Development of the Rabbit NASH Model Resembling Human NASH and Atherosclerosis.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease which may progress into liver fibrosis and cancer. Since NASH patients have a high prevalence of atherosclerosis and ensuing cardiovascular diseases, simultaneous management of NASH and atherosclerosis is required. Currently, rodents are the most common animal models for NASH and accompanying liver fibrosis, but there are great differences in lipoprotein profiles between rodents and humans, which makes it difficult to reproduce the pathology of NASH patients with atherosclerosis. Rabbits can be a promising candidate for assessing NASH and atherosclerosis because lipoprotein metabolism is more similar to humans compared with rodents. To develop the NASH model using rabbits, we treated the Japanese White rabbit with a newly developed high-fat high-cholesterol diet (HFHCD) containing palm oil 7.5%, cholesterol 0.5%, and ferrous citrate 0.5% for 16 weeks. HFHCD-fed rabbits exhibited NASH at 8 weeks after commencing the treatment and developed advanced fibrosis by the 14th week of treatment. In addition to hypercholesterolemia, atherosclerotic lesion developed in the aorta after 8 weeks. Therefore, this rabbit NASH model might contribute to exploring the concurrent treatment options for human NASH and atherosclerosis.

Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways.

Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix-loop-helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cells was examined. RA rapidly and temporarily induced the SHARP-2 mRNA expression in hepatic H4IIE cells. Then, whether the SHARP-2 mRNA expression is altered by dexamethasone (Dex), insulin, and the combination of RA and Dex or RA and insulin was examined. Dex had different effects on the expression of SHARP-2 mRNA in the presence or absence of RA. Then, the molecular mechanisms were investigated using inhibitors of various signaling molecules. The RA-induction of SHARP-2 mRNA level was mainly inhibited by LY294002, staurosporine, and actinomycin D, respectively. Finally, whether RA acts on the transcriptional regulatory region of the SHARP-2 gene was analysed using luciferase reporter gene assay. At least two RA-responsive regions were mapped at the nucleotide sequences between -3,700 and -1,600 of the SHARP-2 gene. In addition, this effect was dependent on the RA receptor and retinoid X receptor. Thus, we conclude that RA stimulated transcription of the SHARP-2 gene via multiple pathways.

Laser-assisted hatching on clinical and neonatal outcomes in patients undergoing single vitrified Blastocyst transfer: A propensity score-matched study.

PURPOSE: This study determined the effect of laser-assisted hatching on the clinical and neonatal outcomes of single vitrified blastocyst transfer. METHODS: From June 2014 to March 2018, 289 matched pairs after propensity score matching were analyzed. During the blastocyst warming procedure, a small section of the zona pellucida area in the empty perivitelline space was sliced off using multiple laser beams. The clinical and neonatal outcomes of the laser-treated group and non-treatment control were analyzed. RESULTS: In the laser-assisted hatching group, significantly higher rates of clinical pregnancy (40.8% vs 29.4%, P < .01) and live delivery (34.3% vs 22.5%, P < .01) were observed compared to the control group. Other variables such as the average gestational weeks, the sex of the baby, birthweight, or congenital malformations were found to have no significant differences in neonatal outcomes. Moreover, all babies were singleton live births. CONCLUSIONS: Single vitrified blastocyst transfer treated with laser-assisted hatching increases the live birth rate and has no adverse effects on neonatal outcomes.

Effect of equilibration time on clinical and neonatal outcomes in human blastocysts vitrification.

PURPOSE: Prolonged exposure to equilibration solutions may be detrimental to an embryo's developmental potential, whereas a shorter exposure may affect the penetration of cryoprotectants into blastomeres. The purpose of this study was to evaluate the effects of different equilibration times on the clinical and neonatal outcomes of human blastocyst vitrification. METHODS: This is a retrospective study based on data collected between November 2008 and November 2015. A total of 192 blastocysts (80 non-expanded and 112 expanded) obtained from 167 patients were analyzed. The blastocysts were divided into two groups according to their equilibration time: 8-11 minutes or 12-15 minutes. The clinical and neonatal outcomes of warmed blastocysts were evaluated. RESULTS: The survival, implantation, and live birth rates of non-expanded blastocysts were not different between the two groups, but they significantly improved for the expanded blastocysts in the 12-15 minutes group compared to the 8-11 minutes group. The results were similar for the neonatal outcomes after vitrified embryo transfer, when partitioned by equilibration time and blastocyst stage at vitrification. CONCLUSIONS: For the non-expanded blastocysts, a shortened equilibration time (8-11 minutes) is sufficient for effective vitrification.

Evaluation of the effect of piezo-intracytoplasmic sperm injection on the laboratory, clinical, and neonatal outcomes.

PURPOSE: Limited research has been published on the effect of piezo-assisted intracytoplasmic sperm injection (P-ICSI). We evaluated the effect of P-ICSI on the laboratory, clinical, and neonatal outcomes. METHODS: This retrospective study was based on the data collected between April 2011 and October 2016. Total 1348 mature oocytes from 145 patients were analyzed. Laboratory, clinical, and neonatal outcomes of those given conventional intracytoplasmic sperm injection (C-ICSI) and those administered P-ICSI were examined. RESULTS: P-ICSI showed significantly more favorable results, with a survival rate of 97.0% (C-ICSI: 94.1%, P < .010) and a fertilization rate of 83.5% (C-ICSI: 70.6%, P < .001). There were no differences in the blastocyst development rate, implantation rate, miscarriage rate, live birth rate, gestational age, birth weight, proportion of male neonates, cesarean section rate, and congenital abnormalities between the two patient groups. CONCLUSIONS: Our comparison of P-ICSI with C-ICSI showed that P-ICSI significantly improved the survival and fertilization.

A chordate species lacking Nodal utilizes calcium oscillation and Bmp for left-right patterning.

Larvaceans are chordates with a tadpole-like morphology. In contrast to most chordates of which early embryonic morphology is bilaterally symmetric and the left-right (L-R) axis is specified by the Nodal pathway later on, invariant L-R asymmetry emerges in four-cell embryos of larvaceans. The asymmetric cell arrangements exist through development of the tailbud. The tail thus twists 90° in a counterclockwise direction relative to the trunk, and the tail nerve cord localizes on the left side. Here, we demonstrate that larvacean embryos have nonconventional L-R asymmetries: 1) L- and R-cells of the two-cell embryo had remarkably asymmetric cell fates; 2) Ca2+ oscillation occurred through embryogenesis; 3) Nodal, an evolutionarily conserved left-determining gene, was absent in the genome; and 4) bone morphogenetic protein gene (Bmp) homolog Bmp.a showed right-sided expression in the tailbud and larvae. We also showed that Ca2+ oscillation is required for Bmp.a expression, and that BMP signaling suppresses ectopic expression of neural genes. These results indicate that there is a chordate species lacking Nodal that utilizes Ca2+ oscillation and Bmp.a for embryonic L-R patterning. The right-side Bmp.a expression may have arisen via cooption of conventional BMP signaling in order to restrict neural gene expression on the left side.

Effect on clinical and neonatal outcomes of blastocelic microsuction prior to vitrification.

PURPOSE: Microsuction (MS) is a technique for mechanically emptying fluid from blastocele using a microneedle. In this study, we evaluated the improvement in clinical and neonatal outcomes of vitrified blastocyst transfer programs when MS of blastocelic fluid was used before vitrification. METHODS: This was a retrospective study based on data collected between March 2014 and August 2016. A total of 317 blastocysts obtained from 211 patients were analyzed. The blastocelic fluid of expanded blastocysts was aspirated completely, and blastocysts were collapsed prior to vitrification. Clinical and neonatal outcomes of warmed blastocysts were compared. RESULTS: The survival rate of the MS blastocyst was significantly higher compared with the nontreatment control (98.7% vs 89.3%, OR: 9.34, 95% CI: 2.35-36.8, P < 0.01). The rates of implantation and live birth were higher in the MS group than in the control group, but the differences were not significant. There were no differences in gestational age, birthweight, proportion of male babies, rates of cesarean section, and congenital abnormalities. CONCLUSION: The MS procedure improved blastocyst survival and had little effect on further embryo development after warming.

[A Case of Liver Metastasis from a Primary Adenocarcinoma of the Appendix Presenting Five Months after the Initial Surgery].

A 70-year-old man with lower right quadrant abdominal discomfort was admitted to our hospital. Colonoscopy identified a villous tumor protruding into the cecal lumen from the appendiceal orifice. Abdominal computed tomography(CT)revealed a cecal tumor with a swollen appendix. An appendiceal cecal tumor with obliterative appendicitis was diagnosed, and we performed an appendicectomy with removal of part of the cecum. On pathological examination, well to moderately differentiated adenocarcinoma with infiltration of the proper muscular layer was diagnosed. No additional treatment was given as the patient refused further surgery and chemotherapy. However, a metastatic tumor in S4/8 of the liver was seen on CT 5 months after the initial surgery. A resection of liver metastasis was performed after chemotherapy. We report herein a rare case of primary appendiceal adenocarcinoma reoccurring shortly after surgery.

Patterning and morphogenesis of the intricate but stereotyped oikoplastic epidermis of the appendicularian, Oikopleura dioica.

Mechanisms for morphogenetic processes that generate complex patterns in a reproducible manner remain elusive. Live imaging provides a powerful tool to record cell behaviors. The appendicularian, Oikopleura dioica, is a planktonic tunicate that has a rapid developmental speed, small number of cells (less than 3500 cells in a juvenile), and a transparent body. The trunk epidermis, called the oikoplastic epithelium (OE), has elaborate cellular arrangements showing a complex pattern to secrete so-called "house" made of extracellular components. The OE is characterized by invariant number, size, and shape of the monolayer epithelial cells. Pattern formation is achieved during 5h of larval development without growth of the body, making this a suitable system for live imaging of a two-dimensional (2D) sheet. First, we subdivided the OE and defined several domains by cellular resolution, and systematically gave names to the constituent cells, since there is no variation among individuals. Time-lapse imaging of the epidermal cells revealed region-specific pattern formation processes. Each identified domain served as a compartment into which distribution of descendant cells of founder cells is restricted. Regulation of orientation, timing, and the number of rounds of cell divisions, but not cell death and migration, was a critical mechanism for determination of final cell arrangement and size. In addition, displacement of epithelial sheet plates was observed in the Eisen domain. Stem-cell-like cell divisions, whereby large mother stem cells generate a chain of small daughter cells, were involved in formation of the Nasse region and ventral sensory organ. These are the first examples of this kind of stem-cell-like cell division in deuterostomes. Furthermore, labeling of the left or right blastomere of the two-cell-stage embryo, which roughly gives rise to the left or right side of the body, respectively, revealed that the boundary of the descendant cells does not match with the midline of the trunk epidermis. Left and right descendants largely invade into the opposite side in an invariant way, suggesting the possibility that specification of the OE cell identities may occur later in development, most probably around hatching, and depending on cell position in the OE epithelial sheet. These detailed descriptions of OE patterning processes provide basic and essential information to analyze further cell behaviors in the generation of elaborate and intricate but stereotyped 2D cellular patterns in this advantageous model system for developmental and cell biological studies in chordates.

The relationship between attachment style and postpartum depression.

Although an increasing number of studies show an association between adult attachment style and mood disorders, the relationship between adult attachment style and depression associated with childbirth is largely unknown. This study investigated the association between women's attachment style, postpartum depression (PPD), and other risk factors. During the 32nd week of pregnancy, 84 women were interviewed using the Attachment Style Interview. Participants also completed self-report questionnaires about reaction to pregnancy, family relationships, current life stresses, and symptoms of depression and anxiety. At one-month postpartum, they were evaluated for postpartum depressive symptoms using the Mini-International Neuropsychiatric Interview. Eighty-two women completed the second self-report questionnaires and were evaluated for PPD. The data of 76 women were eligible for analysis. PPD was present in 21%. An insecure attachment style was significantly related to depression. A multiple logistic regression analysis showed significant effects for insecure attachment, social economic status, and antenatal depression on PPD. Adding the insecure attachment style factor to the logistic model that predicted PPD increased the area under the curve to 0.87 (95% CI .77-.98; p < .05). The inclusion of attachment styles in assessments of perinatal depressive disorders could improve screening and the design of interventions.

Reliability and validity of the Japanese edition of the Defense Style Questionnaire 40.

Defense styles have a close relationship with ego development and psychopathology. The purpose of the present paper was to examine the reliability and validity of the Japanese edition of the Defense Style Questionnaire (DSQ-40; Andrews et al. 1993). Six hundred and six Japanese university students (348 female) completed the DSQ-40 and Maudsley Personality Inventory (MPI). The neurotic tendency had positive correlations with immature and neurotic defense styles and a negative correlation with the mature defense style. The extroversion tendency had positive correlations with the mature and neurotic defense styles and a negative correlation with the immature defense style. There was a significant test-retest correlation for all items of the DSQ-40 (n = 284). The results show that the Japanese version of the DSQ-40 had concurrent validity with the MPI and a test-retest reliability of 2 months, although there was some doubt about the validity of the factor structure of the DSQ-40. Therefore, the DSQ-40 is a useful scale in Japan to measure ego development and ego function through defense styles.