Inequalities in energy drink consumption among UK adolescents: a mixed-methods study.

OBJECTIVE: To examine energy drink consumption among adolescents in the United Kingdom (UK) and associations with deprivation and dietary inequalities. DESIGN: Quantitative dietary and demographic data from the National Diet and Nutrition Survey (NDNS) repeated cross-sectional survey were analysed using logistic regression models. Qualitative data from semi-structured interviews were analysed using inductive thematic analysis. SETTING: UK. PARTICIPANTS: Quantitative data: nationally representative sample of 2587 adolescents aged 11-18 years. Qualitative data: 20 parents, 9 teachers, and 28 adolescents from Hampshire, UK. RESULTS: NDNS data showed adolescents' consumption of energy drinks was associated with poorer dietary quality (OR 0.46 per SD; 95% CI 0.37, 0.58; p<0.001). Adolescents from more deprived areas and lower income households were more likely to consume energy drinks than those in more affluent areas and households (OR 1.40; 95%CI 1.16, 1.69; p<0.001; OR 0.98 per £1000; 95%CI, 0.96, 0.99; p<0.001 respectively). Between 2008 and 2016, energy drink consumption among adolescents living in the most deprived areas increased, but decreased among those living in the most affluent neighbourhoods (p=0.04). Qualitative data identified three themes. First, many adolescents drink energy drinks because of their friends and because the unbranded drinks are cheap. Second, energy drink consumption clusters with other unhealthy eating behaviours and adolescents don't know why energy drinks are unhealthy. Third, adolescents believe voluntary bans in retail outlets and schools do not work. CONCLUSIONS: This study supports the introduction of age-dependent legal restrictions on the sale of energy drinks which may help curb existing socio-economic disparities in adolescents' energy drink intake.

Chemical chaperones reverse early suppression of regulatory circuits during unfolded protein response in B cells from common variable immunodeficiency patients.

B cells orchestrate pro-survival and pro-apoptotic inputs during unfolded protein response (UPR) to translate, fold, sort, secrete and recycle immunoglobulins. In common variable immunodeficiency (CVID) patients, activated B cells are predisposed to an overload of abnormally processed, misfolded immunoglobulins. Using highly accurate transcript measurements, we show that expression of UPR genes and immunoglobulin chains differs qualitatively and quantitatively during the first 4 h of chemically induced UPR in B cells from CVID patients and a healthy subject. We tested thapsigargin or tunicamycin as stressors and 4-phenylbutyrate, dimethyl sulfoxide and tauroursodeoxycholic acid as chemical chaperones. We found an early and robust decrease of the UPR upon endoplasmic reticulum (ER) stress in CVID patient cells compared to the healthy control consistent with the disease phenotype. The chemical chaperones increased the UPR in the CVID patient cells in response to the stressors, suggesting that misfolded immunoglobulins were stabilized. We suggest that the AMP-dependent transcription factor alpha branch of the UPR is disturbed in CVID patients, underlying the observed expression behavior.

Improving pregnant women's diet and physical activity behaviours: the emergent role of health identity.

BACKGROUND: Women who gain too much weight in pregnancy are at increased risk of disease and of having children with increased risk. Interventions to improve health behaviours are usually designed for a general population of pregnant women, and trial outcomes show an average impact that does not represent the differences between individuals. To inform the development of future interventions, this study explored the factors that influenced women's diet and physical activity during pregnancy and aimed to identify the needs of these women with regards to lifestyle support. METHODS: Women who completed a trial of vitamin D supplementation and nurse support in pregnancy were invited to take part in an interview. Seventeen women were interviewed about their lifestyles during pregnancy, the support they had, and the support they wanted. Interview transcripts were coded thematically and analysed to understand the factors that influenced the diets and physical activity levels of these women and their engagement with resources that could provide support. RESULTS: Women identified barriers to eating well or being physically active, and pregnancy-specific issues like nausea and pain were common. Women's interest in maintaining a healthy lifestyle and their engagement with lifestyle support was related to the extent to which they self-identified as healthy people. Health-disengaged women were disinterested in talking about their lifestyles while health-focused women did not feel that they needed extra support. Women between these ends of the 'health identity' spectrum were interested in improving their health, and were able to identify barriers as well as sources of support. CONCLUSIONS: Lifestyle interventions in pregnancy should be adapted to meet the needs of individuals with different health identities, and encouraging a change in health identity may be one way of supporting sustained change in health behaviours.

The relationship between maternal self-efficacy, compliance and outcome in a trial of vitamin D supplementation in pregnancy.

In a randomised controlled trial of vitamin D during pregnancy, we demonstrated that women with lower self-efficacy were more likely to experience practical problems with taking the trial medication and that this was associated with lower compliance and achieved 25(OH)-vitamin D concentrations. INTRODUCTION: The relationship between self-efficacy (the belief that one can carry out a behaviour), compliance with study protocol and outcome was explored within a randomised, double-blind, placebo-controlled trial of vitamin D supplementation in pregnancy. METHODS: In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial, women with circulating plasma 25(OH)-vitamin D of 25-100 nmol/l in early pregnancy were randomised to either 1000 IU cholecalciferol/day or matched placebo from 14 weeks until delivery. Circulating 25(OH)-vitamin D concentrations were assessed at 14 and 34 weeks' gestation. A sequential sub-sample completed Schwarzer's General Self-Efficacy Scale at 14 and 34 weeks and the Problematic Experiences of Therapy Scale at 34 weeks. Women were interviewed about their experiences of the trial and interview transcripts analysed thematically. RESULTS: In 203 women, those with higher self-efficacy were less likely to experience practical problems taking the study medication (odds ratio (OR) 0.81 (95 % confidence interval (CI) 0.69-0.95), p = 0.01). Over half reported practical problems associated with poorer compliance with the protocol requiring women to take the medication daily. Compliance in women who experienced practical problems was 94 % compared with 98 % for those with no problems (p < 0.001). Poorer compliance was also associated with lower concentrations of 25(OH)-D in late pregnancy in the treatment group (ß = 0.54 nmol/l (95 % CI 0.18-0.89), p = 0.003). Thematic analysis suggested common difficulties were remembering to take the medication every day and swallowing the large capsules. CONCLUSIONS: These findings suggest that differences in self-efficacy influence trial outcomes. Such information may help clinicians anticipate responses to routine vitamin D supplementation in pregnancy and identify those who may need more support to comply. TRIAL REGISTRATION: ISRCTN82927713, registered 11/04/2008.

Progression-free survival as surrogate end point for overall survival in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer.

BACKGROUND: The gold standard end point in randomized clinical trials in metastatic breast cancer (MBC) is overall survival (OS). Although therapeutics have been approved based on progression-free survival (PFS), its use as a primary end point is controversial. We aimed to assess to what extent PFS may be used as a surrogate for OS in randomized trials of anti-HER2 agents in HER2+ MBC. METHODS: Eligible trials accrued HER2+ MBC patients in 1992-2008. A correlation approach was used: at the individual level, to estimate the association between investigator-assessed PFS and OS using a bivariate model and at the trial level, to estimate the association between treatment effects on PFS and OS. Correlation values close to 1.0 would indicate strong surrogacy. RESULTS: We identified 2545 eligible patients in 13 randomized trials testing trastuzumab or lapatinib. We collected individual patient data from 1963 patients and retained 1839 patients from 9 trials for analysis (7 first-line trials). During follow-up, 1072 deaths and 1462 progression or deaths occurred. The median survival time was 22 months [95% confidence interval (CI) 21-23 months] and the median PFS was 5.7 months (95% CI 5.5-6.1 months). At the individual level, the Spearman correlation was equal to ρ = 0.67 (95% CI 0.66-0.67) corresponding to a squared correlation value of 0.45. At the trial level, the squared correlation between treatment effects (log hazard ratios) on PFS and OS was provided by R(2) = 0.51 (95% CI 0.22-0.81). CONCLUSIONS: In trials of HER2-targeted agents in HER2+ MBC, PFS moderately correlates with OS at the individual level and treatment effects on PFS correlate moderately with those on overall mortality, providing only modest support for considering PFS as a surrogate. PFS does not completely substitute for OS in this setting.

Greater access to fast-food outlets is associated with poorer bone health in young children.

SUMMARY: A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years. INTRODUCTION: Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children. METHODS: One thousand one hundred and seven children participating in the Southampton Women's Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant's neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets. RESULTS: Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (ß = -0.23 (z-score): 95% CI -0.38, -0.08) and lower BMC after adjustment for bone area and confounding variables (ß = -0.17 (z-score): 95% CI -0.32, -0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (ß = 0.16(z-score): 95% CI 0.00, 0.32 and ß = 0.13(z-score): 95% CI -0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years. CONCLUSIONS: The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.

Current practice of diabetes education in children and adolescents with type 1 diabetes in Germany and Austria: analysis based on the German/Austrian DPV database.

BACKGROUND: Diabetes education of patients and/or parents is an essential part of diabetes care with effects on diabetes outcome. The objective of our study was to describe the current practice of diabetes education in Germany and Austria with regard to training frequency, patient age, migration background and diabetes therapy in a large cohort of pediatric patients with diabetes mellitus type 1 (T1DM). METHODS: We analyzed data from pediatric T1DM patients with diabetes training in 2013 and complete data available for treatment year in the multicenter Diabetes Patienten Verlaufsdokumentation (DPV) registry using sas 9.4. RESULTS: In 2013 21 871 pediatric patients with T1DM were documented [52.4% male, age: 12.70 (9.35-15.30) yr (median (interquartile range)], diabetes duration: 3.80 (1.45-7.00) yr, migration background: 21.4%, twice daily injections: 5.5%, multiple daily injections: 52.5%, insulin-pump therapy: 42%. Of these 32.31% were trained in 2013. Younger patients and their parents were trained more intensely and more frequently as inpatients compared with older patients (0-6 vs. 6-12 and 12-18 yr: teaching units: 13.07 vs. 12.05 and 9.79; inpatient: 79% vs. 72% and 70%). There was also a difference in training frequency with regard to migration background. Severe hypoglycemia or ketoacidosis resulted in intensification of training (4.0 vs. 2.0%; 7.8 vs. 3.1%). Centre-specific education tools were used frequently alone or in combination with published, standardized education programs. CONCLUSION: Training frequency was highest in younger patients and during the first year of diabetes. Acute complications resulted in more frequent diabetes training, indicating that currently many education sessions take place in consequence to these complications.

Color Doppler sonographic dynamic tissue perfusion measurement demonstrates significantly reduced cortical perfusion in children with diabetes mellitus type 1 without microalbuminuria and apparently healthy kidneys.

MOTIVATION: With respect to the devastating consequences of the increasing prevalence of diabetes mellitus, the main reason for end stage renal disease and dialysis in industrialized countries, and the very limited diagnostic and therapeutic possibilities to predict, monitor and prevent diabetic nephropathy (DN), new concepts for early recognition and quantification of the prevailing microvascular changes in DN are urgently needed. MATERIALS AND METHODS: We present the first study of renal cortical tissue perfusion measurement by means of standardized color Doppler sonographic videos evaluated with the PixelFlux software 1 for Dynamic Tissue Perfusion Measurement (DTPM) in 92 patients with DM1 without MA compared to 71 healthy probands. RESULTS: DTPM reveals a highly significant diminution of cortical perfusion in patients with DM1 compared to healthy probands by 31 %, most pronounced in the distal hemicortex (reduction by 50 %) compared to 21 % within the proximal hemicortex. CONCLUSION: Thus, DTPM offers a novel means of numerically describing the state of the renal microvasculature in DM in a patient-friendly, non-invasive, non-ionizing manner.

[Management of the cut-out of various forms of osteosynthesis for proximal femoral fractures]. / Management des Cut-out verschiedener Osteosyntheseformen bei proximalen Femurfrakturen.

Proximal femoral fractures are a common type of injury in older people. A cut-out of the femoral neck screw after initial osteosynthetic surgery of proximal femoral fractures is a frequent and feared complication. There could be different causes for cut-outs. Osteoporosis and necrosis of the femoral head could be biological reasons for cut-outs; however, mechanical factors, such as reduction, implant position and morphological characteristics of fractures also have a major influence on the cut-out rate. The treatment of the cut-out is often complex and depends on the destruction of the femoral head and the acetabulum. If the bone quality is still good and the head is not completely destroyed, a reosteosynthesis can be performed. Conversion to an endoprosthetic replacement is often the only possibility. Endoprosthetic treatment is often complex and associated with a high morbidity.

Atomic diffusion in liquid gallium and gallium-nickel alloys probed by quasielastic neutron scattering and molecular dynamic simulations.

The atomic mobility in liquid pure gallium and a gallium-nickel alloy with 2 at% of nickel is studied experimentally by incoherent quasielastic neutron scattering. The integral diffusion coefficients for all-atom diffusion are derived from the experimental data at different temperatures. DFT-basedab-initiomolecular dynamics (MD) is used to find numerically the diffusion coefficient of liquid gallium at different temperatures, and numerical theory results well agree with the experimental findings at temperatures below 500 K. Machine learning force fields derived fromab-initiomolecular dynamics (AIMD) overestimate within a small 6% error the diffusion coefficient of pure gallium within the genuine AIMD. However, they better agree with experiment for pure gallium and enable the numerical finding of the diffusion coefficient of nickel in the considered melted alloy along with the diffusion coefficient of gallium and integral diffusion coefficient, that agrees with the corresponding experimental values within the error bars. The temperature dependence of the gallium diffusion coefficientDGa(T)follows the Arrhenius law experimentally for all studied temperatures and below 500 K also in the numerical simulations. However,DGa(T)can be well described alternatively by an Einstein-Stokes dependence with the metallic liquid viscosity following the Arrhenius law, especially for the MD simulation results at all studied temperatures. Moreover, a novel variant of the excess entropy scaling theory rationalized our findings for gallium diffusion. Obtained values of the Arrhenius activation energies are profoundly different in the competing theoretical descriptions, which is explained by different temperature-dependent prefactors in the corresponding theories. The diffusion coefficient of gallium is significantly reduced (at the same temperature) in a melted alloy with natural nickel, even at a tiny 2 at% concentration of nickel, as compared with its pure gallium value. This highly surprising behavior contradicts the existing excess entropy scaling theories and opens a venue for further research.

[Unequal social participation in later life]. / Ungleichheit sozialer Teilhabe im Alter.

The concept of active ageing comprises the maintenance of societal participation throughout the life span into old age. "Good" ageing in line with this activity paradigm develops into a starting point of social inequality rather than being its result. Based on the German Ageing Survey (DEAS) we investigated access to volunteering and to educational activities depending on social and spatial aspects of inequality. Societal participation is socially and spatially structured. Individuals from a lower social class are less often involved in educational activities or in volunteering. Moreover, individuals living in economically disadvantaged regions are less likely to participate than in economically strong regions. Disadvantages cumulate if low individual resources overlap with poor economic conditions in the living area. Measures to facilitate participation should be taken on the local level to enhance opportunities for volunteering and educational activities. This should help to sustainably increase the participation of individuals from lower social classes.

Meeting the UK Government's prevention agenda: primary care practitioners can be trained in skills to prevent disease and support self-management.

AIMS: The NHS Long Term Plan has a prevention focus and ambition to support patients to self-manage disease through improving health behaviours. An essential requirement of self-management is behaviour change, but many practitioners have not been trained in skills to support behaviour change. 'Healthy Conversation Skills' (HCS) training was developed at the University of Southampton for this purpose. This article reports on a pilot study that aimed to assess the feasibility of primary care practitioners adopting HCS in their routine practice. It describes their experiences and level of competence post-training. METHODS: Health Education England (Wessex) commissioned HCS training for 18 primary care practitioners. Fifteen of these practitioners were subsequently observed in their consultations at one or two time points; face-to-face semi-structured, reflective feedback interviews were conducted immediately following the observations. Practitioners' HCS competence was assessed from the observations and interviews using a previously developed and published coding rubric. The interview data were analysed thematically to understand practitioners' experiences of using the new skills. RESULTS: Practitioners demonstrated competence in embedding the skills into their routine practice following HCS training. They reflected on how patients liked being asked questions, the usefulness of setting SMARTER (Specific, Measured, Action-oriented, Realistic, Timed, Evaluated and Reviewed) goals and the power of listening. They could also identify facilitators of skill use and ways to overcome challenges such as patients with competing priorities and organisational constraints. They found the skills valuable as a way of empowering patients to make changes to manage their own health. CONCLUSIONS: HCS are acceptable to primary care practitioners, can be readily adopted into their routine consultations and are a helpful strategy for supporting patients to make changes. HCS training has the potential to be a sustainable, scalable and effective way of contributing to the prevention agenda by supporting disease self-management, and hence of addressing today's epidemic of lifestyle-related conditions.

Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureus.

Autologous vaccines (short: autovaccines) have been used since the beginning of the 20th century to treat chronic staphylococcal infections, but their mechanisms of action are still obscure. This prospective pilot study involved four patients with furunculosis who were vaccinated with autologous formalin-killed Staphylococcus aureus cells. Vaccines were individually prepared from the infecting S. aureus strain and repeatedly injected subcutaneously in increasing doses over several months. We characterized the virulence gene repertoire and spa genotype of the infecting and colonising S. aureus strains. Serum antibody responses to secreted and surface-bound bacterial antigens were determined by two-dimensional immunoblotting and flow-cytometry based assays (Luminex). All patients reported clinical improvement. Molecular characterization showed that all strains isolated from one patient over time belonged to the same S. aureus clone. Already before treatment, there was robust antibody binding to a broad range of staphylococcal antigens. Autovaccination moderately boosted the IgG response to extracellular antigens in two patients, while the antibody response of the other two patients was not affected. Similarly, vaccination moderately enhanced the antibody response against some staphylococcal surface proteins, e.g. ClfA, ClfB, SdrD and SdrE. In summary, autovaccination only slightly boosted the pre-existing serum antibody response, predominantly to bacterial surface antigens.

Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins.

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP(®) Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner.

Growth arrest of solid human neuroblastoma xenografts in nude rats by natural IgM from healthy humans.

Neuroblastoma (NB) is the most common extracranial solid neoplasm of infancy and is associated with very poor prognosis in patients with advanced disease. Current therapeutic regimens of advanced NB which combine surgical resection with radiation therapy and/or chemotherapy brought some improvements, but in a significant number of patients, a cure remains elusive. Normal human serum of healthy adults contains natural IgM antibodies that are cytotoxic for human NB cells. In this study, we evaluated the anti-NB activity of these natural IgM antibodies in nude rats bearing solid human NB tumors. A single intravenous (i.v.) injection of purified cytotoxic IgM led to uptake of IgM into the tumors with massive perivascular complement activation and accumulation of neutrophil granulocytes after 24 hours. Five consecutive i.v. injections of purified cytotoxic IgM into NB-bearing animals resulted in complete growth arrest of even large and established solid tumors which lasted for several weeks after discontinuation of the injections, whereas tumors of control animals continued to grow exponentially during the observation period. These studies suggest that natural anti-NB IgM may have a potential as a novel therapeutic modality in the treatment of human NB.

[Tumour of the endolymphatic sac in a 12-year-old child]. / Tumor des Saccus endolymphaticus bei einem 12-jährigen Kind.

We present the case of a 12-year-old boy with right-sided pantonal sensorineural hearing loss. With the help of imaging diagnostics a tumour of the right temporal bone was detected. It was resected using a transmastoid approach. Histopathological study showed a low-grade adenocarcinoma of the endolymphatic sac, known as Heffner tumour. An association with the von-Hippel-Lindau complex - as often reported in the medical literature - could not be proven.

Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells.

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

MHC Class III products: an electron microscopic study of the C3 convertases of human complement.

We have reported a transmission electron microscopic study of the two C3 convertases of human complement and their precursors. The corresponding proteins and complexes of the classical and alternative pathway appear very similar. Cofactors C3b and C4b are nearly indistinguishable and display a characteristic but highly irregular substructure. C2 and Factor B are globular with diameters of 85 +/- 8 A and 80 +/- 8 A and both consist of three discrete globular domains each approximately 40 A in diameter. Bb and C2a each contain two domains connected by a short linker segment. Both domains of Bb and one domain of C2a are 42 A in diameter (28 kd), while the second domain of C2 is 47 A in diameter (39 kd). Attachment of the enzymatic subunits to cofactors occurs through one domain only.

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity.

OBJECTIVE: Mice deficient of the serotonin transporter (5-HTT ko) mice have a reduced brain serotonin content and develop late-onset obesity. To elucidate the pathophysiology of this obesity, we analyzed the expression of the interrelated weight-regulatory molecules: brain-derived neurotrophic factor (BDNF) and leptin receptor (LR) in brain areas associated with nutrition and activity. RESEARCH DESIGN AND METHODS: We investigated feeding behavior, physical activity and metabolic parameters of 5-HTT ko and wild-type mice and measured the expression of BDNF and LR in brain areas associated with nutrition and activity using quantitative real-time PCR. The influence of age, gender and fasting was analyzed. RESULTS: Male 5-HTT ko mice developed obesity without hyperphagia from the age of 5 months. Physical activity was reduced in old male, but not old female, 5-HTT ko mice. The BDNF gene expression in frontal cortex was elevated in young, but reduced in old 5-HTT ko mice. Fasting failed to increase the BDNF gene expression in frontal cortex of young 5 HTT ko mice and in the hypothalamus in old 5-HTT ko mice. The fasting-induced hypothalamic increase of LR was absent in both young and old 5-HTT ko mice. CONCLUSIONS: We propose that low brain serotonin level due to the 5-HTT ko genotype leads to reduced physical activity and low BDNF, which together with the lack of fasting-induced hypothalamic BDNF and LR production results in late-onset obesity. Although lack of the 5-HTT is a genetic vulnerability factor for obesity, female gender is protective.