Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation

Parent‐of‐origin–dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1–6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25‐hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = –0.34 and –0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle‐bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.     

Intraoperative assessment of colorectal anastomotic integrity: a systematic review

Background

Surgeons have attempted to minimize postoperative anastomotic complications by employing intraoperative tests and manoeuvres to assess colorectal anastomotic integrity. These have evolved over time with improvement in operative technology and techniques. This systematic review aims to examine the impact of such intraoperative assessments.

Methods

A systematic review of studies assessing intraoperative anastomotic assessments and their impact on postoperative anastomotic complications was performed. Intraoperative measures undertaken as a result of intraoperative assessments and postoperative anastomotic complications were analysed.

Results

37 Studies were identified. 13 studies evaluated basic mechanical patency tests, ten studies evaluated endoscopic visualisation techniques and 14 studies evaluated microperfusion techniques. Postoperative anastomotic complications were significantly lower in patients tested with basic mechanical patency tests compared to those untested (non-RCT: 4.1 vs. 8.1 %, p = 0.03, RCTs: 5.8 vs. 16.0 %, p = 0.024). There were no differences in postoperative anastomotic complications between tested and non-tested cohorts in non-randomised cohort studies evaluating endoscopic visualisation techniques. However, intraoperative measures taken after abnormal intraoperative tests may have reduced the number of postoperative complications. Perfusion analysis techniques are not in routine widespread clinical practice as yet, but newer techniques such as fluorescent dyes and imaging under near infrared light show technical feasibility.

Conclusions

Intraoperative colorectal anastomotic assessment has evolved together with advancement of technology in the surgical setting. Moderate benefit in terms of lower postoperative anastomotic complications has been shown with basic mechanical patency testing and more recently with intraoperative endoscopic visualisation of colorectal anastomoses. The next advance and possible introduction into routine practice may include the use of microperfusion techniques. The latest in this group of techniques, which utilise autofluorescent dyes such as Indocyanine green, hold great potential. Well-planned controlled studies or ideally, randomised controlled trials need to be conducted to further assess the benefit of these latest techniques.     

Discovery of Thienoimidazole-Based HCV NS5A Genotype 1a and 1b Inhibitors

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Can Toll-Like Receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection?

The current literature describes pivotal mechanisms in which hepatitis B virus (HBV) induces liver diseases including inflammation, cirrhosis and hepatocellular carcinoma (HCC). It appears that differences in genetic and immunological parameters between patients and controls may be responsible for inducing the prolonged forms of the infection. Previous studies demonstrated that Toll-Like Receptors (TLRs) play key roles in viral recognition and inducing appropriate immune responses. Therefore, TLRs can be considered as key sensors for HBV recognition and subsequent induction of immune responses against this virus. It has also been shown that the TLR2 detects several microbial PAMPs either in its homodimer form or in a heterodimer with TLR1 or TLR6 and subsequently activates NF-κB in a MYD88 dependent manner. Therefore, defective TLR2 expression may result in impaired immune responses against HBV which is reported in long-term forms of hepatitis B. This review presents the recent data regarding the status and important roles played by TLR2 in HBV recognition and induction or suppression of immune responses against HBV as well as its roles in the pathogenesis of cirrhosis and HCC in prolonged hepatitis B forms.     

The Effects of Decreasing Maternal Anxiety on Fetal Oxygenation and Nucleated Red Blood Cells Count in the Cord Blood

Objective: Vasoconstriction during anxiety reduces fetal oxygenation and leads to hypoxia. Hypoxia in turn results in increase of the number of nucleated red blood cells (NRBCs) in the cord blood. The present study aimed to assess the effect of decreasing maternal anxiety on fetal oxygenation and NRBCs count in the cord blood. Methods:. In this study, 150 women were randomly divided into two intervention groups [supportive care and acupressure in BL32 (bladder) acupoint] and a control group (hospital routine care). The infants'' cord blood was investigated regarding the number of NRBCs and the intensity of hypoxia after birth. Then, the data were entered into the SPSS statistical software (v. 16) and analyzed using ANOVA, Chi-square test, and logistic regression analysis. Findings : The significant difference was found between the two groups regarding the number of NRBCs counted in the peripheral blood smear (P<0.001). Besides, a significant relationship was observed between the length of the first and second stages of labor and the number of NRBCs in the cord blood (P=0.01). Also, a significant association was observed between the type of delivery and the number of NRBCs in the cord blood in both intervention (P<0.001) and control groups (P=0.03). Conclusion: Doula supportive care and acupressure at BL32 point reduced the length of labor stages as well as the anxiety level. Also, nucleated red blood cells were less in the 2 groups of intervention than in control group. Regarding the fact that nucleated red blood cells cannot be the only factor for hypoxia predicting, for affirmation of this theory study with higher sample size and survey of mothers at high risk are needed.Key Words: Acupressure; Anxiety; Delivery Outcome; Doula     

Effect of age and route of inoculation on outcome of neonatal herpes simplex virus infection in guinea pigs

The morbidity and mortality of neonatal herpes simplex virus infection remains unacceptably high despite antiviral therapy. A better understanding of factors that might contribute to this poor outcome is needed but has been hindered by a lack of a good animal model. The recently described guinea pig model of neonatal HSV-2 infection was used to explore the effect of age and route of inoculation on the outcome of infection. After intranasal inoculation the onset, extent, and severity of the primary disease, as well as the number of recurrent lesion days, varied inversely with age. The route of inoculation also affected the outcome. Newborn animals were inoculated either intradermally on the scalp or by the intranasal, oral or corneal route. Animals inoculated on the scalp had the best outcome with no deaths or evidence of neurologic disease while the intranasal route produced the most severe disease, 88% mortality. Neurologic disease was common after oral (41%) and corneal (56%) inoculation but resolved spontaneously whereas following intranasal (39%) inoculation all animals with neurologic disease died. Recurrent disease manifest by cutaneous lesions was observed in all survivors of each group but also differed by the route of inoculation. The guinea pig model of neonatal HSV-2 disease appears to mimic human disease. The studies presented here show that the outcome of infection is influenced by the age and route of inoculation. © 1996 Wiley-Liss, Inc.