Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia

A prominent feature of several type of cancer is cachexia. This syndrome causes a marked loss of lean body mass and muscle wasting, and appears to be mediated by cytokines and tumour products. There are several proteases and proteolytic pathways that could be responsible for the protein breakdown. In the present study, we investigated whether caspases are involved in the proteolytic process of skeletal muscle catabolism observed in a murine model of cancer cachexia (MAC16), in comparison with a related tumour (MAC13), which does not induce cachexia. Using specific peptide substrates, there was an increase of 54% in the proteolytic activity of caspase-1, 84% of caspase-8, 98% of caspase-3 151% to caspase-6 and 177% of caspase-9, in the gastrocnemius muscle of animals bearing the MAC16 tumour (up to 25% weight loss), in relation to muscle from animals bearing the MAC13 tumour (1-5% weight loss). The dual pattern of 89 kDa and 25 kDa fragmentation of poly (ADP-ribose) polymerase (PARP) occurred in the muscle samples from animals bearing the MAC16 tumour and with a high amount of caspase-like activity. Cytochrome c was present in the cytosolic fractions of gastrocnemius muscles from both groups of animals, suggesting that cytochrome c release from mitochondria may be involved in caspase activation. There was no evidence for DNA fragmentation into a nucleosomal ladder typical of apoptosis in the muscles of either group of mice. This data supports a role for caspases in the catabolic events in muscle involved in the cancer cachexia syndrome. © 2001 Cancer Research Campaign.

Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia

Muscle protein degradation is thought to play a major role in muscle atrophy in cancer cachexia. To investigate the importance of the ubiquitin-proteasome pathway, which has been suggested to be the main degradative pathway mediating progressive protein loss in cachexia, the expression of mRNA for proteasome subunits C2 and C5 as well as the ubiquitin-conjugating enzyme, E2(14k), has been determined in gastrocnemius and pectoral muscles of mice bearing the MAC16 adenocarcinoma, using competitive quantitative reverse transcriptase polymerase chain reaction. Protein levels of proteasome subunits and E2(14k) were determined by immunoblotting, to ensure changes in mRNA were reflected in changes in protein expression. Muscle weights correlated linearly with weight loss during the course of the study. There was a good correlation between expression of C2 and E2(14k) mRNA and protein levels in gastrocnemius muscle with increases of 6-8-fold for C2 and two-fold for E2(14k) between 12 and 20% weight loss, followed by a decrease in expression at weight losses of 25-27%, although loss of muscle protein continued. In contrast, expression of C5 mRNA only increased two-fold and was elevated similarly at all weight losses between 7.5 and 27%. Both proteasome functional activity, and proteasome-specific tyrosine release as a measure of total protein degradation was also maximal at 18-20% weight loss and decreased at higher weight loss. Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E2(14k) mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss. These results suggest that activation of the ubiquitin-proteasome pathway plays a major role in protein loss in gastrocnemius muscle, up to 20% weight loss, but that other factors such as depression in protein synthesis may play a more important role at higher weight loss. © 2005 Cancer Research.

Evaluation of the Heart of Birmingham teaching Primary Care Trust (HoBtPCT): My Choice Weight Management Programme:report commissioned by Heart of Birmingham teaching Primary Care Trust

This report details an evaluation of the My Choice Weight Management Programme undertaken by a research team from the School of Pharmacy at Aston University. The My Choice Weight Management Programme is delivered through community pharmacies and general practitioners (GPs) contracted to provide services by the Heart of Birmingham teaching Primary Care Trust. It is designed to support individuals who are ‘ready to change’ by enabling the individual to work with a trained healthcare worker (for example, a healthcare assistant, practice nurse or pharmacy assistant) to develop a care plan designed to enable the individual to lose 5-10% of their current weight. The Programme aims to reduce adult obesity levels; improve access to overweight and obesity management services in primary care; improve diet and nutrition; promote healthy weight and increased levels of physical activity in overweight or obese patients; and support patients to make lifestyle changes to enable them to lose weight. The Programme is available for obese patients over 18 years old who have a Body Mass Index (BMI) greater than 30 kg/m2 (greater than 25 kg/m2 in Asian patients) or greater than 28 kg/m2 (greater than 23.5 kg/m2 in Asian patients) in patients with co-morbidities (diabetes, high blood pressure, cardiovascular disease). Each participant attends weekly consultations over a twelve session period (the final iteration of these weekly sessions is referred to as ‘session twelve’ in this report). They are then offered up to three follow up appointments for up to six months at two monthly intervals (the final of these follow ups, taking place at approximately nine months post recruitment, is referred to as ‘session fifteen’ in this report). A review of the literature highlights the dearth of published research on the effectiveness of primary care- or community-based weight management interventions. This report may help to address this knowledge deficit. A total of 451 individuals were recruited on to the My Choice Weight Management Programme. More participants were recruited at GP surgeries (n=268) than at community pharmacies (n=183). In total, 204 participants (GP n=102; pharmacy n=102) attended session twelve and 82 participants (GP n=22; pharmacy 60) attended session fifteen. The unique demographic characteristics of My Choice Weight Management Programme participants – participants were recruited from areas with high levels of socioeconomic deprivation and over four-fifths of participants were from Black and Minority Ethnic groups; populations which are traditionally underserved by healthcare interventions – make the achievements of the Programme particularly notable. The mean weight loss at session 12 was 3.8 kg (equivalent to a reduction of 4.0% of initial weight) among GP surgery participants and 2.4 kg (2.8%) among pharmacy participants. At session 15 mean weight loss was 2.3 kg (2.2%) among GP surgery participants and 3.4 kg (4.0%) among pharmacy participants. The My Choice Weight Management Programme improved the general health status of participants between recruitment and session twelve as measured by the validated SF-12 questionnaire. While cost data is presented in this report, it is unclear which provider type delivered the Programme more cost-effectively. Attendance rates on the Programme were consistently better among pharmacy participants than among GP participants. The opinions of programme participants (both those who attended regularly and those who failed to attend as expected) and programme providers were explored via semi-structured interviews and, in the case of the participants, a selfcompletion postal questionnaire. These data suggest that the Programme was almost uniformly popular with both the deliverers of the Programme and participants on the Programme with 83% of questionnaire respondents indicating that they would be happy to recommend the Programme to other people looking to lose weight. Our recommendations, based on the evidence provided in this report, include: a. Any consideration of an extension to the study also giving comparable consideration to an extension of the Programme evaluation. The feasibility of assigning participants to a pharmacy provider or a GP provider via a central allocation system should also be examined. This would address imbalances in participant recruitment levels between provider type and allow for more accurate comparison of the effectiveness in the delivery of the Programme between GP surgeries and community pharmacies by increasing the homogeneity of participants at each type of site and increasing the number of Programme participants overall. b. Widespread dissemination of the findings from this review of the My Choice Weight Management Project should be undertaken through a variety of channels. c. Consideration of the inclusion of the following key aspects of the My Choice Weight Management Project in any extension to the Programme: i. The provision of training to staff in GP surgeries and community pharmacies responsible for delivery of the Programme prior to patient recruitment. ii. Maintaining the level of healthcare staff input to the Programme. iii. The regular schedule of appointments with Programme participants. iv. The provision of an increased variety of printed material. d. A simplification of the data collection method used by the Programme commissioners at the individual Programme delivery sites.

The mode of action of a lipid mobilising factor in cancer cachexia

Cachexia is characterised by a progressive weight loss due to depletion of both skeletal muscle and adipose tissue. The loss of adipose tissue is due to the production of a tumour-derived lipid mobilising factor (LMF), which has been shown to directly induce lipolysis in isolated epididymal murine white adipocytes. The administration of LMF to a non-tumour bearing mice produced a rapid weight loss, with a specific reduction in carcass lipid with also some redistribution of lipid with the accumulation of lipid in the liver. There was also up-regulation of uncoupling protein-1 and -2 mRNA and protein expression in brown adipose tissue, suggesting that an adaptive process occurs due to increased energy mobilisation. There was also up-regulation of UCP-2 in the livers of LMF treated mice, suggesting a protective mechanism to the build up of lipid in the livers, which would produce free radical by-products. LMF was also shown to stimulate cyclic AMP production in CHO-K1 cells transfected with human -3 adrenergic receptors and inhibited by the -β3 antagonist SR59230A. LMF binding was also inhibited by SR59230A in isolated receptors. This suggests that LMF mediates its effects through a β3 adrenergic receptor. There were also changes in glucose and fatty acid uptake in LMF treated mice, which suggests metabolic changes are occurring. The study suggests that a tumour derived lipolytic factor acts through the 3 adrenoceptor producing effects on lipid mobilisation, energy expenditure and glucose metabolism.

A comparison of the provision of the My Choice Weight Management Programme via general practitioner practices and community pharmacies in the United Kingdom

This study aimed to assess the effectiveness of a novel, community-based weight management programme delivered through general practitioner (GP) practices and community pharmacies in one city in the United Kingdom. This study used a non-randomized, retrospective, observational comparison of clinical data collected by participating GP practices and community pharmacies. Subjects were 451 overweight or obese men and women resident in areas of high socioeconomic deprivation (82% from black and minority ethnic groups, 86% women, mean age: 41.1 years, mean body mass index [BMI]: 34.5 kg m−2). Weight, waist circumference and BMI at baseline, after 12 weeks and after 9 months were measured. Costs of delivery were also analysed. Sixty-four per cent of participants lost weight after the first 12 weeks of the My Choice Weight Management Programme. There was considerable dropout. Mean percentage weight loss (last observation carried forward) was 1.9% at 12 weeks and 1.9% at final follow-up (9 months). There was no significant difference in weight loss between participants attending GP practices and those attending pharmacies at both 12 weeks and at final follow-up. Costs per participant were higher via community pharmacy which was attributable to better attendance at sessions among community pharmacy participants than among GP participants. The My Choice Weight Management Programme produced modest reductions in weight at 12 weeks and 9 months. Such programmes may not be sufficient to tackle the obesity epidemic.

Description and preliminary results from a structured specialist behavioural weight management group intervention:Specialist Lifestyle Management (SLiM) programme

Background -  Specialist Lifestyle Management (SLiM) is a structured patient education and self-management group weight management programme. Each session is run monthly over a 6-month period providing a less intensive long-term approach. The groups are patient-centred incorporating educational, motivational, behavioural and cognitive elements. The theoretical background, programme structure and preliminary results of SLiM are presented. Subjects/methods - The study was a pragmatic service evaluation of obese patients with a body mass index (BMI) ≥35 kg/m2 with comorbidity or ≥40 kg/m2 without comorbidity referred to a specialist weight management service in the West Midlands, UK. 828 patients were enrolled within SLiM over a 48-month period. Trained facilitators delivered the programme. Preliminary anonymised data were analysed using the intention-to-treat principle. The primary outcome measure was weight loss at 3 and 6 months with comparisons between completers and non-completers performed. The last observation carried forward was used for missing data. Results - Of the 828 enrolled within SLiM, 464 completed the programme (56%). The mean baseline weight was 135 kg (BMI=49.1 kg/m2) with 87.2% of patients having a BMI≥40 kg/m2 and 12.4% with BMI≥60 kg/m2. The mean weight change of all patients enrolled was −4.1 kg (95% CI −3.6 to −4.6 kg, p=0.0001) at the end of SLiM, with completers (n=464) achieving −5.5 kg (95% CI −4.2 to −6.2 kg, p=0.0001) and non-completers achieving −2.3 kg (p=0.0001). The majority (78.6%) who attended the 6-month programme achieved weight loss with 32.3% achieving a ≥5% weight loss. Conclusions - The SLiM programme is an effective group intervention for the management of severe and complex obesity.

Impact of a cognitive-behavioral weight control program on body weight, diet quality, and smoking cessation in weight-concerned female smokers

Many people use smoking as a weight control mechanism and do not want to quit because they fear weight gain. These weight-concerned smokers tend to be female, are significantly less likely to stop smoking, are less likely to join smoking cessation programs, and will relapse more often than smokers who are not weight-concerned. Research suggests that a woman’s confidence in her ability to control her weight after quitting relates positively with her intention to quit smoking. Likewise, success in smoking cessation has been associated with increased self-efficacy for weight control. It has been shown that success in changing one negative health behavior may trigger success in changing another, causing a synergistic effect. Recently research has focused on interventions for weight-concerned smokers who are ready to quit smoking. The present study investigated the effect of a cognitive based weight control program on self-efficacy for weight control and the effect on smoking behavior for a group of female weight concerned smokers. Two hundred and sixteen subjects who wanted to lose weight but who were not ready to quit smoking were recruited to participate in a 12-week, cognitive-behavioral weight control program consisting of twelve one-hour sessions. Subjects were randomly assigned to either (1) the weight-control program (intervention group), or (2) the control group. Results of this study demonstrated that subjects in the intervention group increased self-efficacy for weight control, which was associated with improved healthy eating index scores, weight loss, increased self-efficacy for quitting smoking, a decrease in number of cigarettes smoked and triggered positive movement in stage of change towards smoking cessation compared to the control subjects. For these subjects, positive changes in self-efficacy for one behavior (weight control) appeared to have a positive effect on their readiness to change another health behavior (smoking cessation). Further study of the psychological variables that influence weight-concerned female smokers’ decisions to initiate changes in these behaviors and their ability to maintain those changes are warranted.

Impact of a comprehensive nutrition and lifestyle education intervention on body weight and health-related outcomes in morbidly-obese Hispanic-Americans following laparoscopic Roux-en-Y gastric bypass

As morbid obesity increasingly affects Hispanic-Americans, the incidence of Roux-en-Y gastric bypass procedures (RYGB) among this population rises. Prospective research on the impact of postoperative educational interventions focused on Hispanic- Americans is needed to prevent premature weight loss plateau, weight regain, nutritional deficiencies, and relapse of obesity-related comorbidities. This randomized-controlled study evaluated the impact of a comprehensive nutrition and lifestyle education intervention (6 biweekly postoperative sessions that incorporated motivational strategies for behavioral change) as compared to a non-comprehensive approach (printed guidelines for healthy lifestyle). The variables to consider are body weight, obesity-related comorbidities (depression, diabetes, dyslipidemia, and others), nutrient status, physical activity, and eating habits in 144 morbidly-obese adult Hispanic-Americans 6 to 12 months following RYGB. Patients were randomly assigned to either the comprehensive intervention (n=72) or the comparison group (n=72). Participants (mean age 44.5 ± 13.5 years) were mainly Cuban-born females (83.3%). Intervention sessions attendance was 64%. At 12 months, both groups lost weight significantly, but those in the comprehensive intervention experienced greater excess weight loss than those in the comparison group (80% vs. 64% from preoperative excess weight, P<.001). Intervention participants were significantly more involved in physical activity (+ 14 min/week vs. – 4 min/week), had decreased depression, joint illness, and required less medication for comorbidities than comparison participants. Additionally, those in the comprehensive intervention had sustained supplement intake experiencing less folate deficiency (P=.014). The non-comprehensive intervention group significantly decreased their protein and supplement intake compared to the intervention group. Patients in the comprehensive intervention had significantly better eating habits reflected by fewer episodes of dumping syndrome, constipation, and night eating, than those in the comparison group who reported greater eating in response to negative emotions (P=.003). These findings support the importance of a comprehensive educational approach to achieve more effective weight reduction and health-related outcomes to prevent relapse of obesity-related comorbidities and nutritional deficiencies in Hispanic-Americans 6 to 12 months following RYGB.

(Table 1) Foraminifera weight, size index and CO3 concentrations of core top sediments

Down water column traverses of core top weights for three planktonic species confirm Lohmann's (1995) relationship between foraminifera shell weight loss and bottom water carbonate ion content. However, they also suggest that the initial shell thickness varies with growth habitat and that the offset between bottom water and pore water carbonate ion concentration varies even on small space scales.

Food preferences and weight change during low-fat and low-carbohydrate diets.

UNLABELLED: Understanding associations between food preferences and weight loss during various effective diets could inform efforts to personalize dietary recommendations and provide insight into weight loss mechanisms. We conducted a secondary analysis of data from a clinical trial in which participants were randomized to either a 'choice' arm, in which they were allowed to select between a low-fat diet (n = 44) or low-carbohydrate diet (n = 61), or to a 'no choice' arm, in which they were randomly assigned to a low-fat diet (n = 49) or low-carbohydrate diet (n = 53). All participants were provided 48 weeks of lifestyle counseling. Food preferences were measured at baseline and every 12 weeks thereafter with the Geiselman Food Preference Questionnaire. Participants were 73% male and 51% African American, with a mean age of 55. Baseline food preferences, including congruency of food preferences with diet, were not associated with weight outcomes. In the low-fat diet group, no associations were found between changes in food preferences and weight over time. In the low-carbohydrate diet group, increased preference for low-carbohydrate diet congruent foods from baseline to 12 weeks was associated with weight loss from 12 to 24 weeks. Additionally, weight loss from baseline to 12 weeks was associated with increased preference for low-carbohydrate diet congruent foods from 12 to 24 weeks. Results suggest that basing selection of low-carbohydrate diet or low-fat diet on food preferences is unlikely to influence weight loss. Congruency of food preferences and weight loss may influence each other early during a low-carbohydrate diet but not low-fat diet, possibly due to different features of these diets. CLINICAL TRIAL REGISTRY: NCT01152359.

Social-Cognitive Determinants of Success in Online Communities for Weight Management

Background: Online communities may be an effective, convenient, and relatively inexpensive intervention platform for individuals seeking assistance with weight management. Recent research suggests that these communities may be as effective as in-person treatments for weight management; however, very little is known about the characteristics that predict weight loss amongst those using an online community. Methods: Within a social-cognitive framework, we sought to identify the psychosocial characteristics that are associated with successful weight management for users of MyFitnessPal, a popular online community for weight management. We recruited participants who were new to the online community and asked them to complete 2 surveys (one at baseline and one 3 months later) that assessed various psychosocial constructs as well as self-reported height and weight. Results: Participants in our sample reported losing, on average, 4.55 kg during the 3-month time period. We found that engaging in weight control behaviors (e.g., monitoring food intake, weighing oneself, etc.) fully mediated the relationship between several of our variables of interest (i.e., baseline self-efficacy and perceived social support within the community) and weight loss. We also found that participants who expected to lose more weight at baseline were significantly more likely to have lost more weight at follow-up. Conclusions: On average, participants in our study lost a clinically meaningful amount of weight. Predictors of weight loss within this community included perceived support within the community (mediated by weight control behaviors), baseline self-efficacy (mediated by weight control behaviors), and baseline outcome expectations. Results of this study can ultimately serve to inform the design of future eHealth interventions for weight management.

Element abundances, loss on ignition, total analyzed abundances, CIA values, and Al-oxide/Ti-oxide ratios of sediment core CRP-2A (Table1)

The CRP-2/2A core, drilled in western McMurdo Sound in October and November 1998, penetrated 624 m of Quaternary. Pliocene, lower Miocene, and Oligocene glacigenic sediments. The palaeoclimatic record of CRP-2/2A is examined using major element analyses of bulk core samples of fine grained sediments (mudstones and siltstones) and the Chemical Index of Alteration (CIA) of Nesbitt & Young (1982). The CIA is calculated from the relative abundances of AI, K, Ca, and Na oxides, and its magnitude increases as the effects of chemical weathering increase. However, changes in sediment provenance can also affect the CIA, and provenance changes are recorded by shifts in the Al2O3/TiO2 ratios and the Nb contents of these CRP-2/2A mudstones. Relatively low CIA values (40-50) occur throughout the CRP-2/2A sequence, whereas the Al2O3/TiO2 ratio decreases upsection. The major provenance change is an abrupt onset of McMurdo Volcanic Group detritus at ~300 mbsf and is best characterized by a rapid increase in Nb content in the sediments. This provenance shift is not evident in the CIA record, suggesting that a contribution from the Ferrar Dolerite to the older sediments was replaced by an input of McMurdo Volcanic Group material in the younger sediments. If this is true, then the relatively uniform CIA values indicate relatively consistent palaeoweathering intensities throughout the Oligocene and early Miocene in the areas that supplied sediment to CRP-2/2A.

The £ for lb challenge – a lose – win – win scenario. Results from a novel workplace-based, peer-led weight management programme

Title: The £ for lb. Challenge – A lose - win – win scenario. Results from a novel workplace-based, peer-led weight management programme in 2016.

Names: Damien Bennett, Declan Bradley, Angela McComb, Amy Kiernan, Tracey Owen

Background: Tackling obesity is a public health priority. The £ for lb. Challenge is the first country wide, workplace-based peer-led weight management programme in the UK or Ireland with participants from a range of private and public businesses in Northern Ireland (NI).
Intervention: The intervention was workplace-based, led by workplace Champions and based on the NHS Choices 12 week weight loss guide. It operated from January to April 2016. Overweight and obese adult workers were eligible. Training of Peer Champions (staff volunteers) involved two half day workshops delivered by dieticians and physical activity professionals.
Outcome measurement: Weight was measured at enrolment and 12 weekly intervals. Changes in weight, % weight, BMI and % BMI were determined for the whole cohort and sex and deprivation subgroups.
Results: There were 1513 eligible participants from 35 companies. Engagement rate was 98%. 75% of participants completed the programme. Mean weight loss was 2.4 kg or 2.7%. Almost a quarter (24%) lost at least 5% initial bodyweight. Male participants were over twice as likely to complete the programme and three times more likely to lose 5% body weight or more. Over £17,000 was raised for NI charities.
Discussion: The £ for lb. Challenge is a successful health improvement programme with important weight loss for many participants, particularly male workers. With high levels of user engagement and ownership and successful multidisciplinary collaboration between public health, voluntary bodies, private and public companies it is a novel workplace based model with potential to expand.

Whipple’s disease infection surgical treatment: presentation of a rare case and literature review

The Whipple’ Disease (W.D.) is a very rare disease with an incidence of 1 per 1.000.000 inhabitants; it is a systemic infection that may mimic a wide spectrum of clinical disorders, which may have a fatal outcome and affects mainly male 40-50 years old. The infective agent is an actinomycete, Tropheryma Whipplei (T.W.) that was isolated 100 years after first description by Wipple, and identified in macrophages of mucosa of the small intestine by biopsy which is characterized by periodic acid-Schiff-positive, products of the inner membrane of his polysaccharide bacterial cell wall. The multisystemic clinical manifestations evolve rapidly towards an organic decay characterized by weight loss, malabsorption, diarrhea, polyathralgia, opthalmoplegia, neuro-psychiatric disorders and sometimes associated to endocarditis. Early antibiotic treatment with trimethoprim and sulfometathaxazole reduces the fatal evolution of the disease. The authors present a rare experience about a female subject in which the clinical gastrointestinal signs were preceded by neuro-psychiatric disorders, and evolved into obstruction and intestinal perforation which required an emergency surgery with temporary ileostomy, recanalized only after adequate medical treatment with a full dose of antibiotic and resolution of clinical disease for the high risks of fistulae for the edema and lymphadenopathy of mucosa. The diagnosis was histologically examined by intestinal biopsy performed during surgery, which showed PAS-positive histiocytes, while PRC polymerase RNA was negative, which confirms the high sensibility of PAS positive and low specificity of RNA polymerase for T.W.

Medications, youth therapeutic cultures and performance consumptions: a sociological approach

This article analyses performance consumptions among young people. The theme is explored along two main axes. The first concerns the social heterogeneity in this field, considered on two levels: the different purposes for those investments - cognitive/mental and physical performance; and the different social contexts - university and work - where performance practices and dispositions may be fostered. The second axis explores the roles of pharmacological and natural consumptions, and their interrelationship, in the dissemination of these practices. The empirical data for this analysis were drawn from an ongoing research project on performance consumptions among young people (aged 18-29 years) in Portugal, including both university students and young workers without university education. The results correspond to the stage of extensive research, for which a questionnaire was organised at a national level, using non-proportional quota sampling. On the one hand, they show that (a) there is a hierarchy of acceptance of consumptions according to their purposes, with cognitive/mental performance showing higher acceptance and (b) both pharmaceuticals and natural products are consumed for every type of performance investment. On the other, the comparison between students and workers introduces a certain heterogeneity in this general backdrop, both in terms of the purposes for their consumptions and their opting for natural or pharmacological resources. These threads of heterogeneity will prompt a discussion of the dynamics of pharmaceuticalisation within the field of performance, in particular how therapeutic cultures may be changing in terms of the way individuals relate to medications, expanding their uses in social life.