Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics

This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so.     

Pterosin-derivate aus der familie pteridaceae

The investigation of four pteridaceous ferns afforded, in addition to known pterosins, six new pterosins and three new pterosides. The structures are elucidated mainly by spectroscopic methods.     

Isolation and functional identification of a novel cDNA for astaxanthin biosynthesis from Haematococcus pluvialis,and astaxanthin synthesis in Escherichia coli

We succeeded in isolating a novel cDNA involved in astaxanthin biosynthesis from the green alga Haematococcus pluvialis, by an expression cloning method using an Escherichia coli transformant as a host that synthesizes -carotene due to the Erwinia uredovora carotenoid biosynthesis genes. The cloned cDNA was shown to encode a novel enzyme, -carotene ketolase (-carotene oxygenase), which converted -carotene to canthaxanthin via echinenone, through chromatographic and spectroscopic analysis of the pigments accumulated in an E. coli transformant. This indicates that the encoded enzyme is responsible for the direct conversion of methylene to keto groups, a mechanism that usually requires two different enzymatic reactions proceeding via a hydroxy intermediate. Northern blot analysis showed that the mRNA was synthesized only in the cyst cells of H. pluvialis. E. coli carrying the H. pluvialis cDNA and the E. uredovora genes required for zeaxanthin biosynthesis was also found to synthesize astaxanthin (3S, 3S), which was identified after purification by a variety of spectroscopic methods.     

Factors associated with caregiving burden and mental health conditions in caregivers of patients with anorexia nervosa in Japan

Background

There are no studies about the caregiving burdens in families of patients with eating disorders in Japan, and only limited studies on the role of caregivers’ stress coping, social support, and mental health. This study examines caregiving burdens, mental health conditions, and associated factors in caregivers of anorexia nervosa (AN) patients in Japan.

Methods

Seventy-nine principal caregivers (70 mothers, 5 fathers, 3 spouses and 1 grandmother; mean age 56.0?±?8.0 years) for outpatients with AN (all female; mean age 26.6?±?7.9 years; BMI 14.6?±?3.2 kg/m²) were evaluated using self-report questionnaires in a cross-sectional study. The questionnaires included caregiving burden (J-ZBI_8), mental health conditions (GHQ28), stress coping styles (CISS), social support (SNQ), severity of the patient’s symptoms from the family’s perspective (ABOS), and family functioning (GF-FAD). Clinical information about the patients was also obtained.

Results

Mean caregiving burden assessed by J-ZBI_8 score was 12.4?±?7.0 (SD). The total GHQ score was 31.6?±?13.7 (Likert scoring) and 9.2?±?7.0 (GHQ scoring). Of the respondents, 48 (60.7 %) indicated a high risk for mental health problems that exceeded the cutoff point of the GHQ. Significantly higher caregiving burden and poor mental health conditions were shown in the group who had contact with patients?>?6 h a day compared to the group with daily patient contact?<?3 h (F (2, 76)?=?3.19, p?=?0.047 and F (2, 76)?=?9.39, p?<?0.001, respectively). Stepwise multiple regression analysis indicated that the factors that significantly predicted the caregiving burden were severity of the patient’s symptoms from the family’s perspective (β?=?0.47, p?<?0.001) and Emotion-Oriented Coping (β?=?0.38, p?=?0.002) (R²?=?0.401), while predictors of mental health conditions were Emotion-Oriented Coping (β?=?0.522, p?<?0.001), Affective Support (β?=??0.419, p?<?0.001), and contact time with patient (β?=?0.201, p?=?0.042) (R²?=?0.602).

Conclusion

Caregivers of AN patients experienced heavy burdens and manifested poor mental health conditions. The severity of the patient’s symptoms from the family’s perspective and the greater use of emotion-oriented coping were associated with higher burdens. Greater use of emotion-oriented coping, less affective support and longer contact with patients were related to worse mental health conditions. Interventions to promote caregivers’ adaptive coping styles may help reduce their caregiving burden and improve their mental health.

     

C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus

In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.     

Production of Staphylococcal Enterotoxins A, B, and C in Colloidal Dispersions

Larger amounts of enterotoxin were produced when Staphylococcus aureus S-6 was grown under still (nonshaken) conditions in a medium that was a paste or gel than were produced in a liquid dispersion with the same colloidal ingredient or in control basal broth (4% NZ Amine-NAK containing 50 mug of thiamine per 100 ml and 1 mg of niacin per 100 ml). Four colloidal ingredients were used which had been previously demonstrated to not support enterotoxin production in buffer. The effect of the type of dispersion occurred earlier than that of the colloidal ingredient, but interactions were found. This effect was not observed when the cells were grown with aeration (shaken). Four other strains of S. aureus followed a similar pattern for enterotoxins A, B, and C, although liquid and paste with cornstarch and carrageenan were the only media compared to the control broth. Enterotoxins A and B were produced earlier by S. aureus S-6, and much greater quantities of enterotoxins were produced for all strains when incubated shaken.