Prevalence of low fat-free mass index and high and very high body fat mass index following lung transplantation.

The aim of this study was to determine the prevalence of low fat-free mass index (FFMI) and high and very high body fat mass index (BFMI) after lung transplantation (LTR). A total of 37 LTR patients were assessed prior to and at 1 month, 1 year and 2 years for FFM and compared to 37 matched volunteers (VOL). FFM was calculated by the Geneva equation and normalized for height (kg/m(2)). Subjects were classified as FFMI "low", <or=17.4 in men and <or=15.0 in women; BFMI "high", 5.2-8.1 in men and 8.3-11.7 in women; or "very high" >8.2 kg/m(2) in men and >11.8 kg/m(2) in women. In 23 M/14 F, body mass index (BMI) was 22.3+/-4.4 and 20.1+/-4.9 kg/m(2), respectively. The prevalence of low FFMI was 80% at 1 month and 33% at 2 years after LTR. Prevalence of very high BFMI increased and was higher in patients than VOL after LTR. The prevalence of low FFMI was high prior to and remained important 2 years after LTR, whereas BFMI was lower prior to and higher 2 years after LTR.

Risk adjustment in Switzerland

In Switzerland the new law on Health Insurance, effective since 1996, introduced pro competitive changes in the market of sickness funds. The legislator expected high mobility between sickness funds of both healthy and sick insured as open enrolment was introduced with the new law. That is why the risk adjustment scheme, that was already introduced 1993, was limited until 2005. However, consumer mobility remained low and risk selection strategies are still profitable, since risk-adjustment is based only on demographic variables. This paper describes risk adjustment, consumer mobility, risk selection activities of sickness funds and the impact of imperfect risk adjustment on the development of HMO and PPO models. The paper concludes with a description of the current political and scientific discussion in Switzerland.

Group motivational intervention in overweight/obese patients in primary prevention of cardiovascular disease in the primary healthcare area

Background The global mortality caused by cardiovascular disease increases with weight. The Framingham study showed that obesity is a cardiovascular risk factor independent of other risks such as type 2 diabetes mellitus, dyslipidemia and smoking. Moreover, the main problem in the management of weight-loss is its maintenance, if it is achieved. We have designed a study to determine whether a group motivational intervention, together with current clinical practice, is more efficient than the latter alone in the treatment of overweight and obesity, for initial weight loss and essentially to achieve maintenance of the weight achieved; and, secondly, to know if this intervention is more effective for reducing cardiovascular risk factors associated with overweight and obesity. Methods This 26-month follow up multi-centre trial, will include 1200 overweight/obese patients. Random assignment of the intervention by Basic Health Areas (BHA): two geographically separate groups have been created, one of which receives group motivational intervention (group intervention), delivered by a nurse trained by an expert phsychologist, in 32 group sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard program of diet, exercise, and the other (control group), receiving the usual follow up, with regular visits every 3 months. Discussion By addressing currently unanswered questions regarding the maintenance in weight loss in obesity/overweight, upon the expected completion of participant follow-up in 2012, the IMOAP trial should document, for the first time, the benefits of a motivational intervention as a treatment tool of weight loss in a primary care setting.

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans.

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.

Group motivational intervention in overweight/obese patients in primary prevention of cardiovascular disease in the primary healthcare area

Background The global mortality caused by cardiovascular disease increases with weight. The Framingham study showed that obesity is a cardiovascular risk factor independent of other risks such as type 2 diabetes mellitus, dyslipidemia and smoking. Moreover, the main problem in the management of weight-loss is its maintenance, if it is achieved. We have designed a study to determine whether a group motivational intervention, together with current clinical practice, is more efficient than the latter alone in the treatment of overweight and obesity, for initial weight loss and essentially to achieve maintenance of the weight achieved; and, secondly, to know if this intervention is more effective for reducing cardiovascular risk factors associated with overweight and obesity. Methods This 26-month follow up multi-centre trial, will include 1200 overweight/obese patients. Random assignment of the intervention by Basic Health Areas (BHA): two geographically separate groups have been created, one of which receives group motivational intervention (group intervention), delivered by a nurse trained by an expert phsychologist, in 32 group sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard program of diet, exercise, and the other (control group), receiving the usual follow up, with regular visits every 3 months. Discussion By addressing currently unanswered questions regarding the maintenance in weight loss in obesity/overweight, upon the expected completion of participant follow-up in 2012, the IMOAP trial should document, for the first time, the benefits of a motivational intervention as a treatment tool of weight loss in a primary care setting.

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4+ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4+ and CD8+ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4+ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Investigations of GaAs based heterostructures for spintronics

In the present work are reported investigations of structural, magnetic and electronic properties of GaAs/Ga1-xInxAs/GaAs quantum wells (QW) having a 0.5 - 1.8 monolayer thick Mn layer, separated from the quantum well by a 3 nm thick spacer. The structure of the samples is analyzed in details by photoluminescence and high-resolution X-ray difractometry and reflectometry, confirming that Mn atoms are practically absent from the QW. Transport properties and crystal structure are analyzed for the first time for this type of QW structures with so high mobility. Observedconductivity and the Hall effect in quantizing magnetic fields in wide temperature range, defined by transport of holes in the quantum well, demonstrate properties inherent to ferromagnetic systems with spin polarization of charge carriersin the QW. Investigation of the Shubnikov ¿ de Haas and the Hall effects gave the possibility to estimate the energy band parameters such as cyclotron mass andFermi level and calculate concentrations and mobilities of holes and show the high-quality of structures. Magnetic ordering is confirmed by the existence of the anomalous Hall effect.

Awareness of human immunodeficiency virus screening guidelines is low in emergency departments of western Switzerland.

Background: Human immunodeficiency virus (HIV) prevalence in Switzerland is 0.4% and 30% of HIV patients are diagnosed with CD4 counts <200 cells/microliter. In 2010, the Swiss Federal Office of Public Health (SFOP) published updated guidelines regarding Physician- Initiated Counseling and Testing (PICT) for HIV. In the new guidelines, when acute HIV infection is suspected or HIV is among the differential diagnoses, an HIV test is performed without risk assessment nor prior counseling, unless the patient specifically refuses it. Counseling and verbal consent are still required when the patient asks for an HIV test or belongs to a high risk group. Whist HIV testing in the emergency departments (ED) is recommended, only 1% of patients are currently screened. Lack of awareness among physicians has been cited in the literature as the first barrier to guideline implementation. Objectives: To test if physicians working in EDs of 5 large teaching hospitals in western Switzerland, admitting 175,000 patients / year, were aware of the updated SFOP guidelines. Methods: A survey was delivered to 167 ED physicians in the summer of 2011. The survey consisted of 26 vignettes designed to test whether physicians would request an HIV test according to the new guidelines and if they knew when the PICT strategy was allowed or counseling required. Finally, physicians were asked the number of HIV tests they had requested in the previous 4 weeks, and if they were aware of the new HIV guidelines. Results are presented as mean and standard deviation, median and interquartile range (IQR), or as proportions; Student's t test was used to compare continuous variables; Results: 143 physicians returned the survey (86%); mean age was 32 ± 8 years, and median postgraduate experience of 6 years (IQR 3-12); 52% were male and 17% were attendings. The percentage of correct responses was 60 ± 13% with no difference between attendings and residents (p = 0.31); 2 of the 3 questions with the lowest scores were failure to recognize situations in which HIV testing was indicated, and the third one a failure to recognize acute HIV infection. 82% of physicians were not aware of the new guidelines. The median number of test requests was 1 (IQR 0-2, range 1-10). Conclusion: ED physicians are not aware of current HIV screening guidelines published by the SFOP, and rarely perform HIV tests. An information campaign is required if ED physicians are expected to play a significant role in the reduction of undiagnosed HIV patients.

Copy number variations and cognitive phenotypes in unselected populations

IMPORTANCE: The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE: To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS: The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES: Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS: Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1 Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P̴1;=̴1;1.06e-04) among 248 (≥250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (≥1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P̴1;=̴1;.005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P̴1;=̴1;1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE: Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health.

Assessment of metabolic fluxes in the mouse brain in vivo using 1H-[13C] NMR spectroscopy at 14.1 Tesla.

(13)C magnetic resonance spectroscopy (MRS) combined with the administration of (13)C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity (1)H-[(13)C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-(13)C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the (13)C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit (13)C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate V(gln) (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor K(dil) (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate V(Lac)/V(Ala) (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

The Influence of Chronic and Situational Social Status on Stereotype Susceptibility

We tested whether stereotypical situations would affect low-status group members' performance more strongly than high-status group members'. Experiment 1 and 2 tested this hypothesis using gender as a proxy of chronic social status and a gender-neutral task thathas been randomly presented to favor boys (men superiority condition), favor girls (women superiority condition), or show no gender preference (control condition). Both experiments found that women's (Experiment 1) and girls' performance (Experiment 2) suffered more from the evoked stereotypes than did men's and boys' ones. This result was replicated in Experiment 3, indicating that short men (low-status group) were more affected compared to tallmen (high-status group). Additionally, men were more affected compared to women when they perceived height as a threat. Hence, individuals are more or less vulnerable to identity threats as a function of the chronic social status at play; enjoying a high status provides protection and endorsing a low one weakens individual performance in stereotypical situations.

Avaluació de l'efecte causat sobre els valors de potència entre un protocol d'entrenament de càrregues baixes i un amb càrregues submàximes

L’objectiu d’aquest estudi és comparar els efectes que produeixen un protocol d’entrenament orientat amb càrregues lleugeres (40%-60% 1RM) i un protocol d’entrenament amb càrregues altes submàximes (90% 1RM), sobre els nivells de potència muscular. L’estudi ha analitzat a 12 futbolistes masculins pertanyents al mateix equip (22,1 ± 2,9 anys, 72,2 ± 6, 8 kg, 1,77 ± 0,15 m). Els exercicis analitzats foren el ½ squat i el press banca. També es va utilitzar un grup control. Els resultats ens van mostrar que el grup d’entrenament amb càrregues lleugeres va obtenir unes millores més considerables sobre els valors de potència (W) en 40% i 60% 1RM i per altre banda en el grup d’entrenament amb càrregues submàximes es van produir uns increments de potència més alts en càrregues altes (80% 1RM). Els resultats referents a la velocitat mitjana (m/s), es van produir de manera més considerable en el grup que va realitzar el treball amb càrregues lleugeres, en totes les intensitats analitzades.

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.