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The title in the original version of this Article contained a typographical error of ‘unresponsive’. The error has now been corrected in the PDF and HTML versions of the Article.

BACKGROUND: Phospholamban (PLN) plays a role in cardiomyocyte calcium handling by acting as a negative regulator of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA). A mutation in the PLN gene leading to the deletion of arginine 14 (R14del) of the PLN protein, is the most frequently identified mutation in patients with dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM) in the Netherlands. Cardiomyopathy patients that carry the PLN-R14del mutation have a worse prognosis than cardiomyopathy patients that do not carry this mutation, evidenced by more appropriate implantable cardioverter-defibrillator (ICD) discharges and more sudden cardiac death (SCD). There is no specific therapeutic treatment available for these patients other than standard heart failure treatment and heart transplantation. PURPOSE: The aim of this study is to generate a mouse model of PLN-R14del-induced cardiomyopathy and to screen for treatment options. First treatment consisted of standard heart failure medication including a beta-blocker (metoprolol) and a mineralocorticoid receptor antagonist (MRA; eplerenone). METHODS: The PLN-R14del mutation was introduced into the genome of C57BL/6N mice and backcrossed into C57BL/6J mice. Cardiac function was assessed using echocardiography, electrocardiography (ECG) and histological and molecular analysis. Metoprolol was orally administered as 350 mg/kg/day via the drinking water and eplerenone was orally administered as 200 mg/kg/day via the chow (n=10-12 per group). All animal studies were performed according to National Institutes of Health (NIH) guidelines and in accordance with national regulations. RESULTS: Homozygous PLN-R14del mice had increased left ventricular (LV) volume with decreased fractional shortening (FS) in comparison to wild-type littermates. In addition, decreased ECG potentials and prolonged QTc were observed. This resulted in decreased survival with a maximum life span of 2 months. Histological analysis showed severe cardiac fibrosis and aggregation of PLN proteins in the cardiomyocytes. Molecular analysis demonstrated increased levels of genes and proteins associated with cardiac stress, fibrosis and endoplasmic reticulum (ER) stress. Administration of eplerenone significantly decreased LV volume and atrial and pulmonary congestion. In addition, gene expression of B-type natriuretic peptide (BNP) and collagen genes was reduced. However, neither metoprolol nor eplerenone could improve cardiac function or survival of these mice. CONCLUSION: Homozygous PLN-R14del mice exactly mimic human disease in an accelerated manner. Administration of standard heart failure treatment including metoprolol and eplerenone does not give beneficial effects in these mice. The findings of this study underline the need for better understanding of the pathology of PLN-R14del-induced cardiomyopathy and problem-targeted therapy.

OBJECTIVE: The tuberculosis (TB) program was carried out in the Changji zone in northwest of China. Directly Observed Treatment, Short-Course (DOTS) is a modern control strategy against tuberculosis recommended by World Health Organization. The purpose of this work is to describe the survival of post-treatment TB (PTB) patients and to identify the risk factors associated with mortality and treatment outcomes, so that effective measures and interventions could be used to decrease the mortality rate. PATIENTS AND METHODS: Registry of 4501 TB patients at Center for Disease Control and Prevention (CDC) treated from 2007 to 2014 were collected. Mortality was used as an outcome measure and calculated per 100 person years of observation (PYO) from the date of completion of the treatment to the date of interview if the patients were alive or to the date of death. Kaplan-Meier and Cox regression methods were used to determine the survival and hazard ratios. An indirect method of standardization was used to calculate the standard mortality ratio (SMR). RESULTS: The average PYO was 5.0 and the total was 21851. Mortality per 100 PYO was 1.9/100 PYO [223/11871] for smear-positive, 3.4/100 PYO [305/9048] for smear-negative and 2.4/100 PYO [22/932] for EPTB cases. Univariate and Cox regression analysis showed that age (p

Objective To describe how district-wide access to HIV/AIDS care was achieved and maintained in Thyolo District, Malawi. Method In mid-2003, the Ministry of Health and Medecins Sans Frontieres developed a model of care for Thyolo district (population 587 455) based on decentralization of care to health centres and community sites and task shifting. Results After delegating HIV testing and counseling to lay counsellors, uptake of testing increased from 1300 tests per month in 2003 to 6500 in 2009. Shifting responsibility for antiretroviral therapy (ART) initiations to non-physician clinicians almost doubled ART enrolment, with a majority of initiations performed in peripheral health centres. By the end 2009, 23 261 people had initiated ART of whom 11 042 received ART care at health-centre level. By the end of 2007, the universal access targets were achieved, with nearly 9000 patients alive and on ART. The average annual cost for achieving these targets was euro 2.6 per inhabitant/year. Conclusion The Thyolo programme has demonstrated the feasibility of district-wide access to ART in a setting with limited resources for health. Expansion and decentralization of HIV/AIDS service-capacity to the primary care level, combined with task shifting, resulted in increased access to HIV services with good programme outcomes despite staff shortages

Purpose of present study is to describe the prevalence and trend of overweight and obesity, as well as its coexistence with stunting, among youngsters in China, from 1982 to 2002. Data from children 7-17 years of age from three cross-sectional national surveys: 1982 China National Nutrition Survey (5 334 boys and 4 793 girls), 1992 China National Nutrition Survey (8 048 boys and 7 453 girls) and 2002 China National Nutrition and Health Survey (23 242 boys and 21 638 girls) were used in this study. Overweight and obesity were defined according to age, sex specific BMI cut-off points from the International Obesity Task Force, while stunting was defined as height-for-age below -2 standard deviation from the NCHS/WHO reference median value. Results: Overweight prevalence of Chinese youngsters was 1.2%, 3.7% and 4.4%, while the obesity prevalence was 0.2%, 0.9% and 0.9% in 1982, 1992 and 2002, respectively. Both the overweight and obesity prevalence and their increment were higher among boys in urban areas. In 1982, 28.4% of overweight and 69.6% of obese youngsters were stunted, this decreased to 22.0% and 46.4% in 1992, and then to 5.7% and 7.7% in 2002, respectively. Conclusion: The prevalence of overweight and obesity in Chinese youngsters were low in 1982. There has been a rapid increase since then. If this trend continues, overweight will soon reach epidemic proportions. Stunting among overweight and obese youngsters decreased dramatically at the same time.

To investigate the relationship between body weight, body dissatisfaction and depression symptoms among Chinese children. METHODS: The fasting body weight and height of the third and fourth grade students (n = 3886, aged 9 or 10 years) from 20 schools in Beijing, China, were measured, and the students were asked to choose the figures of body image and to complete the self-reported children's depression inventory (CDI) questionnaire. RESULTS: The CDI Cronbach's alpha was 0.81. The total CDI score was 9.60 +/- 7.50, 13.2% of children (boys 16.7% vs girls 9.5%) were at risk of developing depression symptoms. Overweight girls, but not boys, had significantly higher total CDI score than their normal weight counteparts. Both obese girls and boys showed a higher negative self-esteem score. More than one fifth underweight girls still wanted to be thinner while more than one third obese boys still wanted to be heavier. Children who wanted to be thinner showed slightly higher scores of ineffectiveness and negative self-esteem. After introducing the body dissatisfaction into the model, overweight was still associated with total CDI score among girls and obesity was still associated with negative self-esteem among both boys and girls. CONCLUSION: Overweight girls show a significantly higher depression symptom score than their normal weight counterparts, which maybe partially explained by body dissatisfaction. Obese boys and girls are both more likely to suffer from low self-esteem, which is partially explained by body dissatisfaction.

Multinationale ondernemingen worden regelmatig voor dilemma’s geplaatst hoe zij op het gebied van mensenrechten moeten handelen. Is het beter om overal ter wereld hetzelfde bedrijfsbeleid op te leggen of moet er ruimte gegeven worden voor locale invulling van beleid? Een goed voorbeeld hiervan is het recht van werknemers op vrije vakvereniging. In sommige landen verhindert locale wetgeving naleving hiervan. Wat doe je dan als bedrijf? Shell is bezig voor zijn werknemers spelregels op te stellen hoe zij kunnen omgaan met de naleving van mensenrechten. Wat zijn Shell’s ervaringen tot nu toe?

Team Veiligheid- en Arbomanagement van TNO Arbeid heeft in 2004 een methodologisch project uitgevoerd gericht op het versterken van kennis en vaardigheden op het gebied van interactief en coöperatief onderzoek, genaamd: ‘Co-operative Inquiry’. De kracht van co-operative inquiry (en aanverwante methodieken zoals naturalistic inquiry) is onder meer gelegen in kennisontwikkeling in samenspraak met de betrokkenen in plaats van kennisontwikkeling waarbij personen op instrumentele wijze worden benaderd voor het vergaren van data. Naast het volgen van het programma zijn voor het realiseren van bovengenoemde doelen in deze beknopte rapportage opgenomen: enkele kernpunten van de benadering ‘co-operative inquiry’; een checklist die bestaat uit criteria voor het voeren van een acquisitiegesprek; een preofferte voor een project dat raakvlakken heeft met de benadering ‘co-operative inquiry’ (AHOLD/Unilever) en een korte afronding; literatuurlijst met titels die in de lijn liggen van co-operative inquiry. De bijlagen bestaan uit een beknopte Engelse samenvatting van het boek van John Heron, ‘Co-operative inquiry: Research into the Human Condition’ (1996) en verslagen van de drie bijeenkomsten.

We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity.

Transcranial Magnetic Stimulation (TMS) is used in several research centres since 1988. Nowadays TMS is in common use in clinical neurophysiology departments in hospitals for measuring conduction speed in motorways. Recently some articles have been published which announce that IMS may have a therapeutic effect on depression. TMS has few side effects but it has caused convulstem in some instances.