GENE EDITING IN PIGS

Genetically modified animals, especially rodents, are widely used in biomedical research. However, non-rodent models are required for efficient translational medicine and preclinical studies. Owing to the similarity in the physiological traits of pigs and humans, genetically modified pigs may be a valuable resource for biomedical research. Somatic cell nuclear transfer (SCNT) using genetically modified somatic cells has been the primary method for the generation of genetically modified pigs. However, site-specific gene modification in porcine cells is inefficient and requires laborious and time-consuming processes. Recent improvements in gene-editing systems, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) system, represent major advances. The efficient introduction of site-specific modifications into cells via gene editors dramatically reduces the effort and time required to generate genetically modified pigs. Furthermore, gene editors enable direct gene modification during embryogenesis, bypassing the SCNT procedure. The application of gene editors has progressively expanded, and a range of strategies is now available for porcine gene engineering. This review provides an overview of approaches for the generation of genetically modified pigs using gene editors, and highlights the current trends, as well as the limitations, of gene editing in pigs

Assessment of Medical Expenditures for Sepsis:Differentiating between Cases with and without Ruled-out Diagnoses

Setting public health priorities requires precise estimation of the burden of disease, including disease-specific medical expenditure. Information on multiple and ruled-out diagnoses on health insurance claims (HICs) has been ignored in traditional analyses of disease-specific medical expenditures in Japan. This study reviewed 448 inpatients with at least one diagnosis of sepsis on their HICs, who were insured by corporate health insurance organizations making claims on services provided from April 2006 to March 2007 in Japan. Subjects in whom sepsis-related diagnoses were specified as “ruled-out” were compared with subjects in whom sepsis-related diagnoses were classified as “not-ruled-out” (i.e., subjects in whom sepsis was considered possibly or likely present). Direct medical expenditure, length of stay (LOS), cost per day, cost of antibiotics, and proportion of administered cephalosporin and carbapenems were significantly higher in subjects classified as not-rule-out. When using health insurance claims in Japan, the statistics of medical expenditures and LOS are influenced by procedures performed to rule out a diagnosis, as well as those performed to treat a confirmed diagnosis of sepsis

Effects of the increase in co-payments from 20 to 30 percent on the compliance rate of patients with hypertension or diabetes mellitus in the Employed Health Insurance System

Objectives: How to contain medical expenditures is a universal problem. The Japanese government has increased patient co-payments to control it. The purpose of this study is to clarify whether the increase in co-payments to 30 percent prevented patients with hypertension or diabetes mellitus from receiving necessary care in the Employee Health Insurance System. Methods: The subjects were 211 patients with hypertension and 66 patients with diabetes mellitus who regularly visited physicians from October 2001 to March 2002 and were defined as a cohort that needed health care, and their medical indicators were examined between April and September 2002 (prestage) and between April and September 2003 (poststage). Results: In the hypertensive patients with no complications, the compliance rate was 89.9 percent and 88.0 percent in the prestage, and poststage, respectively, showing no significant change. In the hypertensive patients with complications, the compliance rate was 90.5 percent and 92.1 percent in the prestage and poststage, respectively, showing no significant change. In the diabetic patients with complications, the compliance rate was 77.5 percent and 79.2 percent, in the prestage and poststage, respectively, with no significant change. In the diabetic patients with no complications, however, the compliance rate was 83.7 percent and 66.7 percent, in the prestage and poststage, respectively. A significant decrease was observed among diabetic patients without complications. Conclusions: Increasing co-payments reduced necessary preventive care in diabetic patients without complications.</p

Design of novel bioactive materials through organic modification of calcium silicate

Bioactive ceramics have attractive feature for bone repair such as direct bone-bonding in the body. However their clinical application is limited to low loaded portions due to their inappropriate mechanical performances such as higher brittleness and lower flexibility than natural bone. The essential condition for artificial materials to show bioactivity is formation of bone-like apatite on their surfaces in body environment. This apatite formation is triggered by silanol (Si–OH) group on the material surfaces and release of Ca2+. These findings bring us an idea that novel bioactive materials with high flexibility can be designed by organic modification of calcium silicate. We synthesized organic–inorganic hybrids from organic polymers including 2-hydroxyethylmethacrylate (HEMA), starch and alginate by modification with alkoxysilane and calcium chloride. The hybrids formed apatite on their surfaces in simulated body fluid (SBF, Kokubo solution). Such a modification was also effective for providing conventional polymethylmethacrylate (PMMA)-based bone cement with bioactivity.IX Conference and Exhibition of the European Ceramic Society: June 19-23, 2005, Portorož, Sloveni

Urbanization and physician maldistribution: a longitudinal study in Japan

<p>Abstract</p> <p>Background</p> <p>The relative shortage of physicians in Japan's rural areas is an important issue in health policy. In the 1970s, the Japanese government began a policy to increase the number of medical students and to achieve a better distribution of physicians. Beginning in 1985, however, admissions to medical school were reduced to prevent a future oversupply of physicians. In 2007, medical school entrants equaled just 92% of their 1982 peers. The urban annual population growth rate is positive and the rural is negative, a trend that may affect denominator populations and physician distribution.</p> <p>Methods</p> <p>Our data cover six time points and span a decade: 1998, 2000, 2002, 2004, 2006, and 2008. The spatial units for analysis are the secondary tier of medical care (STM) as defined by the Medical Service Law and related legislation. We examined trends in the geographic disparities in population and physician distribution among 348 STMs in Japan. We compared populations and the number of physicians per 100,000 populations in each STM. To measure maldistribution quantitatively, we calculated Gini coefficients for physician distribution.</p> <p>Results</p> <p>Between 1998 and 2008, the total population and the number of practicing physicians for every 100,000 people increased by 0.95% and 13.6%, respectively. However, the inequality of physician distribution remained constant, although small and mostly rural areas experienced an increase in physician to population ratios. In contrast, as the maldistribution of population escalated during the same period, the Gini coefficient of population rose. Although the absolute number of practicing physicians in small STMs decreased, the fall in the denominator population of the STMs resulted in an increase in the number of practicing physicians per population in those located in rural areas.</p> <p>Conclusions</p> <p>A policy that increased the number of physicians and the physician to population ratios between 1998 and 2008 in all geographic areas of Japan, irrespective of size, did not lead to a more equal geographical distribution of physicians. The ratios of physicians to population in small rural STMs increased because of concurrent trends in urbanization and not because of a rise in the number of practicing physicians.</p

Liquid Phase Oxidation of Benzene to Phenol with Molecular Oxygen using Carbon-based Fe-Pd and Cu-Pd Catalyst

Liquid phase oxidation of benzene to phenol was carried out with O(2) using carbon-based Fe-Pd and Cu-Pd catalysts at 40℃. The carbon-based Fe-Pd and Cu-Pd catalyst were prepared by modified carbothermal reduction of metal ion exchange method using cation exchange resin as a source of carbon. Fe/carbon, Cu/carbon and Pd/carbon were not effective for the oxidation of benzene to phenol with O(2) when H(2) was used as a catalyst reducing agent, however both Fe/carbon and Cu/carbon catalysts revealed activities when ascorbic acid was used as a reducing agent. Bimetallic catalysts such as Fe-Pd/carbon and Cu-Pd/carbon showed much higher activity for phenol production than the monometallic catalysts even when H(2) was used a reducing agent. Catalytic activity of Fe-Pd catalyst was much (ca. 2.5 times) higher than the Cu-Pd/catalyst. A physical mixture of the single component catalysts such as Fe and Pd or Cu and Pd were not effective in the oxidation of benzene to phenol, suggesting that an intimate contact between Fe or Cu species with Pd species is necessary to formulate an active catalyst

Inverse Correlation between Adiponectin and the Risk of Metabolic Syndrome in Middle-aged Japanese Male Workers

Despite a close association between adiponectin and both hypertension and type 2 diabetes, the relationship between adiponectin and metabolic syndrome has not yet been well-investigated. To examine and evaluate the association between serum adiponectin levels and metabolic syndrome based on Japanese diagnostic criteria, we analyzed adiponectin and anthropometric parameters in 869 male employees aged 40-59 who belonged to a health insurance society in Fukuoka Prefecture and who underwent annual health check-ups from August 2006 to July 2007. Two hundred and thirty-two of the 869 subjects (26.7%) were diagnosed with metabolic syndrome. The serum adiponectin levels were significantly higher in the non-metabolic syndrome group. In a multiple logistic regression analysis, the subjects in the top quartile of serum adiponectin (adjusted odds ratio:0.36;95% confidence interval:0.21-0.63) and the second (adjusted odds ratio:0.51;95% confidence interval:0.31-0.84) quartile had a significantly decreased risk for metabolic syndrome in comparison to the bottom quartile. The dose-response relationship between serum adiponectin levels and metabolic syndrome was significant (p for trend 0.0001) after adjusting for age, body mass index, smoking status, and drinking status. The current findings suggest that hypoadiponectinemia is inversely correlated with the risk of metabolic syndrome in middle-aged Japanese male workers.</p

Canine follicular development treated by hormones

Ovarian follicular dynamics is not well known in dogs. Imaging of ovaries is technically difficult; however, ovaries clamped at a subcutaneous site can more easily be monitored using ultrasound imaging. This study investigated the follicular development of canine ovaries stimulated by hormone treatment using ultrasound imaging of the ovaries clamped at a subcutaneous site. Oestrus was induced using subcutaneous administration of 500 IU equine chorionic gonadotropin (eCG) and 1000 IU human chorionic gonadotropin (hCG) (eCG/hCG). Five bitches were given 1000 IU hCG 11 days after eCG/hCG administration. Examinations with ovarian ultrasonography using a 7.5‐MHz sector transducer, vaginal cytology, and assays of serum oestrogen and progesterone were performed daily until 20 days after eCG/hCG administration. Serosanguineous vaginal discharges and vaginal cytology of two of the bitches were observed. New follicular growth (>1.0 mm in diameter) was observed in all bitches from 2 to 8 days after eCG/hCG administration. The mean diameter of follicles and maximum numbers of follicles per ovary ranged from 2.8 to 5.5 mm and 4 to 16, respectively. The elevation in oestrogen concentrations after eCG/hCG administration was observed in all bitches, and elevation in progesterone concentration (>2 ng mL−1) was observed in three bitches. However, no follicles ovulated until 9 days after hCG administration. In conclusion, although the number of examined bitches were limited, follicular growth in ovaries clamped at a subcutaneous site can be monitored using ultrasound imaging. Ovarian ultrasonography showed that eCG/hCG administration induced new follicular growth and hCG administration induced increases in oestrogen concentrations but not ovulation by hCG administration

The Prevalence and Characteristics of Older Japanese Adults with Polypharmacy, Based on Regionally Representative Health Insurance Claims Data

We aimed to clarify the prevalence of polypharmacy among elderly individuals in Japan. We used the data obtained from a large-scale population-based representative database of health insurance claims in a single prefecture in Japan. We examined all of the outpatient and pharmaceutical health insurance claims for National Health Insurance and those for Late-stage Elderly Health Insurance in Nagasaki Prefecture, Japan between April and June 2016. When two or more claim forms were issued for a patient in a single month, we combined the data and identified the number of prescribed drugs for each person. The definition of polypharmacy is a the prescription of six or more drugs per month. We investigated the prevalence of polypharmacy among the beneficiaries of the two insurance systems. Of the 605,406 beneficiaries of the 2 insurance systems, 121,033 (20.0%) patients with polypharmacy were identified. The prevalence of polypharmacy increased with age, especially among the beneficiaries aged > 85 years, with about half of the beneficiaries having polypharmacy status. About half of the people aged > 85 years in the database had polypharmacy status. When a drug is prescribed to an elderly individual, it is necessary to consider the possibility of polypharmacy-related problems

Rubeosis Iridis Resulting from Agenesis of the Internal Carotid Artery: A Case Report

We report a case of rubeosis iridis resulting from agenesis of the internal carotid artery. Agenesis of the internal carotid artery is a rare congenital anomaly, and most patients do remain asymptomatic, but we should realize that this condition may lead to ocular ischemic changes, the result being rubeosis iridis