Cost effectiveness of romosozumab versus teriparatide for severe postmenopausal osteoporosis in Japan.

This study assessed the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japan, using bone mineral density (BMD) efficacy data. Results show that romosozumab/alendronate produces greater health benefits at a lower cost than teriparatide/alendronate. INTRODUCTION: This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japanese women previously treated with bisphosphonates. METHODS: A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to alendronate for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 78 years, a T-score ≤-2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Japanese healthcare system and used a discount rate of 2% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2020 US dollars) and quality-adjusted life years (QALYs). RESULTS: Base case results showed that, compared with teriparatide/alendronate, romosozumab/alendronate reduced costs by $5134 per patient and yielded 0.045 additional QALYs. Scenario analyses and probabilistic sensitivity analysis confirmed that results are robust to uncertainty in model assumptions and inputs. CONCLUSION: Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.

Exploration of Mental Health Issues of Students among University Health Science Academics in Japan.

Academic educators in universities are well positioned to detect early signs and symptoms of unexplained behaviour change in students that could be the beginning of mental health issues. The purpose of this research was to explore the attitudes, beliefs, knowledge and practices of university academics in Japan towards health science students with psychological/mental health issues. This study used a qualitative descriptive design. Three focus groups using a semi-structured interview guide were conducted with 15 academics teaching health science students. Data were collected between March to October 2019. Themes revealed three areas of interest: 1) Reflection on mental health issues in Japan with sub-themes "family issues"; "society expectations and changes", and "stigma"; 2) Reflection on students' mental health issues with sub-themes "student behaviors", "staff involvement", "barriers encountered"; and, 3) Potential supports with sub-themes "university assistance", "communication and connection", and "interventions and prevention." The findings provide insight and can benefit student populations across diverse cultural university settings. Further research to investigate academic staff support with early recognition of mental ill-health and ability to provide information and advice to students is warranted. Recommendations include mental health education for academics and for students to encourage healthy university campuses and well-being within the community.

Bilateral cerebellar cysts and cerebral white matter lesions with cortical dysgenesis: Expanding the phenotype of LAMB1 gene mutations.

LAMB1 gene analysis should be considered for intellectually disabled patients with cerebellar cysts, white matter signal change, and cortical malformation. Muscular involvement is absent, in contrast to the α-dystroglycanopathy types of congenital muscular dystrophies.

First Elastic Electron Scattering from

The first elastic electron scattering has been successfully performed at the self-confining radioactive-isotope ion target (SCRIT) facility, the world's first electron scattering facility for SCRIT technique achieved high luminosity (over 10^{27} cm^{-2} s^{-1}, sufficient for determining the nuclear shape) with only 10^{8} target ions. While ^{132}Xe used in this time as a target is a stable isotope, the charge density distribution was first extracted from the momentum transfer distributions of the scattered electrons by comparing the results with those calculated by a phase shift calculation.

Effectiveness of fibrin coating in the management of web formation after laryngomicrosurgery.

PURPOSE: To explore the effectiveness of fibrin coating in reducing web formation after endoscopic management of the anterior commissure of the larynx. MATERIALS AND METHODS: Using a spray device that is generally used for laparoscopic operations, we covered the wound with fibrin glue (Bolheal®) to avoid web formation. This technique was employed in cases wherein the anterior commissure was mainly managed by laser operation; the glue was sprayed after vaporization. Fibrinogen was first sprayed and the wound was properly soaked with a swab, which was followed by application of thrombin. We used this method in 17 cases and evaluated voice function by acoustic analysis - pitch perturbation quotient (PPQ) and amplitude perturbation quotient (APQ) - and maximum phonation time (MPT) before and after the operation. RESULTS: No severe web formation was observed at three months after the operation. PPQ values improved from 3.048±2.801% to 0.653±0.463% (p<0.05, paired t-test). APQ values improved from 7.996±5.003% to 3.042±1.872% (p<0.05, paired t-test). Voice quality did not worsen in any of the cases. MPT values improved from 17.2±10.8s to 26.7±14.2s (p<0.05, paired t-test) Voice function improved 3months after the operation in all cases. CONCLUSION: The fibrin coating method is an easy and effective approach to avoid web formation without creating cervical wounds in cases that require handling of the anterior commissure under laryngomicrosurgery.

Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.

Prevalence of Curable Sexually Transmitted Infections in Pregnant Women in Low- and Middle-Income Countries From 2010 to 2015: A Systematic Review.

BACKGROUND: Current literature comparing the prevalence rates of curable sexually transmitted infections (STIs) in pregnant women in various global regions is limited. As a result, antenatal screening practices for curable STIs in pregnant women, specifically Treponema pallidum (syphilis), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV) vary around the world, differing by country and particular STI. METHODS: We conducted a systematic review of publications on STI prevalence among pregnant women in 30 different low- and middle-income countries. We searched PubMed for studies reporting prevalence of syphilis, CT, NG, and TV in pregnant women. English language studies published between January 1, 2010, and March 1, 2015, were included. The adjusted mean STI prevalence by region was calculated via multivariable linear regression adjusting for health care setting, women's mean age, study sample size, and sensitivity of diagnostic test. RESULTS: We identified 75 studies that met inclusion criteria, providing 116 point prevalence estimates for curable STIs among 3,489,621 pregnant women. Adjusted mean prevalence for NG ranged from 1.2% (95% confidence interval [CI], 1.0-1.3) in Latin America to 4.6% (95% CI, 4.0-5.2) in Southern Africa; syphilis prevalence ranged from 1.1% (95% CI, 0.5-1.6) in Asia to 6.5% (95% CI, 4.7-6.3) in Southern Africa; CT ranged from 0.8% (95% CI, 0.4-1.1) in Asia to 11.2% (95% CI, 6.0-16.4) in Latin America; and TV ranged from 3.9% (95% CI, 2.2-5.6) in Latin America to 24.6% (95% CI, 17.9-31.4) in Southern Africa. CONCLUSIONS: Although we observed a wide variation in STI burden in pregnancy after adjusting for age, test, and health care setting, further valid comparison may depend on adjustment for access to care and screening practices.

The prevalence of primary neck and shoulder pain, and its related factors in Japanese postpartum women.

PURPOSE: This study investigated the prevalence, location, and severity of neck and shoulder pain (NSP), its disturbance of quality of life (QOL), and the factors related to NSP in Japanese postpartum women. MATERIALS AND METHODS: The study involved 308 postpartum women who had a medical examination one month after delivery. The questionnaire consisted of the background and details of NSP. Mood states were evaluated using the Profile of Mood States-Brief (POMS-B), Japanese Version. RESULTS: The prevalence of NSP was 73.1%, one-fourth of which occurred after birth. The most common area was the superior part of the trapezium muscles. Prevalence was associated with past history of premenstrual syndrome (PMS), anemia during pregnancy, time per breastfeeding, and the mean POMS-B Fatigue score. Total breastfeeding time a day, the mean POMS-B score for Fatigue, Confusion, Anger-Hostility, and Depression were significantly higher for "worse" after birth than those for "no-change/relief". The disturbance of daily life due to NSP in postpartum women with past history of PMS and Hiesho were significant higher than that for women without those. CONCLUSIONS: The prevalence of NSP in postpartum women was very high. The factors which affect NSP were the mental states, breastfeeding, past history of PMS, and anemia during pregnancy.

Human periodontal ligament cell sheets cultured on amniotic membrane substrate.

OBJECTIVE: Periodontal ligament (PDL) cells and their substrates play key roles in periodontal regeneration. However, there has been no report on the use of amniotic membrane (AM) as a substrate for culturing PDL cells. In the current study, we conducted an analysis of PDL cells cultivated on AM to determine the distribution of factors responsible for maintaining the characteristics of PDL. MATERIALS AND METHODS: Amniotic membrane was obtained from women undergoing cesarean sections, whereas PDL tissue was obtained from human maxillary third molars. The harvested PDL cells were maintained in explant culture for three or four passages, following which they were cultured on AM. RESULTS: After 3 weeks of culture, the PDL cells had grown well on AM. Immunofluorescence showed that these cells were capable of proliferating and potentially maintaining their PDL-like properties. In addition, strong cell-cell adhesion structures, namely desmosomes and tight junctions, were shown to be present between cells. Electron microscopy images showed that the cultured PDL cells had differentiated and proliferated on AM with lateral conjugation and adhesion to AM. CONCLUSION: We conclude that AM may represent a suitable substrate for culturing PDL cells and that PDL cells cultured on AM show sheet formation.

Factors associated with post-natal anxiety among primiparous mothers in Nepal.

BACKGROUND: In Nepal, new mothers are fatigued by childcare responsibilities because of lack of knowledge and preparation for their new role. Knowledge deficit and adherence to traditional health practices place infants at risk. Some cultural practices for the care of newborns may cause tetanus, hypothermia or other life-threatening illnesses. Maternal education, previous experience of newborn care, economic status, relationship problems with husband or mothers-in-law and dissatisfaction with social relations are the variables of interest for this study. AIMS: To examine the association between socio-demographic variables and post-natal anxiety among primiparous mothers in Nepal. DESIGN: The study was designed as a correlational study. SETTING: A major maternity hospital in Kathmandu, Nepal. PARTICIPANTS: The sample were 216 primiparous mothers who were followed at 5-6 weeks after delivery. METHODS: Three instruments were used for data collection: a demographics questionnaire, the Newborn Care Knowledge Questionnaire and the State-Trait Anxiety Inventory for Adults. RESULTS: The mothers' knowledge of newborn care, general educational level and income were inversely related to maternal anxiety, that is, mothers with a lower educational level and socio-economic status demonstrated a higher level of post-natal anxiety. Poor relationships with husbands or mothers-in-law and low social support presented potential for the development of anxiety and depression during post-partum period. CONCLUSION: Maternal education, socio-economic status and knowledge of newborn care were major factors of post-natal anxiety. On the other hand, women with low income and education, poor relationships with their husbands or mothers-in-law, and insufficient social support are vulnerable to the development of moderate to severe anxiety. HEALTH POLICY: Policy implications from these results indicate the need for support and funding from the Ministry of Health for education for women at hospitals, which must work together to offer newborn care education during the ante-natal and post-natal periods.

A transfection method for short interfering RNA with the lipid-like self-assembling nanotube, A6K.

The aim of the present study was to develop a novel transfection method for short interfering RNA (siRNA). A nanotube with surfactant activity, A6K, consisting of six alanine residues and a hydrophilic head, lysine, was compared to the conventional cationic transfectant reagents siFECTOR and Lipofectamine 2000. Cytotoxicity for the human glioblastoma cell lines U87MG, A172, and T98G was examined with the MTS assay. Transfection efficiency was analyzed with FITC-labeled siRNA targeting matrix metalloproteinase (MMP)-2 mRNA by fluorescent activity on microscopy. The ultrastructure of A6K was evaluated by electron microscopy. The level of cytotoxicity associated with A6K in the U87MG cells was significantly lower than with siFECTOR and Lipofectamine 2000. Transfection efficiency for siRNA was increased in a dose- and time-dependent fashion. The relative expression of MMP-2 mRNA to ß-actin was reduced in a dose-dependent manner by real-time RT-PCR analysis. The ultrastructure of the A6K was transformed to micelle formation when mixed with the siRNA. The lipid-like self-assembling peptide, A6K, has genes in the micelle associated with the hydrophilic tail. This transfection method is a novel and stable technique with lower cytotoxicity than the current standard methods.

Spontaneous glomerular and tubulointerstitial lesions in common marmosets (Callithrix jacchus).

Spontaneous progressive nephropathy dominated by glomerular lesions in common marmosets has been reported. However, the histopathologic characteristics, including the relationship between glomerular and tubulointerstitial lesions, have not been described in detail. In the present study, the authors examined the histopathologic characteristics of the background renal lesions in common marmosets (3 males and 9 females, 3 to 8 years old). The severity of glomerular lesions was graded into 3 classes: grade I, no alteration; grade II, hilar/focal increase of mesangial matrix; grade III, global/diffuse increase of mesangial matrix. Tubulointerstitial lesions (tubular regeneration and hyperplasia and interstitial inflammation and fibrosis) were scored according to the area of each lesion. The renal lesions were characterized by enlargement of glomeruli, expanded mesangial area with increase of periodic acid-Schiff reaction-positive matrix, tubular regeneration and hyperplasia, and interstitial inflammation and fibrosis. Glomerular lesions progressed with increasing mesangial matrix and aging. Additionally, the tubulointerstitial lesions became exacerbated with progressing glomerular lesions. Tubular hyperplasia was divided into 4 types according to the structure of the cell layer (simple or stratified-like), the area of increased lining cells (partial or entire), cytoplasmic staining (eosinophilic or basophilic), brush border and thickness of basement membrane, and the activity of cell proliferation. In conclusion, the background renal lesions in common marmosets were characterized by glomerular lesions with increase of mesangial matrix, which progressed with aging, and secondary tubulointerstitial lesions, including tubular hyperplasia. Those lesions were thus diagnosed as progressive glomerulonephropathy in common marmosets.

Genome-wide detection of non-additive quantitative trait loci for semen production traits in beef and dairy bulls.

Semen production traits are important aspects of bull fertility, because semen quantity leads to direct profits for artificial insemination centres, and semen quality is associated with the probability of achieving a pregnancy. Most genome-wide association studies (GWASs) for semen production traits have assumed that each quantitative trait locus (QTL) has an additive effect. However, GWASs that account for non-additive effects are also important in fitness traits, such as bull fertility. Here, we performed a GWAS using models that accounted for additive and non-additive effects to evaluate the importance of non-additive effects on five semen production traits in beef and dairy bulls. A total of 65 463 records for 615 Japanese Black bulls (JB) and 50 734 records for 873 Holstein bulls (HOL), which were previously genotyped using the Illumina BovineSNP50 BeadChip, were used to estimate genetic parameters and perform GWAS. The heritability estimates were low (ranged from 0.11 to 0.23), and the repeatability estimates were low to moderate (ranged from 0.28 to 0.45) in both breeds. The estimated repeatability was approximately twice as high as the estimated heritability for all traits. In this study, only one significant region with an additive effect was detected in each breed, but multiple significant regions with non-additive effects were detected for each breed. In particular, the region at approximately 64 Mbp on Bos taurus autosome 17 had the highest significant non-additive effect on four semen production traits in HOL. The rs41843851 single nucleotide polymorphism (SNP) in the region had a much lower P-value for the non-additive effect (P-value = 1.1 × 10-31) than for the additive effect (P-value = 1.1 × 10-8) in sperm motility. The AA and AB genotypes on the SNP had a higher phenotype than the BB genotype in HOL, and there was no bull with the BB genotype in JB. Our results showed that non-additive QTLs affect semen production traits, and a novel QTL accounting for non-additive effects could be detected by GWAS. This study provides new insights into non-additive QTLs that affect fitness traits, such as semen production traits in beef and dairy bulls.

Range of motion exercise of temporo-mandibular joint with hot pack increases occlusal force in patients with Duchenne muscular dystrophy.

The purpose of this study is to evaluate whether the range of motion exercise of the temporo-mandibular joint (jaw ROM exercise) with a hot pack and massage of the masseter muscle improve biting disorder in Duchenne muscular dystrophy (DMD). The subjects were 18 DMD patients (21.3+/- 4.1 years old). The jaw ROM exercise consisted of therapist-assisted training (2 times a week) and self-training (before each meal every day). The therapist-assisted training consisted of the application of a hot pack on the cheek of the masseter muscle region (15 minutes), the massage of the masseter (10 minutes), and jaw ROM exercise (5 minutes). The self-training involved jaw ROM exercise by opening the mouth to the maximum degree, ten times. These trainings continued for six months. Outcomes were evaluated by measuring the greatest occlusal force and the distance at the maximum degree of mouth opening between an incisor of the top and that of the bottom. Six months later, the greatest occlusal force had increased significantly compared with that at the start of jaw ROM exercise (intermediate values: from 73.8N to 97.3N) (p = 0.005) as determined by the Friedman test and Scheffi's nonparametric test. The patients' satisfaction with meals increased. However, the maximum degree of mouth opening did not change after six months of jaw ROM exercise. Jaw ROM exercise in DMD is effective for increasing the greatest occlusal force.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster.

Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction.

Axillary apocrine carcinoma with Paget's disease and apocrine naevus.

Apocrine carcinoma is a rare malignant sweat-gland neoplasm with apocrine differentiation. There have been some reported cases of apocrine carcinoma with apocrine naevus. We report a case of a 78-year-old man with a painless tumour of the left axilla. Positron emission tomography (PET) showed slight fluorodeoxyglucose (FDG) uptake in both axillae. The patient underwent radical excision of the left axilla with left axillary lymph-node resection. The resected specimen showed apocrine adenocarcinoma with extramammary Paget's disease and apocrine naevus. Two years later, the patient noted enlargement of the right axilla, and PET showed increased FDG uptake. On resection of this enlarging right axilla, an apocrine naevus was found. FDG-PET is a useful method for detecting precancerous lesions, allowing monitoring of abnormal foci that are not suspicious for cancer and have no clinically apparent cause for concern.

[Bentall operation in left sinus of valsalva aneurysm with anomalous origin of left coronary artery and severe aortic regurgitation].

We report a successful Bentall operation in a 74-year-old man with an unruptured left sinus of Valsalva aneurysm and aortic regurgitation. The coronary angiogram showed an absent left main trunk (split origination of left coronary arteries from the same left sinus of Valsalva). We implanted a stented bovine pericardial valve and a Valsalva tube graft as a composite graft. To reconstruct the coronary arteries, we made one left coronary button including both ostia of the left anterior descending coronary artery and circumflex artery, and reimplanted the coronary button with interposition of a short small synthetic graft. Excessive tension of the coronary ostia can be avoided and a new left main trunk can also be created in this manner. Postoperative course was uneventful.