Integrated cognitive behavioral therapy for chronic pain: An open-labeled prospective single-arm trial

Background:We aimed to examine the feasibility of our newly-developed, integrated, and high-intensity individual cognitive behavioral therapy (CBT) protocol for treatment-resistant chronic pain.Methods:We conducted an open-labeled prospective single-arm trial for patients aged 18 years and above, suffering from chronic pain, and diagnosed with somatic symptom disorder with predominant pain. We provided 16 weekly sessions of CBT, each lasting for 50 minutes, which included 4 new strategies: attention shift, memory work, mental practice, and video feedback. For comparison, the study had a pre-test post-test design. The primary outcome was the change from baseline (week 1) to 16, as indicated by the Numerical Rating Scale and Pain Catastrophizing Scale. In addition, we evaluated depression, anxiety, disability, and quality of life as secondary outcomes.Results:Sixteen patients with chronic pain underwent our CBT program. Though there was no reduction in pain intensity, catastrophic cognition showed statistically significant improvement with a large effect size. Depression, anxiety, and disability demonstrated statistically significant improvements, with small to moderate effect sizes. No adverse events were reported.Conclusion:Our newly integrated CBT program for chronic pain may improve catastrophic cognition, depression, anxiety, and disability. Large-scale randomized controlled studies are necessary to investigate the program''s effectiveness in the future.     

Single‐pill combination of cilnidipine,an l‐/n‐type calcium channel blocker,and valsartan reduces the day‐by‐day variability of morning home systolic blood pressure in patients with treated hypertension: A sub‐analysis of the HOPE‐combi survey

We examined the effects of a fixed‐dose single‐pill combination of cilnidipine (10 mg), an L‐/N‐type calcium channel blocker, and valsartan (80 mg) (SPC of Cil/Val) on the day‐by‐day variability of morning home systolic blood pressure (MHSBP) in 616 patients with treated hypertension for 12 months as a sub‐analysis of the HOPE‐Combi survey, multicentral, post‐marketing, and prospective observational survey. The SPC of Cil/Val was administrated once a day in the morning. The SPC of Cil/Val decreased the standard deviation (SD, from 6.3 ± 4.8 to 5.1 ± 3.8 mmHg, p < .01), coefficient of variation (from 4.3 ± 3.2 to 3.8 ± 2.9%, p < .05), average real variability (ARV, from 7.9 ± 6.6 to 6.3 ± 5.1 mmHg, p < .01), and the difference between maximum and minimum (MMD, from 11.9 ± 9.2 to 9.7 ± 7.2 mmHg, p < .01) of MHSBP. The variability of MHSBP increased with age; however, this was not increased in patients ≥70 years at the baseline. In elderly patients (≥70 years, N = 283), the SPC of Cil/Val decreased the SD (from 6.9 ± 5.6 to 5.6 ± 4.4 mmHg, p < .01), ARV (from 8.6 ± 7.7 to 6.9 ± 5.7 mmHg, p < .05), and MMD (from 13.2 ± 10.7 to 10.7 ± 8.3 mmHg, p < .01) of MHSBP at 12 months; the reduction in these MHSBP variability parameters was comparable to that in adults <70 years. These results suggest that the SPC of Cil/Val is effective in reducing day‐by‐day variability of MHSBP in elderly patients.     

Fluorination and chlorination effects on quinoxalineimides as an electron-deficient building block for n-channel organic semiconductors

The quinoxalineimide (QI) unit, containing the electron-withdrawing quinoxaline and imide groups, is an electron-deficient building block for organic semiconductor materials. In this study, three fluorinated or chlorinated QIs (QI-1F, QI-2F, and QI-2Cl), have been designed and developed. We report the impact of the fluorination or chlorination of the QI unit on the electronic structures and charge carrier transport properties as compared to unsubstituted QI (QI-2H) bearing the same n-hexyl side chains. The frontier molecular orbital energy levels downshifted with the incorporation of fluorine or chlorine atoms onto the π-framework of QI. Single-crystal structure analyses revealed that all QI-based molecules have an entirely planar backbone and are packed into two-dimensional slipped stacks with diagonal electronic coupling that enables two-dimensional charge carrier transport. Notably, the doubly fluorinated or chlorinated QIs formed compact molecular packing in the single-crystal structures through an infinite intermolecular network relative to unsubstituted QI (QI-2H). The field-effect transistor-based QI molecules exhibited typical n-channel transport properties. As compared to unsubstituted QI (QI-2H), the chlorinated QI exhibited improved electron mobilities up to 7.1 × 10⁻³ cm² V⁻¹ s⁻¹. The threshold voltages of the fluorinated or chlorinated QI devices were clearly smaller than that of QI-2H, which reflects the lowest unoccupied molecular orbital levels of the molecules. This study demonstrates that the fluorinated or chlorinated QIs are versatile building blocks in creating n-channel organic semiconductor materials.

Three fluorinated or chlorinated quinoxalineimide units (QI-1F, QI-2F, and QI-2Cl) have been designed and developed.     

Effect of truncal vagotomy on GIP release induced by intraduodenal glucose or fat in dogs

In order to elucidate the role of the vagus nerve in the release of gastric inhibitory polypeptide (GIP), mongrel dogs were given a 4-min intraduodenal infusion of 10 g glucose or 5 g soybean oil before and again 1 month after truncal vagotomy (TV). The basal GIP concentrations were significantly elevated after TV. The plasma GIP levels following glucose infusion in the vagotomized dogs were significantly higher than those in the untreated dogs, whereas the GIP levels following fat infusion were not affected by TV. These results suggest that TV influences glucose-induced GIP release but not fat-induced GIP release, indicating that different mechanisms of the vagus nerve may be involved in glucose- and fat-induced GIP secretions.     

Expression of nitric oxide synthase isoforms in the human placenta is not altered by labor

Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 +/- 0.1652 (eNOS/GAPDH, mean +/- SEM) and 12.8 +/- 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 +/- 0.2042 (eNOS/GAPDH) and 11.4 +/- 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 +/- 0.2436 (iNOS/GAPDH) and 10.7 +/- 2.1 AU respectively, similar to those not in labor, 1.9254 +/- 0.8004 (iNOS/GAPDH) and 13.3 +/- 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the placental tissues in labor was 23.6 +/- 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 +/- 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.