Long-range hydrogen-bond relay catalyses the excited-state proton transfer reaction.

Solvent (e.g., water)-catalyzed proton transfer (SCPT) via the relay of hydrogen (H)-bonds plays a key role in proton migration. In this study, a new class of 1H-pyrrolo[3,2-g]quinolines (PyrQs) and their derivatives were synthesized, with sufficient separation of the pyrrolic proton donating and pyridinic proton accepting sites to probe excited-state SCPT. There was dual fluorescence for all PyrQs in methanol, i.e., normal (PyrQ) and tautomer 8H-pyrrolo[3,2-g]quinoline (8H-PyrQ) emissions. The fluorescence dynamics unveiled a precursor (PyrQ) and successor (8H-PyrQ) relationship and the correlation of an increasing overall excited-state SCPT rate (kSCPT) upon increasing the N(8)-site basicity. kSCPT can be expressed by the coupling reaction kSCPT = Keq × kPT, where kPT denotes the intrinsic proton tunneling rate in the relay and Keq denotes the pre-equilibrium between randomly and cyclically H-bonded solvated PyrQs. Molecular dynamics (MD) simulation defined the cyclic PyrQs and analyzed the H-bond and molecular arrangement over time, which showed the cyclic PyrQs incorporating ≧3 methanol molecules. These cyclic H-bonded PyrQs are endowed with a relay-like proton transfer rate, kPT. MD simulation estimated an upper-limited Keq value of 0.02-0.03 for all studied PyrQs. When there was little change in Keq, the distinct kSCPT values for PyrQs were at different kPT values, which increased as the N(8) basicity increased, which was induced by the C(3)-substituent. kSCPT was subject to a deuterium isotope effect, where the kSCPT of 1.35 × 1010 s-1 for PyrQ-D in CH3OD was 1.68 times slower than that (2.27 × 1010 s-1) of PyrQ in CH3OH. MD simulation provided a similar Keq for PyrQ and PyrQ-D, leading to different proton tunneling rates (kPT) between PyrQ and PyrQ-D.

Bacillus amyloliquefaciens PMB05 Increases Resistance to Bacterial Wilt by Activating Mitogen-Activated Protein Kinase and Reactive Oxygen Species Pathway Crosstalk in Arabidopsis thaliana.

Bacterial wilt caused by Ralstonia solanacearum can infect many crops, causing significant losses worldwide. The use of beneficial microorganisms is considered a feasible method for controlling this disease. Our previous study showed that Bacillus amyloliquefaciens PMB05 can control bacterial wilt through intensifying immune signals triggered by a pathogen-associated molecular pattern (PAMP) from R. solanacearum. It is still uncertain whether induction of the mitogen-activated protein kinase (MAPK) pathway during PAMP-triggered immunity (PTI) is responsible for enhancing disease resistance. To gain more insights on how the presence of PMB05 regulates PTI signaling, its association with the MAPK pathway was assayed. Our results showed that the activation of MPK3/6 and expression of wrky22 upon treatment with the PAMP, PopW, was increased during co-treatment with PMB05. Moreover, the disease resistance conferred by PMB05 to bacterial wilt was abolished in mekk1, mkk5, and mpk6 mutants. To determine the relationship between the MAPK pathway and plant immune signals, the assay on reactive oxygen species (ROS) generation and callose deposition showed that only the ROS generation was strongly reduced in these mutants. Because ROS generation is highly correlated with RbohD, the results revealed that the effects of PMB05 on both PopW-induced ROS generation and disease resistance to bacterial wilt were eliminated in the rbohD mutant, suggesting that the generation of ROS is also required for PMB05-enhanced disease resistance. Taken together, we concluded that the crosstalk between the initiation of ROS generation and further activation of the MAPK pathway is necessary when PMB05 is used to improve disease resistance to bacterial wilt. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Factors Related to Family Caregivers' Readiness for the Hospital Discharge of Advanced Cancer Patients.

Background: Many family caregivers of advanced cancer patients worry about being unable to provide in-home care and delay the discharge. Little is known about the influencing factors of discharge readiness. Methods: This study aimed to investigate the influencing factors of family caregivers' readiness, used a cross-sectional survey, and enrolled 123 sets of advanced cancer patients and family caregivers using convenience sampling from four oncology wards in a medical centre in northern Taiwan. A self-developed five-point Likert questionnaire, the "Discharge Care Assessment Scale", surveyed the family caregivers' difficulties with providing in-home care. Results: The study showed that the discharge readiness of family caregivers affects whether patients can be discharged home. Moreover, the influencing factors of family caregivers' discharge readiness were the patient's physical activity performance status and expressed discharge willingness; the presence of someone to assist family caregivers with in-home care; and the difficulties of in-home care. The best prediction model accuracy was78.0%, and the Nagelkerke R2 was 0.52. Conclusion: Discharge planning should start at the point of admission data collection, with the influencing factors of family caregivers' discharge readiness. It is essential to help patients increase the likelihood of being discharged home.

Low-Light Enhancement Using a Plug-and-Play Retinex Model With Shrinkage Mapping for Illumination Estimation.

Low-light photography conditions degrade image quality. This study proposes a novel Retinex-based low-light enhancement method to correctly decompose an input image into reflectance and illumination. Subsequently, we can improve the viewing experience by adjusting the illumination using intensity and contrast enhancement. Because image decomposition is a highly ill-posed problem, constraints must be properly imposed on the optimization framework. To meet the criteria of ideal Retinex decomposition, we design a nonconvex Lp norm and apply shrinkage mapping to the illumination layer. In addition, edge-preserving filters are introduced using the plug-and-play technique to improve illumination. Pixel-wise weights based on variance and image gradients are adopted to suppress noise and preserve details in the reflectance layer. We choose the alternating direction method of multipliers (ADMM) to solve the problem efficiently. Experimental results on several challenging low-light datasets show that our proposed method can more effectively enhance image brightness as compared with state-of-the-art methods. In addition to subjective observations, the proposed method also achieved competitive performance in objective image quality assessments.

Influence Analysis of Sustainability Perceptions on Sense of Community and Support for Sustainable Community Development in Relocated Communities.

This study aims to examine a theoretical model using sustainability perceptions, including environmental; sociocultural; economic; and life satisfaction, sense of community, and support for sustainable community development among the indigenous people of two relocated communities in Taiwan. A total of 747 usable questionnaires were collected and analyzed using structural equation modeling. The analytical results indicated that sense of community is an antecedent of support for sustainable community development in both relocated communities. Life satisfaction perceptions can influence the sense of community in Rinari. Additionally, environmental and economic perceptions are antecedents of the sense of community in New Laiyi. Finally, this study provides theoretical implications to fill the gaps in previous research, and offers valuable insights for promoting residents' support for sustainable community development in aboriginal communities; thus, this study has significant contributions, theoretically and practically.

Acquired Resistance to Isoniazid During Isoniazid Monotherapy in a Subject with Latent Infection Following Household Rifampicin-Resistant Tuberculosis Contact: A Case Report.

Appropriate treatment is the key element in eliminating tuberculosis (TB), and requires prompt diagnosis. We presented a case of a household contact of rifampicin-resistant TB revealing reactive IFN-gamma release assay with unsuspicious clinical and radiologic examinations. She was diagnosed with latent tuberculosis infection (LTBI) and treated with isoniazid monotherapy. On the ninth month, she developed a progressive cough and was found to harbor active TB disease with added resistance to isoniazid. An individualized anti-TB regimen consisting of moxifloxacin, kanamycin, prothionamide, ethambutol, and pyrazinamide was prescribed for 20 months, leading to sputum culture conversion and improvement of the reported symptom. No recurrence was observed on one-year follow-up. Assuming high compliance to therapy, we propose that the patient may have been underdiagnosed and received sub-optimal treatment leading to acquired-drug resistance. Conventional diagnosis methods based on immunological assay and radiographical findings may be insufficient to distinguish the incipient and subclinical states of TB from LTBI.

Effects of Vigiis 101-LAB on a healthy population's gut microflora, peristalsis, immunity, and anti-oxidative capacity: A randomized, double-blind, placebo-controlled clinical study.

Vigiis 101-LAB capsules are produced from the fermentation of Lactobacillus paracasei subsp. paracasei NTU 101. We tested effects of Vigiis 101-LAB capsules I or II (5 or 10 billion CFU/day, respectively) on gut microflora in clinical trial I, and on peristalsis, immunity, and anti-oxidative capacity in clinical trial II, during a 4-week randomized, double-blind, placebo-controlled, adaptive-design study. In trial I, 36 subjects were divided into capsule I and placebo groups. After 4 weeks, Bifidobacterium spp. and Lactobacillus spp. counts were significantly higher in the feces of treatment subjects, with increases of 4.01- and 4.25-fold, respectively. In trial II, 52 subjects were divided into capsule II and placebo groups. After 4 weeks, the treatment group was found to have improved motility, decreased food transit time, and significantly increased immunoglobulin G, immunoglobulin M, and antioxidant activity. Thus, daily administration of Vigiis 101 capsule II can improve peristalsis, immunity, and anti-oxidative capacity.

Bacillus amyloliquefaciens Strain PMB05 Intensifies Plant Immune Responses to Confer Resistance Against Bacterial Wilt of Tomato.

Tomato is an economic crop worldwide. Many limiting factors reduce the production of tomato, with bacterial wilt caused by Ralstonia solanacearum being the most destructive disease. Our previous study showed that the disease resistance to bacterial soft rot is enhanced by Bacillus amyloliquefaciens strain PMB05. This enhanced resistance is associated with the intensification of pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI). To determine whether the PTI-intensifying Bacillus spp. strains are able to confer disease resistance to bacterial wilt, their effects on PTI signals triggered by PAMP from R. solanacearum and on the occurrence of bacterial wilt were assayed. Before assay, a gene that encodes harpin from R. solanacearum, PopW, was applied as a PAMP. Results revealed that the B. amyloliquefaciens strain PMB05 was the one strain among 9 Bacillus rhizobacterial strains which could significantly intensify the PopW-induced hypersensitive response (HR) on Arabidopsis leaves. Moreover, we observed that the signals of PopW-induced reactive oxygen species generation and callose deposition were increased, confirming that the PTI was intensified by PMB05. The intensification of the PopW-triggered HR by PMB05 in Arabidopsis was reduced upon treatment with inhibitors in PTI pathways. Furthermore, the application of Bacillus spp. strains on tomato plants showed that only the use of PMB05 resulted in significantly increased resistance to bacterial wilt. Moreover, the PTI signals were also intensified in the tomato leaves. Taken together, we demonstrated that PMB05 is a PTI-intensifying bacterium that confers resistance to tomato bacterial wilt. Screening of plant immunity intensifying rhizobacteria is a possible strategy to control tomato bacterial wilt.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Toxicity assessment of electrochemical advanced oxidation process-treated groundwater from a gas station with petrochemical contamination.

Electrochemical advanced oxidation process (EAOP) is known for its efficient and fast degradation of organic pollutants in polluted water treatment. In this study, the EAOP using a boron-doped diamond (BDD) anode was applied to treat two-season groundwater samples collected from four sampling wells (GS1 to GS4) with petrochemical contaminants including methyl tert-butyl ether (MTBE), benzene, toluene, chlorobenzene, total organic compounds (TOC), and total petroleum hydrocarbons (TPH) at a gas station in southern Taiwan. Moreover, toxicity tests (ATP, p53, and NF-κB bioassays) were performed to evaluate the biological responses of raw and EAOP-treated groundwater. Results show that the concentrations of chlorobenzene before and after EAOP treatment were all below its method detection limit. High degradation efficiencies were observed for MTBE (100%), benzene (100%), toluene (100%, except that of GS2 in the first season), TPH (94-97%, except that of GS4 in the first season), and TOC (85-99%). Cell viability for both the raw groundwater (81.2 ± 13.5%) and EAOP-treated samples (84.7 ± 11.7%) as detected using the ATP bioassay showed no significant difference (p = 0.715). A mean reduction in the DNA damage (739 to 165 ng DOX-equivalency L-1 (ng DOX-EQ. L-1)) and inflammatory response levels (460 to 157 ng TNFα-equivalency L-1 (ng TNFα-EQ. L-1)) were observed for EAOP-treated samples subjected to p53 and NF-κB bioassays. Overall, the significances of the average degradation efficiency, DNA damage, and inflammatory response before and after groundwater with EAOP treatment was observed to be significant (p < 0.05). p53 and NF-κB bioassays might be applied to assess ecotoxic risk in the environment.

Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/FGT Glioblastoma-Bearing Rat Model.

Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.

Fatty Acid Inhibition Sensitizes Androgen-Dependent and -Independent Prostate Cancer to Radiotherapy via FASN/NF-κB Pathway.

Elevated fatty acid synthase (FASN) has been reported in both androgen-dependent and -independent prostate cancers. Conventional treatment for prostate cancer is radiotherapy (RT); however, the following radiation-induced radioresistance often causes treatment failure. Upstream proteins of FASN such as Akt and NF-κB are found increased in the radioresistant prostate cancer cells. Nevertheless, whether inhibition of FASN could improve RT outcomes and reverse radiosensitivity of prostate cancer cells is still unknown. Here, we hypothesised that orlistat, a FASN inhibitor, could improve RT outcomes in prostate cancer. Orlistat treatment significantly reduced the S phase population in both androgen-dependent and -independent prostate cancer cells. Combination of orlistat and RT significantly decreased NF-κB activity and related downstream proteins in both prostate cancer cells. Combination effect of orlistat and RT was further investigated in both LNCaP and PC3 tumour-bearing mice. Combination treatment showed the best tumour inhibition compared to that of orlistat alone or RT alone. These results suggest that prostate cancer treated by conventional RT could be improved by orlistat via inhibition of FASN.

Using Dynamic Changes of Chlorophyll Fluorescence in Arabidopsis thaliana to Evaluate Plant Immunity-Intensifying Bacillus spp. Strains.

The integral defense responses of plants triggered by the small molecules of plant pathogens are regarded as plant immunity. The pathogen-associated molecular pattern-triggered immunity (PTI) occurs on the recognition of a pathogen by receptors on plant cell surfaces as an infection begins. During the activation of PTI, the effectiveness of a plant's photosynthetic system may be altered. In this study, chlorophyll fluorescence was used to assay the dynamic changes of PTI. When we used flg22Pst as an elicitor, we found that the photosynthetic electron transport rate (ETR) of Arabidopsis thaliana Col-0 was significantly decreased at 2, 4, and 24 h on treatment with a PTI-intensifying protein, plant ferredoxin-like protein (PFLP). In addition, this reduction in the photosynthetic ETR was also carried out with a PTI-intensifying Bacillus amyloliquefaciens strain, PMB05, on the induction of flg22Pst. The disease resistance against bacterial soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) was still enhanced by PMB05. Interestingly, among the eight tested Bacillus species strains, the PTI triggered by HrpNPcc from P. carotovorum subsp. carotovorum exhibited an ETR that was significantly decreased by PMB05. Furthermore, this decrease was consistent with rapid H2O2 generation and callose deposition triggered by HrpNPcc and the disease resistance against bacterial soft rot. Taken together, such results led us to conclude that the assay based on the ETR established in this study can be used as a model for evaluating the effectiveness of plant immunity-intensifying microbes for controlling plant diseases.

Residue Levels of Organochlorine Pesticides in Breast Milk and Its Associations with Cord Blood Thyroid Hormones and the Offspring's Neurodevelopment.

Previous studies have demonstrated that organochlorine pesticide (OCP) exposure has a negative impact on the neurological function of infants. Only a few reports have investigated the thyroid and growth hormones and their relationship to neurodevelopment after human exposure to OCPs, especially in the case of infants. Our goal was to determine whether breastmilk OCP residues were associated with negative impacts and/or alterations in the neurodevelopment of infants among specific southern Taiwanese mother-breastfed infant pairs. Our subjects (n = 55 pairs) were recruited from southern Taiwan between 2007 and 2010. The thyroid and growth hormone levels in the cord blood samples collected after childbirth were determined. The breastmilk was gathered within one month after childbirth for the determination of OCP levels using a high-resolution gas chromatograph with mass spectrometry, and the neurodevelopment of 10-12-month-old infants was examined using the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III). It was observed that 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE) (mean = 10.3 ng/g lipid) was the most predominant OCP compound in the breastmilk samples. At higher concentrations (>75th percentile), specific OCPs were associated with significantly lower levels of thyroid and growth hormones than at lower concentrations (<75th percentile). Significantly higher odds ratios (ORs) were observed for binary cognitive (OR = 8.09, p = 0.025 for 4,4'-DDT), language (OR = 11.9, p = 0.013 for 4,4'-DDT) and social-emotional (OR = 6.06, p = 0.01 for trans-CHL) composite scores for specific OCPs belonging to the lower exposure group as compared to the higher OCP exposure group. The five domain Bayley-III infant neurodevelopment outcomes were negatively associated with specific OCPs in the breast milk samples based on the redundancy analysis (RDA) test. Bayley-III scales, which include cognitive, language, motor, social-emotional, and adaptive behavior scales, could be predicted by 4,4'-DDT, endrin, endosulfan I, heptachlor, or heptachlor epoxide using multivariate linear regression models with adjustment for maternal age, pre-pregnant BMI, parity, and infant gender. In conclusion, although our study showed that postnatal exposure to breast milk OCPs may be associated with infant neurodevelopmental outcomes and that prenatal exposure, if extrapolated from breastmilk levels, is associated with changes in thyroid and growth hormones that may have effects on neurodevelopment, these associations are only suggestive; thus, further studies are recommended for confirmation.

Synergistic effects of tetrandrine combined with ionizing radiation on a murine colorectal carcinoma­bearing mouse model.

Tetrandrine (TET), a traditional Chinese clinical agent, has been used for the treatment of many diseases, including cancers. The purpose of the present study was to investigate the combined effects of TET and ionizing radiation (IR) on murine CT26 colorectal adenocarcinoma cells in vitro and in vivo. A CT26 cell line transfected with dual HSV­1 thymidine kinase and firefly luciferase (luc) reporter genes was used. The half­maximal inhibitory concentration (IC50) of TET in CT26/tk­luc cells was ~10 µM. An additive effect was observed after combination of both agents based on a colony formation assay. Apoptosis and cleaved caspase­3 levels were increased significantly in cells after combination treatment, as shown by flow cytometric analysis, DNA fragmentation and western blotting. However, tumor growth inhibition and therapeutic efficacy of TET combined with IR in vivo were identified to be synergistic, as monitored by tumor growth delay time, measured with a digital caliper. A significant inhibition of tumor growth was identified in the combination group compared with the radiation only group. Furthermore, non­invasive bioluminescent imaging (BLI) and gamma scintigraphy were also used to evaluate therapeutic efficacy. Both modalities revealed that the best tumor growth control was under combination treatment among all groups. The present study demonstrated that TET is not only beneficial for chemotherapy, but also has potential as a radiosensitizer for the treatment of cancer.

PFLP-Intensified Disease Resistance Against Bacterial Soft Rot Through the MAPK Pathway in PAMP-Triggered Immunity.

Bacterial soft rot is a devastating disease affecting a variety of vegetable crops worldwide. One strategy for controlling this disease could be the ectopic expression of the plant ferredoxin-like protein (pflp) gene. PFLP was previously shown to intensify pathogen-associated molecular pattern-triggered immunity (PTI), an immune response triggered, for example, by the flagellin epitope flg22. To gain further insight into how PFLP intensifies PTI, flg22 was used as an elicitor in Arabidopsis thaliana. First, PFLP was confirmed to intensify the rapid generation of H2O2, callose deposition, and the hypersensitive response when coinfiltrated with flg22. This response correlated with increased expression of the FLG22-induced receptor kinase 1 gene, which is part of the mitogen-activated protein kinase (MAPK) pathway. Although the increased response to flg22 alone did not depend on the MAPK pathway genes MEKK1, MKK5, and MPK6, the protective effect of PFLP decreased when plants mutated in these genes were inoculated with Pectobacterium carotovorum subsp. carotovorum. Furthermore, expression of PR1 and PDF1.2 also increased upon treatment with flg22 in the presence of PFLP. Taken together, these results suggest that activation of the MAPK pathway contributes to the increased resistance to bacterial soft rot observed in plants treated with PFLP.

National surveillance of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins/furans in soil in Taiwan.

In this study, the polychlorinated dibenzo-p-dioxin/furan (PCDD/F) levels in 381 soil samples coming from different background areas (n = 238) and contaminated areas (n = 143) in Taiwan were investigated from 2011 to 2015 using high resolution gas chromatograph/high resolution mass spectrometry (HRGC/HRMS). The contaminated areas showed higher PCDD/F contamination as compared to the background areas (1230 vs 749 pg/g dry weight (dw)); 14.0 vs 6.25 pg WHO2005-TEQ/g dw). The lowest levels were recorded in the outlying islands (1.28 pg WHO2005-TEQ/g dw). PCDD/F congener distribution profiles in the background and contaminated areas as well as on the islands varied. OCDD was the dominant congener in almost all locations, including the northern background (87.7%) and central contaminated (74.2%) areas. Other dominant species included OCDF and 1,2,3,4,6,7,8-HpCDD. Levels of PCDD/F-TEQs in Taiwanese soils, including the background areas, were higher than in some developing countries and regions with global background levels due to high industrialization except for the contaminated areas. Geographic differences in dioxin-contaminated soils were also shown in this study. Higher soil dioxin-TEQs were observed in locations with high populations and population densities. Despite the limitations, the economic status of Taiwan represented by the annual averaged family income (AAFI) was positively correlated to soil dioxin-TEQs.

Comparing the Effectiveness of Combined External Beam Radiation and Hyperthermia Versus External Beam Radiation Alone in Treating Patients With Painful Bony Metastases: A Phase 3 Prospective, Randomized, Controlled Trial.

PURPOSE: To compare the response, duration of pain relief, and time to achieve complete pain relief after radiation therapy (RT) with or without hyperthermia (HT) in patients with painful bony metastases. METHODS AND MATERIALS: Cancer patients with bony metastases and pain score ≥4 on the Brief Pain Inventory (BPI) were randomized to RT of 30 Gy in 10 fractions combined with HT (RT + HT) versus RT alone. Hyperthermia was performed by the Thermotron RF-8, with maintenance of the target temperature for 40 minutes per treatment within 2 hours after RT, twice weekly for 2 weeks. Patients were stratified by lesion number (solitary or multiple), BPI score (4-6 vs 7-10), and primary site. The primary endpoint was complete response (CR) (BPI = 0 with no increase of analgesics) within 3 months after treatment. This study was registered with ClinicalTrials.gov. RESULTS: The study was terminated early after an interim analysis of 57 patients, 3 years after the first enrollment (November 2013 to November 2016): 29 patients in the RT + HT group and 28 patients in the RT-alone group. The CR rate at 3 months after treatment was 37.9% in the RT + HT group versus 7.1% in the RT-alone group (P=.006). The accumulated CR rate within 3 months after treatment was 58.6% in the RT + HT group versus 32.1% in the RT-alone group (P=.045). Median time to pain progression was 55 days in patients with CR (n=9) in the RT-alone group, whereas the endpoint was not reached during the 24-week follow-up in the RT + HT group (P<.01). CONCLUSIONS: The addition of HT to RT significantly increases the pain control rate and extends response duration compared with RT alone for painful bony metastases.

Characterization of the role of endogenous nitric oxide in myogenic vascular oscillations during cooling-evoked hemodynamic perturbations of rats.

Rapid immersion of a rat's limbs into 4 °C water, a model of cold stress, can elicit hemodynamic perturbations (CEHP). We previously reported that CEHP is highly relevant to sympathetic activation and nitric oxide production. This study identifies the role of nitric oxide in CEHP. Conscious rats were pretreated with the nitric oxide synthase inhibitor L-NAME (NG-nitro-l-arginine methyl ester) alone or following the removal of sympathetic influences using hexamethonium or guanethidine. Rats were then subjected to a 10 min cold-stress trial. Hemodynamic indices were telemetrically monitored throughout the experiment. The analyses included measurements of systolic blood pressure; heart rate; dicrotic notch; short-term cardiovascular oscillations and coherence between blood pressure variability and heart rate variability in regions of very low frequency (0.02-0.2 Hz), low frequency (0.2-0.6 Hz), and high frequency (0.6-3.0 Hz). We observed different profiles of hemodynamic reaction between hexamethonium and guanethidine superimposed on L-NAME, suggesting an essential role for a functional adrenal medulla release of epinephrine under cold stress. These results indicate that endogenous nitric oxide plays an important role in the inhibition of sympathetic activation and cardiovascular oscillations in CEHP.