This study examines patterns of electricity use by households in Sydney who have installed solar photovoltaic (PV) technology compared to those who have not in order to assess the impact of ...government solar incentive schemes, and to identify whether conservation or rebound (increased consumption) effects are associated with rooftop PV. Findings have significance in determining whether a rebound effect needs to be factored into projected energy/carbon savings from solar PV installation. At issue is the robustness of carbon mitigation estimates included in future rounds of international climate change agreements as well as local forecasts of future electricity demand affecting the national grid. Analysis and modelling was undertaken on billing data for the period 2007–2014 on a representative sample of 4819 households. The sample comprised three groups: households who were early adopters and installed PV under a 60c/kWh gross feed-in tariff scheme, a group who installed under a 20c/KWh gross feed-in scheme and a control group with no PV. Econometric modelling undertaken on energy consumption behaviour of households with versus without local renewable energy generation revealed that on a kWh basis, the rebound effect is estimated to erode up to one fifth of the carbon benefit of renewable energy generated by solar PV.
•Solar households generate up to 40% of their total electricity consumption.•Solar households have higher levels of electricity consumption relative to those with no PV.•Installation of solar PV (with feed-in tariff incentive) erodes up to 21% of the carbon mitigation benefit due to rebound.
Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological ...interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl- l -carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. l -Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl- l -carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions.
There is increasing evidence for a role of MaxiK potassium channel-activity in regulating the metabolism and intracellular signaling of non-contractile bladder mucosal tissues. At present however no ...studies have determined the impact of urothelial MaxiK-activity on overall bladder metabolism. To address this we have investigated the effect of bladder lumen instillation of the MaxiK inhibitor, iberiotoxin (IBTX), on mucosal and detrusor metabolism using metabolomics. Since IBTX does not cross plasma membranes, when instilled into the bladder lumen it would only effect urothelially expressed MaxiK-activity. Surprisingly IBTX treatment caused more effect on the metabolome of the detrusor than mucosa (the levels of 17% of detected detrusor metabolites were changed in comparison to 6% of metabolites in mucosal tissue following IBTX treatment). In mucosal tissues, the major effects can be linked to mitochondrial-associated metabolism whereas in detrusor there were additional changes in energy generating pathways (such as glycolysis and the TCA cycle). In the detrusor, changes in metabolism are potentially a result of IBTX effecting MaxiK-linked signaling pathways between the mucosa and detrusor, secondary to changes in physiological activity or a combination of both. Overall we demonstrate that urothelial MaxiK-activity plays a significant role in determining mitochondrially-associated metabolism in mucosal tissues, which effects the metabolism of detrusor tissue. Our work adds further evidence that the urothelium plays a major role in determining overall bladder physiology. Since decreased MaxiK-activity is associated with several bladder pathophysiology's, the changes in mucosal metabolism reported here may represent novel downstream targets for therapeutic interventions.
Current treatments for overactive bladder (OAB) are often discontinued due to side effects or lack of efficacy. The goal of this study was to determine if combining a phosphodiesterase type 4 ...inhibitor (PDE4i); with a type 5 inhibitor (PDE5i); would have a beneficial effect on OAB symptoms and if a reduced dose of PDE4i in combination with PDE5i could also provide a beneficial effect in OAB. We hypothesized that PDE5i and PDE4i combination treatment could be utilized to reduce non-voiding contractions and smooth muscle disruption in a rat model of OAB.
Fifty-eight age-matched Sprague-Dawley rats underwent PBOO and daily gavage with PDE4i alone (roflumilast; 1mg/kg), PDE5i alone (tadalafil;10mg/kg), high dose combination (PDE4i 1mg/kg, PDE5i 10mg/kg), low dose combination (PDE4i 0.2mg/kg, PDE5i 10mg/kg), or vehicle for 28 days. Fourteen animals underwent sham PBOO with vehicle. Rats underwent conscious and anesthetized cystometry 28 days after PBOO and were euthanized for qualitative bladder histology. One-way ANOVA on ranks with a Dunn's post hoc test was used to indicate statistically significant differences between groups (p<0.05).
Bladder & urethral weight was significantly increased after PBOO with vehicle, PDE4i alone, and PDE5i alone, but not with either combination treatment. Frequency of non-voiding contractions during both conscious and anesthetized cystometry increased significantly after PBOO with vehicle, but not after PDE4i or high dose combination treatments compared to sham PBOO. Threshold pressure for voiding was significantly decreased with high dose combination compared to vehicle. PBOO treated with PDE4i alone or high dose combination showed less bladder smooth muscle fibrosis than vehicle, PDE5i alone, or low dose combination treatments.
A PDE4i and PDE5i combination treatment has potential benefit in reducing OAB symptoms, but future research is needed.
Background
The majority of breast cancer patients use complementary and/or integrative therapies during and beyond cancer treatment to manage symptoms, prevent toxicities, and improve quality of ...life. Practice guidelines are needed to inform clinicians and patients about safe and effective therapies.
Methods
Following the Institute of Medicine’s guideline development process, a systematic review identified randomized controlled trials testing the use of integrative therapies for supportive care in patients receiving breast cancer treatment. Trials were included if the majority of participants had breast cancer and/or breast cancer patient results were reported separately, and outcomes were clinically relevant. Recommendations were organized by outcome and graded based upon a modified version of the US Preventive Services Task Force grading system.
Results
The search (January 1, 1990–December 31, 2013) identified 4900 articles, of which 203 were eligible for analysis. Meditation, yoga, and relaxation with imagery are recommended for routine use for common conditions, including anxiety and mood disorders (Grade A). Stress management, yoga, massage, music therapy, energy conservation, and meditation are recommended for stress reduction, anxiety, depression, fatigue, and quality of life (Grade B). Many interventions (n = 32) had weaker evidence of benefit (Grade C). Some interventions (n = 7) were deemed unlikely to provide any benefit (Grade D). Notably, only one intervention, acetyl-l-carnitine for the prevention of taxane-induced neuropathy, was identified as likely harmful (Grade H) as it was found to increase neuropathy. The majority of intervention/modality combinations (n = 138) did not have sufficient evidence to form specific recommendations (Grade I).
Conclusions
Specific integrative therapies can be recommended as evidence-based supportive care options during breast cancer treatment. Most integrative therapies require further investigation via well-designed controlled trials with meaningful outcomes.
Physicians are often asked about complementary therapies by patients with cancer, and data show that the interest in and use of these therapies among patients with cancer is common. Therefore, it is ...important to assess the current evidence base on the benefits and risks of complementary therapies (modalities not historically used in modern Western medicine).
A systematic literature review was carried out and recommendations were made according to the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines development methodology.
A large number of randomized controlled trials, systematic reviews, and meta-analyses, as well as a number of prospective cohort studies, met the predetermined inclusion criteria. These trials addressed many different issues pertaining to patients with lung cancer, such as symptoms of anxiety, mood disturbance, pain, quality of life, and treatment-related side effects. The available data cover a variety of interventions, including acupuncture, nutrition, mind-body therapies, exercise, and massage. The body of evidence supports a series of recommendations. An evidenced-based approach to modern cancer care should integrate complementary therapies with standard cancer therapies such as surgery, radiation, chemotherapy, and best supportive care measures.
Several complementary therapy modalities can be helpful in improving the overall care of patients with lung cancer.
There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the ...development of diabetic bladder disorder (DBD). In the present study, we compared the metabolome of detrusor and urothelial layer in a 1-mo streptozotocin-induced rat model of type 1 diabetes with nondiabetic controls. Our studies revealed that diabetes caused both common and differential changes in the detrusor and urothelial layer's metabolome. Diabetes resulted in similar changes in the levels of previously described diabetic markers in both tissues, such as glucose, lactate, 2-hydroxybutyrate, branched-chain amino acid degradation products, bile acids, and 1,5-anhydroglucitol, as well as markers of oxidative stress. In the detrusor (but not the urothelial layer), diabetes caused activation of the pentose-phosphate and polyol pathways, concomitant with a reduction in the TCA cycle and β-oxidation. Changes in detrusor energy-generating pathways resulted in an accumulation of sorbitol that, through generation of advanced glycation end products, is likely to play a central role in the development of DBD. In the diabetic urothelial layer there was decreased flux of glucose via glycolysis and changes in lipid metabolism, particularly prostaglandin synthesis, which also potentially contributes to detrusor dysfunction.
Abstract
The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that β
3
integrins negatively regulate ...G protein-coupled signaling by directly inhibiting the Gα
13
-p115RhoGEF interaction. Furthermore, whereas β
3
deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a β
3
-derived Gα
13
-binding peptide or Gα
13
knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the β
3
-derived Gα
13
-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion.
PDF
