Expression Patterns of BDNF with Central Anorexigenic Signaling Pathways Involving PACAP in the Hypothalamic Ventromedial Nuclei

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid polypeptide belonging to the secretin super family of peptides. PACAP binds to its type 1 receptor (PAC1R) with greater affinity than for the receptors for vasoactive intestinal polypeptides (VIP), VPAC1 and VPAC2. Although mRNA for PACAP and its receptor PAC1R are found throughout the central nervous system, they are abundantly expressed in the hypothalamic ventromedial nuclei (VMN). In male Sprague Dawley rats, infusions of PACAP into the VMN produce a robust decrease in food intake with concomitant increased energy expenditure, decreased body weight, and significantly elevated brain-derived neurotrophic factor (BDNF) mRNA expression in the VMN. This latter effect of PACAP on BDNF mRNA expression has been shown to occur in other brain regions. Exogenous BDNF in the VMN regulates energy homeostasis in a manner similar to that of PACAP with decreased feeding and increased metabolism. Although the physiological responses to individual PACAP and BDNF infusions in the VMN lead to decreased feeding behavior and body weight loss, the anatomical distribution of these two cell signals in the VMN has not been established. PACAP-induced changes in BDNF mRNA expression in the VMN may reveal an important interaction with PACAP signaling in the control of feeding behavior. In the present study, we have employed double-labeled fluorescent in-situ hybridization (FISH) to examine the expression patterns of PACAP, PAC1R and BDNF mRNA containing neuronal cells. In the VMN, PACAP mRNA expressing cells co-express BDNF, PAC1R, and VGLUT2. BDNF mRNA expressing cells co-express PAC1R and PACAP. Coupled with previous behavioral data demonstrating PACAP- and BDNF-induced changes in feeding behavior, the co-expression of BDNF with PACAP and PAC1R mRNA in the VMN suggest a potential functional relationship between the two signaling peptides in the regulation of energy homeostasis. The specific and integrated contributions of PACAP and BDNF in the VMN towards regulating energy homeostasis and feeding behavior still remain to be studied

A New Obesity Model Reveals the Hypophagic Properties of PACAP Involve the Regulation of Homeostatic Feeding in the Ventromedial Hypothalamic Nucleus and Hedonic Feeding in the Nucleus Accumbens

Binge eating in humans is a complex disorder that often involves discrete, compulsive feeding sessions of highly palatable foods even in the absence of a deprivation state or hunger. Binging can be effectively modeled in rodents by providing subjects with limited access to a palatable food source (Western Diet; WD) as an adjunct to ad lib access to normal chow (Standard Chow; SC). Although this design recapitulates several fundamental characteristics observed in binge eating disorder, the binge eating observed in this paradigm is likely a product of both hedonic and homeostatic drives with the need to balance energy stores still present. To isolate these feeding drives, we have developed a novel feeding regimen that modifies the classic limited access binge model to effectively delineate and separate homeostatic feeding from motivational feeding. This is achieved by entraining male Sprague-Dawley rats to a restricted feeding schedule (two hours per day) of SC followed by a short 15 minute limited access meal of either SC or WD (Restrict Fed-Limited Access; RFLA). The RFLA paradigm allows for the examination of pituitary adenylate-cyclase activating polypeptide (PACAP) on palatable food consumption in a fully satiated subject. PACAP has previously been shown to suppress feeding behavior when injected into the hypothalamus. In the current study, PACAP injected into the ventromedial hypothalamic nuclei (VMN) suppressed the two hour homeostatic SC meal, but not the subsequent 15 minute limited access meal of WD. By contrast, PACAP bilaterally administered into the nucleus accumbens (NAc) produced the opposite effect with PACAP suppressing the consumption of WD but not SC. Thus, PACAP mediated signaling in the VMN appears to be involved in homeostatic regulation of energy stores, whereas PACAP signaling in the NAc regulates feeding driven by palatability or hedonic qualities

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Last updated: 10/19/201

Attitudes and Performance: An Analysis of Russian Workers

This paper investigates the relationship between locus of control and performance among Russian employees, using survey data collected at 28 workplaces in 2002 in Taganrog and at 47 workplaces in 2003 in Ekaterinburg. We develop a measure that allows us to categorize the Russian employees participating in our survey as exhibiting an internal or external locus of control. We then assess the extent to which there are significant differences between “internals” and “externals” in work-related attitudes that may affect performance. In particular, we focus on (1) attitudes about outcomes associated with hard work, (2) level of job satisfaction, (3) expectation of receiving a desired reward, and (4) loyalty to and involvement with one’s organization. In each case we identify where gender and generational differences emerge. Our main objective is to determine whether Russian employees who exhibit an internal locus of control perform better than employees with an external locus of control. Our performance measures include earnings, expected promotions, and assessments of the quantity and quality of work in comparison to others at the same organization doing a similar job. Controlling for a variety of worker characteristics, we find that (1) individuals who exhibit an internal locus of control perform better, but this result is not always statistically significant; (2) even among “internals,” women earn significantly less than men and have a much lower expectation of promotion; (3) even among “internals,” experience with unemployment has a negative influence on performance.http://deepblue.lib.umich.edu/bitstream/2027.42/40144/3/wp758.pd

Lay beliefs of TB and TB/HIV co-infection in Addis Ababa, Ethiopia: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Knowledge about lay beliefs of etiology, transmission and treatment of TB, and lay perceptions of the relationship between TB and HIV is important for understanding patients' health seeking behavior and adherence to treatment. We conducted a study to explore lay beliefs about TB and TB/HIV co-infection in Addis Ababa, Ethiopia.</p> <p>Findings</p> <p>We conducted a qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients in Addis-Ababa, Ethiopia. We found that a predominant lay belief was that TB was caused by exposure to cold. Excessive sun exposure, exposure to mud, smoking, alcohol, khat and inadequate food intake were also reported as causes for TB. Such beliefs initially led to self-treatment. The majority of patients were aware of an association between TB and HIV. Some reported that TB could transform into HIV, while others said that the body could be weakened by HIV and become more susceptible to illnesses such as TB. Some patients classified TB as either HIV-related or non-HIV-related, and weight loss was a hallmark for HIV-related TB. The majority of patients believed that people in the community knew that there was an association between TB and HIV, and some feared that this would predispose them to HIV-related stigma.</p> <p>Conclusion</p> <p>There is a need for culturally sensitive information and educational efforts to address misperceptions about TB and HIV. Health professionals should provide information about causes and treatment of TB and HIV to co-infected patients.</p

Conflict in the Indian Kashmir Valley II: psychosocial impact

ABSTRACT: BACKGROUND: India and Pakistan have disputed ownership of the Kashmir Valley region for many years, resulting in high level of exposure to violence among the civilian population of Kashmir (India). A survey was done as part of routine programme evaluation to assess confrontation with violence and its consequences on mental health, health service usage, and socio-economic functioning. METHODS: We undertook a two-stage cluster household survey in two districts of Kashmir (India) using questionnaires adapted from other conflict areas. Analysis was stratified for gender. RESULTS: Over one-third of respondents (n=510) were found to have symptoms of psychological distress (33.3%, CI: 28.3-38.4); women scored significantly higher (OR 2.5; CI: 1.7-3.6). A third of respondents had contemplated suicide (33.3%, CI: 28.3-38.4). Feelings of insecurity were associated with higher levels of psychological distress for both genders (males: OR 2.4, CI: 1.3-4.4; females: OR 1.9, CI: 1.1-3.3). Among males, violation of modesty, (OR 3.3, CI: 1.6-6.8), forced displacement, (OR 3.5, CI: 1.7-7.1), and physical disability resulting from violence (OR 2.7, CI: 1.2-5.9) were associated with greater levels of psychological distress; for women, risk factors for psychological distress included dependency on others for daily living (OR 2.4, CI: 1.3-4.8), the witnessing of killing (OR 1.9, CI: 1.1-3.4), and torture (OR 2.1, CI: 1.2-3.7). Self-rated poor health (male: OR 4.4, CI: 2.4-8.1; female: OR 3.4, CI: 2.0-5.8) and being unable to work (male: OR 6.7, CI: 3.5-13.0; female: OR 2.6, CI: 1.5-4.4) were associated with mental distress. CONCLUSIONS: The ongoing conflict exacts a huge toll on the communities' mental well-being. We found high levels of psychological distress that impacts on daily life and places a burden on the health system. Ongoing feelings of personal vulnerability (not feeling safe) were associated with high levels of psychological distress. Community mental health programmes should be considered as a way reduce the pressure on the health system and improve socio-economic functioning of those suffering from mental health problems

Barriers to prompt and effective malaria treatment among the poorest population in Kenya

<p>Abstract</p> <p>Background</p> <p>Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya.</p> <p>Methods</p> <p>The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n = 708 households); 24 focus group discussions; semi-structured interviews with health workers (n = 34); and patient exit interviews (n = 359).</p> <p>Results</p> <p>Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in the quality of care and poor adherence to treatment regimes. Availability barriers identified were related to facility opening hours, organization of health care services, drug and staff shortages.</p> <p><b>Conclusions</b></p> <p>Ensuring that all individuals suffering from malaria have prompt access to effective treatment remains a challenge for resource constrained health systems. Policy actions to address the multiple barriers of access should be designed around access dimensions, and should include broad interventions to revitalize the public health care system. Unless additional efforts are directed towards addressing access barriers among the poor and vulnerable, malaria will remain a major cause of morbidity and mortality in sub-Saharan Africa.</p