Nanoshell Formation at the Electrically Charged Gas-Water Interface of Collapsing Microbubbles: Insights from Atomic Force Microscopy Imaging.

AFM imaging has revealed intriguing features when bulk nanobubbles were deposited on a positively charged substrate. Numerous spherical objects, each less than 20 nm in diameter, were observed on the substrate. These objects were adorned with noticeable, tiny protrusions, each measuring a few nanometers. These findings suggest the presence of solid shells contributing to the stability of the gas bodies. Furthermore, electrically charged microbubbles appear to play a critical role in the formation of these solid shells. The collapse of microbubbles in an electrolyte aqueous solution containing iron ions leads to a condensing ionic cloud, creating conditions necessary for solid nucleation at the interface. At the end of the collapsing process, concurrent multinucleation may result in the deposition of solid material on the interface, forming solid shells with specific structures on the surfaces. This study illuminates the phenomenon of electrically charged gas-water interfaces during microbubble collapse and highlights the generation of stabilized nanoshells in aqueous solutions without the need for chemical stabilizers.

Mineralization of Poly(vinyl alcohol) by Ozone Microbubbles under a Wide Range of pH Conditions.

Poly(vinyl alcohol) (PVA) is a well-known recalcitrant pollutant that threatens ecological systems and human health. In this study, ozone-microbubble treatment was evaluated as a physicochemical method to mineralize PVA in solution for wastewater treatment. Microbubbles are very small bubbles (<50 µm in diameter) and shrink in water because of the rapid dissolution of the interior gas. Ozone microbubbles were generated by a hybrid microbubble generator in PVA solutions with pH conditions of 2, 7, and 10. Ordinary ozone bubbling was also performed as control tests. The change in the total-organic-carbon content was measured to evaluate the efficiency of the system for wastewater treatment. Ordinary ozone bubbling was not able to mineralize aqueous PVA solutions under nonalkaline conditions, and approximately 30% of the total organic carbon remained at pH 2 and 7. Conversely, ozone microbubbles effectively mineralized PVA in aqueous solution to almost 0% in total organic carbon regardless of the pH condition. Effective mineralization of PVA, a recalcitrant organic chemical, demonstrates the potential of ozone-microbubble systems for physicochemical wastewater treatment.

Association between COVID-19 emergency declarations and physical activity among community-dwelling older adults enrolled in a physical activity measurement program: Evidence from a retrospective observational study using the regression discontinuity design.

BACKGROUND: The current study examines the negative impact of the coronavirus disease 2019 (COVID-19) emergency declarations on physical activity among the community-dwelling older adults, the participants of a physical activity measurement program, in Japan. METHODS: This retrospective observational study included 1,773 community-dwelling older adults (aged 74.6 ± 6.3 years, 53.9% women) who had participated in the physical activity measurement project from February 2020 to July 2021. We measured physical activity using a tri-axial accelerometer during 547 consecutive days. Three emergency declarations, requesting people to avoid going outside, occurred during the observational period. We multiply-imputed missing values for daily physical activity, such as steps, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) for several patterns of datasets according to the maximum missing rates on a person level. We mainly report the results based on less than 50% of the maximum missing rate (n = 1,056). Other results are reported in the supplemental file. Changes in physical activity before and after the start of each emergency declaration were examined by the regression discontinuity design (RDD) within 14-, 28-, and 56-day bandwidths. RESULTS: For all the participants in the multiply-imputed data with the 14-day bandwidth, steps (coefficients [[Formula: see text]][Formula: see text] 964.3 steps), LPA ([Formula: see text] 5.5 min), and MVPA ([Formula: see text] 4.9 min) increased after the first emergency declaration. However, the effects were attenuated as the RDD bandwidths were widened. No consistent negative impact was observed after the second and third declarations. After the second declaration, steps ([Formula: see text]-609.7 steps), LPA ([Formula: see text]-4.6 min), and MVPA ([Formula: see text]-2.8 min) decreased with the 14-day bandwidth. On the other hand, steps ([Formula: see text] 143.8 steps) and MVPA ([Formula: see text] 1.3 min) increased with the 56-day bandwidth. For the third declaration, LPA consistently decreased with all the bandwidths ([Formula: see text]-2.1, -3.0, -0.8 min for the 14, 28, 56-day bandwidth), whereas steps ([Formula: see text]-529 steps) and MVPA ([Formula: see text]-2.6 min) decreased only with the 28-day bandwidth. CONCLUSIONS: For the community-dwelling older adults who regularly self-monitor their physical activity, the current study concludes that there is no evidence of consistently negative impacts of the emergency declarations by the COVID-19 pandemic.

Oxygen nanobubble water affects wound healing of fibroblast WI-38 cells.

This study investigated the usefulness of oxygen nanobubble water (O2NBW) for wound repair by analyzing its effect on the wound-healing process in human lung fibroblasts (WI-38 cells). The WI-38 cells were treated with 0%, 50%, and 100% O2NBW. The cell viability, reactive oxygen species (ROS) production, and wound healing following treatment were determined to elucidate the effects of O2NBW. Our findings revealed that O2NBW had no cytotoxic effects on WI-38 cells, but instead increased cell numbers. The production of ROS was inhibited in the presence of O2NBW. Further, O2NBW induced migration and wound closure in WI-38 cells. In addition, the mRNA expression levels of antioxidant enzymes and wound-healing-related genes were evaluated. The results demonstrated that O2NBW enhanced the expression levels of all representative genes. In conclusion, our findings suggest that O2NBW could affect ROS production and wound healing in WI-38 cells and genes associated with the antioxidant system and wound healing.

Accelerated germination of aged recalcitrant seeds by K+-rich bulk oxygen nanobubbles.

Bulk nanobubbles, measuring less than 200 nm in water, have shown their salient properties in promoting growth in various species of plants and orthodox seeds, and as potential drug-delivery carriers in medicine. Studies of recalcitrant seeds have reported markedly increased germination rates with gibberellin treatment; however, neither the mechanism promoting germination nor the implication for food safety is well elucidated. In our study, recalcitrant wasabi (Eutrema japonicum) seeds treated with bulk oxygen nanobubbles (BONB) containing K+, Na+, and Cl- (BONB-KNaCl) showed significantly accelerated germination. As germination progressed, 99% of K+ ions in the BONB-KNaCl medium were absorbed by the seeds, whereas Ca2+ ions were released. These results suggest that the germination mechanism involves the action of K+ channels for migration of K+ ions down their concentration gradient and Ca2+ pumps for the movement of Ca2+ ions, the first potential discovery in germination promotion in recalcitrant seeds using nutrient solutions with BONB-KNaCl.

Free-Radical Generation from Bulk Nanobubbles in Aqueous Electrolyte Solutions: ESR Spin-Trap Observation of Microbubble-Treated Water.

Microbubbles are very fine bubbles that shrink and collapse underwater within several minutes, leading to the generation of free radicals. Electron spin resonance spectroscopy (ESR) confirmed the generation of hydroxyl radicals under strongly acidic conditions. The drastic environmental change caused by the collapse of the microbubbles may trigger radical generation via the dispersion of the elevated chemical potential that had accumulated around the gas-water interface. The present study also confirmed the generation of ESR signals from the microbubble-treated waters even after several months had elapsed following the dispersion of the microbubbles. Bulk nanobubbles were expected to be the source of the spin-adducts of hydroxyl radicals. Such microbubble stabilization and conversion might be caused by the formation of solid microbubble shells generated by iron ions in the condensed ionic cloud around the microbubble. Therefore, the addition of a strong acid might cause drastic changes in the environment and destroy the stabilized condition. This would restart the collapsing process, leading to hydroxyl radical generation.

SARS-CoV-2 detection by fluorescence loop-mediated isothermal amplification with and without RNA extraction.

Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-LAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.

Long-term safety and efficacy of nalmefene in Japanese patients with alcohol dependence.

AIM: The safety and efficacy of nalmefene in Japanese patients with high or very high World Health Organization drinking risk level of alcohol dependence were assessed in a multicenter, randomized, double-blind, placebo-controlled, phase 3 (lead-in) study. Here, the long-term safety and efficacy of nalmefene in an open-label extension of the lead-in study are presented. METHODS: Patients who completed the 24-week lead-in study were eligible for the extension study, where they were treated with nalmefene 20 mg as needed for 24 weeks. The long-term safety and efficacy of nalmefene 20 mg during the total 48-week period were evaluated. Treatment-emergent adverse events during the study period were recorded and change from baseline in the number of heavy drinking days and total alcohol consumption were calculated. RESULTS: Overall, long-term nalmefene 20 mg was well tolerated; the main treatment-emergent adverse events reported in ≥5% of patients included nasopharyngitis (37.2%), nausea (36.5%), somnolence (21.2%), dizziness (16.8%), malaise (14.6%), and vomiting (12.4%). The number of heavy drinking days and total alcohol consumption decreased from baseline to 48 weeks (mixed model for repeated measures, least squares mean ± standard error, -15.09 ± 0.77 days/month and -53.20 ± 2.29 g/day, respectively) during the study. CONCLUSION: This long-term evaluation in Japanese patients with high or very high drinking risk levels of alcohol dependence indicated that nalmefene was safe, well tolerated, and efficacious.

Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo-controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease.

INTRODUCTION: Symptomatic anti-Alzheimer's disease (AD) drugs have been commonly used for the treatment of AD. Knowing the natural courses of patients with AD on placebo is highly relevant for clinicians to understand their efficacy and for investigators to design clinical studies. METHODS: The data on rating scales for dementia such as Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Severe Impairment Battery were extracted from eight previous Japanese Phase II and III studies. Natural courses of Japanese AD patients in placebo groups were evaluated and statistically analyzed in a pooled and retrospective fashion. RESULTS: Decreases in ADAS-cog and Severe Impairment Battery was larger at week 22 or 24 than at week 12. Scores of ADAS-cog appeared to deteriorate faster in moderate AD than in mild AD. DISCUSSION: The present data will provide clinicians following up patients with AD with helpful information on how to manage AD patients and investigators with instruction for clinical study design.

Nalmefene in alcohol-dependent patients with a high drinking risk: Randomized controlled trial.

AIMS: Reducing alcohol consumption is one treatment approach for alcohol-dependent patients. This study compared nalmefene 20 mg and 10 mg with placebo, combined with psychosocial support, in alcohol-dependent Japanese patients with a high or very high drinking risk level (DRL). METHODS: This was a multicenter, randomized, double-blind, phase 3 study conducted in alcohol-dependent patients with a high or very high DRL. Patients were randomized to 24 weeks of treatment with as-needed nalmefene 20 mg, 10 mg, or placebo with psychosocial support. The primary endpoint was change in heavy drinking days (HDD) from baseline to week 12. A key secondary endpoint was the change in total alcohol consumption (TAC) from baseline to week 12. RESULTS: At week 12, 234, 206, and 154 patients who received placebo, nalmefene 20 mg, and 10 mg were included in the primary endpoint analysis. Compared with placebo, nalmefene was associated with significant reductions in HDD at week 12 (difference in 20 mg group, -4.34 days/month; 95% confidence interval [CI]: -6.05 to -2.62; P < 0.0001; difference in 10 mg group, -4.18 days/month; 95%CI: -6.05 to -2.32; P < 0.0001), as well as a significant reduction in TAC at week 12 (P < 0.0001). The incidence of treatment-emergent adverse events was 87.9%, 84.8%, and 79.2% in the groups receiving nalmefene 20 mg, 10 mg, and placebo, respectively. These events were mostly of mild or moderate severity. CONCLUSIONS: Nalmefene 20 mg or 10 mg effectively reduced alcohol consumption and was well tolerated in alcohol-dependent patients with a high or very high DRL.

Application of DNA markers for discrimination between Japanese and Australian Wagyu beef.

The objective of this study was to discriminate between original Japanese and Australian Wagyu beef, which is sold in the Singapore markets, using six previously developed DNA markers. To effectively evaluate the six markers for breed identification, the probability of identification as Australian Wagyu beef was calculated based on the estimated allele frequencies using 130 Australian Wagyu individuals. The combined use of six markers would allow the discrimination of Australian Wagyu beef with an estimated probability of 0.776. The probability to discriminate Australian Wagyu from Japanese Wagyu beef was sufficiently high. In addition, Australian Wagyu has maternal mitochondrial DNA of Bos indicus cattle with moderate high frequency of 0.377. The DNA marker system could also be used as a deterrent force against false sales, and contribute to the reduction and prevention of incorrect or falsified labeling of beef.

Efficacy and safety of paliperidone palmitate three-monthly formulation in East Asian patients with schizophrenia: subgroup analysis of a global, randomized, double-blind, Phase III, noninferiority study.

OBJECTIVE: To demonstrate the efficacy and safety of paliperidone palmitate three-monthly (PP3M) formulation in an East Asian population with schizophrenia by subgroup analysis of a double-blind (DB), multicenter, noninferiority study. PATIENTS AND METHODS: Of 1,429 patients who entered the open-label (OL) phase, 510 were East Asian (China: 296 [58%], Japan: 175 [34%], South Korea: 19 [4%] and Taiwan: 20 [4%]). In the 17-week OL phase, patients received paliperidone palmitate once-monthly (PP1M) formulation on day 1 (150 mg eq.), day 8 (100 mg eq.) and once-monthly thereafter (50-150 mg eq., flexible). Following the OL phase, patients (n=344 East Asian) entered DB phase and were randomized (1:1) to PP1M (n=174) or PP3M (n=170). Primary efficacy endpoint was the percentage of patients who remained relapse free at the end of the 48-week DB phase, using Kaplan-Meier cumulative survival estimate. Secondary efficacy endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale, Clinical Global Impression Severity, Personal and Social Performance scores and symptomatic remission. Additional assessments included caregiver burden and safety. RESULTS: A total of 285/344 (83%) randomized East Asian patients completed the DB phase. The percentage of patients who had a relapse event was similar on comparing PP3M (17 [10.2%]) to PP1M (20 [11.8%]), and also for Japan (PP3M: 9 [17.6%], PP1M: 13 [23.2%]) and China (PP3M: 6 [5.9%], PP1M: 7 [6.9%]). Mean change from baseline in secondary efficacy parameters was similar to the global population, regardless of treatment. Symptomatic remission was attained by 50% of the treated patients. Caregiver burden was significantly reduced (P<0.001) following treatment with PP3M/PP1M. Frequency of treatment-emergent adverse events in PP3M group during DB phase was greater in the East Asian subgroup (81%) than the global population (68%) and was higher in Japan (92%) than China (75%). CONCLUSION: Results suggest that PP3M is efficacious in the East Asian subgroup. Although treatment-emergent adverse events were slightly higher in the East Asian subgroup versus the global population, no new safety signals were identified.

Defining the relative performance of isothermal assays that can be used for rapid and sensitive detection of foot-and-mouth disease virus.

This study describes the first multiway comparison of portable isothermal assays for the detection of foot-and-mouth disease virus (FMDV), benchmarked against real-time reverse transcription RT-PCR (rRT-PCR). The selected isothermal chemistries included reverse transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription recombinase polymerase amplification (RT-RPA). The analytical sensitivity of RT-LAMP was comparable to rRT-PCR (101 RNA copies), while RT-RPA was one log10 less sensitive (102 RNA copies). Diagnostic performance was evaluated using a panel of 35 samples from FMDV-positive cattle and eight samples from cattle infected with other vesicular viruses. Assay concordance for RT-LAMP and RT-RPA was 86-98% and 67-77%, respectively, when compared to rRT-PCR, with discordant samples consistently having high rRT-PCR cycle threshold values (no false-positives were detected for any assay). In addition, a hierarchy of sample preparation methods, from robotic extraction to simple dilution of samples, for epithelial suspensions, serum and oesophageal-pharyngeal (OP) fluid were evaluated. Results obtained for RT-LAMP confirmed that FMDV RNA can be detected in the absence of RNA extraction. However, simple sample preparation methods were less encouraging for RT-RPA, with accurate results only obtained when using RNA extraction. Although the evaluation of assay performance is specific to the conditions tested in this study, the compatibility of RT-LAMP chemistry with multiple sample types, both in the presence and absence of nucleic acid extraction, provides advantages over alternative isothermal chemistries and alternative pen-side diagnostics such as antigen-detection lateral-flow devices. These characteristics of RT-LAMP enable the assay to be performed over a large diagnostic detection window, providing a realistic means to rapidly confirm positive FMD cases close to the point of sampling.

Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study.

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation.

Paliperidone palmitate: Japanese postmarketing mortality results in patients with schizophrenia.

OBJECTIVE: Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population. RESEARCH DESIGN AND METHODS: All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed. RESULTS: During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person-years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy. CONCLUSIONS: Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes.

Daytime symptoms of restless legs syndrome--clinical characteristics and rotigotine effectiveness.

OBJECTIVE: To elucidate the prevalence and clinical characteristics of daytime restless legs syndrome (RLS) among patients with idiopathic RLS and investigate the effectiveness of rotigotine for daytime RLS. METHODS: In 256 enrolled RLS patients, we investigated factors associated with the presence of RLS symptoms throughout the day. We also assessed the duration of daytime RLS symptoms at hourly intervals, time of initial symptom onset during the day, and associations between duration of daytime and nighttime RLS symptoms. In addition, we compared changes in duration and frequency of RLS symptoms during daytime and nighttime after randomly assigning patients to a 13-week treatment with rotigotine, a dopamine agonist patch with 24-hour action, or placebo. RESULTS: Eighty-one (31.6%) patients had daytime RLS symptoms. Only the International Restless Legs Syndrome Study Group rating scale total score was significantly associated with the presence of daytime RLS symptoms (p < 0.01) on multiple logistic regression analysis. Daytime RLS symptom onset was at 6 a.m. in 44.4% of patients; symptom duration increased significantly toward nighttime. There was a significant positive association between duration of daytime and nighttime RLS symptoms (p < 0.0001) and a greater statistically significant reduction of daytime RLS symptom duration with rotigotine treatment than with placebo (p = 0.03). CONCLUSIONS: Daytime symptoms are frequent in patients with RLS and may be associated with increased severity of the disorder and prolonged nighttime RLS symptoms. Rotigotine could become an important treatment choice for daytime symptoms.

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

OBJECTIVE: To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. METHODS: This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. RESULTS: The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. CONCLUSIONS: Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.

Prevalence of helicobacter in laboratory mice in Thailand.

Prevalence of Helicobacter is mostly unknown in laboratory animals in Thailand. The 221 mice feces/cecum from 8 universities, 2 pharmaceutical companies and 3 research institutions in Thailand were surveyed for the prevalence and distribution of Helicobacter species by using the Electrochemical DNA chip. Helicobacter were detected 23/46 samples in Specific Pathogen Free (SPF) and 168/175 in conventional condition. Prevalence of Helicobacter were 98%, 96%, 92% and 78% in South (n=40), Northeast (n=40), North (n=25) and Central area (n=116), respectively. Only Central area holds SPF facility resulting in Helicobacter prevalence that seems to be lower than other areas. Three species of Helicobacter were detected in feces/cecum samples by sequence analysis: H. rodentium (67.0%, 148 samples), Helicobacter sp. MIT 01-6451 (15.4%, 34 samples), and unidentified Helicobacter species (14.1%, 9 samples). The results suggested that H. rodentium is the most common species of Helicobacter in laboratory mice in Thailand.

The prediction of response to galantamine treatment in patients with mild to moderate Alzheimer's disease.

The prediction of efficacy in long-term treatment of acetylcholinesterase inhibitors (AChEIs) is a major clinical issue, although no consistently strong predictive factors have emerged thus far. The present analyses aimed to identify factors for predicting long-term outcome of galantamine treatment. Analyses were conducted with data from a 24 weeks randomized, double-blind, placebo controlled trial to evaluate the efficacy and the safety of galantamine in the treatment of 303 patients with mild to moderate AD. Patients were divided into responders (4 or more point improvement of ADAScog scores at 24 weeks of treatment) and non-responders. We explored whether patients' background (e.g. sex, age, and duration of disease) and scores of cognitive scales at early stage, are relevant to the long-term response to AChEIs. Predictive values were estimated by the logistic regression model. The responder rate was 31.7%. We found that changes in scores of ADAS-J cog subscales between week 4 and baseline, especially word recognition, can be a good variable to predict subsequent response to galantamine, with approximately 75% of predictive performance. Characteristics of patients, including demographic characteristics, severity of disease and neuropsychological features before treatment were poorly predictive. The present study indicate that initial response to galantamine administration in patients with mild to moderate AD seems to be a reliable predictor of response of consequent galantamine treatment. Patients who show improvement of episodic memory function during the first 4 weeks of galantamine administration may be likely to particularly benefit from galantamine treatment.

Photodynamic therapy for multiple central type lung cancer - a case report.

In case of central type lung cancer, it happens that tumors tend to grow at many foci of bronchial tree, sometimes simultaneously and sometimes not. And these patients with such abnormalities often suffer from pulmonary emphysema or chronic bronchitis because of heavy smoking habits. So it is important to choose the treatment which preserve the pulmonary function in these cases. Today among several kinds of treatments, photodynamic therapy (PDT) is the definite method to maintain lung function. We report here a case of multiple central type lung cancer treated successfully by PDT.