Crystallographic interface control of the plasmonic photocatalyst consisting of gold nanoparticles and titanium(iv) oxide.

A big question in the field of plasmonic photocatalysis is why a typical photocatalyst consisting of gold nanoparticles and rutile titanium(iv) oxide (Au/R-TiO2) usually exhibits activity much higher than that of Au/anatase TiO2 (Au/A-TiO2) under visible-light irradiation. Shedding light on the origin should present important guidelines for the material design of plasmonic photocatalysts. Au nanoparticles (NPs) were loaded on ordinary irregular-shaped TiO2 particles by the conventional deposition precipitation method. Transmission electron microscopy analyses for the Au/TiO2 particles ascertain that faceting of Au NPs is induced on R-TiO2 by using a domain-matching epitaxial junction with the orientation of (111)Au//(110)R-TiO2 , whereas non-faceted hemispherical Au NPs are exclusively formed on A-TiO2. The faceting probability of Au NPs (P f) on R-TiO2 increases with decreasing Au particle size (d Au) to reach 14% at d Au = 3.6 nm. A clear positive correlation between the photocatalytic activity and P f in several test reactions indicates that the heteroepitaxial junction-induced faceting of Au NPs is the principal factor for governing the plasmonic photocatalytic activity of Au/TiO2. In light of this finding, R-TiO2 nanorods with a high percentage (95%) of {110} facets were hydrothermally synthesized and used for the support of Au NPs. Consequently, the P f value increases to as much as 94% to enhance the photocatalytic activity with respect to that of Au/R-TiO2 with P f = 14% by factors of 2.2-4.4 depending on the type of reaction.

Kampo Medicine for Essential Voice Tremor.

Voice tremor is a common symptom in the elderly, as well as in patients who have had Parkinson's disease and related disorders, and other neurologic conditions. In this study, we analyzed 26 patients whose essential tremor symptoms involved phonation alone and were treated in our clinic alone as essential voice tremor. Kampo medicine yokukansan was found to be effective in the treatment of essential voice tremor compared with clonazepam. We suggest that yokukansan may be one of the best choices for first-line treatment of essential voice tremor.

Attitude and perceptions toward miscarriage: a survey of a general population in Japan.

Miscarriage is the greatest complication of pregnancy, and 70-80% of early miscarriages are mostly due to chromosomal abnormalities in the embryo. There is no evidence that stress is a direct cause of miscarriage. Despite these findings, in a national US survey on the causes of miscarriage, many Americans mistakenly attributed miscarriage to the mental state or behavior of the women. We conducted a survey to assess public attitudes and perceptions regarding the cause and prevalence of miscarriage in Japan. We sent out a questionnaire consisting of 17 questions. The 5000 recipients consisted of men and women (1:1 ratio) aged 18-69 who resided in Aichi Prefecture. A total of 1257 recipients (25%) responded to the questionnaire and 1219 valid respondents (24%) were included in the analyses. Of these, 62% considered a genetic abnormality of the fetus as the cause of miscarriage. Participants who were female, highly educated, married and healthy gave significantly more correct responses. On the other hand, the majority wrongly assumed that a stressful event (65%) and long-standing stress (75%) to be causes of miscarriage. Participants who had no history of miscarriage as well as males answered significantly more incorrectly. Sixty-five percent of respondents thought that miscarriage occurred less than 15% of all pregnancies. Among respondents who had experienced miscarriage personally, 53 and 36% felt guilty and lonely, respectively. Many respondents blamed the woman for the miscarriage either in terms of her behavior or mental stress and considered the frequency of miscarriage to be lower than it actually is.

Slow, slurred speech as an initial complaint in amyotrophic lateral sclerosis.

OBJECTIVE: Otorhinolaryngologic examinations at an early stage, particularly those conducted by vocal specialists, can make potentially important contributions to the diagnosis of bulbar-onset ALS patients. METHODS: We analyzed 2623 patients (2010-2017) visited the ENT Voice Clinic, National Hospital Organization Tokyo Medical Center, with the primary complaint of speech or vocal dysfunction at the initial visit. Among those, 12 patients visited the voice clinic after consultations with other physicians but before receiving a diagnosis and we initially suspected bulbar-onset ALS due to slow, slurred speech (SSS). We analyzed the detail of those suspected ALS cases. RESULTS: Every patient suspected ALS patients consulted an average of 2.2 physicians before visiting the voice clinic and a total of 3.2 physicians before receiving the final diagnosis. The mean speech symptom duration before visiting the vocal clinic was 7.83 months in ALS, 24 months in MSA patients. The duration until final diagnosis after we referred them to neurologists was 2.16 months and 15.3 months, respectively. CONCLUSION: Otolaryngologists and primary care physicians to consider the possibility of ALS when patients present even with an only symptom of SSS. They should then refer such patients to neurologists for definitive diagnoses, leading to early detection and treatment of ALS.

Development of Oropharyngeal Scope Type II with Integrated Tongue Depressor for Examination of the Oropharynx: NTOP2016 Study.

The oropharynx is examined by focusing an electric light, penlight, or forehead mirror on a desired visual field using a tongue depressor. However, it is extremely difficult to obtain objective recorded evidence for display with these methods, and the tools for examination have remained virtually unchanged for the past century. Treatment of the pharynx/oral cavity is exceedingly difficult, particularly in elderly patients and children. Therefore, there is an increasing need to develop a method for displaying the visual field during oropharyngeal examinations which is acceptable to patients, which can easily be applied at all medical institutions, which can be displayed to third parties, and which can be used by doctors for recording data and determining treatment. We earlier developed a dedicated device for this purpose (Improved Type I) and have now made further improvements. This study aims to evaluate the utility of the improved type II oropharyngeal endoscope as a tool for objective examination.

Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation.

Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small molecule-mediated, selective degradation of dysregulated proteins. We have devised a protein-knockdown system that utilizes chimeric molecules termed specific and nongenetic IAP-dependent protein erasers (SNIPERs) to induce ubiquitylation and proteasomal degradation of various target proteins. SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen by a PEG linker, and we have previously reported that this SNIPER efficiently degrades the ERα protein. Here, we report that derivatization of the IAP ligand module yields SNIPER(ER)s with superior protein-knockdown activity. These improved SNIPER(ER)s exhibited higher binding affinities to IAPs and induced more potent degradation of ERα than does SNIPER(ER)-87. Further, they induced simultaneous degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and delayed degradation of X-linked IAP (XIAP). Notably, these reengineered SNIPER(ER)s efficiently induced apoptosis in MCF-7 human breast cancer cells that require IAPs for continued cellular survival. We found that one of these molecules, SNIPER(ER)-110, inhibits the growth of MCF-7 tumor xenografts in mice more potently than the previously characterized SNIPER(ER)-87. Mechanistic analysis revealed that our novel SNIPER(ER)s preferentially recruit XIAP, rather than cIAP1, to degrade ERα. Our results suggest that derivatized IAP ligands could facilitate further development of SNIPERs with potent protein-knockdown and cytocidal activities against cancer cells requiring IAPs for survival.

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands.

Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named specific and nongenetic inhibitor of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show novel SNIPERs capable of inducing proteasomal degradation of the androgen receptor (AR). Through derivatization of the SNIPER(AR) molecule at the AR ligand and IAP ligand and linker, we developed 42a (SNIPER(AR)-51), which shows effective protein knockdown activity against AR. Consistent with the degradation of the AR protein, 42a inhibits AR-mediated gene expression and proliferation of androgen-dependent prostate cancer cells. In addition, 42a efficiently induces caspase activation and apoptosis in prostate cancer cells, which was not observed in the cells treated with AR antagonists. These results suggest that SNIPER(AR)s could be leads for an anticancer drug against prostate cancers that exhibit AR-dependent proliferation.

Detectable voice change with the edrophonium test in laryngeal myasthenia gravis.

A case of laryngeal myasthenia gravis in a 65-year-old woman presenting with hoarseness as the sole symptom is reported. Voice spectrography was performed before and after injection of intravenous edrophonium. There was a marked improvement in the patient's voice after the administration of edrophonium, which was confirmed by the changes seen on the sound spectrogram. This was the only objective indication of a diagnosis of myasthenia gravis. No thymoma was seen on chest X-ray and the patient was negative for anti-acetylcholine receptor antibodies. Treatment for laryngeal myasthenia gravis was initiated and the patient's vocal problems resolved. This case emphasizes the need to consider systemic diseases in the differential diagnosis of hoarseness and demonstrates the need for careful follow-up in such patients.

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.

Preferential Enrichment of DL-Leucine Using Cocrystal Formation With Oxalic Acid Under Nonequilibrium Crystallization Conditions.

By utilizing the preferential enrichment (PE) technique, we achieved an improved enantiomeric resolution of DL-leucine (Leu) using a 1:1 cocrystal (DL-) of DL-Leu and oxalic acid. The crystal structure analysis of DL- indicated the occurrence of a novel type of phase transition and subsequent preferential redissolution of one enantiomer from the resulting crystals into solution.

[Inferior vena cava thrombosis reaching the right atrium after removal of the central venous catheter at femoral vein in a patient with diabetic ketoacidosis].

A 19-year-old male was admitted with diabetic ketoacidosis. A central venous catheter for fluid loading and insulin administration was inserted from the right femoral vein. The catheter was placed for 4days and was removal. Three days after removal thrombus was pointed out with echocardiography. Cardiac ultrasound revealed floating thrombi in the right atrium. Venography demonstrated a large thrombus from the right femoral vein to the end of the inferior vena cava. Emergency surgery was performed. A tubular thrombus was trapped from the inferior vena cava departure at the right atrium under cardiopulmonary bypass. The surgeon also implanted an inferior vena caval filter. The patient was weaned from ventilator assist next day and was discharged from the hospital 13 days later. This case suggests that deep vein thrombosis should be checked in diabetic ketoacidosis even after removal of a central venous catheter implanted at the femoral vein.

Human endonuclease V is a ribonuclease specific for inosine-containing RNA.

Deamination of DNA bases can create missense mutations predisposing humans to cancer and also interfere with other basic molecular genetic processes; this deamination generates deoxyinosine from deoxyadenosine. In Escherichia coli, the highly conserved endonuclease V is involved in alternative excision repair that removes deoxyinosine from DNA. However, its exact activities and roles in humans are unknown. Here we characterize the FLJ35220 protein, the human homologue of E. coli endonuclease V, hEndoV as a ribonuclease specific for inosine-containing RNA. hEndoV preferentially binds to RNA and efficiently hydrolyses the second phosphodiester bond located 3' to the inosine in unpaired inosine-containing ssRNA regions in dsRNA. It localizes to the cytoplasm in cells. The ribonuclease activity is promoted by Tudor staphylococcal nuclease and detected on inosine-containing dsRNA created by the action of adenosine deaminases acting on RNA. These results demonstrate that hEndoV controls the fate of inosine-containing RNA in humans.

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: a Japanese multicenter study.

OBJECTIVE: This multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD). METHODS: To identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis. RESULTS: The patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation. CONCLUSION: Forty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.

REM sleep behavior disorder in Japanese patients with Parkinson's disease: a multicenter study using the REM sleep behavior disorder screening questionnaire.

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson's disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson's Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p < 0.01). As to the major autonomic dysfunctions, severe constipation was significantly more frequent in PD patients with RBD than in those without it (p < 0.01). The RBD symptoms of 53 patients (39.0%) preceded the onset of PD motor symptoms. The median interval from the onset of RBD symptoms to PD motor symptoms was 17.5 years, and 3 patients had intervals of over 50 years. This large-scale multicenter study revealed that RBD is a frequent non-motor symptom in Japanese patients with PD, which may precede the onset of motor symptoms. Moreover, RBD that increases with the duration and severity of PD may be associated with autonomic dysfunction.

A method for detecting genetic toxicity using the RNA synthesis response to DNA damage.

To date, biological risk assessment studies of chemicals that induce DNA lesions have been primarily based on the action of DNA polymerases during replication. However, DNA lesions interfere not only with replication but also with transcription. Therefore, detecting the damaging effects of DNA lesions during transcription might be important for estimating the safety of chemical mutagens and carcinogens. However, methods to address these effects have not been developed. Here, we report a simple, non-isotopic method for determining the toxicity of chemical agents by visualizing transcription in a mammalian cell system. The method is based on the measurement of the incorporation of bromouridine (as the uridine analogue) into the nascent RNA during RNA synthesis inhibition (RSI) induced by the stalling of RNA polymerases at DNA lesions on the transcribed DNA strand, which triggers transcription-coupled nucleotide excision repair (TC-NER). When we tested chemical agents (camptothecin, etoposide, 4-nitroquinoline-1-oxide, mitomycin C, methyl methanesulfonate, and cisplatin) in HeLa cells by the method, RSI indicative of genomic toxicity was observed in the nucleoli of the tested cells. This procedure provides the following advantages: 1) it uses common, affordable mammalian cells (HeLa cells, WI38VA13 cells, human dermal fibroblasts, or Chinese hamster ovary cells) rather than genetically modified microorganisms; 2) it can be completed within approximately 8 hr after the cells are prepared because RNA polymerase responses during TC-NER are faster than other DNA damage responses (replication, recombination, and apoptosis); and 3) it is safe because it uses non-radioactive bromouridine and antibodies to detect RNA synthesis on undamaged transcribed DNA strands.

Camptocormia in Japanese patients with Parkinson's disease: a multicenter study.

OBJECTIVE: The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients. BACKGROUND: Although camptocormia has been recognized as a prominent phenomenon in PD, the previous epidemiological reports were limited, especially in terms of sample size. METHODS: We evaluated 531 PD patients (disease duration: 7.0 ± 5.5 years, mean ± standard deviation). We examined their clinical features and the prevalence of camptocormia. RESULTS: Camptocormia was detected in 22 patients (4.1%) and found in patients who were older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P < 0.05), compared to the patients without camptocormia. Patients with camptocormia showed significantly higher frequencies of autonomic symptoms, such as constipation and urinary incontinence (P < 0.05). CONCLUSIONS: Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms.

Multiple folding structures mediated by metal coordination of acyclic multidentate ligand.

Four kinds of folded structures are formed upon the metal complexation of a bis(N(2)O(2)) ligand in which two oxime-type N(2)O(2) chelate ligands are connected by a flexible diethyleneoxy linker. The N(2)O(2) coordination sites are intended for d-block transition-metal ions, and the diethyleneoxy linker can interact with hard metal cations. Meso double helical, folded Omega-shaped, S-shaped helical, and single helical structures were formed depending on the metal combination. The difference in the affinity to metal cations resulted in variation of the folding modes and enabled the structural conversion between the folded structures.