High Cardio-Ankle Vascular Index Values in Idiopathic Sudden Sensorineural Hearing Loss Patients Indicate Better Prognosis.

OBJECTIVE: Vascular disorders and viral infections are the presumed etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) and acute sensorineural hearing loss, with no identifiable cause. However, no clinical test for estimating the extent of vascular involvement in ISSNHL has been reported despite its potential impact on prognosis and treatment. We investigated the correlation between the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, and hearing improvement to ascertain its usefulness as an additional indicator of ISSNHL prognosis and etiology. METHODS: We enrolled 182 patients diagnosed with definite ISSNHL. The percentage of mild ISSNHL patients and that of patients experiencing no change were compared between the high-CAVI and low-CAVI groups. Age, initial and final pure-tone average (PTA) values, CAVI, presence or absence of vertigo, and medical histories were retrospectively reviewed and included in univariate and multivariate analyses. RESULTS: The percentage of mild ISSNHL patients was smaller in the high-CAVI group than in the low-CAVI group, whereas the percentage of patients experiencing no change was smaller in the high-CAVI group than in the low-CAVI group, although patients in the high-CAVI group were significantly older than those in the low-CAVI group. The Cox proportional hazard model revealed that high CAVI, hypertension, younger age, and initial PTA <90 dB were associated with hearing improvement. CONCLUSIONS: ISSNHL in patients with high CAVI was more severe but had a better prognosis than that in those with low CAVI. CAVI may help evaluate diseases of vascular and other etiologies, as well as ISSNHL.

An adolescent boy with kleptomania and attention-deficit hyperactivity disorder treated with methylphenidate and guanfacine: A case report.

We present the case of a patient, a boy of 16 years of age at initial presentation, with kleptomania, an impulse disorder characterized by an impulse to steal unneeded items, and attention-deficit hyperactivity disorder (ADHD). The patient's parents reported that he would frequently impulsively steal items and money that he did not need. Cognitive and physical assessments revealed no abnormalities, and the patient had no history of substance abuse. The patient was diagnosed with kleptomania and ADHD. The patient was started on Osmotic Release Oral System Methylphenidate (OROS-MPH), a medication commonly used to treat ADHD, and experienced improvement in ADHD symptoms and stealing behavior. At 19 years of age, it was discovered that the patient's behavioral symptoms were uncontrolled during times of the day when the blood concentration of MPH was likely to have waned. After starting an additional dose of guanfacine at night, his symptoms during these times of day improved. While existing research is not definitive, there may be a connection between ADHD and kleptomania. Further, there are some reports that treatment of ADHD with MPH also reduced stealing behavior, aligning with our present findings. We discuss the potential mechanisms behind these improvements and further present the first evidence of the efficacy of guanfacine in the treatment of kleptomania.

A case of schizophrenia with congenital color vision deficiency: From the perspective of color universal design to promote medication adherence.

Color-blindness, or more accurately, color vision deficiency (CVD), which is the inability or decreased ability to distinguish different colors, is one of the commonest visual disorders. Patients with schizophrenia usually have multiple types of visual processing impairments, including color vision impairments. Here, we present a case of schizophrenia with congenital CVD. The patient was aware of his color deficiency since elementary school. We assessed his ability to distinguish medicines based on their color, including those that he had been previously prescribed. Although he could distinguish all of the tablets, he could not distinguish the color of the blister packs, specifically that of the bromazepam 2 mg pack (green) from the 1 mg pack (red). This case suggests that CVD patients might misunderstand the color of medications, which might lead to medication errors, or poor drug adherence. The color universal design principle should be considered when designing tablets and their blister packs, in order to improve medication adherence.

Association between fat mass by bioelectrical impedance analysis and bone mass by quantitative ultrasound in relation to grip strength and serum 25-hydroxyvitamin D in postmenopausal Japanese women: the Unzen study.

BACKGROUND: Whether fat mass or lean mass affects bone mass in postmenopausal women is controversial. This study aimed to explore the association between body composition measured by bioelectrical impedance analysis (BIA) and bone mass measured by quantitative ultrasound (QUS) in postmenopausal women in Japan. METHODS: We conducted a cross-sectional study, The Unzen Study, on 382 community-dwelling postmenopausal Japanese women (mean (standard deviation) age: 68.2 (7.2) years) who participated in periodic health examinations. The stiffness index (SI) was measured using QUS, and body composition (e.g., fat mass and muscle mass) was measured using BIA. Grip strength was measured. Fasting blood samples were collected, and 25-hydroxyvitamin D (25(OH)D), tartrate-resistant acid phosphatase-5b (TRACP-5b), and parathyroid hormone (PTH) levels were measured. Data on current smoking, alcohol consumption, exercise, and any comorbidities (heart disease, lung disease, stroke, or diabetes mellitus) were collected. RESULTS: The SI increased with increasing quartiles of fat mass and muscle mass (both p for trend <  0.001), respectively. There were positive correlations between SI and log (25(OH)D) or grip strength. Fat mass significantly correlated with grip strength. Multiple linear regression analysis showed that higher fat mass was independently and significantly associated with higher SI after adjusting for age, height, comorbidity, current smoking, alcohol consumption, exercise, log (25(OH)D), log (TRACP-5b), log (PTH), and grip strength (p = 0.001). In contrast, no association was observed between muscle mass and SI. CONCLUSIONS: Fat mass, but not muscle mass, was a significant determinant of SI in community-dwelling postmenopausal Japanese women.

Association between serum 25-hydroxyvitamin D and physical performance measures in middle-aged and old Japanese men and women: The Unzen study.

PURPOSE: Regarding epidemiological studies, the role of vitamin D in musculoskeletal functionality (muscle weakness and physical performance) among elderly people is still controversial. The purpose of the present study was to investigate the associations between 25-hydroxyvitamin D [25(OH)D] and physical performance among community-dwelling middle-aged and old Japanese men and women. METHODS: The subjects were community-dwelling 297 men and 415 women aged 50 years and over. Data on height (m) and weight (kg) were collected. Serum 25(OH)D, parathyroid hormone, calcium, and albumin levels were measured. Serum 25(OH)D was classified into deficiency group: < 20 ng/mL, insufficiency group: 20-30 ng/mL, and sufficiency group: ≧ 30 ng/mL. Physical performance was assessed by grip strength, chair stand time, and functional reach. Information on current smoking, alcohol drinking, regular exercise, any comorbidities (hypertension, heart disease, diabetes mellitus, lung disease, and stroke), and pain (lumbar and knee) was collected. RESULTS: Vitamin D deficiency and insufficiency based on serum 25(OH)D levels were observed in 15.2% and 56.9% of men and 52.0% and 43.6% of women, respectively. In men, higher serum 25(OH)D levels were associated with better grip strength (p for trend = 0.003), chair stand time (p for trend = 0.042), and functional reach (p for trend <0.001). On the other hand, these parameters were not associated with serum 25(OH)D levels in women. CONCLUSION: A higher level of serum 25(OH)D was associated with better physical performance in men but not in women.

Cytological Appearances of Ovarian Seromucinous Borderline Tumor in Ascites: Presentation of 2 Cases.

BACKGROUND: Seromucinous borderline tumor (SMBT) is a rare neoplasm which was newly defined in the 2014 WHO classification. Although the clinical and histopathological characteristics of SMBT have been well described, its cytological characteristics have not. We recently experienced 2 cases of SMBT which were defined by cytological findings of ascites. CASE PRESENTATION: Case 1 was a 65-year-old Japanese woman. Preoperative imaging studies revealed abundant ascites and a cystic tumor, with a solid component measuring 13 cm on the left ovary. Radical surgery was performed during the intraoperative diagnosis of ovarian borderline tumor, made by histological examinations of frozen tumor sections. The cytological smears of preoperatively and intraoperatively collected ascites showed many atypical cells resembling reactive mesothelial cells. Alcian-blue staining of cell block sections revealed intracytoplasmic mucin, and the results of immunohistochemistry were consistent with SMBT. The final pathological diagnosis of tumor was SMBT. Case 2 was a 28-year-old Japanese woman. Preoperative imaging studies revealed a small amount of ascites and cystic tumors with solid components in the bilateral ovaries. She initially underwent fertility preservation surgery. SMBT was suspected by cytological examination of smears of intraoperatively collected ascites and the findings of cell block. She underwent additional radical surgery based on a final pathological diagnosis of SMBT. CONCLUSION: In our experience, the tumor cells of SMBT in ascites mimicked reactive mesothelial cells. The nuclear atypia of SMBTs was intermediate between that of reactive mesothelial cells and serous carcinoma. The immunohistochemistry and mucin staining using cell block were very helpful for facilitating the cytodiagnosis of SMBT.

Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.

BACKGROUND: An increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women. METHODS: The subjects were community-dwelling men (n = 358) and women (n = 503) aged ≥ 40 years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected. RESULTS: Serum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ≥ 80 years than those in the age groups of 40-49, 50-59, and 60-69 years. Serum ucOC concentrations in women were higher in the age groups of 50-59 and 60-69 years than those at 40-49 years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men. CONCLUSIONS: Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.

Inhibitory effect of the tea polyphenol, (-)-epigallocatechin gallate, on growth of cervical adenocarcinoma cell lines.

To investigate the effect of (-)-epigallocatechin gallate (EGCG) on cervical adenocarcinoma, we performed a cell proliferation assay. TRAP assay is used for telomerase activity, flow cytometry analysis and pKi-67 immunofluoroscein staining in cervical adenocarcinoma cell lines (OMC-4, TMCC-1). Our results showed that EGCG inhibited the proliferation assay, TRAP assay for telomerase activity of both cell lines. Although cell apoptosis was induced, we observed that the expression of pKi-67 was suppressed. Our data suggest that EGCG may be effective for the treatment of cervical adenocarcinoma. The mechanisms of the anti-tumor effects were revealed to be the inhibition of telomerase activity, the induction of apoptosis and cell cycle dysregulation.

A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 11q: comparison with chromosome 21q.

It was generally believed that autosomal CpG islands (CGIs) escape methylation. However, our comprehensive analysis of allelic methylation status of 149 CGIs on human chromosome 21q revealed that a sizable fraction of them are methylated on both alleles even in normal blood cells. Here, we performed a similar analysis of 656 CGIs on chromosome 11q, which is gene-rich in contrast with 21q. The results indicate that 11q contains less methylated CGIs, especially those with tandem repeats and those in the coding or 3'-untranslated regions (UTRs), than 21q. Thus, methylation status of CGIs may substantially differ from one chromosome to another.

Analysis of nuclear chromatin distribution in cervical glandular abnormalities.

OBJECTIVE: To measure the intensity of hematoxylin staining for the analysis of chromatin distribution and to define a clear set of standards. STUDY DESIGN: Cervical smears obtained from 12 patients with glandular lesions, 5 with squamous lesions and 3 without cervical lesions were used for NIH image analysis (public domain NIH image program developed at the U.S. National Institute of Health, available through the Internet by anonymous ftp from zippy.nimh.nih.gov or on floppy disk from the National Technical Information Service, Springfield, Virginia). In addition, the same cervical smears were restained with propidium iodide, and the DNA content in the nuclei was compared with that with hematoxylin staining. RESULTS: Chromatin distribution was categorized into 3 patterns. Pattern A was that for which the highest staining density was localized in the periphery of the nucleus, while in pattern C it was localized in the center of the nucleus. Pattern B was the intermediate type between patterns A and C. In patients with adenocarcinoma, pattern B was predominant; pattern C was also relatively frequent in this group. In atypical glandular cells observed in patients with squamous lesions, patterns A and B were predominant and pattern C rarely seen. Analysis of DNA content in the nucleus revealed that nuclei showing pattern B contained significantly higher quantities of DNA than those showing pattern A. CONCLUSION: Nuclear chromatin distribution seems to correlate well with DNA content, and analysis of the chromatin distribution pattern is helpful for the diagnosis of cervical glandular neoplasia.

A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q.

Approximately half of all human genes have CpG islands (CGIs)around their promoter regions. Although CGIs usually escape methylation, those on Chromosome X in females and those in the vicinity of imprinted genes are exceptions: They have both methylated and unmethylated alleles to display a "composite" pattern in methylation analysis. In addition, aberrant methylation of CGIs is known to often occur in cancer cells. Here we developed a simple HpaII-McrBC PCR method for discrimination of full, null, incomplete, and composite methylation patterns, and applied it to all computationally identified CGIs on human Chromosome 21q. This comprehensive analysis revealed that, although most CGIs (103 out of 149)escape methylation, a sizable fraction (31 out of 149)are fully methylated even in normal peripheral blood cells. Furthermore, we identified seven CGIs showing the composite methylation, and demonstrated that three of them are indeed methylated monoallelically. Further analyses using informative pedigrees revealed that two of the three are subject to maternal allele-specific methylation. Intriguingly, the other CGI is methylated in an allele-specific but parental-origin-independent manner. Thus, the cell seems to have a broader repertoire of methylating CGIs than previously thought, and our approach may contribute to uncover novel modes of allelic methylation.

Characterization and imprinting status of OBPH1/Obph1 gene: implications for an extended imprinting domain in human and mouse.

Human 11p15.5, as well as its orthologous mouse 7F4/F5, is known as the imprinting domain extending from IPL/Ipl to H19. OBPH1 and Obph1 are located beyond the presumed imprinting boundary on the IPL/Ipl side. We determined full-length cDNAs and complete genomic structures of both orthologues. We also investigated their precise imprinting and methylation status. The orthologues resembled each other in genomic structure and in the position of the 5' CpG island and were expressed ubiquitously. OBPH1 and Obph1 were predominantly expressed from the maternal allele only in placenta, with hypo- and not differentially methylated 5' CpG islands in both species. These results suggested that the imprinting domain would extend beyond the presumed imprinting boundary and that methylation of the 5' CpG island was not associated with the imprinting status in either species. It remains to be elucidated whether the gene is under the control of the KIP2/LIT1 subdomain or is regulated by a specific mechanism. Analysis of the precise genomic sequence around the region should help resolve this question.