The Human Touch: Skin Temperature during the Rubber Hand Illusion in Manual and Automated Stroking Procedures

A difference in skin temperature between the hands has been identified as a physiological correlate of the rubber hand illusion (RHI). The RHI is an illusion of body ownership, where participants perceive body ownership over a rubber hand if they see it being stroked in synchrony with their own occluded hand. The current study set out to replicate this result, i.e., psychologically induced cooling of the stimulated hand using an automated stroking paradigm, where stimulation was delivered by a robot arm (PHANToM^TM force-feedback device). After we found no evidence for hand cooling in two experiments using this automated procedure, we reverted to a manual stroking paradigm, which is closer to the one employed in the study that first produced this effect. With this procedure, we observed a relative cooling of the stimulated hand in both the experimental and the control condition. The subjective experience of ownership, as rated by the participants, by contrast, was strictly linked to synchronous stroking in all three experiments. This implies that hand-cooling is not a strict correlate of the subjective feeling of hand ownership in the RHI. Factors associated with the differences between the two designs (differences in pressure of tactile stimulation, presence of another person) that were thus far considered irrelevant to the RHI appear to play a role in bringing about this temperature effect.     

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease

Purpose

The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown.

Methods

A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m², and the remaining patients were considered to be without significant CKD (eGFR?≥?60 mL/min/1.73m²).

Results

Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value?=?50; sensitivity 75 % and specificity 75 %).

Conclusion

The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.     

Differences in Body Fat Distribution Play a Role in the Lower Levels of Elevated Fasting Glucose amongst Ghanaian Migrant Women Compared to Men

Background

Despite higher levels of obesity, West African migrant women appear to have lower rates of type 2 diabetes than their male counterparts. We investigated the role of body fat distribution in these differences.

Methods

Cross-sectional study of Ghanaian migrants (97 men, 115 women) aged 18–60 years in Amsterdam, the Netherlands. Weight, height, waist and hip circumferences were measured. Logistic regression was used to explore the association of BMI, waist and hip measurements with elevated fasting glucose (glucose≥5.6 mmol/L). Linear regression was used to study the association of the same parameters with fasting glucose.

Results

Mean BMI, waist and hip circumferences were higher in women than men while the prevalence of elevated fasting glucose was higher in men than in women, 33% versus 19%. With adjustment for age only, men were non-significantly more likely than women to have an elevated fasting glucose, odds ratio (OR) 1.81, 95% CI: 0.95, 3.46. With correction for BMI, the higher odds among men increased and were statistically significant (OR 2.84, 95% CI: 1.32, 6.10), but with consideration of body fat distribution (by adding both hip and waist in the analysis) differences were no longer significant (OR 1.56 95% CI: 0.66, 3.68). Analysis with fasting glucose as continuous outcome measure showed somewhat similar results.

Conclusion

Compared to men, the lower rates of elevated fasting glucose observed among Ghanaian women may be partly due to a more favorable body fat distribution, characterized by both hip and waist measurements.     

Independent Validation of an Existing Model Enables Prediction of Hearing Loss after Childhood Bacterial Meningitis

Objective

This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice.

Study design

116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values.

Results

Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort.

Conclusions

Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing.     

Psychiatric Diagnosis Revisited: Towards a System of Staging and Profiling Combining Nomothetic and Idiographic Parameters of Momentary Mental States

Background

Mental disorders may be reducible to sets of symptoms, connected through systems of causal relations. A clinical staging model predicts that in earlier stages of illness, symptom expression is both non-specific and diffuse. With illness progression, more specific syndromes emerge. This paper addressed the hypothesis that connection strength and connection variability between mental states differ in the hypothesized direction across different stages of psychopathology.

Methods

In a general population sample of female siblings (mostly twins), the Experience Sampling Method was used to collect repeated measures of three momentary mental states (positive affect, negative affect and paranoia). Staging was operationalized across four levels of increasing severity of psychopathology, based on the total score of the Symptom Check List. Multilevel random regression was used to calculate inter- and intra-mental state connection strength and connection variability over time by modelling each momentary mental state at t as a function of the three momentary states at t-1, and by examining moderation by SCL-severity.

Results

Mental states impacted dynamically on each other over time, in interaction with SCL-severity groups. Thus, SCL-90 severity groups were characterized by progressively greater inter- and intra-mental state connection strength, and greater inter- and intra-mental state connection variability.

Conclusion

Diagnosis in psychiatry can be described as stages of growing dynamic causal impact of mental states over time. This system achieves a mode of psychiatric diagnosis that combines nomothetic (group-based classification across stages) and idiographic (individual-specific psychopathological profiles) components of psychopathology at the level of momentary mental states impacting on each other over time.     

The Superfast Human Extraocular Myosin Is Kinetically Distinct from the Fast Skeletal IIa,IIb, and IId Isoforms

Humans express five distinct myosin isoforms in the sarcomeres of adult striated muscle (fast IIa, IId, the slow/cardiac isoform I/β, the cardiac specific isoform α, and the specialized extraocular muscle isoform). An additional isoform, IIb, is present in the genome but is not normally expressed in healthy human muscles. Muscle fibers expressing each isoform have distinct characteristics including shortening velocity. Defining the properties of the isoforms in detail has been limited by the availability of pure samples of the individual proteins. Here we study purified recombinant human myosin motor domains expressed in mouse C₂C₁₂ muscle cells. The results of kinetic analysis show that among the closely related adult skeletal isoforms, the affinity of ADP for actin·myosin (K_AD) is the characteristic that most readily distinguishes the isoforms. The three fast muscle myosins have K_AD values of 118, 80, and 55 μm for IId, IIa, and IIb, respectively, which follows the speed in motility assays from fastest to slowest. Extraocular muscle is unusually fast with a far weaker K_AD = 352 μm. Sequence comparisons and homology modeling of the structures identify a few key areas of sequence that may define the differences between the isoforms, including a region of the upper 50-kDa domain important in signaling between the nucleotide pocket and the actin-binding site.     

Patronage in a Holy Place: Preliminary research notes on a ‘parallel structure’ in a Yugoslav pilgrimage centre*

Eric Wolf has argued that the study of patron‐client relations and other ‘parallel structures’ may be useful for furthering our understanding of complex societies. As for political patronage, Wolfs suggestion has been taken to heart. As far as religion is concerned, his suggestion has barely met with any response at all. Data obtained from a Yugoslav peasant community seem to indicate that Wolf s proposition is applicable to the religious field as well. In Medjugorje, a pilgrimage centre in Bosnia‐Hercegovina, a patronage network has evolved around a small group of young local seers. The relations with the ‘official’, clergy‐run Marian devotion are rather strained. This article explores the dynamics of that parallel structure of the institutional Church, and discusses if and in what respects this visionary‐centered patronage network differs from patron‐client configurations in the political field.     

CT Coronary Angiography Is Feasible for the Assessment of Coronary Artery Disease in Chronic Dialysis Patients,Despite High Average Calcium Scores

Purpose

Significant obstructive coronary artery disease (CAD) is common in asymptomatic dialysis patients. Identifying these high risk patients is warranted and may improve the prognosis of this vulnerable patient group. Routine catheterization of incident dialysis patients has been proposed, but is considered too invasive. CT-angiography may therefore be more appropriate. However, extensive coronary calcification, often present in this patient group, might hamper adequate lumen evaluation. The objective of this study was to assess the feasibility of CT-angiography in this patient group.

Methods

For this analysis all patients currently participating in the ICD2 trial (ISRCTN20479861), with no history of PCI or CABG were included. The major epicardial vessels were evaluated on a segment basis (segment 1–3, 5–8, 11 and 13) by a team consisting of an interventional and an imaging specialist. Segments were scored as not significant, significant and not interpretable.

Results

A total of 70 dialysis patients, with a mean age of 66±8 yrs and predominantly male (70%) were included. The median calcium score was 623 [79, 1619].Over 90% of the analyzed segments were considered interpretable. The incidence of significant CAD on CT was 43% and was associated with cardiovascular events during follow-up. The incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in patients with no significant CAD (p<0.01).

Conclusion

Despite the high calcium scores CT-angiography is feasible for the evaluation of the extent of CAD in dialysis patients. Moreover the presence of significant CAD on CT was associated with events during follow-up.     

Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling

Background

The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).

Methodology/Principal Findings

In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dt_max and dP/dt_min with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.

Conclusions/Significance

Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.     

Analytical methods for structural ensembles and dynamics of intrinsically disordered proteins

Intrinsically disordered proteins, proteins that do not have a well-defined three-dimensional structure, make up a significant proportion of our proteome and are particularly prevalent in signaling and regulation. Although their importance has been realized for two decades, there is a lack of high-resolution experimental data. Molecular dynamics simulations have been crucial in reaching our current understanding of the dynamical structural ensemble sampled by intrinsically disordered proteins. In this review, we discuss enhanced sampling simulation methods that are particularly suitable to characterize the structural ensemble, along with examples of applications and limitations. The dynamics within the ensemble can be rigorously analyzed using Markov state models. We discuss recent developments that make Markov state modeling a viable approach for studying intrinsically disordered proteins. Finally, we briefly discuss challenges and future directions when applying molecular dynamics simulations to study intrinsically disordered proteins.