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.     

Maternal sensitivity and infant autonomic and endocrine stress responses

Background

Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life.

Aims

To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task.

Study design

Observational repeated measures study.

Subjects

Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants.

Outcome measures

Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained.

Results

Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers.

Conclusions

Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health.     

Radiative Thermal Effects in Large Scale Additive Manufacturing of Polymers: Numerical and Experimental Investigations

The present paper addresses experimental and numerical investigations of a Large Scale Additive Manufacturing (LSAM) process using polymers. By producing large components without geometrical constraints quickly and economically, LSAM processes have the capability to revolutionize many industries. Accurate prediction and control of the thermal history is key for a successful manufacturing process and for achieving high quality and good mechanical properties of the manufactured part. During the LSAM process, the heat emitted by the nozzle leads to an increase in the temperature of the previously deposited layer, which prepares the surface for better adhesion of the new layer. It is therefore necessary to take into account this part of heat source in the transient heat transfer equation to correctly and completely describe the process and predict the temperature field of the manufactured part. The present study contributes to experimental investigations and numerical analysis during the LSAM process. During the process, two types of measurements are performed: firstly, the heat emitted by the nozzle is measured via a radiative heat sensor; secondly, the temperature field is measured using an infrared camera while varying the process speed. At the same time, a numerical simulation model is developed in order to validate the experimental results. The temperature fields of the manufactured parts computed by numerical simulations are in very good agreement with the temperature fields measured by infrared thermograph with the contribution of the nozzle’s heat exchange.     

Timing of vasopressor initiation and mortality in septic shock: a cohort study

Introduction

Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.

Methods

Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.

Results

In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and only a trend to longer duration of ventilator support (P = 0.055) among survivors.

Conclusion

Marked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.     

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL- 10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.     

Metronidazole and amebiasis

Previous reports indicate that metronidazole is highly effective in the therapy of colonic amebiasis and in the treatment of hepatic amebic abscesses when combined with aspiration. A retrospective review of 15 cases of intestinal amebiasis and 12 patients with amebic liver abscesses treated with metronidazole alone is reported. Based on the literature and the clinical response of the patients reported herein, metronidazole is the initial drug of choice in the therapy of amebic colitis because of its ease of administration, efficacy, and low toxicity. In the treatment of hepatic amebic abscesses, metronidazole alone is adequate therapy for most cases, but occasionally there will be progression of the disease despite standard dosages of the drug.     

Ileocecal Tuberculosis

Three cases of ileocecal tuberculosis are presented with a review of pathogenesis, diagnosis and therapy.
Emphasis is placed upon preoperative suspicion and the indications for resectional surgery in combination with antituberculous drugs in the management of the patients.     

Blood transfusion and postoperative infection in orthopedic patients

Adverse effects of the transfusion of homologous blood on tumor recurrence and resistance to bacterial infection have been reported previously, but the findings are inconclusive. A retrospective review of patients undergoing orthopedic surgery was conducted, and the rate of the postoperative infectious complications was compared among those receiving homologous blood, autologous blood, both types, or no transfusion support. An overall postoperative infection rate of 6.1 percent was observed: 6.9 percent among persons receiving homologous blood, 5.0 percent among those receiving autologous blood, 11.9 percent among those receiving both homologous and autologous blood, and 4.9 percent among those not receiving transfusions (p = 0.37). Among patients receiving homologous blood, a subset of 15 patients received homologous whole blood and had an infection rate of 20 percent. Significant predictors of postoperative infection included increasing age, spinal surgery, high admission hematocrit, and greater time in surgery. Of factors relating to transfusion, only the use of homologous whole blood was a significant predictor of postoperative infection, which suggests a detrimental effect of homologous plasma. It can be concluded that, in this group of patients undergoing relatively nontraumatic surgery, several variables that are not related to transfusion, as well as the use of homologous whole blood, were significant predictors of postoperative infection.