'I have been all in, I have been all out and I have been everything in-between': A 2-year longitudinal qualitative study of weight loss maintenance.

BACKGROUND: Qualitative studies investigating weight management experiences are usually cross-sectional or of short duration, which limits understanding of the long-term challenges. METHODS: Eleven women [mean (SD) age 44.9 (9.8) years; body mass index 40.3 (4.0) kg m-2 ] participated in this longitudinal qualitative study, which included up to 20 weeks of total diet replacement (825-853 kcal day-1 ) and ongoing support for weight loss maintenance (WLM), to 2 years. Semi-structured interviews were conducted at baseline and programme end, as well as at key intervals during the intervention. Questions examined five theoretical themes: motivation, self-regulation, habits, psychological resources and social/environmental influences. Data were coded and analysed in nvivo (https://qsrinternational.com/nvivo) using the framework method. RESULTS: In total, 64 interviews were completed (median, n = 6 per participant). Mean (SD) weight loss was 15.7 (9.6) kg (14.6% body weight) at 6 months and 9.6 (9.9) kg (8.8% body weight) at 2 years. The prespecified theoretical model offered a useful framework to capture the variability of experiences. Negative aspects of obesity were strong motivations for weight loss and maintenance. Perceiving new routines as sustainable and developing a 'maintenance mindset' was characteristic of 'Maintainers', whereas meeting emotional needs at the expense of WLM goals during periods of stress and negative mood states was reported more often by 'Regainers'. Optimistic beliefs about maintaining weight losses appeared to interfere with barrier identification and coping planning for most participants. CONCLUSIONS: People tended to be very optimistic about WLM without acknowledging barriers and this may undermine longer-term outcomes. The potential for regain remained over time, mainly as a result of emotion-triggered eating to alleviate stress and negative feelings. More active self-regulation during these circumstances may improve WLM, and these situations represent important targets for intervention.

Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany-A retrospective analysis of real-world data.

In type 2 diabetes patients treated in German primary care practices, the use of dipeptidyl peptidase-4 inhibitor (DPP4i) in combination with metformin was associated with a significant decrease in the risk of developing bone fractures compared to metformin monotherapy. INTRODUCTION: The goal of this study was to analyze the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) use on the risk of bone fracture in patients diagnosed with type 2 diabetes mellitus (T2DM) in Germany. METHODS: Patients with an initial prescription of metformin between 2008 and 2014 from 1262 German general practitioner practices were selected. We matched 4160 DPP4i ever users to never users (1:1) based on age, sex, diabetes duration, body mass index, index year, and physician type. The primary outcome measure was the rate of bone fractures within five years of the start of metformin or DPP-4i therapy. Time-dependent Cox regression models were used to estimate hazard ratios (HRs) for fractures as a function of the DPP4i therapy. RESULTS: The mean age among the patients was 61.6 years (SD = 11.1 years), 59.6% were men, and 3.1% were followed in diabetologist practices. The mean diabetes duration was 1.5 years (SD = 2.4 years), HbA1c levels were 7.1% in DPP4i users and 6.6% in non-users, and body mass index was 31.5 kg/m2 (SD = 5.0 kg/m2). Within five years of the index date, 6.4% of users and 8.3% of non-users developed bone fractures (log-rank p-value < 0.001). Within five years of the index date, 7.4% of female and 4.7% of male users and 13.3% of female and 8.8% of male non-users were diagnosed with bone fractures (both log-rank p-values < 0.001). The use of DPP4i was associated with a significant decrease in the risk of developing bone fractures (all patients HR = 0.67, 95% CI 0.54-0.84; women HR = 0.72, 95% CI 0.54-0.97; men HR = 0.62, 95% CI 0.44-0.88). CONCLUSION: DPP4i use was associated with a decrease in the risk of bone fracture.

Oral contraceptive use and fracture risk-a retrospective study of 12,970 women in the UK.

In the present retrospective case-control study, we compared 6485 women with fractures and 6485 women without fractures from 135 general practitioner offices in the UK. Women without bone fractures were statistically more likely to have been exposed to oral contraception, depending on their age and therapy duration. INTRODUCTION: The aim of this analysis was to compare the risk of bone fracture in women using hormonal contraception with that in women who have never used hormonal contraception. METHODS: A total of 6485 women (mean age 37.8 years) with an initial diagnosis of fracture between January 2010 and December 2015 were identified in 135 doctors' offices in the UK Disease Analyzer database. In this nested case-control study, each case with a fracture was matched (1:1) to a control without a fracture for age, index year, and follow-up time. In total, 12,970 individuals were available for analysis. The main outcome of the study was the risk of fracture as a function of combined oral contraceptive (OC) therapy. Multivariate logistic regression models were used to determine the effect of OC therapy and its duration on the risk of fracture in the entire population and in four age-specific subgroups. RESULTS: Women without bone fractures were significantly more likely to have used oral contraception (OR 0.81). The usage of oral contraception was associated with a significantly lower risk of bone fracture (OR 0.81, 95% CI 0.74-0.90). This effect was strongest in the age groups 18-25 and 26-35 and in patients with an OC treatment duration of more than 1 year. CONCLUSIONS: The present study revealed that women without bone fractures were significantly more likely to have had exposure to combined oral contraception, especially where the duration of intake was at least 5 years.

Is being resolute better than being pragmatic when it comes to breastfeeding? Longitudinal qualitative study investigating experiences of women intending to breastfeed using the Theoretical Domains Framework.

Background: In the UK, initiating then discontinuing breastfeeding before two weeks post-partum is common. The aim of this longitudinal qualitative study was to explore which psychosocial factors may influence discontinuation. Methods: A sample of 10 pregnant women intending to breastfeed were recruited. A longitudinal qualitative design was used to capture views prior to and two weeks following birth. Semi-structured interviews were conducted underpinned by the Theoretical Domains Framework to explore a comprehensive list of psychosocial factors. Results: Four women discontinued breastfeeding at the time of the second interview. Pre-partum differences were identified between maintainers and discontinuers; discontinuers appeared to have stronger intentions to breastfeed based on their self-determination, self-confidence and perception of fewer barriers to breastfeeding. Post-partum, discontinuers highlighted how they felt physically unable to carry on; their feeding experiences elicited negative emotions and pain. Negative emotions appeared to be exacerbated by original breastfeeding beliefs and advice given by healthcare professionals. Conclusions: The women in this study who discontinued breastfeeding showed less cognitive flexibility, which appeared to exacerbate post-partum emotional distress, when they encountered difficulties. Women with strong intentions and self-determination might benefit from support in anticipating potential barriers and identifying ways of overcoming them.

Successful behavioural strategies to increase physical activity and improve glucose control in adults with Type 2 diabetes.

AIMS: To explore which behaviour change techniques and other intervention features are associated with increased levels of physical activity and improved HbA1c in adults with Type 2 diabetes. METHODS: Moderator analyses were performed on a dataset of 21 behaviour change techniques and six intervention features identified in a systematic review of behavioural interventions (N = 1975 patients with Type 2 diabetes) to establish their associations with changes in physical activity and HbA1c . RESULTS: Four behaviour change techniques (prompt focus on past success, barrier identification/problem-solving, use of follow-up prompts and provide information on where and when to perform physical activity) had statistically significant associations with increased levels of physical activity. Prompt review of behavioural goals and provide information on where and when to perform physical activity behaviour had statistically significant associations with improved HbA1c . Pedometer use was associated with decreased levels of physical activity. CONCLUSIONS: These data suggest that clinical care teams can optimise their consultations by incorporating specific behaviour change techniques that are associated with increased levels of physical activity and improved long-term glycaemic control.

Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials.

OBJECTIVE: To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Medline, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Studies were identified through to January 2014. Randomised trials of interventions to maintain weight loss provided to initially obese adults (aged ≥ 18) after weight loss of ≥ 5% body weight with long term (≥ 12 months) follow-up of weight change (main outcome) were included. STUDY APPRAISAL AND SYNTHESIS: Potential studies were screened independently and in duplicate; study characteristics and outcomes were extracted. Meta-analyses were conducted to estimate the effects of interventions on weight loss maintenance with the inverse variance method and a random effects model. Results are presented as mean differences in weight change, with 95% confidence intervals. RESULTS: 45 trials involving 7788 individuals were included. Behavioural interventions focusing on both food intake and physical activity resulted in an average difference of -1.56 kg (95% confidence interval -2.27 to -0.86 kg; 25 comparisons, 2949 participants) in weight regain compared with controls at 12 months. Orlistat combined with behavioural interventions resulted in a -1.80 kg (-2.54 to -1.06; eight comparisons, 1738 participants) difference compared with placebo at 12 months. All orlistat studies reported higher frequencies of adverse gastrointestinal events in the experimental compared with placebo control groups. A dose-response relation for orlistat treatment was found, with 120 mg doses three times a day leading to greater weight loss maintenance (-2.34 kg, -3.03 to -1.65) compared with 60 mg and 30 mg three times a day (-0.70 kg, 95% confidence interval -1.92 to 0.52), P=0.02. CONCLUSIONS: Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance.

Perceived hazards of transfusion: can a clinician tool help patients' understanding?

OBJECTIVE: To evaluate the use of a tool prompting counselling behaviour for blood transfusion by assessing clinicians' self-reported counselling behaviours, and changes in patients' beliefs about transfusion. METHODS AND MATERIALS: Mixed quantitative and qualitative methodology undertaken in two phases. In phase 1, clinicians' responses (n = 12) to a semi-structured questionnaire were analysed to identify the content of discussions with patients about different aspects of receiving a blood transfusion. The content of discussions was coded using illness representation concepts from the Common Sense Self-Regulation Model. Phase 2 included patients (n = 14) scheduled for elective surgery who completed a questionnaire on their beliefs about transfusion before and after counselling. RESULTS: The most frequently coded illness representations targeted by clinicians using the tool were 'consequence of treatment' (32%) and 'cure/control' (30.5%). Two patient beliefs showed significant change following counselling using the checklist. After counselling, patients were more likely to disagree/strongly disagree with the statement that doctors relied too much on transfusion (P = 0.034) and more likely to agree/strongly agree that blood transfusion can result in new health problems (P = 0.041). CONCLUSION: This pilot study provides insight into how clinicians use a tool for blood transfusion counselling and shows the potential to influence patients' beliefs about transfusion. Whilst the checklist has a role in standardising practice, this pilot study highlights the need for optimising its use before undertaking a fully randomised evaluation of the tool.

Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (P

Randomized controlled trial of a one-minute intervention changing oral self-care behavior.

Non-compliance with oral self-care recommendations, despite education and motivation, is a major problem in preventive dentistry. Forming concrete if-then action plans has been successful in changing self-care behavior in other areas of preventive medicine. This is the first trial to test the effects of a brief planning intervention on interdental hygiene behavior. Two hundred thirty-nine participants received a packet of floss, information, and a flossing guide. They were randomly assigned to a control or an intervention group. The intervention took 1.16 minutes and consisted of forming a concrete plan of where, when, and how to floss. Baseline measures and two-week and two-month follow-ups included self-report, residual floss, and theory of planned behavior variables. The intervention significantly affected flossing in that group at two-week and two-month follow-ups, as compared with the control group. This study provides evidence for the effects of a concise intervention on oral self-care behavior.

Quantitative architecture distinguishes prefrontal cortical systems in the rhesus monkey.

The prefrontal cortex encompasses a large and heterogeneous set of areas, whose borders have been variously mapped in different architectonic studies. Differences in cortical maps present a formidable problem in comparing data across studies and in constructing databanks on the connections and functional attributes of cortical areas. Here we used quantitative approaches to cortical mapping to investigate (i) if architectonic areas of the prefrontal cortex in adult rhesus monkeys have unique profiles and (ii) if groups of architectonic areas belonging to distinct cortical types, ranging from agranular to eulaminate, have similar features. In addition, we used multidimensional analyses to see if, and how, prefrontal areas form clusters when multiple features are considered simultaneously. We used quantitative unbiased sampling procedures to estimate the areal and laminar density of neurons, glia and neurons positive for the calcium binding proteins parvalbumin (PV), calbindin (CB) and calretinin (CR) among 21 prefrontal areas or subdivisions of areas. Neuronal density varied among the prefrontal cortices (range: 38 569 +/- 4078 to 58 708 +/- 2327 neurons/mm(3)); it was lowest in caudal orbitofrontal and medial areas (OPAll, OPro, 13, 24a, 32, M25) and highest in lateral prefrontal areas (subdivisions of areas 46 and 8). Neurons positive for PV were most prevalent in lateral prefrontal areas and least prevalent in caudal orbitofrontal and medial pre-frontal areas, whereas the opposite trend was noted for neurons that expressed CB. Neurons positive for CR did not show regional differences, and the density of glia showed small variations among prefrontal cortices. The differences among areas, along with differences in the thickness of individual areas and layers, were used to establish a quantitative profile for each area. The results showed that differences in the density of neurons, and the preponderance of neurons positive for PV and CB, were related to different architectonic types of areas found within the prefrontal cortex. Conventional as well as multiparameter statistical analyses distinguished at one extreme the agranular and dysgranular (limbic) cortices, which were characterized by prominent deep layers (V-VI), the lowest neuronal density, the highest ratio of glia/neurons, and the lowest density of PV and the highest for CB. At the other extreme, lateral eulaminate cortices were characterized by the highest density of neurons, a prominent granular layer IV, denser supragranular (II-III) than infragranular (V-VI) layers, and a balanced distribution of neurons positive for PV and CB. The results provide insights into potentially different rates of development or maturation of limbic and eulaminate prefrontal areas, and their differential vulnerability in neurological and psychiatric diseases. The quantitative methods used provide an objective approach to construct maps, address differences in nomenclature across studies, establish homologies in different species and provide a baseline to identify changes in pathologic conditions.

Regional variation in brain capillary density and vascular response to ischemia.

Differences in brain neuroarchitecture have been extensively studied and recent results demonstrated that regional differences in the physiological properties of glial cells are equally common. Relatively little is known on the topographic differences in vascular supply, distribution and density of brain capillaries in different CNS regions. We developed a simple method consisting of intravascular injection of fluorescent dyes coupled to immunocytochemical techniques that allows for simultaneous observation of glia-neuronal-vascular interactions in immersion-fixed brain specimens from small rodents. This technique permits quantitative evaluation of regional differences in glial/neuronal distribution and the study of their relationship to vascular densities. Variations of this technique also allow the detection of abnormal microvasculature (i.e. 'leaky' vessels), a useful feature for studies of blood-brain barrier function in health and disease. By use of quantitative confocal microscopy, the three-dimensional geometry of cortical and hippocampal structures revealed remarkable differences in vascularization between cortical gray/white matter junction, and hippocampal formation (CA1 and CA3 regions). Significant differences were also observed within the same investigative region: CA1 was characterized by low capillary density compared to neighboring CA3. Following an ischemic insult, CA1 vessels had more extensive blood-brain barrier leakage than CA3 vessels. We conclude that in addition to neuronal and glial heterogeneity, cortical structures are also endowed with region-specific vascular patterns characterized by distinct pathophysiological responses.

Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy.

PURPOSE: It has been suggested that altered drug permeability across the blood-brain barrier (BBB) may be involved in pharmacoresistance to antiepileptic drugs (AEDs). To test this hypothesis further, we measured multiple drug resistance (MDR) gene expression in endothelial cells (ECs) isolated from temporal lobe blood vessels of patients with refractory epilepsy. ECs from umbilical cord or temporal lobe vessels obtained from aneurysm surgeries were used as comparison tissue. METHODS: cDNA arrays were used to determine MDR expression. MDR protein (MRP1) immunocytochemistry and Western blot analysis were used to confirm cDNA array data. RESULTS: We found overexpression of selected MDR and significantly higher P-glycoprotein levels in "epileptic" versus "control" ECs. Specifically, MDR1, cMRP/MRP2, and MRP5 were upregulated in epileptic tissue, whereas Pgp3/MDR3 levels were comparable to those measured in comparison tissue. The gene encoding cisplatin resistance--associated protein (hCRA-alpha) also was overexpressed in epileptic tissue. Immunocytochemical analysis revealed that MDR1 immunoreactivity was localized primarily in ECs; MRP1 protein levels also were significantly higher in epileptic tissue. CONCLUSIONS: Complex MDR expression changes may play a role in AEDs pharmacoresistance by altering the permeability of AEDs across the BBB.

Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster.

The expression of two second chromosome-linked cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster was measured in various strains. Six different strains, including ry(506) and 91-C, showed low or undetectable levels of CYP6A2 and CYP6A8 mRNAs, suggesting that low expression is the wild-type phenotype of Cyp6a2 and Cyp6a8 genes. In the 91-R and MHIII-D23 strains, however, both these genes are overexpressed. In order to examine the genetic basis of Cyp6a2 and Cyp6a8 expression, CYP6A2 and CYP6A8 RNA levels were measured in the F1 hybrids of overproducer (91-R and MHIII-D23) and underproducer (ry(506) and 91-C) strains. Results showed that the total amounts of CYP6A2 and CYP6A8 mRNAs in the F1 hybrids were lower than half the amounts of these RNAs found in the overproducer parental strains. This suggested that the underproducer strains carry loci which downregulate Cyp6a2 and Cyp6a8 gene expression. To determine the chromosome linkage of these loci, several stocks homozygous for the second chromosome of overproducer 91-R strain and, therefore, homozygous for the Cyp6a2-91R and Cyp6a8-91R alleles were synthesized. The third chromosomes in all these stocks were from the underproducer ry(506) strain. The levels of expression of both Cyp6a2-91R and Cyp6a8-91R genes in these three stocks were significantly lower than that observed in the 91-R strain. One of these stocks, named iso-2, showing reduced expression, was used to synthesize two new isogenic stocks by resubstituting the third chromosome of ry(506) origin with third chromosomes of the 91-R strain. Expression of both Cyp6a2-91R and Cyp6a8-91R alleles was found to be much higher in these two resubstituted isogenic stocks than in the progenitor iso-2 stock. Taken together, these results suggest that the second chromosome-linked Cyp6a2 and Cypa8 genes are regulated by loci present on the third chromosome, and the wild-type function of these loci is to repress these two Cyp genes. The data also suggest that Cyp6a2 and Cyp6a8 overexpression in the 91-R and MHIII-D23 strains is more likely due to mutation in the repressor locus (or loci) rather than in the cis-regulatory sequences of the Cyp6a2 and Cyp6a8 genes.

Medial prefrontal cortices are unified by common connections with superior temporal cortices and distinguished by input from memory-related areas in the rhesus monkey.

Medial prefrontal cortices in primates have been associated with emotion, memory, and complex cognitive processes. Here we investigated whether the pattern of cortical connections could indicate whether the medial prefrontal cortex constitutes a homogeneous region, or if it can be parceled into distinct sectors. Projections from medial temporal memory-related cortices subdivided medial cortices into different sectors, by targeting preferentially caudal medial areas (area 24, caudal 32 and 25), to a lesser extent rostral medial areas (rostral area 32, areas 14 and 10), and sparsely area 9. Area 9 was distinguished by its strong connections with premotor cortices. Projections from unimodal sensory cortices reached preferentially specific medial cortices, including a projection from visual cortices to area 32/24, from somatosensory cortices to area 9, and from olfactory cortices to area 14. Medial cortices were robustly interconnected, suggesting that local circuits are important in the neural processing in this region. Medial prefrontal cortices were unified by bidirectional connections with superior temporal cortices, including auditory areas. Auditory pathways may have a role in the specialization of medial prefrontal cortices in species-specific communication in non-human primates and language functions in humans.

Transcription signals of mitochondrial and nuclear genes for mitochondrial proteins in dicot plants.

Mitochondria contain several large multisubunit enzyme complexes that are composed of proteins encoded in the nuclear and mitochondrial genomes. Particularly for correct assembly of these enzyme complexes, expression of the respective mitochondrial and nuclear genes has to be coordinated to ensure correct stoichiometries of the protein subunits. Part of this control and the response to specific demands is exercised at the level of transcription. To determine the respective transcription signals we have analyzed the mitochondrial promoters in dicot plants and the promoter structure for nuclear-encoded genes of the respiratory chain complex I. We summarize the results of these investigations and extend the mitochondrial promoter survey to the mitochondrial genome in Arabidopsis thaliana.

Cotranscription of the rpl5-rps14-cob gene cluster in pea mitochondria.

In pea mitochondria the rpl5, rpsl4 and cob ORFs are clustered in a unique genomic environment and are cotranscribed into a 4.7-kb primary transcript and several other polycistronic RNAs with sizes between 4.0 and 2.3 kb. All of the larger RNAs terminate at a common 3' end, 52 nucleotides downstream of the cob gene. Transcription is initiated at a promoter about 1.3 kb upstream of the rpl5 start codon. The promoter sequence 5'-AATAAGAGA-3' corresponds to the highly conserved 5'-CRTAAGAGA-3' motif often found in promoters in dicot plants. Functional analysis in a homologous in vitro transcription system showed the pea rpl5 promoter to be active, despite the presence of an altered base in first position of the promoter motif. In Oenothera, in contrast to pea, transcription of the rpl5 gene is driven by a promoter motif that conforms perfectly to the consensus sequence. Double inverted repeats located in the 3' flanking regions of the rpsl4 and cob ORFs in pea were investigated with respect to their possible role in defining transcript termini and their potential function in controlling exo- and endonucleolytic processing or transcript stabilization.

Continuous primary sequence requirements in the 18-nucleotide promoter of dicot plant mitochondria.

The nucleotide requirements of mitochondrial promoters of dicot plants were studied in detail in a pea in vitro transcription system. Deletions in the 5' regions of three different transcription initiation sites from pea, soybean, and Oenothera identified a crucial AT-rich sequence element (AT-Box) comprising nucleotide positions -14 to -9 relative to the first transcribed nucleotide. Transversion of the AT-Box sequence to comple- mentary nucleotide identities results in an almost complete loss of promoter activity, suggesting that primary structure rather than a simple accumulation of adenines and thymidines in this region is essential for promoter activity. This promoter segment thus appears to be involved in sequence specific binding of a respective protein factor(s) rather than merely loosening and melting the DNA helix during or for an initiation event. Manipulation of nucleotide identities in the 3' portion of the pea atp9 promoter and the respective 3'-flanking region revealed that essential sequences extend to positions +3/+4 beyond this transcription start site. Efficient transcription initiation at an 18-base pair promoter sequence ranging from nucleotide positions -14 to +4 integrated into different sequence contexts shows this element to be sufficient for autonomous promoter function independent of surrounding sequences.