Can a self-management education program for patients with chronic obstructive pulmonary disease improve quality of life ?

OBJECTIVE:

To assess the effects of a self-management program on health-related quality of life (HRQoL) and morbidity commonly associated with chronic obstructive pulmonary disease (COPD).

METHODS:

A total of 57 outpatients with stable COPD received four weeks of self-management education, while 45 patients received usual care. Patients were evaluated at baseline, at three months and one year following the educational intervention. The primary outcome variable was HRQoL measured by the St George’s Respiratory Questionnaire (SGRQ). The secondary outcome variables were number of emergency room visits and hospitalizations for exacerbation.

RESULTS:

The intervention group’s HRQoL improved significantly at three months (total score A=−5.0 [P=0.006]) and 12 months (total score A=−6.7 [P<0.001]), as evidenced by decreased scores on the SGRQ. In contrast, the SGRQ scores increased significantly in the control group at three months (total score A=+3.7 [P= 0.022]) and 12 months (total score A=+3.4 [P=0.032]). Global impact appeared to be responsible for the change in the intervention group. Moreover, in the intervention group, the number of hospitalizations dropped from 0.7/person/year to 0.3/person/year (P=0.017), and emergency room visits dropped from 1.1 person/year to 0.2/person/year (P=0.002), while subjects in the control group did not experience any significant decreases in these parameters.

CONCLUSIONS:

A planned education program improved HRQoL while decreasing the number of emergency room visits and hospitalizations in patients with stable COPD; this improvement persisted at 12 months.     

Standardised versus actual white cell counts in estimating thick film parasitaemia in African children under five

In patients with malaria, parasitaemia is usually estimated by assuming 8000 white cell counts (WCC) per microlitre of blood. In a sample of 3044 African children under 5 years of age with uncomplicated falciparum malaria, parasitaemia estimated using standardised WCC was compared to parasitaemia calculated based on each child's own WCC. The two methods produced comparable results. However, WCC were >8000 in under-fives with an inverse relationship with age, resulting in the standard approximation method significantly underestimating parasitaemia in the youngest age group and overestimating parasitaemia in the oldest age groups.     

Mass spectrometry for the evaluation of cardiovascular diseases based on proteomics and lipidomics

The identification and quantification of proteins and lipids is of major importance for the diagnosis, prognosis and understanding of the molecular mechanisms involved in disease development. Owing to its selectivity and sensitivity, mass spectrometry has become a key technique in analytical platforms for proteomic and lipidomic investigations. Using this technique, many strategies have been developed based on unbiased or targeted approaches to highlight or monitor molecules of interest from biomatrices. Although these approaches have largely been employed in cancer research, this type of investigation has been met by a growing interest in the field of cardiovascular disorders, potentially leading to the discovery of novel biomarkers and the development of new therapies. In this paper, we will review the different mass spectrometry-based proteomic and lipidomic strategies applied in cardiovascular diseases, especially atherosclerosis. Particular attention will be given to recent developments and the role of bioinformatics in data treatment. This review will be of broad interest to the medical community by providing a tutorial of how mass spectrometric strategies can support clinical trials.     

Georges Gilles de la Tourette (1857–1904)

Journal of Neurology -     

An update in the management of obesity: the weight of CNS targets

Obesity is one of the most important and disturbing global epidemic that affects humans, with more than 2 billion people overweight and 700 million obese predicted for 2015 by the World Health Organization. Obesity treatment represents then one of the most exciting challenges for the academic researchers and the pharmaceutical industry. But to date, this community failed to develop safe and effective treatments with a good risk/benefit profile. Indeed, most of the drugs previously used as anti-obesity agents have been withdrawn from the market for safety issues, and therapeutic options in form of a medication are currently very limited. This last decade however, new advances in our understanding of central pathways controlling food intake, body weight and energy homeostasis have led to the discovery of new molecular targets that could provide interesting options in the fight against obesity. This review aims to be an overview of the new patents exploiting the anorexigenic properties of the central catabolic pathways or aimed at blocking the orexigenic effects of the anabolic pathways, in the hope to develop new anti-obesity drugs.     

Differential Adaptation of Human Gut Microbiota to Bariatric Surgery�CInduced Weight Loss: Links With Metabolic and Low-Grade Inflammation Markers

OBJECTIVE

Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure.

RESEARCH DESIGN AND METHODS

Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB.

RESULTS

Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at M0 and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at M0 and throughout the follow-up after surgery independently of changes in food intake.

CONCLUSIONS

These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake.Obesity is characterized by increased fat mass accumulation and the development of comorbidities including other metabolic and cardiovascular diseases. Even though some but not all environmental factors have been elucidated, the increasing epidemic of obesity appears virtually impossible to control, and the mechanisms associated with fat mass expansion need to be identified. Obesity is considered a low-grade inflammatory disease with adipose tissue contributing to this state via the secretion of molecules capable of altering metabolic homeostasis (1,2). A novel factor identified to play a role in human obesity and associated metabolic risks is the commensal microbiota of the intestine (3).A role for the intestinal microbiota in harvesting energy from food (4) and regulating body fat storage (5) was proposed in rodents. Germ-free mice colonized by microbiota increase their body fat and develop insulin resistance in spite of a 30% decrease in food intake. These changes were associated with a dysbiosis in obese mice: an increased representation of the Firmicutes phylum and a reduced representation of the Bacteroidetes phylum (6). Other studies suggested a contribution of the gut microbiota-produced lipopolysaccharides to inflammation and development of metabolic syndrome (7–9). In humans, increased endotoxemia (circulating lipopolysaccharides) was found to be associated with increased fat consumption (10). In obese patients losing weight throughout low calorie diets, diminished Bacteroidetes and increased Firmicutes were found trended to that of lean control subjects at the end of the dietary intervention (11). However, modification of the Firmicutes-to-Bacteroidetes ratio observed in obese individuals was not confirmed in other studies (12). No study has clearly explored the association between these bacterial changes and improvement of metabolic or inflammatory phenotypes associated with weight modification over time.Roux-en-Y gastric bypass (RYGB) surgery is an increasingly effective model to study in this context. RYGB leads to major improvements in metabolic and inflammatory markers (13). This procedure allows for an understanding of the molecular adaptations underlying the observed health benefits and the potential role of calorie restriction in changes in gut microbiota pattern.Our present work analyzed the microbiota profiles in the feces of morbidly obese subjects before and after RYGB. We examined the association between gut microbiota changes and a range of body composition, metabolic, and inflammatory markers. These results provide new insight regarding gut microbiota changes in obese subjects after RYGB and highlight some bacterial groups as possible factors associated with changes in nutritional status and others with metabolic and inflammatory parameters.     

��-Cell Failure in Diet-Induced Obese Mice Stratified According to Body Weight Gain: Secretory Dysfunction and Altered Islet Lipid Metabolism Without Steatosis or Reduced ��-Cell Mass

OBJECTIVE

C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about β-cell failure in these mice.

RESEARCH DESIGN AND METHODS

DIO mice were separated in two groups according to body weight gain: low- and high-HFD responders (LDR and HDR). We examined whether mild hyperglycemia in HDR mice is due to reduced β-cell mass or function and studied islet metabolism and signaling.

RESULTS

HDR mice were more obese, hyperinsulinemic, insulin resistant, and hyperglycemic and showed a more altered plasma lipid profile than LDR. LDR mice largely compensated insulin resistance, whereas HDR showed perturbed glucose homeostasis. Neither LDR nor HDR mice showed reduced β-cell mass, altered islet glucose metabolism, and triglyceride deposition. Insulin secretion in response to glucose, KCl, and arginine was impaired in LDR and almost abolished in HDR islets. Palmitate partially restored glucose- and KCl-stimulated secretion. The glucose-induced rise in ATP was reduced in both DIO groups, and the glucose-induced rise in Ca²⁺ was reduced in HDR islets relatively to LDR. Glucose-stimulated lipolysis was decreased in LDR and HDR islets, whereas fat oxidation was increased in HDR islets only. Fatty acid esterification processes were markedly diminished, and free cholesterol accumulated in HDR islets.

CONCLUSIONS

β-Cell failure in HDR mice is not due to reduced β-cell mass and glucose metabolism or steatosis but to a secretory dysfunction that is possibly due to altered ATP/Ca²⁺ and lipid signaling, as well as free cholesterol deposition.While insulin resistance is a common feature in most obese subjects, insulin secretion is increased to compensate for its reduced action and normoglycemia is maintained (1,2). In obese type 2 diabetes subjects, however, β-cell compensation fails due to marked impairment of glucose-stimulated insulin secretion (GSIS), often with reduced β-cell mass (2). The relationship between β-cell function and mass as causative factors in β-cell failure and diabetes progression is debated, with emphasis on the relevance of “functional β-cell mass” rather than total mass (2). Increased adiposity leads to elevated circulating free fatty acids (FFAs) and triglycerides, and in vitro and in vivo studies have indicated a causative role for dyslipidemia in insulin resistance (1,3). Although FFAs are necessary for the amplification of GSIS, their excess supply may also have a role in β-cell failure (4), as prolonged elevation of FFA levels both in vivo and in vitro cause β-cell dysfunction (5,6) and, at least in vitro, apoptosis (7).At least part of the β-cell compensation to insulin resistance is due to an increase in β-cell mass (4). Either long-term high-fat diet (HFD) (8) or a short-term lipid infusion (9) can result in increased β-cell mass without augmentation of GSIS, indicating that β-cell function and mass are not necessarily linked. Rodent studies have indicated that HFD leads to increased β-cell mass (8), which is also observed in normoglycemic obese individuals (10). Unclear at present is the dynamics between the factors driving compensatory increase in β-cell mass and function and those reducing them through the various stages of type 2 diabetes development, particularly as FFA may do both. Genetic islet susceptibility may be a critical determinant of these dynamics, both in humans and animal models (4,11,12).Even though studies employing genetically modified models (e.g., Zucker Diabetic Fatty rats, db/db mice) have helped in understanding some of these pathological processes (13–16), several of these models are of extreme nature, with rapid development of pronounced type 2 diabetes. These models, therefore, differ from human obesity-linked type 2 diabetes, which usually develops more gradually. In an attempt to gain insight into the basis of β-cell failure in a mild model of diabetes, we recently developed a new model of type 2 diabetes, the 60% pancreatectomized obese hyperlipidemic Zucker Fatty rat (14). In this model, severe β-cell dysfunction was found without any evidence of a falling β-cell mass or islet steatosis (14). More detailed examination of the pancreatectomized Zucker Fatty rat islets showed marked depletion of insulin stores and altered glycerolipid metabolism (14). The Zucker Fatty rat, as opposed to the Zucker Diabetic Fatty rat, however, does not have genetic predisposition to diabetes, as it maintains normoglycemia despite severe obesity-related insulin resistance (4). The diet-induced obese (DIO) C57BL/6 mouse gradually develops hyperglycemia (17). This suggests that DIO islets are unable to fully compensate for the obesity-related insulin resistance, as occurs in human type 2 diabetes.In the present study, we investigated β-cell dysfunction in DIO mice stratified into two groups according to the effect of HFD on body weight: the low responders to HFD (LDR) were less obese, developed intermediate severity of insulin resistance, and had only mild impairment in glycemia. The high responders to HFD (HDR) were more obese, insulin resistant, and hyperinsulinemic and were clearly hyperglycemic. Thus, the LDR and HDR groups allowed for analysis and comparison of islet β-cell mass and function in response to different levels of insulin resistance with corresponding very mild perturbation of glucose homeostasis and overt but mild hyperglycemia, respectively. When extended to obese humans, these two groups correspond to the pre-diabetes and early diabetes situations.