Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance

BACKGROUND: Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE PRESENTATION: During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery

Associations between fatigue impact and physical and neurobehavioural factors: An exploration in people with progressive multiple sclerosis

Background: Fatigue is common in people with multiple sclerosis (MS). Understanding the relationship between fatigue, physical and neurobehavioural factors is important to inform future research and practice. Few studies explore this explicitly in people with progressive MS (pwPMS). // Objective: To explore relationships between self-reported fatigue, physical and neurobehavioural measures in a large, international progressive MS sample of cognitively impaired people recruited to the CogEx trial. // Methods: Baseline assessments of fatigue (Modified Fatigue Impact Scale; MFIS), aerobic capacity (VO2peak), time in moderate-vigorous physical activity (MVPA; accelerometery over seven-days), walking performance (6-minute walk test; 6MWT), self-reported walking difficulty (MS Walking Scale; MSWS-12), anxiety and depression (Hospital Anxiety and Depression Scale; HADS and Beck Depression Inventory-II; BDI-II), and disease impact (MS Impact Scale-29, MSIS-29) were assessed. Participants were categorised as fatigued (MFISTotal >=38) or non-fatigued (MFISTotal ≤38). // Statistical Analysis: Differences in individuals categorised as fatigued or non-fatigued were assessed (t-tests, chi square). Pearson's correlation and partial correlations (adjusted for EDSS score, country, sex, and depressive symptoms) determined associations with MFISTotal, MFISPhysical, MFISCognitive and MFISPsychosocial, and the other measures. Multivariable logistic regression evaluated the independent association of fatigue (categorised MFISTotal) with physical and neurobehavioural measures. // Results: The sample comprised 308 pwPMS (62 % female, 27 % primary progressive, 73 % secondary progressive), mean age 52.5 ± 7.2 yrs, median EDSS score 6.0 (4.5–6.5), mean MFISTotal 44.1 ± 17.1, with 67.2 % categorised as fatigued. Fatigued participants walked shorter distances (6MWT, p = 0.043), had worse MSWS-12 scores (p < 0.001), and lower average % in MVPA (p = 0.026). The magnitude of associations was mostly weak between MFISTotal and physical measures (r = 0.13 to 0.18), apart from the MSWS-12 where it was strong (r = 0.51). The magnitude of correlations were strong between the MFISTotal and neurobehavioural measures of anxiety (r = 0.56), depression (r = 0.59), and measures of disease impact (MSIS-physical r = 0.67; MSIS-mental r = 0.71). This pattern was broadly similar for the MSIF subscales. The multivariable model indicated a five-point increase in MSWS-12 was associated with a 14 % increase in the odds of being fatigued (OR [95 %CI]: 1.14 [1.07–1.22], p < 0.0001) // Conclusion: Management of fatigue should consider both physical and neurobehavioural factors, in cognitively impaired persons with progressive MS

An Analysis of Factors Contributing to the Development of Total Parenteral Nutrition‐Induced Cholestasis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141659/1/jpen0586.pd

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Dietary effects on multi-element composition of European eel (Anguilla anguilla) otoliths

Otolith microchemistry is widely used as a tool to track individual migration pathways of diadromous fish under the assumption that the elemental composition of fish otoliths is directly influenced by the physicochemical properties of the surrounding water. Nevertheless, several endogenous factors are reported to affect element incorporation into fish otoliths and might lead to misinterpretations of migration studies. This study experimentally examined the influence of eight different diets on the microchemical composition of European eel (Anguilla anguilla) otoliths using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Seven natural prey types and one artificial diet were fed during 8 weeks in freshwater circuits. Results show for the first time that food has no significant influence on the incorporation of Na, Sr, Ba, Mg, Mn, Cu and Y into European eel otoliths. This indicates that the incorporation of elements usually chosen for migration studies is not affected by diet and that individual feeding behaviour of A. anguilla will not lead to any misinterpretation of migration pathways

The counselling self-estimate inventory (COSE): Does it work in Chinese counsellors?

Counselling self-efficacy is an important construct for research and evaluation in counsellors' competencies and training effectiveness. Larson et al. developed the Counselling Self-Estimate Inventory (COSE) for counsellors in America and examined its factor structure using exploratory factor analysis. They recommended a five-factor model (microskills, counselling process, difficult client behaviour, cultural competence, and awareness of values) and the use of the COSE for future research. However, little research has investigated the validity of the COSE in the context of counselling Chinese students in schools. In the present study, the factor structure of responses to the Chinese version of the Counselling Self-Estimate Inventory in a sample of 578 Hong Kong secondary school guidance teachers was examined using the EQS approach to confirmatory factor analysis. The results showed that while a five-factor model was fairly able to fit the data, the deletion of items related to the awareness of values factor yielded a better fitting model. The discussion of potential uses and limitations of the C-COSE in the context of preparing and supervising school guidance personnel in student counselling is relevant to counselling psychologists and researchers in Hong Kong and other parts of the world.postprin

Cold Physiology: Postprandial Blood Flow Dynamics and Metabolism in the Antarctic Fish Pagothenia borchgrevinki

Previous studies on metabolic responses to feeding (i.e. the specific dynamic action, SDA) in Antarctic fishes living at temperatures below zero have reported long-lasting increases and small peak responses. We therefore hypothesized that the postprandial hyperemia also would be limited in the Antarctic fish Pagothenia borchgrevinki. The proportion of cardiac output directed to the splanchnic circulation in unfed fish was 18%, which is similar to temperate fish species. Contrary to our prediction, however, gastrointestinal blood flow had increased by 88% at twenty four hours after feeding due to a significant increase in cardiac output and a significant decrease in gastrointestinal vascular resistance. While gastric evacuation time appeared to be longer than in comparable temperate species, digestion had clearly commenced twenty four hours after feeding as judged by a reduction in mass of the administered feed. Even so, oxygen consumption did not increase suggesting an unusually slowly developing SDA. Adrenaline and angiotensin II was injected into unfed fish to investigate neuro-humoral control mechanisms of gastrointestinal blood flow. Both agonists increased gastrointestinal vascular resistance and arterial blood pressure, while systemic vascular resistance was largely unaffected. The hypertension was mainly due to increased cardiac output revealing that the heart and the gastrointestinal vasculature, but not the somatic vasculature, are important targets for these agonists. It is suggested that the apparently reduced SDA in P. borchgrevinki is due to a depressant effect of the low temperature on protein assimilation processes occurring outside of the gastrointestinal tract, while the gastrointestinal blood flow responses to feeding and vasoactive substances resemble those previously observed in temperate species

Minimum pricing of alcohol versus volumetric taxation:which policy will reduce heavy consumption without adversely affecting light and moderate consumers?

Background We estimate the effect on light, moderate and heavy consumers of alcohol from implementing a minimum unit price for alcohol (MUP) compared with a uniform volumetric tax. Methods We analyse scanner data from a panel survey of demographically representative households (n = 885) collected over a one-year period (24 Jan 2010–22 Jan 2011) in the state of Victoria, Australia, which includes detailed records of each household's off-trade alcohol purchasing. Findings The heaviest consumers (3% of the sample) currently purchase 20% of the total litres of alcohol (LALs), are more likely to purchase cask wine and full strength beer, and pay significantly less on average per standard drink compared to the lightest consumers (A$1.31 [95$2.21 [95% CI 2.10–2.31]). Applying a MUP of A$1 per standard drink has a greater effect on reducing the mean annual volume of alcohol purchased by the heaviest consumers of wine (15.78 LALs [95$393.60 [95% CI 374.19–413.00]) and beer ($108.26 [95$552.46 [95% CI 530.55–574.36] and $163.92 [95% CI 152.79–175.03], respectively). Both a MUP and uniform volumetric tax have little effect on changing the annual cost of wine and beer for light and moderate consumers, and likewise little effect upon their purchasing. Conclusions While both a MUP and a uniform volumetric tax have potential to reduce heavy consumption of wine and beer without adversely affecting light and moderate consumers, a MUP offers the potential to achieve greater reductions in heavy consumption at a lower overall annual cost to consumers