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Parkinson's disease (PD) is characterized by major alterations of neurotransmitter activity due to damage of the substantia nigra. Changes in neuropeptide concentration within the basal ganglia may play an important role in the putative dopaminergic–peptidergic interactions associated with the disease. Cholecystokinin (CCK) modulates the release of dopamine in the mesolimbic pathway and affects dopamine-related behavior.We analyzed genetic variations in the CCK gene, in both the coding and promoter region, in order to investigate the role of polymorphism in idiopathic PD. Four polymorphic sites of the CCK gene (-196G/A, -45C/T, 1270C/G, 6662C/T) were found in PD patients and controls. Complete linkage disequilibrium was observed between the -45 locus and the 1270 locus, and also a possible linkage disequilibrium was found between the -45 and -196 loci. A significant difference was found in the distributions of three identified genotypes at the -45 locus between 116 PD patients and 95 age-matched control subjects (χ2=7.95, p=0.018, Bonferroni correction; p=0.054). In addition, a significant difference was obtained amongst the three genotypic groups at the -45 locus when compared between PD patients who experienced hallucinations (n=23) and those (n=93) who did not (χ2=8.08, p=0.018, Bonferroni correction; p=0.126).Our data suggested that mutations at the -45 locus in the promoter region of the CCK gene may influence vulnerability to hallucinations in PD patients treated with l-dopa. [ABSTRACT FROM AUTHOR]

Topical metronidazole is not currently approved in Japan as a treatment for the indication of rosacea, although 0.75% metronidazole gel was authorized in 2014 for the management of cancerous skin ulcers. We conducted a randomized, double-blind, vehicle-controlled study to evaluate the efficacy and safety of 0.75% metronidazole gel in Japanese patients with inflammatory lesions (papules/pustules) and erythema associated with moderate to severe rosacea. Overall, 130 patients were randomly assigned to receive 0.75% metronidazole gel (n = 65) or vehicle (n = 65), and 120 patients completed 12 weeks of treatment. The primary efficacy outcome was the proportion of patients who achieved both of the following at week 12: an improvement of >50% in the number of inflammatory lesions (papules/pustules) and a positive change of at least one degree in erythema severity. This composite outcome was achieved by 72.3% of metronidazole-treated patients versus 36.9% of vehicle-treated patients, with the between-group difference demonstrating significant improvement with 0.75% metronidazole gel (p < 0.0001). All secondary efficacy endpoints (patients achieving a score of ≥3 for percent change in the number of inflammatory lesions at week 12; patients achieving a score of ≥3 for change in erythema severity at week 12; patients achieving an Investigator's Global Assessment score of 0 or 1 at week 12; percent change over time in the number of inflammatory lesions; change over time in erythema severity) also showed improvement in the 0.75% metronidazole gel group. The incidence of adverse events was higher with metronidazole (40.0%) than with vehicle (29.2%). Of these, treatment-related, treatment-emergent adverse events occurred in 9.2% and 6.2% in the metronidazole and the vehicle group, respectively, but there were no new safety concerns. Overall, the results of this study have confirmed the efficacy and safety of 0.75% metronidazole gel in Japanese patients with rosacea., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Glycopyrronium tosylate cloth, an anticholinergic drug, has been approved for the topical treatment of primary axillary hyperhidrosis in the USA, but its effects in Japanese patients have not been previously investigated. This 4-week, randomized, double-blind, vehicle-controlled, multicenter study was conducted to evaluate the efficacy and safety of glycopyrronium tosylate cloth for primary axillary hyperhidrosis patients in Japan. Eligible patients, who were ≥9 years of age and had primary axillary hyperhidrosis ≥6 months, with gravimetrically-measured sweat production ≥50 mg/5 min, and Hyperhidrosis Disease Severity Scale ≥3 (moderate) were randomized 1:1:1 to once daily topical glycopyrronium tosylate 3.75%, 2.5%, or vehicle. Overall, 497 patients (163 in the glycopyrronium tosylate 3.75% group, 168 in the glycopyrronium tosylate 2.5% group, and 166 in the vehicle group, hereinafter in this order) were randomized. Statistically higher proportions of patients in the glycopyrronium tosylate groups achieved ≥2-point improvement in Hyperhidrosis Disease Severity Scale and ≥50% reduction in sweat production from baseline versus vehicle at week 4 (51.6%, 41.1%, and 16.4%, respectively; p < 0.001 in both cases). Higher responder rates in the glycopyrronium tosylate groups compared with the vehicle group occurred as early as week 1. The most common treatment-emergent adverse events in patients treated with glycopyrronium tosylate were photophobia, mydriasis, thirst, and dysuria. Most treatment-emergent adverse events were mild as determined by the investigators. The incidence of treatment-emergent adverse events leading to treatment modification was low in the three groups. The 4-week use of topical glycopyrronium tosylate improved the patient-reported outcome measure Hyperhidrosis Disease Severity Scale and objectively-evaluated sweat production with a favorable benefit/risk profile., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Objectives: The purpose of the present study was to investigate the influence of dental education on eye gaze distribution when perceiving facial profile images with varying degrees of lip protrusion., Methods: Fifty-one subjects with dental education (dental-education group) and 47 without dental education (no-dental-education group) were included in this study. The eye gaze distribution of the subjects was recorded for 10 seconds using a non-contact eye tracker when determining whether or not the subjects judged each various facial profile image inappropriate. The facial profile images had varying degrees of upper-lip and lower-lip protrusion. The frequency of eye fixation (lasting >0.06 seconds) was counted. The duration was measured as the total time of eye fixation. The facial images were divided into 4 regions of interest (ROIs): the forehead (ROI-I); the orbit and nose root (ROI-II); the nose tip and upper lip (ROI-III); and the lower lip and chin (ROI-IV). The frequency and duration of eye fixation on each ROI was compared., Results: The frequency of eye fixation on ROI-II was greater in comparison to ROI-I and ROI-IV. The frequency of eye fixation on ROI-III was also greater in comparison to ROI-I and ROI-IV. The duration of eye fixation on ROI-III in the dental-education group was longer in comparison to the no-dental-education group., Conclusions: Dental education influenced the eye fixation on the nose tip and upper lip when perceiving facial profile images., (© 2020 American Dental Education Association.)

Background: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported., Methods: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing., Results: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2*2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2*1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A chi2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (chi2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed., Conclusion: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.