Chronic widespread pain and cause of death: a 25-year follow-up study.

Introduction: Chronic widespread pain (CWP) has been suggested as a risk factor for mortality in cardiovascular diseases and malignancies. Different definition of CWP makes it difficult to compare previous studies. Objectives: The aim was to study whether mortality and certain causes of death were increased among people with CWP and whether the definition of CWP influenced outcome. Methods: This 25-year follow-up study included 2425 people from the general population, at baseline divided into 3 pain groups: CWP, chronic regional pain, and no chronic pain (NCP). Chronic widespread pain was defined according to the ACR1990 (CWPACR1990) and the more stringent WP2019 (CWPWP2019) criteria. Causes of death were derived from official national register. Mortality, adjusted for age, sex, socioeconomic status, and smoking habits were analyzed with Cox regression. Results: Overall mortality was not higher in people with CWPACR1990 (hazard ratio [HR] 1.08, P = 0.484) compared with NCP but significantly higher when using CWPWP2019 (HR 1.32, P = 0.033). People with CWPWP2019 had a higher mortality in diseases of the circulatory system (HR 1.32, P = 0.033) but not for neoplastic diseases. CWPACR1990 showed an increased mortality in malignancies of digestive organs. An increased mortality in influenza, pneumonia, acute kidney failure, and chronic kidney disease was observed for the CWPWP2019 definition. Conclusion: The more stringent WP2019 definition of CWP showed an excess risk for death, especially within diseases of the circulatory system. The results suggest that WP2019 defines a more vulnerable group in the population. Chronic widespread pain should be acknowledged in the clinic as a risk factor for increased mortality.

Radiation of the urinary bladder attenuates the development of lipopolysaccharide-induced cystitis.

In the present study we assessed how ionizing radiation affects TLR4-stimulated immune activation in lipopolysaccharide (LPS)-induced cystitis. LPS or saline was administered intravesically to female rats followed by urinary bladder irradiation (20 Gy) 24 h later or sham treatment. Presence in the urinary bladder of inflammatory cells (mast cells, CD3+, ionized calcium-binding adapter molecule 1 (Iba-1)+, CD68+, CD40+, CD80+, CD11c + and CD206 + cells) and expression of oxidative stress (8-OHdG), hypoxia (HIF1α) and anti-oxidative responses (NRF2, HO-1, SOD1, SOD2, catalase) were assessed 14 days later with western blot, qPCR and/or immunohistochemistry. LPS stimulation resulted in a decrease of Iba-1 + cells in the urothelium, an increase in mast cells in the submucosa and a decrease in the bladder protein expression of HO-1, while no changes in the bladder expression of 8-OHdG, NRF2, SOD1, SOD2, catalase and HIF1α were observed. Bladder irradiation inhibited the LPS-driven increase in mast cells and the decrease in Iba1 + cells. Combining LPS and radiation increased the expression of 8-OHdG and number of CD3-positive cells in the urothelium and led to a decrease in NRF2α gene expression in the urinary bladder. In conclusion, irradiation may attenuate LPS-induced immune responses in the urinary bladder but potentiates LPS-induced oxidative stress, which as a consequence may have an impact on the urinary bladder immune sensing of pathogens and danger signals.

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base.

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal.

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.