Insights into the challenges and facilitators to physical activity among brooklyn teens enroled in a weight management programme.

PURPOSE: A qualitative study was carried out to explore obese adolescents' understanding of physical activity, perceptions of the ideal body type and to identify facilitators of and barriers to physical activity. METHODS: Twenty-two adolescents 12-18 years of age and 14 of their parents were recruited from an obesity intervention programme in Brooklyn, New York, from June to November 2017. Data were collected using focus groups and individual semi-structured interviews, followed by interpretative phenomenological analysis of the transcripts. RESULTS: The adolescents wanted to 'lose some weight', but not to be 'thin' or 'look hungry'. Most females desired a 'slim-thick' figure, which was 'a flat stomach with big thighs, and curvy'. Fun and support from parents, peers and programme staff facilitated achieving their physical activity goals. Barriers included low self-efficacy, inactive families, fear of neighbourhood gangs and crime and perceptions that the parks were small and overcrowded, with limited physical activity options for adolescents. CONCLUSION: These findings highlight the need to consider local norms concerning body image when designing obesity interventions. To effectively reduce childhood obesity in New York City, policy should prioritize the promotion of public safety, improvement of neighbourhood parks and increase options for physical activity. PATIENT OR PUBLIC CONTRIBUTION: The voices and narratives of patients and their families informed this study.

Rules on informed consent and advance directives at the end-of-life: the new Italian law.

End-of-life decisions are an emergent issue for bioethical debates and practical concerns among health professionals. On December 2017, Italy enacted a new law named "Rules about informed consent and advance directives", which promotes the relationship of care in a fiduciary sense through the implementation of a correct and exhaustive information. It is also prescribed to record in writing all the patients' decisions about consent or refusal. Furthermore, the law explicitly forbids unreasonable therapeutic obstinacy for terminal patient, legitimizing deep palliative sedation. Finally, the law establishes the use of "advance directives" as a written document by which adults and capable people can express their wishes regarding health treatments and diagnostic tests in anticipation of a possible future incapacity. The law provides that doctors must comply with these directives, unless they appear clearly incongruous or not corresponding to the patient's current clinical condition.

A rare case of Spinal Epidural Abscess following mesotherapy: a challenging diagnosis and the importance of clinical risk management. Considerations concerning uncommon risk factor for development of Spinal Epidural Abscess and its prevention.

Spinal Epidural Abscess (SEA) is a rare pyogenic infection localized between dura mater and vertebral periostium. The development of SEA is associated with the presence of medical co-morbidities and risk factors that facilitate bacterial dissemination. It is possible distinguish two type of SEA: primary SEA due to pathogen hematogenous dissemination and secondary SEA resulting from direct inoculation of pathogen. This entity, very uncommon, shows a prevalence peak between the 5th and the 7th decade of life with predominance in males. The case is a 44 years old Caucasian man with chronic low back pain, treated with physiotherapy and anti-inflammatory drugs. Following an episode of acute severe exacerbation of pain, the patient underwent four session of dorsal and lumbo-sacral area mesotherapy. One month after the last session, the patient experienced acute sever lumbar pain, radiated to left lower limb and accompanied by fever and vomiting. During hospitalization, elevated levels of white blood cells and C Reactive Protein (CRP) were found. Moreover, a vertebral magnetic resonance imaging revealed the presence of intramedullary lesion. Furthermore, methicillin sensitive staphylococcus aureus was isolated from three blood cultures and antibiotic therapy was performed. In our case the patient had the typical SEA onset, without any specific risk factors excepting the execution of four session of mesotherapy. Aim of this study is to explain risk factors for the SEA development and to clarify how act as preventive measure, because also acupuncture can promote bacterial infection.

Development of the Patient's Experience and Attitude Colposcopy Eindhoven Questionnaire (PEACE-q).

BACKGROUND: No validated instruments for the evaluation of patient satisfaction in colposcopy do exist. Therefore, this study reports on the development of a Patient's Experience and Attitude to Colposcopy questionnaire. METHODS: Patients who recently received colposcopy participated in a focus group. A panel of experts evaluated the transcriptions and agreed on a 15-item draft questionnaire. The draft questionnaire was completed by 68 women who subsequently came for a colposcopy. For construct validation, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were performed as well as reliability analysis. Concurrent validity was assessed with the 4-item Patient Health questionnaire (PHQ-4). RESULTS: Construct validation resulted in an 8-item patient perception scale with good psychometric properties (Cronbach's alpha: 0.76) and excellent model fit. Two subscales could be discriminated: patient procedure perception scale (alpha: 0.89) and caregiver attitude perception scale (alpha: 0.71). Both subscales intercorrelated moderately (r = 0.28, p = 0.045). The subscale patient perception correlated significantly with the PHQ-4 scale and its anxiety subscale, not with the depression subscale. CONCLUSIONS: We developed a Patient's Experience and Attitude to Colposcopy questionnaire with adequate psychometric properties. Future application in out-patient clinics should further evaluate its clinical relevance.

Healthcare utilization in patients with first-time implantable cardioverter defibrillators (data from the WEBCARE study).

BACKGROUND: Knowledge of the level of healthcare utilization (HCU) and the predictors of high HCU use in patients with an implantable cardioverter defibrillator (ICD) is lacking. We examined the level of HCU and predictors associated with increased HCU in first-time ICD patients, using a prospective study design. METHODS: ICD patients (N = 201) completed a set of questionnaires at baseline and 3, 6, and 12 months after inclusion. A hierarchical multiple linear regression with three models was performed to examine predictors of HCU. RESULTS: HCU was highest between baseline and 3 months postimplantation and gradually decreased during 12 months follow-up. During the first year postimplantation, only depression (ß = 0.342, P = 0.002) was a significant predictor. Between baseline and 3 months follow-up, younger age (ß = -0.220, P < 0.01), New York Heart Association class III/IV (ß = 0.705, P = 0.01), and secondary indication (ß = 0.148, P = 0.05) were independent predictors for increased HCU. Between 3 and 6 months follow-up, younger age (ß = -0.151, P = 0.05) and depression (ß = 0.370, P < 0.001) predicted increased HCU. Between 6 and 12 months only depression (ß = 0.355, P = 0.001) remained a significant predictor. CONCLUSIONS: Depression was an important predictor of increased HCU in ICD patients in the first year postimplantation, particularly after 3 months postimplantation. Identifying patients who need additional care and provide this on time might better meet patients' needs and lower future HCU.

Regional variation in the management of metastatic gastric cancer in Ontario.

BACKGROUND: Geographic variation in cancer care is common when clear clinical management guidelines do not exist. In the present study, we sought to describe health care resource consumption by patients with metastatic gastric cancer (gc) and to investigate the possibility of regional variation. METHODS: In this population-based cohort study of patients with stage iv gastric adenocarcinoma diagnosed between 1 April 2005 and 31 March 2008, chart review and administrative health care data were linked to study resource utilization outcomes (for example, clinical investigations, treatments) in the province of Ontario. The study took a health care system perspective with a 2-year time frame. Chi-square tests were used to compare proportions of resource utilization, and analysis of variance compared mean per-patient resource consumption between geographic regions. RESULTS: A cohort of 1433 patients received 4690 endoscopic investigations, 12,033 computed tomography exams, 12,774 radiography exams, and 5059 ultrasonography exams. Nearly all patients were seen by a general practitioner (98%) and a specialist (99%), and were hospitalized (95%) or visited the emergency department (87%). Fewer than half received chemotherapy (43%), gastrectomy (37%), or radiotherapy (28%). The mean number of clinical investigations, physician visits, hospitalizations, and instances of patient accessing the emergency department or receiving radiotherapy or stent placement varied significantly by region. CONCLUSIONS: Variations in health care resource utilization for metastatic gc patients are observed across the regions of Ontario. Whether those differences reflect differential access to resources, patient preference, or physician preference is not known. The observed variation might reflect a lack of guidelines based on high-quality evidence and could partly be ameliorated with regionalization of gc care to high-volume centres.

E-health to manage distress in patients with an implantable cardioverter-defibrillator: primary results of the WEBCARE trial.

UNLABELLED: The Web-based distress management program for patients with an implantable cardioverter-defibrillator (ICD; WEBCARE) was developed to mitigate distress and enhance health-related quality of life in ICD patients. This study investigated the treatment effectiveness at 3-month follow-up for generic and disease-specific outcome measures. METHODS: Consecutive patients implanted with a first-time ICD from six hospitals in the Netherlands were randomized to either the "WEBCARE" or the "usual care" group. Patients in the WEBCARE group received a 12-week fixed, six-lesson behavioral treatment based on the problem-solving principles of cognitive behavioral therapy. RESULTS: Two hundred eighty-nine patients (85% response rate) were randomized. The prevalence of anxiety and depression ranged between 11% and 30% and 13% and 21%, respectively. No significant intervention effects were observed for anxiety (ß = 0.35; p = .32), depression (ß = -0.01; p = .98) or health-related quality of life (Mental Component Scale: ß = 0.19; p = .86; Physical Component Scale: ß = 0.58; p = .60) at 3 months, with effect sizes (Cohen d) being small (range, 0.06-0.13). There were also no significant group differences as measured with the disease-specific measures device acceptance (ß = -0.37; p = .82), shock anxiety (ß = 0.21; p = .70), and ICD-related concerns (ß = -0.08; p = .90). No differences between treatment completers and noncompleters were observed on any of the measures. CONCLUSIONS: In this Web-based intervention trial, no significant intervention effects on anxiety, depression, health-related quality of life, device acceptance, shock anxiety, or ICD-related concerns were observed. A more patient tailored approach targeting the needs of different subsets of ICD patients may be warranted. TRIAL REGISTRATION: clinicaltrials.gov. Identifier: NCT00895700.

Disease management for co-morbid depression and anxiety in diabetes mellitus: design of a randomised controlled trial in primary care.

BACKGROUND: Depression and anxiety are common co-morbid health problems in patients with type 2 diabetes. Both depression and anxiety are associated with poor glycaemic control and increased risk of poor vascular outcomes and higher mortality rates. Results of previous studies have shown that in clinical practice, treatment of depression and anxiety is far from optimal as these symptoms are frequently overlooked and undertreated. METHODS/DESIGN: This randomised controlled trial will examine the effectiveness of a disease management programme treating symptoms of depression and anxiety in primary care patients with Type 2 diabetes. Patients will be randomized on patient level in 1:1 ratio. Random block sizes of 2 and 4 are used. The disease management programme consists of screening, stepped treatment and monitoring of symptoms (n = 80). This will be compared to care as usual (n = 80). DISCUSSION: The disease management model for co-morbid depression and anxiety in primary care patients with diabetes is expected to result in reduced symptoms of depression and anxiety, improved quality of life, reduced diabetes specific distress and improved glyceamic control, compared to care as usual. TRIAL REGISTRATION: Dutch Trial Register NTR2626.

Hungarian hospital antibiotic consumption at the regional level, 1996-2005.

BACKGROUND: Regional variations in antibiotic consumption in outpatients have been reported previously, but nothing is as yet known about the regional distribution of antibiotic consumption in the hospital sector in Hungary. This study was designed to explore regional variations and investigate determinants of antibiotic consumption in hospital care in Hungary. MATERIALS AND METHODS: Regional distribution-based antibiotic sales data were obtained for a 10-year period (1996-2005) for the 20 Hungarian counties. Systemic antibacterial use (Anatomical Therapeutic Chemical code: J01) was expressed as the number of defined daily doses (DDD) per 100 patient-days. The multiple linear regression model was applied to investigate the determinants of regional differences in hospital antibiotic consumption. Independent variables related to health care access, utilization of hospital resources, doctors' workload, type of hospital care provided, and patient's characteristics and infections were considered as possible determinants, and data on these variables were obtained for 2 years (2004, 2005). We also tested the association between hospital and ambulatory care antibiotic consumption in Hungarian regions using the Pearson correlation test. RESULTS: For each year during the 1996-2005 study period, there were large and stable variations in total hospital antibiotic consumption (e.g., min-max(1996): 16.0-28.2; min-max(2005): 15.2-32.2 DDD per 100 patient-days) depending on the region. In the two developed models (Model 1 and Model 2), the number of reported infections accounted for 53% of the observed regional variations in hospital antibiotic consumption (Model 1), and the number of reported infections together with the case-mix index were responsible for 61% (Model 2) . Total antibiotic consumption in hospitals showed a positive correlation (R = 0.71, p = 0.002) with total antibiotic consumption in ambulatory care. CONCLUSION: The case-mix index and the number of reported infections explained some of the observed regional variations. However, the moderate value of the models in explaining these regional variations suggest that determinants which could not be explored in this preliminary study may also contribute to regional differences. Future studies should aim at collecting data for each individual hospital as well as data on possible determinants for hospital antibiotic consumption.

Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase.

Aspartate-beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the biosynthetic pathway through which bacteria, fungi, and the higher plants synthesize amino acids, including lysine and methionine and the cell wall component diaminopimelate from aspartate. Blocks in this biosynthetic pathway, which is absent in mammals, are lethal, and inhibitors of ASADH may therefore serve as useful antibacterial, fungicidal, or herbicidal agents. We have determined the structure of ASADH from Escherichia coli by crystallography in the presence of its coenzyme and a substrate analogue that acts as a covalent inhibitor. This structure is comparable to that of the covalent intermediate that forms during the reaction catalyzed by ASADH. The key catalytic residues are confirmed as cysteine 135, which is covalently linked to the intermediate during the reaction, and histidine 274, which acts as an acid/base catalyst. The substrate and coenzyme binding residues are also identified, and these active site residues are conserved throughout all of the ASADH sequences. Comparison of the previously determined apo-enzyme structure [Hadfield et al. J. Mol. Biol. (1999) 289, 991-1002] and the complex presented here reveals a conformational change that occurs on binding of NADP that creates a binding site for the amino acid substrate. These results provide a structural explanation for the preferred order of substrate binding that is observed kinetically.

The use of micro-organisms for L-ascorbic acid production: current status and future perspectives.

L-Ascorbic acid (L-AA) has been industrially produced for around 60 years in a primarily chemical process utilising D-glucose (D-glc) as starting material. Current world production is estimated at approximately 80,000 tonnes per annum with a worldwide market in excess of U.S. $600 million. We present a brief overview of research geared to exploiting micro-organisms for the industrial production of vitamin C, with emphasis on recent approaches using genetically engineered bacterial strains. We also discuss the potential for direct production of L-AA exploiting novel biochemical pathways with particular reference to yeast fermentations. The potential advantages of these novel approaches over current chemical and biotechnological processes are outlined.

Combined MR-relaxation and MR-cryoporometry in the study of bone microstructure.

MR-Relaxation (MRR) of 1H nuclei and MR-Cryoporometry (MRC) are combined to assess their feasibility and their potential in the study of bone microstructure. In principle, both techniques are able to give information on the structure of the pore space confining the fluids. Cow femur samples were carefully cored and cleaned in order to remove the natural fluids inside. For MRR analysis quasi-continuous distributions of T(1) and T(2) were obtained on samples fully saturated with water. Cyclohexane was used as a saturating fluid for MRC analysis. All T(1) and T(2) quasi-continuous distributions of water confined in bone samples are more than three decades wide, showing sufficient details to differentiate the samples. Pore size distributions obtained by MRC also differentiate the samples showing different characteristics of the pore space structure in the range of the highest sensitivity of the method (typically 3 to 100 nm, mesopore range). In particular, in samples where MRR shows a large fraction of signal with relaxation times below 10(2) ms, MRC indicates a large fraction of pore volume with pore sizes in the mesopore range.

Copy-DNA cloning and characterisation of a potato alpha-glucosidase: expression in Escherichia coli and effects of down-regulation in transgenic potato.

Polymerase chain reaction-based methodology was used to obtain a cDNA clone (MAL2) from potato (Solanum tuberosum L.) with the sequence characteristics of an alpha-glucosidase. Phylogenetic analysis of the deduced polypeptide encoded by this cDNA demonstrated that the most similar sequences were alpha-glucosidases and alpha-xylosidases of plant origin. The MAL2 cDNA was expressed in Escherichia coli and the recombinant MAL2 protein was affinity-purified. MAL2 catalysed the hydrolysis of a range of maltooligomers and p-nitrophenyl-alpha-D-glucopyranoside with a pH optimum of 5.5-5.7. The substrate with the lowest Km value was maltotetraose (3.7 mM). The MAL2 expression product did not catalyse the hydrolysis of xyloglucan oligosaccharides, p-nitrophenyl-alpha-D-xylopyranoside or gelatinised potato starch. MAL2 was down-regulated in transgenic potato plants using an antisense approach. In several independent transgenic antisense lines, MAL2 expression was severely down-regulated. Despite this, no decrease in total extractable alpha-glucosidase and alpha-xylosidase activity could be detected in tissues from the transgenic plants. In glasshouse trials, no visible phenotype, change in tuber yield or carbohydrate content was associated with MAL2 down-regulation. The implications of these results are discussed.

The unique features of starch metabolism in red algae.

Red algae (Rhodophyceae) are photosynthetic eukaryotes that accumulate starch granules outside of their plastids. The starch granules from red algae (floridean starch) show structural similarities with higher plant starch granules but lack amylose. Recent studies have indicated that the extra-plastidic starch synthesis in red algae proceeds via a UDP glucose-selective alpha-glucan synthase, in analogy with the cytosolic pathway of glycogen synthesis in other eukaryotes. On the other hand, plastidic starch synthesis in green cells occurs selectively via ADP glucose in analogy with the pathway of glycogen synthesis in prokaryotes from which plastids have evolved. Given the emerging consensus of a monophyletic origin of plastids, it would appear that the capacity for starch synthesis selectively evolved from the alpha-glucan synthesizing machinery of the host ancestor and its endosymbiont in red algae and green algae, respectively. This implies the evolution of fundamentally different functional relationships between the different subcellular compartments with regard to photosynthetic carbon metabolism in these organisms. It is suggested that the biochemical and molecular elucidation of floridean starch synthesis may offer new insights into the metabolic strategies of photosynthetic eukaryotes.

Alteration of the specificity of malate dehydrogenase by chemical modulation of an active site arginine.

Malate dehydrogenase from Escherichia coli is highly specific for the oxidation of malate to oxaloacetate. The technique of site-specific modulation has been used to alter the substrate binding site of this enzyme. Introduction of a cysteine in place of the active site binding residue arginine 153 results in a mutant enzyme with diminished catalytic activity, but with K(m) values for malate and oxaloacetate that are surprisingly unaffected. Reaction of this introduced cysteine with a series of amino acid analog reagents leads to the incorporation of a range of functional groups at the active site of malate dehydrogenase. The introduction of a positively charged group such as an amine or an amidine at this position results in improved affinity for several inhibitors over that observed with the native enzyme. However, the recovery of catalytic activity is less dramatic, with less than one third of the native activity achieved with the optimal reagents. These modified enzymes do have altered substrate specificity, with alpha-ketoglutarate and hydroxypyruvate no longer functioning as alternative substrates.

Structural analyses of a malate dehydrogenase with a variable active site.

Malate dehydrogenase specifically oxidizes malate to oxaloacetate. The specificity arises from three arginines in the active site pocket that coordinate the carboxyl groups of the substrate and stabilize the newly forming hydroxyl/keto group during catalysis. Here, the role of Arg-153 in distinguishing substrate specificity is examined by the mutant R153C. The x-ray structure of the NAD binary complex at 2.1 A reveals two sulfate ions bound in the closed form of the active site. The sulfate that occupies the substrate binding site has been translated approximately 2 A toward the opening of the active site cavity. Its new location suggests that the low catalytic turnover observed in the R153C mutant may be due to misalignment of the hydroxyl or ketone group of the substrate with the appropriate catalytic residues. In the NAD.pyruvate ternary complex, the monocarboxylic inhibitor is bound in the open conformation of the active site. The pyruvate is coordinated not by the active site arginines, but through weak hydrogen bonds to the amide backbone. Energy minimized molecular models of unnatural analogues of R153C (Wright, S. K., and Viola, R. E. (2001) J. Biol. Chem. 276, 31151-31155) reveal that the regenerated amino and amido side chains can form favorable hydrogen-bonding interactions with the substrate, although a return to native enzymatic activity is not observed. The low activity of the modified R153C enzymes suggests that precise positioning of the guanidino side chain is essential for optimal orientation of the substrate.