Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats.

INTRODUCTION: Tobacco product flavors may change the sensory properties of nicotine, such as taste and olfactory cues, which may alter nicotine reward and aversion and nicotine taking behavior. The hedonic or aversive value of a taste stimulus can be evaluated by examining affective orofacial movements in rodents. AIMS AND METHODS: We characterized taste responses to various oral nicotine concentrations using the taste reactivity test in rats. We also evaluated the impact of menthol and benzaldehyde (cherry, almond) flavorants on both ingestive and aversive responses to oral nicotine. Adult Sprague-Dawley rats (n = 5-10 per sex per group) were implanted with intraoral catheters and received 20 infusions (200 µl/ea). Nicotine (1-100 µg/mL) was evaluated in taste reactivity test to determine taste responses to nicotine. Later, the effects of menthol (50 µg/mL) and benzaldehyde (100 µg/mL) on the taste responses to nicotine were determined. RESULTS: Nicotine at low concentrations (3 µg/mL in males, 1 µg/mL in females) elicited significantly greater ingestive responses compared with water, whereas higher nicotine concentrations (≥30 µg/mL in males, ≥10 µg/mL in females) elicited significant aversive reactions. Thus, intraoral nicotine induced both hedonic and aversive responses in a concentration- and sex-dependent manner. Females were more sensitive to nicotine's concentration. The addition of menthol or benzaldehyde significantly increased the hedonic responses to nicotine, and significantly decreased the aversive nicotine responses. CONCLUSIONS: Oral nicotine induces both hedonic and aversive taste responses, which may represent liking and disliking. Menthol and benzaldehyde can alter the orosensory experience of nicotine, which may influence nicotine's abuse liability. IMPLICATIONS: Our work represents a model to study impact of flavors on oral nicotine liking and disliking responses in rats. Moreover, our findings show that menthol and benzaldehyde alter the orosensory experience of nicotine, suggesting that both could influence nicotine's abuse liability.

Empowered and disempowered voices of low-income people with disabilities on the initiation of government-funded, managed health care

The health and healthcare of vulnerable populations is an international concern. In 2011, a Midwestern state within the U.S. mandatorily transitioned 38,000 Medicaid recipients from a fee-for-service system into a managed care program in which managed care companies were contracted to provide recipients’ healthcare for a capitated rate. In addition to cost savings through reductions in preventable and unnecessary hospital admissions, the goals of the managed care program (MCP) included: (1) access to a more functional support system, which can support high and medium risk users in the development of care plans and coordination of care, and (2) choice among competent providers. The population transitioned was a high-need, high-cost, low-income, and low-power group of individuals. The evaluation research team used focus groups as one of many strategies to understand the experience of users during the first two years of this complex change effort. The article explores empowerment in terms of users and their family caregivers’ ability to make meaningful choices and access resources with regard to their healthcare. Specifically, factors empowering and disempowering users were identified within three thematic areas: (1) enrollment experiences, (2) access to care and (3) communication with managed care organizations and providers. While the change was not optional for users, a disempowering feature, there remained opportunities for other empowering and disempowering processes and outcomes through the transition and new managed care program. The results are from 74 participants: 65 users and 9 family caregivers in 11 focus groups and six interviews across two waves of data collection. MCP users felt disempowered by an initial lack of providers, difficulty with transportation to appointments, and challenges obtaining adequate medication. They felt empowered by having a choice of providers, good quality of transportation services and clear communication from providers and managed care organizations. Recommendations for increasing prospects for the empowerment of healthcare users with disabilities within a managed care environment are presented

La salud y su atención en poblaciones vulnerables preocupa internacionalmente. Un Estado del medio-oes te estadounidense en 2011 traspasó obligatoriamente a 38.000 receptores de Medicaid de un sistema de pago por servicio a un programa de asistencia gestionada en el que se contrataba a empresas de asistencia gestionada para la prestación de asistencia sanitaria a los usuarios por una cuota por persona. Además de los ahorros por la disminución de admisiones hospitalarias evitables e innecesarias, los objetivos del pro grama gestionado de asistencia incluían: (1) el acceso a un sistema de apoyo más funcional para usuarios de un riesgo elevado y medio en el desarrollo de planes de asistencia y coordinación de la misma y (2) la elección entre proveedores competentes. La población a la que afecta este traspaso era un grupo de personas muy necesitadas, que entrañaban costes elevados, con un nivel bajo de ingresos y de poder. El equipo investigador de evaluación utilizó grupos de discusión como una de las muchas estrategias para entender la experiencia de los usuarios durante los dos primeros años de este esfuerzo complejo de cambio. El artículo explora el "empowerment" en cuanto a los usuarios y a la capacidad de quienes prestan asistencia a su familia de tomar las decisiones oportunas y acceder a los recursos relativos la prestación de asistencia sanitaria.En concreto, los factores que reforzarían o debilitarían a los usuarios pueden pertenecer a tres áreastemáticas: (1) experiencias de enrolamiento, (2) acceso a la asistencia y (3) la comunicación con las organizacionescon quienes proporcionan asistencia sanitaria gestionada. A pesar de que el cambio no era optativopara los usuarios, un aspecto negativo, aún quedaba margen para otros procesos de capacitación, incapacitación y resultados gracias a la transición y al nuevo programa gestionado de asistencia. Se dispone de resultadosde 74 participantes, 65 usuarios y 9 personas que prestan asistencia a la familia en 11 grupos dediscusión, con 6 entrevistas en dos tandas de recogida de datos. Los usuarios del programa gestionado deasistencia sintieron desvalimiento por la falta inicial de proveedores, los problemas de transporte a las citasy para conseguir la medicación adecuada. En cambio se sintieron reforzados por el hecho de tener unagama de proveedores, una buena calidad de servicios de transporte y comunicación clara por parte de los proveedores y de las organizaciones de asistencia gestionada. Se ofrecen recomendaciones para mejorar las perspectivas de reforzamiento (empowerment) de los usuarios de asistencia sanitaria con discapacidades en un entorno de prestación gestionada de asistencia

School and community-based childhood obesity: implications for policy and practice.

This introduction to a special issue of the Journal of Prevention and Intervention in the Community on the topic of childhood obesity prevention lays some of the basis for the state of affairs of the childhood obesity epidemic in the United States as of 2012 and the need for and types of existing prevention and intervention efforts underway. At the intersection of public health and community psychology, each of the five articles presents some insights into how prevention and intervention efforts currently underway are fairing and offers some implications for program developers and policy makers to start to turn around the epidemic. Given the key role schools play, successful strategies for engaging schools are presented in the introduction. The authors of this special issue also emphasize the need to involve whole communities in order to attain the intended changes of reductions in overweight and obesity rates and increases in positive health outcomes.

Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies.

The etiology of cutaneous T-cell lymphoma (CTCL) remains unknown, with potential infectious causes having been explored. This contribution evaluates the evidence suggesting an infectious etiology and pathogenesis of the disease, characterizes the relationships between various specific pathogens and CTCL, and discusses some of the difficulties in establishing a causal link between infectious agents and CTCL carcinogenesis. Researchers have evaluated CTCL specimens for evidence of infection with a variety of agents, including human T-lymphotropic virus, Epstein-Barr virus, human herpesvirus-8, and Staphylococcus aureus, although other pathogens also have been detected in CTCL. Although there is significant evidence implicating one or more infectious agents in CTCL, studies to date have not linked definitively any pathogen to disease development, and various studies have yielded conflicting results.

Prospective evaluation of gastroenterologist-guided, nurse-administered standard sedation for spiral deep small bowel enteroscopy.

BACKGROUND: Sedation of patients for deep small bowel enteroscopy presents unique challenges and is traditionally provided by anesthesiologists. No study has directly evaluated gastroenterologist-guided, nurse-administered sedation for deep enteroscopy. Further, no comparison exists between gastroenterologist-guided versus anesthesiologist-guided sedation during deep enteroscopy. AIMS: To evaluate safety and efficacy of performing deep (spiral) enteroscopy using gastroenterologist-guided sedation and compare outcomes between patients receiving gastroenterologist-guided and anesthesiologist-guided sedation. METHODS: This prospective case series contains 91 consecutive patients who underwent deep enteroscopy with spiral Endo-Ease Discovery SB overtube. Of the patients, 64 received gastroenterologist-guided and 27 received anesthesiologist-guided sedation. RESULTS: In the 64 patients receiving gastroenterologist-guided sedation, successful completion occurred in 59 of 64 enteroscopies (92.2%). Mean insertion depth was 231.0+/-85.8 cm beyond the ligament of Treitz. Total procedure time was 39.9+/-15.7 min (diagnostic time 34.7+/-12.3 min; therapy time 5.2+/-8.9 min). Positive findings were noted in 32 cases (50.0%), with therapy performed in 27 cases (42.2%). Six minor complications occurred. Compared to the anesthesiologist-guided sedation group, there was no difference in patient characteristics except mean American Society of Anesthesiologists score (2.5+/-0.5 in gastroenterologist-guided group versus 2.7+/-0.6 in anesthesiologist-guided group; p=0.046) and presence of adhesions (ten in gastroenterologist-guided group and zero in anesthesiologist-guided group; p=0.030). Outcomes for both groups were not significantly different except for shorter times in the gastroenterologist-guided group (39.9+/-15.7 min versus 46.0+/-12.1 min; p=0.047) and more frequent findings in the anesthesiologist-guided group (50.0% vs. 74.1%; p=0.034). CONCLUSIONS: Deep enteroscopy using the spiral overtube can be successfully and safely accomplished with gastroenterologist-guided, nurse-administered standard sedation.

The spiral enteroscopy training initiative: results of a prospective study evaluating the Discovery SB overtube device during small bowel enteroscopy (with video).

BACKGROUND AND AIM: Indications for small-bowel enteroscopy are increasing, but advancing the endoscope to the ileum remains challenging, especially for less experienced operators. The aim was to evaluate the ease of use, safety, and efficacy of the Discovery SB overtube (Spirus Medical, Stoughton, Massachusetts, USA) during SB enteroscopy by physicians with no experience of the device. PATIENTS AND METHODS: Thirty-three "untrained" endoscopists performed spiral enteroscopy during one of four 2-day training modules. Data were prospectively collected. Patient demographics, depth and time to maximal insertion, total procedure time, and findings were recorded. Trauma was documented during scope withdrawal. Day 1 and day 2 results were compared. RESULTS: Ninety procedures were successfully performed in 95 patients (72.6 % women, age = 48.8 +/- 14.2 years). Endoscopists each performed a mean of five procedures. Mean time to maximal insertion was 20.9 +/- 6.4 minutes. Mean depth achieved was 262.0 +/- 57.4 cm. Total procedure time was 33.6 +/- 8.0 minutes. In 90.3 %, 94.6 %, and 83.9 % of patients, respectively, a trauma score less than 3 was recorded in the esophagus, stomach, and intestine (scale = 0 - 5). There were no perforations, nor significant associations between trauma score and patient age, body mass index, depth of insertion, time to maximal insertion, total procedure time, or day 1 vs. day 2 procedures. Depth of insertion was greater on day 2 than on day 1 (276.9 +/- 53.7 cm vs. 252.0 +/- 58.0 cm, P = 0.043). CONCLUSIONS: Discovery SB provides safe advancement of the enteroscope into the distal small bowel. Maximum depth of insertion appears comparable to that of balloon enteroscopy while taking less time. The device is easy to use and may be effectively operated in as few as five training cases.

Measuring In-Group and Out-Group Helping in Communal Living: Helping and Substance Abuse Recovery.

With a national U.S. sample of communal-living residents in substance abuse recovery, the tendency to help members inside and/or outside their community was examined. Study 1 (n = 670) developed of the Communal Living In-Group Helping Scale to distinguish helping directed toward housemates vs. others. Study 2 (n = 419) used this communal helping measure and a general altruism scale to explore gender, ethnicity, and 12-Step sponsorship related to in-group (housemates) and out-group (others in the community) behaviors. Results revealed significant sex differences and significantly higher helping for both men and women was reported among 12-Step sponsors along two dimensions. Implications focused on gender-related differences in social helping interactions and in-group formation in recovery communities.

Effect of oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin in the rat.

The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12.7 +/- 3.3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 +/- 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 +/- 5% (10 ng [mercapto-proprionic acid1, D-Tyr(Et)2,Thr4,Orn8]-oxytocin/min), 13 +/- 5% (5 ng desGly9[D-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 +/- 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 +/- 5% associated with oxytocin infusion was significantly decreased to 4 +/- 3% (5 ng desGly9[D-Trp2,D-Thr4,Orn8]-dC6 oxytocin/min) and 1 +/- 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/ min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10.1 +/- 2.1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.

Do vasopressin and oxytocin have synergistic renal effects in the conscious rat?

The renal effects of arginine vasopressin and oxytocin were studied in the conscious unrestrained rat infused with 0.077 M NaCl. Peptides were infused at rates of 24 and 160 pmol/min (vasopressin) or 30 and 200 pmol/min (oxytocin) either alone or as a combination of the two lower or two higher doses. The rates of infusion were selected to give ratios of oxytocin:vasopressin similar to those seen in the plasma of euhydrated and dehydrated rats. Vasopressin produced dose-dependent antidiuretic and natriuretic responses, the natriuresis commencing after 15-30 min infusion. Oxytocin produced dose-dependent diuretic and natriuretic responses, the natriuresis commencing within the first 15 min of infusion. Combined infusion of vasopressin and oxytocin produced dose-dependent antidiuretic responses which were comparable to those seen with vasopressin alone. The natriuretic response from combined infusion at the higher rate appeared to have the greater magnitude for individual 15-min periods of the vasopressin response combined with the longer duration of the oxytocin response. Although the total natriuretic response was therefore greater, this difference failed to reach significance. Only the higher rates of infusion of vasopressin and oxytocin significantly increased the clearance of sodium, by 53 +/- 23 and 62 +/- 18% and glomerular filtration rate (GFR) by 23 +/- 4 and 23 +/- 4% respectively. The clearance of sodium during the combined hormone infusion was significantly greater (109 +/- 21%), while the rise in GFR at 23 +/- 5% was comparable to that seen when each hormone was given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of vasopressin and oxytocin on glomerular filtration rate in the conscious rat: contribution to the natriuretic response.

Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were determined in the conscious unrestrained rat infused with hypotonic saline. The effects of vasopressin infused at 24 and 160 pmol/min and oxytocin infused at 30 and 200 pmol/min were determined. The lower doses of each hormone gave plasma concentrations within the physiological range whereas the higher doses produced plasma concentrations equivalent to those seen following dehydration. Vasopressin produced dose-dependent antidiuretic and natriuretic responses. Hormone infused at both rates increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. Fractional excretion of sodium was significantly elevated by both doses. Oxytocin produced dose-dependent diuretic and natriuretic responses. Again both rates of infusion increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. The lower dose caused a significant increase in the fractional excretion of sodium. It appears, therefore, that increases in GFR may have a role in the natriuretic response to both hormones. However, this response can also be seen when GFR remains unchanged. This fact, together with the observed increases in the fractional excretion of sodium, indicates that these hormones have additional tubular actions.

Tris reversibly inhibits secretion of albumin and alpha-1-antitrypsin at different sites.

We have investigated the effect of the weak base Tris on the processing and secretion of albumin and alpha-1 antitrypsin by hepatocytes in culture. We show that the secretion of both proteins is 90% inhibited by 30 mM Tris. The post-synthetic processing of both proteins is inhibited to the same extent. These effects are completely reversible. Cell fractionation indicates that albumin accumulates in the Golgi, whereas alpha-1 antitrypsin fails to leave the endoplasmic reticulum.

Potassium depletion inhibits the intracellular transport of secretory proteins between the endoplasmic reticulum and the Golgi complex.

In this paper we show that hepatocytes that have been depleted of K+ secrete albumin, alpha-1-anti-trypsin and transferrin at a slower rate than cells to which K+ has been returned. K+ depletion has no effect on the intracellular nucleotide pools, and we provide evidence that the inhibitions of secretion caused by depletion of K+ and depletion of ATP are independent. Studies of the processing of alpha-1-anti-trypsin show that K+ depletion inhibits the formation of the mature form of the protein, but that immature forms are never secreted. In cells to which K+ was returned, secretion of the mature form was restored. This implies that transport is blocked at a point before the proteins reach the processing enzymes. Proteins delayed by K+ depletion are not removed from the secretory pathway, but are free to mix with protein synthesized subsequently. These data are supported by subcellular fractionation experiments, which show that the secretory proteins are delayed before reaching the Golgi complex, and by immunoelectron microscopic studies. These show that in K+-deficient cells the morphology of both the endoplasmic reticulum and the Golgi complex is normal. The secretory proteins are trapped in smooth vesicles that contain reaction product when incubated for glucose-6-phosphatase, a marker for the endoplasmic reticulum.

The processing and secretion of rat serum albumin by oocytes from Xenopus laevis.

Microinjection of rat liver mRNA into Xenopus oocytes led to the synthesis of intracellular proalbumin and the secretion of mature albumin into the incubation medium. The ionophore monensin abolished the secretion of albumin but not the processing of the precursor. A variety of protease inhibitors were added to the incubation medium but there was no detectable inhibition of proalbumin cleavage.

Subcellular localisation of inositol lipid kinases in rat liver.

The subcellular distribution of the enzymes which phosphorylate phosphatidylinositol sequentially to form phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate was investigated in rat liver. We demonstrate that whilst phosphatidylinositol kinase is present in Golgi, lysosomes and plasma membranes, the kinase that forms phosphatidylinositol 4,5-bisphosphate is localised predominantly at the plasma membrane. The role of the inositol lipid kinases in cell function is discussed.

Secretion and biosynthesis of N-acetyl-beta-D-hexosaminidases by human placental tissues in vitro.

Chorionic villi selectively secrete the B isoenzyme and, to a lesser extent, the A isoenzyme of lysosomal beta-hexosaminidase when incubated in vitro, suggesting that this tissue could contribute to maternal serum beta-hexosaminidase B and A activities in vivo. The results make it unlikely, however, that the placenta is the source of the I2 isoenzyme found in maternal serum. Samples of amnion and term chorion laeve secreted predominantly the B isoenzyme whereas first-trimester chorion laeve secreted the A, B and I2 isoenzymes. Amnion and chorion laeve may, therefore, be a source of the A, B and I2 activities found in amniotic fluid. Chorionic villi supported the cycloheximide-sensitive incorporation of [3H]leucine into immunoreactive beta-hexosaminidase thereby providing direct evidence for enzyme biosynthesis. Newly synthesized beta-hexosaminidase was detectable in the medium only after extended incubation and the secretion of beta-hexosaminidase activity continued at normal rates for several hours in the absence of protein synthesis. These results indicate that enzyme synthesis is not a primary factor in the regulation of enzyme secretion.

Human Z alpha 1-antitrypsin accumulates intracellularly and stimulates lysosomal activity when synthesised in the Xenopus oocyte.

Microinjection of human liver mRNA from a patient homozygous for alpha 1-antitrypsin deficiency (PiZZ) into Xenopus oocytes led to a 2--10-fold increase in lysosomal activity. Stimulation of lysosomal activity was not observed when mRNA from a normal human liver (alpha 1-antitrypsin PiMM), or water was injected into the oocyte. This lysosomal activity was oocyte derived and was not due to translation products of the human liver mRNA. Thus a protein that accumulates intracellularly in the secretory pathway is capable of stimulating lysosomal activity.

Xenopus oocytes can synthesise but do not secrete the Z variant of human alpha 1-antitrypsin.

Human liver mRNA was prepared from a patient homozygous for alpha 1-antitrypsin deficiency (PiZZ) and from a normal subject (PiMM). Both liver RNAs were microinjected into Xenopus oocytes and alpha 1-antitrypsin identified by immunoprecipitation. The normal M variant of alpha 1-antitrypsin is synthesised and secreted by Xenopus oocytes, the abnormal Z protein is not secreted and an intracellular form accumulates in the oocytes. In the presence of tunicamycin an unglycosylated form of M alpha 1-antitrypsin appears in the incubation medium but no corresponding unglycosylated version of the Z protein is secreted.