One-Stage Vs. Two-Step One Anastomosis Duodenal Switch (OADS/SADI-S): A Safety and Efficacy Single-Center Propensity-Score Matched Analysis.

INTRODUCTION: One Anastomosis Duodenal Switch (OADS/SADI-S) is used both as a one stage and a second-step procedure, either planned or revisional after a failed sleeve gastrectomy. However, there is lack of adjusted comparative evidence validating its use. MATERIAL AND METHODS: Propensity-score matched comparison between patients submitted to one-stage vs. two-step OADS, adjusted by age, gender, and initial body mass index (BMI). RESULTS: One hundred ninety-five patients (130 one-stage and 65 two-step OADS) were included, with mean initial BMI 52.4 kg/m2. Overall complication rate was 6.6% in the short-term (3.3% Clavien-Dindo ≥ III), and 7.3% in the long-term, with no differences between groups. Follow-up at 1 and 3 years was 83.6% and 61.5%. After one-stage OADS, total weight loss was 36.6 ± 8.2% at 1 year and 30.4 ± 10.3% at 3 years, vs. 30.2 ± 9.4% and 25.6 ± 10.2% after two-steps OADS (p = 0.021). Resolution rates of diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea were 86.4%, 80.4%, 78.0%, and 73.3%, with no differences between groups. CONCLUSION: One-stage OADS is a safe and effective bariatric technique for patients with grade III and IV obesity. The two-step strategy does not reduce postoperative risks and may compromise weight loss results at mid-term.

Potential for the anaerobic oxidation of benzene and naphthalene in thermophilic microorganisms from the Guaymas Basin.

Unsubstituted aromatic hydrocarbons (UAHs) are recalcitrant molecules abundant in crude oil, which is accumulated in subsurface reservoirs and occasionally enters the marine environment through natural seepage or human-caused spillage. The challenging anaerobic degradation of UAHs by microorganisms, in particular under thermophilic conditions, is poorly understood. Here, we established benzene- and naphthalene-degrading cultures under sulfate-reducing conditions at 50°C and 70°C from Guaymas Basin sediments. We investigated the microorganisms in the enrichment cultures and their potential for UAH oxidation through short-read metagenome sequencing and analysis. Dependent on the combination of UAH and temperature, different microorganisms became enriched. A Thermoplasmatota archaeon was abundant in the benzene-degrading culture at 50°C, but catabolic pathways remained elusive, because the archaeon lacked most known genes for benzene degradation. Two novel species of Desulfatiglandales bacteria were strongly enriched in the benzene-degrading culture at 70°C and in the naphthalene-degrading culture at 50°C. Both bacteria encode almost complete pathways for UAH degradation and for downstream degradation. They likely activate benzene via methylation, and naphthalene via direct carboxylation, respectively. The two species constitute the first thermophilic UAH degraders of the Desulfatiglandales. In the naphthalene-degrading culture incubated at 70°C, a Dehalococcoidia bacterium became enriched, which encoded a partial pathway for UAH degradation. Comparison of enriched bacteria with related genomes from environmental samples indicated that pathways for benzene degradation are widely distributed, while thermophily and capacity for naphthalene activation are rare. Our study highlights the capacities of uncultured thermophilic microbes for UAH degradation in petroleum reservoirs and in contaminated environments.

Intestinal Bipartition After Failed Sleeve Gastrectomy: a Safe and Simple Alternative Technique in a Challenging Case with Vascular Anomalies.

Sleeve gastrectomy (SG) is the most performed bariatric surgery worldwide but approximately 50% of patients will present insufficient weight loss or weight regain after surgery. In 2004, Santoro et al. described an alternative revisional technique other than DS and RYGBP called intestinal bipartition (IB). It involves a pre-pyloric gastro-ileal and an ileo-ileal anastomosis without exclusion of intestinal segments. Duodenal dissection is not necessary, making it an easier and more reproducible technical alternative to DS. its preliminary reports show good weight control with resolution of obesity related comorbidities. We present our technical suggestions to perform a safe IB in a patient with a failed SG in whom revisional DS or RYGBP were not feasible due to a vascular anomaly.

Identification of tipifarnib sensitivity biomarkers in T-cell acute lymphoblastic leukemia and T-cell lymphoma.

Patients diagnosed with T-cell leukemias and T-cell lymphomas (TCLs) still have a poor prognosis and an inadequate response to current therapies, highlighting the need for targeted treatments. We have analyzed the potential therapeutic value of the farnesyltransferase inhibitor, tipifarnib, in 25 TCL cell lines through the identification of genomic and/or immunohistochemical markers of tipifarnib sensitivity. More than half of the cell lines (60%) were considered to be sensitive. Tipifarnib reduced cell viability in these T-cell leukemia and TCL cell lines, induced apoptosis and modified the cell cycle. A mutational study showed TP53, NOTCH1 and DNMT3 to be mutated in 84.6%, 69.2% and 30.0% of sensitive cell lines, and in 62.5%, 0% and 0% of resistant cell lines, respectively. An immunohistochemistry study showed that p-ERK and RelB were associated as potential biomarkers of tipifarnib sensitivity and resistance, respectively. Data from RNA-seq show that tipifarnib at IC50 after 72 h downregulated a great variety of pathways, including those controlling cell cycle, metabolism, and ribosomal and mitochondrial activity. This study establishes tipifarnib as a potential therapeutic option in T-cell leukemia and TCL. The mutational state of NOTCH1, p-ERK and RelB could serve as potential biomarkers of tipifarnib sensitivity and resistance.

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection.

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the effect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who suffered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR.

Endobronchial ultrasound elastography for diagnosing mediastinal and hilar lymph nodes. / Elastografía asociada a la ecografía endobronquial en el estudio de adenopatías hiliares y mediastínicas.

INTRODUCTION: The main objective was to analyze the technical variability of EBUS-elastography in the differentiation of benign and malignant hilar and mediastinal lymph nodes. As a secondary objective, the results of the EBUS-elastography in said differentiation were analyzed, comparing them with the anatomopathological results. MATERIAL AND METHODS: Prospective and analytical study of lymph nodes in which EBUS-elastography was performed. Elastographic variables and their variability were analyzed. RESULTS: 24 patients and 38 lymph nodes were evaluated. Of these, 60.5% had a history of neoplasia, 71% of them were EBUS-elastography with diagnostic intention, 53% were mediastinal staging of lung cancer. Both procedures were performed in 25% of the patients. Lymph nodes were classified into elastographic colour patterns, red being characteristic of elastic tissues and blue of rigid tissues. The lymphadenopathies with apredominantly blue pattern were associated with an anatomopathological result of malignancy (86% vs. 14%, OR 20.4 (3.1 -245.1) p-value = .00015). Malignant lymph nodes presented less colour dispersion in the frequency histograms and a higher ratio of blue pixels and higher strain ratio. These variables showed a variability of 8.7, 9.9 and 31.6% respectively in repetitions in the same adenopathy. Finally, a 66% of consistency was obtained in the event of colour pattern variability (p .0000). CONCLUSIONS: EBUS-elastography is feasible during EBUS and may be helpful in predicting malignant lymph node infiltration. The quantitative elastographic data show low variability in repetitions in the same adenopathy. The strain ratio is the most variable elastographic parameter.

Dominant-negative ATF5 rapidly depletes survivin in tumor cells.

Survivin (BIRC5, product of the BIRC5 gene) is highly expressed in many tumor types and has been widely identified as a potential target for cancer therapy. However, effective anti-survivin drugs remain to be developed. Here we report that both vector-delivered and cell-penetrating dominant-negative (dn) forms of the transcription factor ATF5 that promote selective death of cancer cells in vitro and in vivo cause survivin depletion in tumor cell lines of varying origins. dn-ATF5 decreases levels of both survivin mRNA and protein. The depletion of survivin protein appears to be driven at least in part by enhanced proteasomal turnover and depletion of the deubiquitinase USP9X. Survivin loss is rapid and precedes the onset of cell death triggered by dn-ATF5. Although survivin downregulation is sufficient to drive tumor cell death, survivin over-expression does not rescue cancer cells from dn-ATF5-promoted apoptosis. This indicates that dn-ATF5 kills malignant cells by multiple mechanisms that include, but are not limited to, survivin depletion. Cell-penetrating forms of dn-ATF5 are currently being developed for potential therapeutic use and the present findings suggest that they may pose an advantage over treatments that target only survivin.

Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects.

BACKGROUND & AIMS: Broccoli sprouts represent an interesting choice of healthy food product as they are rich in glucosinolates and their cognate bioactive metabolites, isothiocyanates able to counteract the negative effects of diverse pathologies. As obesity is linked to an inflammatory component, the aim of the study was to evaluate the anti-inflammatory action of broccoli sprouts in overweight adult subjects. METHODS: An in vivo controlled study was performed in 40 healthy overweight subjects (ClinicalTrials.gov ID NCT 03390855). Treatment phase consisted on the consumption of broccoli sprouts (30 g/day) during 10 weeks and the follow-up phase of 10 weeks of normal diet without consumption of these broccoli sprouts. Anthropometric parameters as body fat mass, body weight, and BMI were determined. Inflammation status was assessed by measuring levels of TNF-α, IL-6, IL-1ß and C-reactive protein. RESULTS: IL-6 levels significantly decreased (mean values from 4.76 pg/mL to 2.11 pg/mL with 70 days of broccoli consumption, p < 0.001) and during control phase the inflammatory levels were maintained at low grade (mean values from 1.20 pg/mL to 2.66 pg/mL, p < 0.001). C-reactive protein significantly decreased as well. CONCLUSIONS: This study represents an advance in intervention studies as the broccoli sprouts were included in a daily dietary pattern in quantities that reflect a real consumption. Further studies are necessary to elucidate the role of this healthy rich and nutritious food product, but these promising results support the current evidence on the healthy properties of Brassica varieties.

Diagnostic Value of Elastography and Endobronchial Ultrasound in the Study of Hilar and Mediastinal Lymph Nodes.

BACKGROUND: The aim of this study was to explore elastography features and its ability to distinguish between benign and malignant lymph nodes by comparing the results with an anatomopathologic examination used as gold standard. METHODS: Patients were randomized in 2 groups [endobronchial ultrasound (EBUS) and EBUS-elastography]. Echographic characteristics of the lymph nodes were collected in both categories. In the EBUS-elastography group, elastographic data were also determined. RESULTS: A total of 100 lymph nodes were evaluated. Group 1 (EBUS) consisted of 57 lymph nodes. Group 2 (EBUS-elastography) included 43 lymph nodes. In group 2, lymph nodes with predominantly blue pattern were associated with a pathologic determination of malignancy, and the probability of presenting malignant infiltration with this color pattern was 86.7% (P=0.00004). Malignant lymph nodes presented less color dispersion (48.8 vs. 94.8, P=0.00013), higher ratio of blue pixels (66% vs. 32.5%, P=0.016), and higher strain ratio (7.1 vs. 2.48, P=0.005). The cut-off points to distinguish between benign and malignant lymph nodes were 4 for strain ratio, 61 for frequency histograms, and 52 for blue pixel ratio. The area under the curve of the ROC curves were 0.75, 0.83, and 0.87, respectively. Group 2 presented a lower number of nondiagnostic samples (2.3% vs. 21%, P=0.001) and a higher rate of malignant results (42% vs. 16%, P=0.005). CONCLUSION: EBUS-elastography is feasible during EBUS and may be helpful in predicting malignant lymph node infiltration. It could improve anatomopathologic sample collection and increase diagnostic efficiency.

Effectiveness of an mHealth-Based Electronic Decision Support System for Integrated Management of Chronic Conditions in Primary Care: The mWellcare Cluster-Randomized Controlled Trial.

BACKGROUND: The burden of noncommunicable diseases and their risk factors has rapidly increased worldwide, including in India. Innovative management strategies with electronic decision support and task sharing have been assessed for hypertension, diabetes mellitus, and depression individually, but an integrated package for multiple chronic condition management in primary care has not been evaluated. METHODS: In a prospective, multicenter, open-label, cluster-randomized controlled trial involving 40 community health centers, using hypertension and diabetes mellitus as entry points, we evaluated the effectiveness of mWellcare, an mHealth system consisting of electronic health record storage and an electronic decision support for the integrated management of 5 chronic conditions (hypertension, diabetes mellitus, current tobacco and alcohol use, and depression) versus enhanced usual care among patients with hypertension and diabetes mellitus in India. At trial end (12-month follow-up), using intention-to-treat analysis, we examined the mean difference between arms in change in systolic blood pressure and glycated hemoglobin as primary outcomes and fasting blood glucose, total cholesterol, predicted 10-year risk of cardiovascular disease, depression score, and proportions reporting tobacco and alcohol use as secondary outcomes. Mixed-effects regression models were used to account for clustering and other confounding variables. RESULTS: Among 3698 enrolled participants across 40 clusters (mean age, 55.1 years; SD, 11 years; 55.2% men), 3324 completed the trial. There was no evidence of difference between the 2 arms for systolic blood pressure (Δ=-0.98; 95% CI, -4.64 to 2.67) and glycated hemoglobin (Δ=0.11; 95% CI, -0.24 to 0.45) even after adjustment of several key variables (adjusted differences for systolic blood pressure: - 0.31 [95% CI, -3.91 to 3.29]; for glycated hemoglobin: 0.08 [95% CI, -0.27 to 0.44]). The mean within-group changes in systolic blood pressure in mWellcare and enhanced usual care were -13.65 mm Hg versus -12.66 mm Hg, respectively, and for glycated hemoglobin were -0.48% and -0.58%, respectively. Similarly, there were no differences in the changes between the 2 groups for tobacco and alcohol use or other secondary outcomes. CONCLUSIONS: We did not find an incremental benefit of mWellcare over enhanced usual care in the management of the chronic conditions studied. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02480062.

Protocol for the mWellcare trial: a multicentre, cluster randomised, 12-month, controlled trial to compare the effectiveness of mWellcare, an mHealth system for an integrated management of patients with hypertension and diabetes, versus enhanced usual care in India.

INTRODUCTION: Rising burden of cardiovascular disease (CVD) and diabetes is a major challenge to the health system in India. Innovative approaches such as mobile phone technology (mHealth) for electronic decision support in delivering evidence-based and integrated care for hypertension, diabetes and comorbid depression have potential to transform the primary healthcare system. METHODS AND ANALYSIS: mWellcare trial is a multicentre, cluster randomised controlled trial evaluating the clinical and cost-effectiveness of a mHealth system and nurse managed care for people with hypertension and diabetes in rural India. mWellcare system is an Android-based mobile application designed to generate algorithm-based clinical management prompts for treating hypertension and diabetes and also capable of storing health records, sending alerts and reminders for follow-up and adherence to medication. We recruited a total of 3702 participants from 40 Community Health Centres (CHCs), with ≥90 at each of the CHCs in the intervention and control (enhanced care) arms. The primary outcome is the difference in mean change (from baseline to 1 year) in systolic blood pressure and glycated haemoglobin (HbA1c) between the two treatment arms. The secondary outcomes are difference in mean change from baseline to 1 year in fasting plasma glucose, total cholesterol, predicted 10-year risk of CVD, depression, smoking behaviour, body mass index and alcohol use between the two treatment arms and cost-effectiveness. ETHICS AND DISSEMINATION: The study has been approved by the institutional Ethics Committees at Public Health Foundation of India and the London School of Hygiene and Tropical Medicine. Findings will be disseminated widely through peer-reviewed publications, conference presentations and other mechanisms. TRIAL REGISTRATION: mWellcare trial is registered with Clinicaltrial.gov (Registration number NCT02480062; Pre-results) and Clinical Trial Registry of India (Registration number CTRI/2016/02/006641). The current version of the protocol is Version 2 dated 19 October 2015 and the study sponsor is Public Health Foundation of India, Gurgaon, India (www.phfi.org).

Human neutrophils phagocytose and kill Acinetobacter baumannii and A. pittii.

Acinetobacter baumannii is a common cause of health care associated infections worldwide. A. pittii is an opportunistic pathogen also frequently isolated from Acinetobacter infections other than those from A. baumannii. Knowledge of Acinetobacter virulence factors and their role in pathogenesis is scarce. Also, there are no detailed published reports on the interactions between A. pittii and human phagocytic cells. Using confocal laser and scanning electron microscopy, immunofluorescence, and live-cell imaging, our study shows that immediately after bacteria-cell contact, neutrophils rapidly and continuously engulf and kill bacteria during at least 4 hours of infection in vitro. After 3 h of infection, neutrophils start to release neutrophil extracellular traps (NETs) against Acinetobacter. DNA in NETs colocalizes well with human histone H3 and with the specific neutrophil elastase. We have observed that human neutrophils use large filopodia as cellular tentacles to sense local environment but also to detect and retain bacteria during phagocytosis. Furthermore, co-cultivation of neutrophils with human differentiated macrophages before infections shows that human neutrophils, but not macrophages, are key immune cells to control Acinetobacter. Although macrophages were largely activated by both bacterial species, they lack the phagocytic activity demonstrated by neutrophils.

The Role of Topical Timolol in the Treatment of Infantile Hemangiomas: A Systematic Review and Meta-analysis.

To date the efficacy and safety of topical timolol in the treatment of infantile hemangioma has not been reviewed and analysed systematically. We collated all published data on the efficacy and safety of topical timolol in the treatment of infantile hemangioma. A total of 31 studies with 691 patients were included. The fixed effects pooled estimate of the response rate defined as any improvement from baseline of infantile hemangioma after treatment with topical timolol was significant (RR = 8.96; 95% CI 5.07-15.47; heterogeneity test p = 0.99), and the treatment was overall well tolerated. However, the quality of evidence was low to moderate. Topical timolol is an effective treatment for small infantile hemangioma, with no significant adverse effects noted. However, there is still a need for adequately powered randomised controlled trials.

The Effect of Regular Intake of Dry-Cured Ham Rich in Bioactive Peptides on Inflammation, Platelet and Monocyte Activation Markers in Humans.

Background and aims: Dietary studies have shown that active biopeptides provide protective health benefits, although the mediating pathways are somewhat uncertain. To throw light on this situation, we studied the effects of consuming Spanish dry-cured ham on platelet function, monocyte activation markers and the inflammatory status of healthy humans with pre-hypertension. Methods: Thirty-eight healthy volunteers with systolic blood pressure of >125 mmHg were enrolled in a two-arm crossover randomized controlled trial. Participants received 80 g/day dry-cured pork ham of >11 months proteolysis or 100 g/day cooked ham (control product) for 4 weeks followed by a 2-week washout before "crossing over" to the other treatment for 4 more weeks. Soluble markers and cytokines were analyzed by ELISA. Platelet function was assessed by measuring P-selectin expression and PAC-1 binding after ADP (adenosine diphosphate) stimulation using whole blood flow cytometry. Monocyte markers of the pathological status (adhesion, inflammatory and scavenging receptors) were also measured by flow cytometry in the three monocyte subsets after the interventional period. Results: The mean differences between dry-cured ham and cooked ham followed by a time period adjustment for plasmatic P-selectin and interleukin 6 proteins slightly failed (p = 0.062 and p = 0.049, respectively), notably increased for MCP-1 levels (p = 0.023) while VCAM-1 was not affected. Platelet function also decreased after ADP stimulation. The expression of adhesion and scavenging markers (ICAM1R, CXCR4 and TLR4) in the three subsets of monocytes was significantly higher (all p < 0.05). Conclusions: The regular consumption of biopeptides contained in the dry-cured ham but absent in cooked ham impaired platelet and monocyte activation and the levels of plasmatic P-selectin, MCP-1 and interleukin 6 in healthy subjects. This study strongly suggests the existence of a mechanism that links dietary biopeptides and beneficial health effects.

Lung, gastric and colorectal cancer mortality by occupation and industry among working-aged men in Japan.

We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25-64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8-11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were "administrative and managerial" (by occupation) and "mining" (by industry). For gastric cancer, the highest mortality rate was "agriculture" (by occupation) and "mining" (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fisheries, and those in professional and engineering categories had higher relative mortality risks for lung, gastric, and colorectal cancers. By industry; mining, electricity and gas, fisheries, and agriculture and forestry had the higher mortality risks for those cancers. Unemployed men had higher mortality rates than men in any occupation and industry for all three cancers. Overall, this study suggests that for Japanese men, occupations and industries may be a key social determinant of health.

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB. We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening. METHODS: Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990-2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates. RESULTS: During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons). CONCLUSIONS: Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.

Why do thin people have elevated all-cause mortality? Evidence on confounding and reverse causality in the association of adiposity and COPD from the British Women's Heart and Health Study.

Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women's Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3-3.1 versus OR = 1.2; 95% CI 0.7-1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding.

An international ecological study of adult height in relation to cancer incidence for 24 anatomical sites.

BACKGROUND: Anthropometric indices associated with childhood growth and height attained in adulthood, have been associated with an increased incidence of certain malignancies. To evaluate the cancer-height relationship, we carried out a study using international data, comparing various cancer rates with average adult height of women and men in different countries. METHODS: An ecological analysis of the relationship between country-specific cancer incidence rates and average adult height was conducted for twenty-four anatomical cancer sites. Age-standardized rates were obtained from GLOBOCAN 2008. Average female (112 countries) and male (65 countries) heights were sourced and compiled primarily from national health surveys. Graphical and weighted regression analysis was conducted, taking into account BMI and controlling for the random effect of global regions. RESULTS: A significant positive association between a country's average adult height and the country's overall cancer rate was observed in both men and women. Site-specific cancer incidence for females was positively associated with height for most cancers: lung, kidney, colorectum, bladder, melanoma, brain and nervous system, breast, non-Hodgkin lymphoma, multiple myeloma, corpus uteri, ovary, and leukemia. A significant negative association was observed with cancer of the cervix uteri. In males, site-specific cancer incidence was positively associated with height for cancers of the brain and nervous system, kidney, colorectum, non-Hodgkin lymphoma, multiple myeloma, prostate, testicular, lip and oral cavity, and melanoma. CONCLUSION: Incidence of cancer was associated with tallness in the majority of anatomical/cancer sites investigated. The underlying biological mechanisms are unclear, but may include nutrition and early-life exposure to hormones, and may differ by anatomical site.

Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

BACKGROUND: High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. METHODS AND RESULTS: We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P=4×10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6×10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5×10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). CONCLUSIONS: Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.

Health related quality of life improvement in breast cancer patients: secondary outcome from a simple blinded, randomised clinical trial.

OBJECTIVE: To determine the effectiveness of an early physiotherapy intervention for the prevention of secondary lymphoedema on health-related quality of life in women who also received an education program after breast cancer surgery. METHODS: One hundred and fifty three women diagnosed with unilateral breast cancer (stage I-II) treated with breast surgery, which included axillary lymph-node dissection, from Hospital Príncipe de Asturias, Alcalá de Henares, Madrid (Spain) were randomly assigned into two groups. Subjects in early physiotherapy group (n = 76) received a physiotherapy intervention combined with a therapeutic education program; women in the control group (n = 77) received only the therapeutic education program. Both interventions were delivered by two different physiotherapists of Physiotherapy in Women's Health Research Group at Physiotherapy Department of Alcala University. Health related quality of life was measured with EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires in 5 assessments: after surgery just before group interventions started (A1), after the 3-week group interventions finished (A2); and a follow-up period in 3 (A3), 6 (A4) and 12 (A5) months after surgical intervention. RESULTS: Greater change in quality of life was observed for early physiotherapy group arm compared to control group, although no strong statistical evidence was found (p > .05) for most of the dimensions except for physical function and social function areas (p < .003). CONCLUSIONS: The control group with therapeutic education program reported a clear improvement in the perception of quality of life. Adding early physiotherapy to the therapeutic education program did not show statistically significant changes in the global score or in most of the dimensions, but showed an improvement in the physical and social dimensions.