57 research outputs found
Attention to eye contact in the West and East: Autonomic responses and evaluative ratings
Eye contact has a fundamental role in human social interaction. The special appearance of the human eye (i.e., white sclera contrasted with a coloured iris) implies the importance of detecting another person's face through eye contact. Empirical studies have demonstrated that faces making eye contact are detected quickly and processed preferentially (i.e., the eye contact effect). Such sensitivity to eye contact seems to be innate and universal among humans; however, several studies suggest that cultural norms affect eye contact behaviours. For example, Japanese individuals exhibit less eye contact than do individuals from Western European or North American cultures. However, how culture modulates eye contact behaviour is unclear. The present study investigated cultural differences in autonomic correlates of attentional orienting (i.e., heart rate) and looking time. Additionally, we examined evaluative ratings of eye contact with another real person, displaying an emotionally neutral expression, between participants from Western European (Finnish) and East Asian (Japanese) cultures. Our results showed that eye contact elicited stronger heart rate deceleration responses (i.e., attentional orienting), shorter looking times, and higher ratings of subjective feelings of arousal as compared to averted gaze in both cultures. Instead, cultural differences in the eye contact effect were observed in various evaluative responses regarding the stimulus faces (e.g., facial emotion, approachability etc.). The rating results suggest that individuals from an East Asian culture perceive another's face as being angrier, unapproachable, and unpleasant when making eye contact as compared to individuals from a Western European culture. The rating results also revealed that gaze direction (direct vs. averted) could influence perceptions about another person's facial affect and disposition. These results suggest that cultural differences in eye contact behaviour emerge from differential display rules and cultural norms, as opposed to culture affecting eye contact behaviour directly at the physiological level.Public Library of Science open acces
Population Pharmacokinetics and Pharmacodynamics of Dobutamine in Neonates on the First Days of Life
Aims:
To describe the pharmacokinetics (PK) and concentration‐related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects modelling.
Methods:
Dosing, plasma concentration and haemodynamic monitoring data from a dose‐escalation study were analysed with a simultaneous population PK and pharmacodynamic model. Neonates receiving continuous infusion of dobutamine 5–20 μg kg−1 min−1 were included. Left ventricular ejection fraction (LVEF) and cardiac output of right and left ventricle (RVO, LVO) were measured on echocardiography; heart rate (HR), mean arterial pressure (MAP), peripheral arterial oxygen saturation and cerebral regional oxygen saturation were recorded from patient monitors.
Results:
Twenty‐eight neonates with median (range) gestational age of 30.4 (22.7–41.0) weeks and birth weight (BW) of 1618 (465–4380) g were included. PK data were adequately described by 1‐compartmental linear structural model. Dobutamine clearance (CL) was described by allometric scaling on BW with sigmoidal maturation function of postmenstrual age (PMA). The final population PK model parameter mean typical value (standard error) estimates, standardised to median BW of 1618 g, were 41.2 (44.5) L h−1 for CL and 5.29 (0.821) L for volume of distribution, which shared a common between subject variability of 29% (17.2%). The relationship between dobutamine concentration and RVO/LVEF was described by linear model, between concentration and LVO/HR/MAP/cerebral fractional tissue oxygen extraction by sigmoidal Emax model.
Conclusion:
In the postnatal transitional period, PK of dobutamine was described by a 1‐compartmental linear model, CL related to BW and PMA. A concentration–response relationship with haemodynamic variables has been established
Premature ovarian failure and ovarian autoimmunity
Premature ovarian failure (POF) is defined as a syndrome characterized by
menopause before the age of 40 yr. The patients suffer from anovulation
and hypoestrogenism. Approximately 1% of women will experience menopause
before the age of 40 yr. POF is a heterogeneous disorder with a
multicausal pathogenesis involving chromosomal, genetic, enzymatic,
infectious, and iatrogenic causes. There remains, however, a group of POF
patients without a known etiology, the so-called "idiopathic" form. An
autoimmune etiology is hypothesized for the POF cases with a concomitant
Addison's disease and/or oophoritis. It is concluded in this review that
POF in association with adrenal autoimmunity and/or Addison's disease
(2-10% of the idiopathic POF patients) is indeed an autoimmune disease.
The following evidence warrants this view: 1) The presence of
autoantibodies to steroid-producing cells in these patients; 2) The
characterization of shared autoantigens between adrenal and ovarian
steroid-producing cells; 3) The histological picture of the ovaries of
such cases (lymphoplasmacellular infiltrate around steroid-producing
cells); 4) The existence of various autoimmune animal models for this
syndrome, which underlines the autoimmune nature of the disease. There is
some circumstantial evidence for an autoimmune pathogenesis in idiopathic
POF patients in the absence of adrenal autoimmunity or Addison's disease.
Arguments in support of this are: 1) The presence of cellular immune
abnormalities in this POF patient group reminiscent of endocrine
autoimmune diseases such as IDDM, Graves' disease, and Addison's disease;
2) The more than normal association with IDDM and myasthenia gravis. Data
on the presence of various ovarian autoantibodies and anti-receptor
antibodies in these patients are, however, inconclusive and need further
evaluation. A strong argument against an autoimmune pathogenesis of POF in
these patients is the nearly absent histological confirmation (the
presence of an oophoritis) in these cases (< 3%). However, in animal
models using ZP immunization, similar follicular depletion and fibrosis
(as in the POF women) can be detected. Accepting the concept that POF is a
heterogenous disorder in which some of the idiopathic forms are based on
an abnormal self-recognition by th
Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 x 10(-8)) with GDM, mapping to/near MTNR1B (P = 4.3 x 10(-54)), TCF7L2 (P = 4.0 x 10(-16)), CDKAL1 (P = 1.6 x 10(-4)), CDKN2A-CDKN2B (P = 4.1 x 10(-9)) and HKDC1 (P = 2.9 x 10(-8)). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.Peer reviewe
Primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC
Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation
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