Vasopressin and parental expressed emotion in the transition to fatherhood

In the last decades, parenting researchers increasingly focused on the role of fathers in child development. However, it is still largely unknown which factors contribute to fathers’ beliefs about their child, which may be crucial in the transition to fatherhood. In the current randomized within-subject experiment, the effect of nasal administration of vasopressin (AVP) on both Five Minute Speech Sample-based (FMSS) expressed emotion and emotional content or prosody was explored in 25 prospectivefathers. Moreover, we explored how the transition to fatherhood affected these FMSS-based parameters, using prenatal and early postnatal measurements. Analyses revealed that FMSS-based expressed emotion and emotional content were correlated, but not affected by prenatal AVP administration. However,child’s birth was associated with an increase in positivity and a decrease in emotional prosody, suggesting that the child’s birth is more influential with regard to paternal thoughts and feelings than prenatal AVP administration

Birth of a Father: Fathering in the First 1,000 Days

As a result of societal changes, fathers participate more actively in child care than they used to. In this article, we propose a context-dependent biobehavioral model of emergent fatherhood in which sociocultural, behavioral, hormonal, and neural factors develop and interact during the first 1,000 days of fatherhood. Sociocultural factors, including different expectations of fathers and varying opportunities for paternal caregiving through paid paternal leave, influence paternal involvement. Levels of hormones (e.g., testosterone, vasopressin, oxytocin, cortisol) predict fathers’ parenting behaviors, and involvement in caregiving in turn affects their hormones and brain responses to infant stimuli. The birth of the first child marks the transition to fatherhood and may be a critical period in men’s lives, with a smoother transition to fatherhood predicting more optimal involvement by fathers in subsequent years. A focus on prenatal and early postnatal fathering may pave the way for developing interventions that effectively support fathering during pregnancy and in the first years of their children’s lives

Development and feasibility of the prenatal video-feedback intervention to promote positive parenting for expectant fathers

Objective: the transition period in which men become fathers might provide an important window of opportunity for parenting interventions that may produce long-term positive effects on paternal care and, consequently, child development. Existing prenatal programs traditionally focus on maternal and infant health and seldom involve the father. Study design: This paper describes an interaction-based prenatal parenting intervention program for first-time fathers using ultrasound images, the Prenatal video Feedback Intervention to promote Positive Parenting (VIPP-PRE). We randomised a group of expectant fathers (N = 73) to either the VIPP-PRE or a control condition. Results: Expectant fathers thought the VIPP-PRE was more helpful and influenced their insights into their babies to a greater extent than the control condition. Expectant fathers receiving the VIPP-PRE reported that they particularly liked seeing and interacting with their unborn children as well as receiving feedback on these interactions. The intervention was well received and was considered feasible by both expectant fathers and sonographers and midwives. Discussion: We discuss the VIPP-PRE based on the experiences and perspectives of fathers, interveners, and sonographers and midwives

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

Objectives: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. Methods: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. Results: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). Conclusions: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. S

Specific Heat of URu2_{2}Si2_{2} in Fields to 42 T: Clues to the 'Hidden Order'

The large $\Delta$C observed at 17.5 K in URu$_{2}$Si$_{2}$ is inconsistent with the small, 0.04 $\mu_{B}$ moment measured for the antiferromagnetism observed starting (perhaps coincidentally) at the same temperature. We report measurements of this specific heat transition, thought to be due to some 'hidden order', in magnetic fields between 24 and 42 T, i. e. through the field region where three metamagnetic transtions are known to occur at 35.8, 37.3, and 39.4 T. The response of $\Delta$C in single crystal URu$_{2}$Si$_{2}$ to magnetic field, which includes a change to $\Delta$C being possibly associated with a first order phase transition for high fields, is analyzed to shed further light on the possible explanations of this unknown ordering process. At fields above 35 T, a new high field phase comes into being; the connection between this high field phase revealed by the specific heat and earlier magnetization data is discussed

High Field Studies of the Hidden Order Transition in URu2_2Si2_2

We studied in detail the low temperature/high magnetic field phases of URu$_{2}$Si$_{2}$ single crystals with specific heat, magnetocaloric effect, and magnetoresistance in magnetic fields up to 45 T. Data obtained down to 0.5 K, and extrapolated to T = 0, show a suppression of the hidden order phase at H$_{o}$(0) = 35.9 $\pm$ 0.35 T and the appearance of a new phase for magnetic fields in excess of H$_{1}$(0) = 36.1 $\pm$ 0.35 T observed \textit{only} at temperatures lower than 6 K. In turn, complete suppression of this high field state is attained at a critical magnetic field H$_{2}$(0) = 39.7 $\pm$ 0.35 T. No phase transitions are observed above 40 T. We discuss our results in the context of itinerant vs. localized \textit{f}-electron behavior and consider the implications for the hidden order phase.Comment: 4 pages, 3 figures Submitted May 10, 2002. Revised Sep 17, 200

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Pharmacokinetics of a sustained release formulation of PDGFβ-receptor directed carrier proteins to target the fibrotic liver

Liver fibrogenesis is associated with excessive production of extracellular matrix by myofibroblasts that often leads to cirrhosis and consequently liver dysfunction and death. Novel protein-based antifibrotic drugs show high specificity and efficacy, but their use in the treatment of fibrosis causes a high burden for patients, since repetitive and long-term parenteral administration is required as most proteins and peptides are rapidly cleared from the circulation. Therefore, we developed biodegradable polymeric microspheres for the sustained release of proteinaceous drugs. We encapsulated the drug carrier pPB-HSA, which specifically binds to the PDGF beta R that is highly upregulated on activated myofibroblasts, into microspheres composed of hydrophilic multi-block copolymers composed of poly(L-lactide) and poly ethylene glycol/poly(is an element of-caprolactone), allowing diffusion-controlled release. Firstly, we estimated in mice with acute fibrogenesis induced by a single CCl4 injection the half-life of I-125-labeled pPB-HSA at 40 min and confirmed the preferential accumulation in fibrotic tissue. Subsequently, we determined in the Mdr2-/- mouse model of advanced biliary liver fibrosis how the subcutaneously injected microspheres released pPB-HSA into both plasma and fibrotic liver at 24 h after injection, which was maintained for six days. Although the microspheres still contained protein at day seven, pPB-HSA plasma and liver concentrations were decreased. This reduction was associated with an antibody response against the human albumin-based carrier protein, which was prevented by using a mouse albumin-based equivalent (pPB-MSA). In conclusion, this study shows that our polymeric microspheres are suitable as sustained release formulation for targeted protein constructs such as pPB-HSA. These formulations could be applied for the long-term treatment of chronic diseases such as liver fibrosis

Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition.

BACKGROUND: The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. METHODS: SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD +-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. FINDINGS: LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. INTERPRETATION: Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. FUNDING: This work was supported by the Bill and Melinda Gates Foundation, the Sickkids Research Institute, the Canadian Institutes of Health Research, and the University Medical Center Groningen