Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice.

The mechanisms of pancreatic pain, a cardinal symptom of pancreatitis, are unknown. Proinflammatory agents that activate transient receptor potential (TRP) channels in nociceptive neurons can cause neurogenic inflammation and pain. We report a major role for TRPV4, which detects osmotic pressure and arachidonic acid metabolites, and TRPA1, which responds to 4-hydroxynonenal and cyclopentenone prostaglandins, in pancreatic inflammation and pain in mice. Immunoreactive TRPV4 and TRPA1 were detected in pancreatic nerve fibers and in dorsal root ganglia neurons innervating the pancreas, which were identified by retrograde tracing. Agonists of TRPV4 and TRPA1 increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in these neurons in culture, and neurons also responded to the TRPV1 agonist capsaicin and are thus nociceptors. Intraductal injection of TRPV4 and TRPA1 agonists increased c-Fos expression in spinal neurons, indicative of nociceptor activation, and intraductal TRPA1 agonists also caused pancreatic inflammation. The effects of TRPV4 and TRPA1 agonists on [Ca(2+)](i), pain and inflammation were markedly diminished or abolished in trpv4 and trpa1 knockout mice. The secretagogue cerulein induced pancreatitis, c-Fos expression in spinal neurons, and pain behavior in wild-type mice. Deletion of trpv4 or trpa1 suppressed c-Fos expression and pain behavior, and deletion of trpa1 attenuated pancreatitis. Thus TRPV4 and TRPA1 contribute to pancreatic pain, and TRPA1 also mediates pancreatic inflammation. Our results provide new information about the contributions of TRPV4 and TRPA1 to inflammatory pain and suggest that channel antagonists are an effective therapy for pancreatitis, when multiple proinflammatory agents are generated that can activate and sensitize these channels.

Chronic limitations of neo-liberal capitalism and oligopolistic markets: an urgent case for socialized capital

Purpose – The purpose of this paper is to highlight the serious limitations of neo-liberal capitalism and urge for a shift to socialized capital before further economic deterioration leads to a succession of global conflicts. Design/methodology/approach – This conceptual paper adopts a macro perspective in presenting argument on how global, financial markets integration and capital flow liberalization have led to inadequate market and corporate governance measures. The argument is couched in a selected literature and is preceded by a proposed solution – the requirement for socialized capital. An analysis of the nature of socialized capital is outlined and the questions that require attention identified if a paradigm shift from neo-liberal capitalism is to take place. Findings – The need to urgently shift to a new philosophy of capitalism is overwhelming. Emphasized is that capital needs to adopt a socialised identity and is supported by investment horizons of 30 years or more. It is argued that non-market (e.g. state, NGOs, civil society) intervention is critical in setting appropriate frameworks within which socialized capital can operate. Research limitations/implications – This is a theoretical paper, in which questions are raised which require transparent, public debate. Originality/value – The paper presents the case for a fundamental reconsideration of present day markets, the role of capital and the influence of elites in determining the public good.

Technology acceptance and care self-management: consideration in context of chronic care management

With an aging global population, the number of people living with a chronic illness is expected to increase significantly by 2050. If left unmanaged, chronic care leads to serious health complications, resulting in poor patient quality of life and a costly time bomb for care providers. If effectively managed, patients with chronic care tend to live a richer and more healthy life, resulting in a less costly total care solution. This chapter considers literature from the areas of technology acceptance and care self-management, which aims to alleviate symptoms and/or reason for non-acceptance of care, and thus minimise the risk of long-term complications, which in turn reduces the chance of spiralling health expenditure. By bringing together these areas, the chapter highlights areas where self-management is failing so that changes can be made in care in advance of health deterioration.

HIV-related stigma, asset inheritance and chronic poverty: vulnerability and resilience of widows and caregiving children and youth in Tanzania and Uganda

This paper develops a framework of risk and protective factors to conceptualise the relationship between HIV-related stigma, asset inheritance and chronic poverty among widows and caregiving children and youth in eastern Africa. Analysis of two qualitative studies with 85 participants in rural and urban areas of Tanzania and Uganda reveals that gendered and generational inequalities and stigmatisation sometimes led to property grabbing and chronic poverty. Human and social capital and preventative measures however may help widows and caregiving young people in HIV-affected households to safeguard land and other assets, within a wider supportive environment that seeks to tackle structural inequalities.

Mismatch Negativity (MMN) reveals inefficient auditory ventral stream function in chronic auditory comprehension impairments

Background: Auditory discrimination is significantly impaired in Wernicke’s aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. Methods: Behavioural auditory discrimination thresholds of CVC syllables and pure tones were measured in WA (n=7) and control (n=7) participants. Threshold results were used to develop multiple-deviant mismatch negativity (MMN) oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). Results: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. Conclusions: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.

Impact of chronic neonicotinoid exposure on honeybee colony performance and queen supersedure

BACKGROUND: Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees. METHODOLOGY/PRINCIPAL FINDINGS: To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (-28%) and brood (-13%), as well as a reduction in honey production (-29%) and pollen collections (-19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees' genetic background. CONCLUSIONS/SIGNIFICANCE: Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet, significant detrimental short and long-term impacts on colony performance and queen fate suggest that neonicotinoids may contribute to colony weakening in a complex manner. Further, we highlight the importance of the genetic basis of neonicotinoid susceptibility in honeybees which can vary substantially.

Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk randomised, double-blind, placebo-controlled trial in healthy older adults

Background: Research indicates that chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although, there has been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. Objective: To investigate whether eight weeks of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. Design: High flavanone (HF: 305mg) 100% orange juice and equicaloric low flavanone (LF: 37mg) orange flavored cordial (500ml) were consumed daily for eight weeks by thirty seven healthy older adults (mean age 67 years) according to a crossover, double blind, randomized design separated by a four week washout. Cognitive function, mood and blood pressure were assessed at baseline and follow up with standardized validated tests. Results: Global cognitive function was significantly better following eight week consumption of flavanone-rich juice relative to eight week consumption of the low flavanone control. No significant effects on mood or blood pressure were observed. Conclusions: Chronic daily consumption of flavanone-rich 100% orange juice over eight weeks is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in ageing and the mechanisms which underlie these effects should be investigated.

The influence of chronic conditions and the environment on pubertal development. An example from medieval England

Adolescence is a unique period in human development encompassing sexual maturation (puberty) and the physical and psychological transition into adulthood. It is a crucial time for healthy development and any adverse environmental conditions, poor nutrition, or chronic infection can alter the timing of these physical changes; delaying menarche in girls or the age of peak height velocity in boys. This study explores the impact of chronic illness on the tempo of puberty in 607 adolescent skeletons from medieval England (AD 900-1550). A total of 135 (22.2%) adolescents showed some delay in their pubertal development, and this lag increased with age. Of those with a chronic condition, 40.0% (n=24/60) showed delay compared to only 20.3% (n=111/547) of the non-pathology group. This difference was statistically significant. A binary logistic regression model demonstrated a significant association between increasing delay in pubertal stage attainment with age in the pathology group. This is the first time that chronic conditions have been directly associated with a delay in maturation in the osteological record, using a new method to assess stages of puberty in skeletal remains.

Chronic Diseases: Chronic Diseases and Development 2 Health, agricultural, and economic effects of adoption of healthy diet recommendations

Transition to diets that are high in saturated fat and sugar has caused a global public health concern as the pattern of food consumption is a mayor modifiable risk factor for chronic non-communicable diseases Although agri food systems are intimately associated with this transition, agriculture and health sectors are largely disconnected in their priorities policy, and analysis with neither side considering the complex inter relation between agri trade patterns of food consumption health, and development We show the importance of connection of these perspectives through estimation of the effect of adopting a healthy diet on population health, agricultural production trade the economy and livelihoods, with a computable general equilibrium approach On the basis of case studies from the UK and Brazil we suggest that benefits of a healthy diet policy will vary substantially between different populations, not only because of population dietary intake but also because of agricultural production trade and other economic factors

Impact of chronic disease on quality of life among the elderly in the state of Sao Paulo, Brazil: a population-based study

Objectives. To assess the impact of chronic disease and the number of diseases on the various aspects of health-related quality of life (HRQOL) among the elderly in Sao Paulo, Brazil. Methods. The SF-36 (R) Health Survey was used to assess the impact of the most prevalent chronic diseases on HRQOL. A cross-sectional and population-based study was carried out with two-stage stratified cluster sampling. Data were obtained from a multicenter health survey administered through household interviews in several municipalities in the state of Sao Paulo. The study evaluated seven diseases-arthritis, back-pain, depression/anxiety, diabetes, hypertension, osteoporosis, and stroke-and their effects on quality of life. Results. Among the 1958 elderly individuals (60 years of age or older), 13.6% reported not having any of the illnesses, whereas 45.7% presented three or more chronic conditions. The presence of any of the seven chronic illnesses studied had a significant effect on the scores Of nearly all the SF-36 (R) scales. HRQOL achieved lower scores when related to depression/anxiety, osteoporosis, and stroke. The higher the number of diseases, the greater the negative effect on the SF-36 (R) dimensions. The presence of three or more diseases significantly affected HRQOL in all areas. The bodily pain, general health, and vitality scales were the most affected by diseases. Conclusions. The study detected a high prevalence of chronic diseases among the elderly population and found that the degree of impact on HRQOL depends on the type of disease. The results highlight the importance of preventing and controlling chronic diseases in order to reduce the number of comorbidities and lessen their impact on HRQOL among the elderly.

Chronic colitis associated with HIV infection can be related to intraepithelial infiltration of the colon by CD8+T lymphocytes

Gastrointestinal complications in AIDS patients with diarrhoea are common clinical manifestations, frequently diagnosed by colonoscopy as non-specific colitis. We retrospectively study colon biopsies diagnosed as chronic colitis associated with HIV (CCH). Biopsies were sorted as patients with AIDS (serum CD4 < 200 cell/mm(3)) but without any clear infectious process (n = 12) and patients without HIV infection (n = 24). There are low numbers of CD4+ T lymphocytes in lamina propria of AIDS patients, but CD8+ T populations in this area appear to be similar in all studied groups, regardless of HIV infection or laboratory evidence of a specific agent. We found the clear evidence of CD8+ T cells infiltration in colonic mucosa in HIV patients with microscopic colitis. An imbalance of lymphocyte subpopulations in the colon, both in the lamina propria and epithelium, could result in an intraepithelial CD8 infiltration, involved in the pathogenesis of CCH in AIDS patients.

Lineage-Negative Bone Marrow Cells Protect Against Chronic Renal Failure

Progressive renal failure continues to be a challenge. The use of bone marrow cells represents a means of meeting that challenge. We used lineage-negative (Lin(-)) cells to test the hypothesis that Lin(-) cell treatment decreases renal injury. Syngeneic Fischer 344 rats were divided into four groups: sham ( laparotomy only, untreated); Nx (five-sixth nephrectomy and untreated); NxLC1 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA expression of interleukin (IL)-1 beta, tumor necrosis factor-alpha, and IL-6 was lower in NxLC rats than in Nx rats. On postnephrectomy day 60, NxLC rats presented less proteinuria, glomerulosclerosis, anemia, renal infiltration of immune cells, and protein expression of monocyte chemoattractant protein-1, as well as decreased interstitial area. Immunostaining for proliferating cell nuclear antigen showed that, in comparison with sham rats, Nx rats presented greater cell proliferation, whereas NxLC1 rats and NxLC3 rats presented less cell proliferation than did Nx rats. Protein expression of the cyclin-dependent kinase inhibitor p21 and of vascular endothelial growth factor increased after nephrectomy and decreased after Lin(-) cell treatment. On postnephrectomy day 120, renal function (inulin clearance) was significantly better in Lin(-) cell-treated rats than in untreated rats. Lin(-) cell treatment significantly improved survival. These data suggest that Lin(-) cell treatment protects against chronic renal failure. STEM CELLS 2009; 27: 682-692

Chronic Suppurative Otitis Media in Cleft Palate: Microorganism Etiology and Susceptibilities

Objective: To investigate the microbial etiology of suppurative chronic otitis media (SCOM) in patients with complete cleft lip and palate and isolated cleft palate and to determine the sensitivity of isolated microorganisms to antibiotics by drug diffusion from impregnated discs in agar and the minimum inhibitory concentration of each drug to these microorganisms by drug dilution in agar. Design/Patients: Effusion samples of SCOM obtained from 40 patients with cleft lip and palate registered at the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, at Bauru, Brazil, were bacteriologically analyzed by cultures. The isolated bacteria were submitted to an in vitro susceptibility test to clinically used drugs. Results: Positive cultures were obtained in 100% of studied cases. Among the 57 strains observed, the most frequent were Pseudomonas aeruginosa (35%), Staphylococcus aureus (15.5%), Enterococcus faecalis (14%), and Proteus mirabilis (12%). The frequency of Gram-negative bacilli (enterobacteriaceae and nonfermentative bacilli) was 67%. Pseudomonas aeruginosa presented the highest sensitivity to ciprofloxacin, and enterobacteriaceae exhibited the highest sensitivity to gentamicin. The strains of S. aureus and E. faecalis presented the highest sensitivity to imipenem and sulfamethoxazole/trimethoprim, respectively. Conclusion: Patients with cleft lip and palate presenting with SCOM exhibited 100% positive cultures, with the highest frequency of Pseudomonas and enterobacteriaceae. With regard to the action of antibiotics, imipenem was effective against the four species of isolated microorganisms, followed by ciprofloxacin, which was effective against 75% of isolated species.