional assays at human muscarinic M1-M5 receptors expressed in Chinese hamster ovary cells. Clozapine was a full agonist at the muscarinic M4 receptor (EC50 = 11 nM), producing inhibition of forskolin-stimulated cAMP accumulation. In contrast, clozapine potently antagonized agonist-induced responses at the other four muscarinic receptor subtypes. Selective stimulation of M4 receptors may, in part, explain the hypersalivation observed clinically with clozapine. Moreover, the unique overall muscarinic profile of clozapine may contribute to its atypical antipsychotic efficacy.

Aerobic training and diabetic nephropathy in the obese Zucker rat.

The effects of aerobic exercise training on diabetes control and the development of renal microvascular disease were studied in the obese Zucker rat, an animal model of noninsulin dependent diabetes mellitus (NIDDM). Training consisted of 12 weeks of treadmill running, beginning at six weeks of age. Eight trained obese Zucker rats were compared to 15 obese sedentary controls and to 22 sedentary lean nondiseased littermates. Fasting blood glucose, percent of glycated hemoglobin, serum insulin, serum total cholesterol, body weight and kidney weight, creatinine clearance, urine total protein excretion, urine albumin excretion, and morphometric analyses of cortical glomeruli by light and electron microscopy were performed to evaluate metabolic control, renal function, and structure. Training was associated with less albuminuria, less mesangial volume expansion, and less glomerular basement membrane thickening compared to obese sedentary NIDDM animals. These results suggest that exercise training reduces the glomerular ultrastructural lesions and attenuates the albumin excretion rate in this rat model of obesity-related diabetes.

Modulation of dopamine binding in the fetal rat: effects of milk and exogenous opioid manipulation.

Presentation of milk to the newborn rat promotes changes in sensory and motor behavior and concomitant changes in both endogenous opioid and dopamine systems. The present study employed an in vivo binding technique with a tritiated ligand for the D2 receptor ([3H]raclopride) to examine the effects of intraoral milk infusion and opioid manipulations on dopamine activity in the term rat fetus (E21). In Experiment 1, fetuses received a series of milk infusion, which resulted in decreased occupancy at D2 receptors by the endogenous ligand, dopamine, in striatal, septal, and hypothalamic brain regions. In Experiment 2, fetuses were pretreated with morphine, the mu-agonist [D-Ala2,NMe-Phe4,Gly5-ol]-enkephalin (DAMGO), the kappa-agonist U50,488, or saline. Opioid manipulations had no effect on binding at D2 receptors. These results confirm that intraoral milk infusion can modulate activity in the dopamine system of the near-term fetal rat.

Use of blood glucose data by families of children and adolescents with IDDM.

OBJECTIVE: Prospective evaluation of the use of blood glucose test results for treatment actions by families of youth with IDDM. RESEARCH DESIGN AND METHODS: Forty-seven patients with IDDM used reflectance meters with memory for SMBG for 28 days. Parents kept weekly diaries of six types of uses of SMBG data. We collected SMBG data from the reflectance meters, HbA1 and serum fructosamine assays, and measures of behavioral factors that could affect use of SMBG data. RESULTS: Families recorded a mean of 4.85 data-based actions during the 28-day study, and 74% of the families reported at least one such action. Fifty percent of recorded actions consisted of management of hypoglycemia and, among the remainder, only 18% were anticipatory, proactive actions. Partial correlation analysis showed that families with more frequent use of SMBG data had less parent-child conflict about diabetes, more diabetes knowledge, and better overall treatment adherence. Use of SMBG data was unrelated to objective indices of the need for treatment adjustments or to diabetic control. CONCLUSIONS: Most families made active use of their SMBG data, but few of these actions were proactive. Behavioral factors were stronger predictors of family use of SMBG data than were objective indices of the need for treatment adjustments. The results illustrate the need for further research on use of SMBG data and methods to enhance its impact on diabetic control.