Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

Reductive fractionation of woody biomass into lignin monomers and cellulose by tandem metal triflate and Pd/C catalysis

A catalytic process for the upgrading of woody biomass into mono-aromatics, hemi-cellulose sugars and a solid cellulose-rich carbohydrate residue is presented. Lignin fragments are extracted from the lignocellulosic matrix by cleavage of ester and ether linkages between lignin and carbohydrates by the catalytic action of homogeneous Lewis acid metal triflates in methanol. The released lignin fragments are converted into lignin monomers by the combined catalytic action of Pd/C and metal triflates in hydrogen. The mechanism of ether bond cleavage is investigated by lignin dimer models (benzyl phenyl ether, guaiacylglycerol-β-guaiacyl ether, 2-phenylethyl phenyl ether and 2-phenoxy-1-phenylethanol). Metal triflates are involved in cleaving not only ester and ether linkages between lignin and the carbohydrates but also β-O-4 ether linkages within the aromatic lignin structure. Metal triflates are more active for β-O-4 ether bond cleavage than Pd/C. On the other hand, Pd/C is required for cleaving α-O-4, 4-O-5 and β-β linkages. Insight into the synergy between Pd/C and metal triflates allowed optimizing the reductive fractionation process. Under optimized conditions, 55 wt% mono-aromatics - mainly alkylmethoxyphenols - can be obtained from the lignin fraction (23.8 wt%) of birch wood in a reaction system comprising birch wood, methanol and small amounts of Pd/C and Al(III)-triflate as catalysts. The promise of scale-up of this process is demonstrated

Selective production of mono-aromatics from lignocellulose over Pd/C catalyst:The influence of acid co-catalysts

The ‘lignin-first’ approach has recently gained attention as an alternative whole biomass pretreatment technology with improved yield and selectivity of aromatics compared with traditional upgrading processes using technical lignins. Metal triflates are effective co-catalysts that considerably speed up the removal of lignin fragments from the whole biomass. As their cost is too high in a scaled-up process, we explored here the use of HCl, H2SO4, H3PO4 and CH3COOH as alternative acid co-catalysts for the tandem reductive fractionation process. HCl and H2SO4 were found to show superior catalytic performance over H3PO4 and CH3COOH in model compound studies that simulate lignin-carbohydrate linkages (phenyl glycoside, glyceryl trioleate) and lignin intralinkages (guaiacylglycerol-β-guaiacyl ether). HCl is a promising alternative to the metal triflate as co-catalyst in the reductive fraction of woody biomass. Al(OTf)3 and HCl respectively afforded 46 wt% and 44 wt% lignin monomers from oak wood sawdust in a tandem catalytic systems with Pd/C at 180 ⁰C in 2 h. The retention of cellulose in the solid residue was nearly similar.\u3cbr/\u3e\u3cbr/\u3

The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression

An Interactive Computer Kiosk Module for the Treatment of Recurrent Uncomplicated Cystitis in Women

OBJECTIVE: To validate and implement a computer module for the management of uncomplicated urinary tract infections (UTI). PARTICIPANTS: Women age 18 to 64 years, with a previous UTI, voiding symptoms, and absence of complicating features (comorbidities, vaginal discharge, back pain, emesis, and fever/chills). MEASUREMENTS: The computer module was validated against clinician diagnosis and urine culture. Following validation, the module was implemented in the urgent care clinic as a management option for women with suspected UTI; computer-directed therapy (CDT)-eligible women received antibiotic treatment without a clinician examination. Patient satisfaction with the module and return visits for UTI-related complaints were assessed. RESULTS: In the validation study, 18 of 68 women (26%) were CDT-eligible. Clinicians diagnosed 17/18 CDT-eligible women with uncomplicated UTI. Sixty-seven percent of CDT-eligible women had a positive urine culture. Since implementation, 162 women have accessed the module, and 35% have received CDT. Ninety-eight percent (95% confidence interval: 95% to 100%) found the program easy to use and 95% (89% to 100%) would recommend it to friends/family. Two (4%) CDT-treated women had a return visit to our institution for a UTI-related illness within 2 weeks. CONCLUSIONS: A computer module accurately identifies women with culture-confirmed, uncomplicated UTIs. Patients are highly satisfied with the module

12-month outcome and predictors of recurrence in psychiatric treatment of depression – a retrospective study.

Many individuals treated for depression suffer relapse or recurrence after treatment. Known risk factors include number of previous depressive episodes and residual symptoms after treatment. Both relapse/recurrence rates and predictors of relapse/recurrence, however, may differ between various settings. To perform a naturalistic evaluation of the sustained effectiveness of treatment for adult clinical depression in a psychiatric out-patient setting and to examine psychosocial and clinical predictors of relapse/recurrence. 51 individuals, who were successfully treated/discharged from psychiatric care 12 months prior, were assessed regarding current depressive status and regarding relapse and recurrence. Logistic regression was used to assess the predictive impact of the variables measured. At the 12-month follow-up, 26 % of the participants were in complete remission, 45 % were in partial remission, and 29 % were clinically depressed. In 1 year, 61 % suffered a new depressive episode. Having a greater number of previous episodes and having no partner significantly increased the risk of relapse or recurrence. A high prevalence of depression and partially remitted depression is reported at 12-month follow up, and a large proportion of the sample would likely benefit from active treatment. Relapse/recurrence rates are higher in this study than in many other studies, and it may be hypothesized that they are generally higher in psychiatric settings than in primary care. If so, this would indicate the need for a different treatment strategy in the psychiatric care of depression, with emphasis on long-term management of depression