Various studies on functionalization of water-splitting photocatalysts have been performed toward their practical usage. Control of the cocatalyst has been investigated, and recently, in addition to particle-size control, alloying has been extensively used to achieve this goal. It is essential to investigate photocatalysts with precisely controlled cocatalysts to obtain a detailed understanding of the effect of heteroatom doping of the cocatalyst on the photocatalytic activity and thereby establish clear design guidelines for functionalization. However, previous studies have investigated photocatalysts with a variety of particle sizes and doping ratios (chemical compositions). In this study, we succeeded in loading precisely controlled Au24Pd and Au24Pt clusters on BaLa4Ti4O15, which is one of the most advanced photocatalysts, using precisely synthesized alloy clusters as the precursor. Experiments with the photocatalysts loaded with precisely controlled cocatalysts revealed the following three features of heteroatom doping of cocatalysts: (1) Pd is located at the surface of the metal-cluster cocatalyst, whereas Pt is located at the interface between the metal-cluster cocatalyst and the photocatalyst. (2) Pd doping decreases the water-splitting activity, whereas Pt doping improves the water-splitting activity. (3) This opposite doping effect is strongly related to the doping position of the heteroatom. Furthermore, when Pt doping is combined with surface protection of the cocatalyst with a Cr2O3 shell, a photocatalyst with higher activity and stability can be obtained. These results will lead to clear design guidelines for creating water-splitting photocatalysts with high activity and stability.

The ability to prevent radiotherapy-induced toxicity without affecting antitumor efficacy has the potential to enhance the therapeutic benefit for cancer patients without increasing their risk of serious adverse effects. Among the currently available cytoprotective agents capable of protecting normal tissue against damage caused by either chemo- or radiotherapy, only amifostine has been shown in clinical trials to reduce radiation-induced toxicity. Most notably, it reduces the incidence of xerostomia, which is a clinically significant long-term toxicity arising in patients undergoing irradiation of head and neck cancers. In vitro studies with the active metabolite of amifostine (WR-1065) have shown it to prevent both radiation-induced cell death and radiation-induced mutagenesis. The potential of this agent to prevent secondary tumors, as well as other radiation-induced toxicities is now the focus of ongoing research. Among other novel approaches to radioprotection being explored are methods to increase levels of the antioxidant mitochondrial enzyme manganese superoxide dismutase (MnSOD). In addition, the use of epoetin alfa, alone or in combination with cytoprotectants (e.g., amifostine), to treat radiation-induced anemia is also being investigated. The objective of developing newer cytoprotective therapies is to improve the therapeutic ratio by reducing the acute and chronic toxicities associated with more intensive and more effective anticancer therapies.

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BackgroundInsomnia is common. However, no systematic reviews have examined the effect of exercise on patients with primary and secondary insomnia, defined as both sleep disruption and daytime impairment. This systematic review and meta-analysis aimed to examine the effectiveness/efficacy of exercise in patients with insomnia.MethodsWe searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify all randomized controlled trials that examined the effects of exercise on various sleep parameters in patients with insomnia. All participants were diagnosed with insomnia, using standard diagnostic criteria or predetermined criteria and standard measures. Data on outcome measures were subjected to meta-analyses using random-effects models. The Cochrane Risk of Bias Tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of the individual studies and the body of evidence, respectively.ResultsWe included nine studies with a total of 557 participants. According to the Pittsburgh Sleep Quality Index (mean difference [MD], 2.87 points lower in the intervention group; 95% confidence interval [CI], 3.95 points lower to 1.79 points lower; low-quality evidence) and the Insomnia Severity Index (MD, 3.22 points lower in the intervention group; 95% CI, 5.36 points lower to 1.07 points lower; very low-quality evidence), exercise was beneficial. However, exercise interventions were not associated with improved sleep efficiency (MD, 0.56% lower in the intervention group; 95% CI, 3.42% lower to 2.31% higher; moderate-quality evidence). Only four studies noted adverse effects. Most studies had a high or unclear risk of selection bias.DiscussionOur findings suggest that exercise can improve sleep quality without notable adverse effects. Most trials had a high risk of selection bias. Higher quality research is needed.

The ability of thiol-containing reducing agents to activate transcription factors leading to changes in gene expression and enzyme activities provides an additional mechanism to potentially protect against radiation-induced cell killing. Manganese superoxide dismutase (Sod2) is one such gene whose expression levels have been shown to be elevated after exposure to the thiol compounds WR-1065 and N-acetyl-L-cysteine (NAC), resulting in an increase in radiation resistance. To further characterize this effect, SA-NH sarcoma cells, both wild-type and a clone stably transfected with a plasmid containing an IkappaBalpha gene mutated at serines 32 and 36, which prevents the inducible phosphorylation of these residues and the subsequent activation of NFkappaB (SA-NH+mIkappaBalpha1), were grown to confluence and then exposed to amifostine's free thiol WR-1065 at a concentration of 4 mM for 30 min. Effects of thiol exposure on NFKB activation in SA-NH+mIkappaBalpha1 cells were determined by a gel shift assay, and changes in Sod2 protein levels in these cells 24 h after exposure to 40 microM or 4 mM WR-1065 were measured by Western blot analysis and compared with wild-type cells exposed to the NFkappaB inhibitor BAY 11-7082. Changes in radiation response, measured immediately after thiol exposure or 24 h later, were determined using a colony-forming assay and were correlated with NFKB activation and Sod2 protein levels. The effects of captopril, mesna and NAC, each at a dose of 4 mM, on radiation response were also determined and contrasted with those of WR-1065. Only WR-1065 and captopril protected SA-NH cells when present during irradiation, i.e. 1.57 and 1.31 times increase in survival at 2 Gy, respectively. All four thiols were protective if irradiation with 2 Gy occurred 24 h later; i.e. increases in survival of 1.40, 1.22, 1.35, and 1.25 times were found for WR-1065, captopril, mesna and NAC, respectively. This delayed radioprotective effect correlated with elevated Sod2 protein levels in wild-type SA-NH tumor cells but was not observed in SA-NH+mIkappaBalpha1 cells, indicating that interference with thiol-induced NFKB activation abrogates this delayed radioprotective effect. Because the delayed radioprotective effect is readily demonstrable at a radiation dose of 2 Gy 24 h after exposure to clinically approved thiol-containing drugs such as amifostine, captopril, mesna and NAC, it suggests a new potential concern regarding the issue of tumor protection and the use of these agents in cancer therapy.

without any antidepressant prescriptions or with suboptimal prescriptions and the variable prescription patterns through the decades might suggest some unresolved gaps between evidence and practice.

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Context. Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.Objectives. We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.Methods. A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]eItem 5) $ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.Results. Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P ¼ 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P ¼ 0.048). Clinically meaningful pain improvement ($30%) was reported by 44.1% (n ¼ 15) of patients in Group D vs. 18.2% (n ¼ 6) in Group P (P ¼ 0.02); 32.4% (n ¼ 11) vs. 3.0% (n ¼ 1) of patients in Groups D and P, respectively, reported pain reduction $ 50% (P ¼ 0.002).Conclusion. Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine. J Pain Symptom