One Last Chance: The Economic Case for a New Approach to Fisheries Management in New England

Documents the decline of the New England fishing industry as a result of mismanagement, presents examples of successful and sustainable fisheries, and examines the viability of proposed community-based, fishermen-run cooperatives as a solution

European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV.

BACKGROUND: Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). SUMMARY OF GUIDELINES: All HIV-infected persons should be screened at regular intervals for a history of metabolic disease, dyslipidaemia, diabetes mellitus, hypertension and alteration of body composition; cardiovascular risk and renal function should also be assessed. Efforts to prevent cardiovascular disease will vary in intensity depending on an individual's absolute risk of ischaemic heart disease and should be comprehensive in nature. Lifestyle interventions should focus on counselling to stop smoking, modify diet and take regular exercise. A healthy diet, exercise and maintaining normal body weight tend to reduce dyslipidaemia; if not effective, a change of ART should be considered, followed by use of lipid-lowering medication in high-risk patients. A pre-emptive switch from thymidine analogues is recommended to reduce the risk of development or progression of lipoatrophy. Intra-abdominal fat accumulation is best managed by exercise and diet. Prevention and management of type 2 diabetes mellitus and hypertension follow guidelines used in the general population. When using medical interventions to prevent and/or treat metabolic disease(s), impairment of the efficacy of ART should be avoided by considering the possibility of pharmacokinetic interactions and compromised adherence. Specialists in HIV and specialists in metabolic diseases should consult each other, in particular in difficult-to-treat cases. CONCLUSION: Multiple and relatively simple approaches exist to prevent metabolic diseases in HIV-infected persons; priority should be given to patients at high risk of contracting these diseases

The snow must go on: Ground ice encasement, snow compaction and absence of snow differently cause soil hypoxia, CO2 accumulation and tree seedling damage in boreal forest

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Uridine Metabolism in HIV-1-Infected Patients: Effect of Infection, of Antiretroviral Therapy and of HIV-1/ART-Associated Lipodystrophy Syndrome

Background Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood. Methods Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. Results Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40-4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55-4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. Conclusions HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations

Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement

Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels

The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC). Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples. Results: MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-beta 1 (TGF-beta 1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-beta 1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells. Conclusions: The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-beta 1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.Peer reviewe

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without 18F-choline PET-CT detected simultaneous integrated boost

<p>Abstract</p> <p>Background</p> <p>In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without ¹⁸F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study.</p> <p>Methods</p> <p>Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq ¹⁸F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV_PET). A dose of 76Gy was prescribed to the prostate (PTV_prostate) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite).</p> <p>Results</p> <p>With a median cut-off standard uptake value (SUV) of 3, a median GTV_PETof 4.0 cm³and PTV_boost(GTV_PETwith margins) of 17.3 cm³was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D.</p> <p>Conclusions</p> <p>Treatment planning with ¹⁸F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.</p

Working conditions as predictors of retirement intentions and exit from paid employment: a 10-year follow-up of the English Longitudinal Study of Ageing

This work was funded by the Economic and Social Research Council and the Medical Research Council as part of the Lifelong Health and Well-Being (LLHW) initiative (grant number ES/L002892/1)