Role of Heme Pocket Water in Allosteric Regulation of Ligand Reactivity in Human Hemoglobin

Water molecules can enter the heme pocket after the escape of ligand from myoglobins and hemoglobins, hydrogen bond with the distal histidine, and introduce steric barriers to ligand rebinding. The photodissociated CO complexes of human hemoglobin and its isolated α and β chains were subjected to spectrokinetic analysis of the effect of heme hydration on ligand rebinding. A strong coupling was observed between heme hydration and quaternary state. This coupling may contribute significantly to the 20–60-fold difference between the R- and T-state bimolecular CO binding rate constants and thus to the modulation of ligand reactivity that is the hallmark of hemoglobin allostery. Heme hydration proceeded over the course of several kinetic phases in the tetramer, including the R to T quaternary transition. An initial 150 ns hydration phase increased the R-state distal pocket water occupancy, n(w)(R), to a level similar to that of the isolated α (~60%) and β (~10%) chains, resulting in a modest barrier to ligand binding. A subsequent phase, concurrent with the first step of the R → T transition, further increased the level of heme hydration, increasing the barrier. The final phase, concurrent with the final step of the allosteric transition, brought the water occupancy of the T-state tetramer, n(w)(T), even higher and close to full occupancy in both the α and β subunits (~90%). This hydration level could present an even larger barrier to ligand binding and contribute significantly to the lower iron reactivity of the T state toward CO

Spinodal-assisted crystallization in polymer melts

Recent experiments in some polymer melts quenched below the melting temperature have reported spinodal kinetics in small-angle x-ray scattering before the emergence of a crystalline structure. To explain these observations we propose that the coupling between density and chain conformation induces a liquid-liquid binodal within the equilibrium liquid-crystalline solid coexistence region. A simple phenomenological theory is developed to illustrate this idea, and several experimentally testable consequences are discussed. Shear is shown to enhance the kinetic role of the hidden binodal

Psychometric Properties of the German Version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER)

Dysfunctional trauma-related cognitions are associated with posttraumatic stress disorder (PTSD). The psychometric properties of the German version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223 children and adolescents (7–16 years) with a history of different traumatic events. Confirmatory factor analyses supported the original two-factor structure—permanent and disturbing change (CPTCI-PC) and fragile person in a scary world (CPTCI-SW). The total scale and both subscales showed good internal consistency. Participants with PTSD had significantly more dysfunctional trauma-related cognitions than those without PTSD. Dysfunctional posttraumatic cognitions correlated significantly with posttraumatic stress symptoms (PTSS; r = .62), depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric properties and may facilitate evaluation of treatments and further research on the function of trauma-related cognitions in children and adolescents. (Partial) correlations provide empirical support for the combined DSM-5 symptom cluster negative alterations in cognitions and mood

Health related quality of life in Malaysian children with thalassaemia

BACKGROUND: Health Related Quality of Life (HRQoL) studies on children with chronic illness such as thalassaemia are limited. We conducted the first study to investigate if children with thalassaemia have a lower quality of life in the four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical, emotional, social and role (school) functioning compared to the healthy controls allowing for age, gender, ethnicity and household income. METHODS: The PedsQL 4.0 was administered to children receiving blood transfusions and treatments at Hospital Kuala Lumpur, Malaysia using PedsQL 4.0 generic Scale Score. Accordingly, the questionnaire was also administered to a control group of healthy school children. Socio-demographic data were also collected from patients and controls using an interview schedule designed for the study. RESULTS: Of the 96 thalassaemia patients approached, 78 gave consent to be interviewed giving a response rate of 81.3%. Out of 235 healthy controls approached, all agreed to participate giving a response rate of 100%. The mean age for the patients and schoolchildren is 11.9 and 13.2 years respectively. The age range for the patients and the schoolchildren is between 5 to 18 years and 7 to 18 years respectively. After controlling for age and demographic background, the thalassaemia patients reported having significantly lower quality of life than the healthy controls. CONCLUSION: Thalassaemia has a negative impact on perceived physical, emotional, social and school functioning in thalassaemia patients which was also found to be worse than the children's healthy counterparts. Continuing support of free desferal from the Ministry of Health should be given to these patients. More understanding and support especially from health authorities, school authorities and the society is essential to enhance their quality of life

A longitudinal examination of the relationship between trauma-related cognitive factors and internalising and externalising psychopathology in physically injured children

Cognitive models of posttraumatic stress disorder (PTSD) highlight maladaptive posttrauma appraisals, trauma memory qualities, and coping strategies, such as rumination or thought suppression, as key processes that maintain PTSD symptoms. Anxiety, depression and externalising symptoms can also present in children in the aftermath of trauma, yet there has been little empirical investigation of the potential relevance of posttrauma cognitive processes for such difficulties. Here, we examined whether: a) acute maladaptive cognitive processes (specifically, maladaptive appraisals, memory qualities, and cognitive coping) were associated with symptoms of PTSD, internalising, and externalising at 1-month posttrauma (T1); and b) changes in these cognitive processes predicted symptom change at a follow-up assessment 6 months later (T2). We recruited 132 6–13 year old children and their parents from emergency departments following the child’s experience of an acute trauma. Children self-reported on their maladaptive appraisals, trauma-memory and cognitive coping strategies, along with symptoms of PTSD, anxiety and depression. Parents also rated children’s internalising and externalising symptoms. We found each cognitive process to be robustly associated with PTSD and non-PTSD internalising symptoms at T1, and change in each predicted change in symptoms to T2. Maladaptive appraisals and cognitive coping were unique predictors of children’s posttrauma internalising. Effects were partially retained even controlling for co-occurring PTSD symptoms. There was less evidence that trauma-specific cognitive processes were associated with externalising symptoms. Findings suggest aspects of cognitive models of PTSD are applicable to broader posttrauma psychopathology, and have implications for how we understand and target children’s posttrauma psychological adjustment

On deciding to have a lobotomy:either lobotomies were justified or decisions under risk should not always seek to maximise expected utility

In the 1940s and 1950s thousands of lobotomies were performed on people with mental disorders. These operations were known to be dangerous, but thought to offer great hope. Nowadays, the lobotomies of the 1940s and 1950s are widely condemned. The consensus is that the practitioners who employed them were, at best, misguided enthusiasts, or, at worst, evil. In this paper I employ standard decision theory to understand and assess shifts in the evaluation of lobotomy. Textbooks of medical decision making generally recommend that decisions under risk are made so as to maximise expected utility (MEU) I show that using this procedure suggests that the 1940s and 1950s practice of psychosurgery was justifiable. In making sense of this finding we have a choice: Either we can accept that psychosurgery was justified, in which case condemnation of the lobotomists is misplaced. Or, we can conclude that the use of formal decision procedures, such as MEU, is problematic

An international survey of patients with thalassemia major and their views about sustaining life-long desferrioxamine use

BACKGROUND: Management of thalassemia major requires patients to have life-long access to a treatment regimen of regular blood transfusions coupled with iron chelation therapy. The objective of this study was to investigate patients' reasons for missing iron chelation therapy with desferrioxamine, and the support to sustain life-long adherence to treatment. METHODS: From October 1999 to May 2000 a survey of patients with thalassemia major was conducted in ten countries: Cyprus, Egypt, Greece, Hong Kong, India, Iran, Italy, Jordan, Taiwan, and the United States. RESULTS: 1,888 questionnaires (65%) were returned. Most patients (1,573) used desferrioxamine, and 79% administered a dose at least 4 days a week. Inaccessibility of the drug was a common reason for missing a dose in India (51%), and in Iran (25%), whereas, in any other country, it was a reason for less than 17% of patients. Overall, 58% reported reasons for missing a dose related to their beliefs or feelings about the medication, and 42% drug-related side effects. CONCLUSION: Many patients miss doses of desferrioxamine and an opportunity remains to develop interventions that provide more support to sustain use of desferrioxamine

Defensive coping and health-related quality of life in chronic kidney disease: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Coping with the stresses of chronic disease is considered as a key factor in the perceived impairment of health related quality of life (HRQL). Little is known though about these associations in chronic kidney disease (CKD). The present study aimed to investigate the relationship of defensive coping and HRQL among patients in different CKD stages, after adjusting for psychological distress, sociodemographic and disease-related variables.</p> <p>Methods</p> <p>The sample consisted of 98 CKD patients, attending a university nephrology department. Seventy-nine (79) pre-dialysis patients of disease stages 3 to 4 and 19 dialysis patients were included. HRQL was assessed by the 36-item Short-Form health survey (SF-36), defensive coping by the Rationality/Emotional Defensiveness (R/ED) scale of the Lifestyle Defense Mechanism Inventory (LDMI) and psychological distress by the depression and anxiety scales of the revised Hopkins Symptom CheckList (SCL-90-R). Regression analyses were carried out to examine the association between SF-36 dimensions and defensive coping style.</p> <p>Results</p> <p>Patients on dialysis had worse scores on SF-36 scales measuring physical aspects of HRQL. In the fully adjusted analysis, a higher defensive coping score was significantly associated with a lower score on the mental component summary (MCS) scale of the SF-36 (worse mental health). In contrast, a higher defensive score showed a small positive association with the physical component summary (PCS) scale of the SF-36 (better health), but this was marginally significant.</p> <p>Conclusions</p> <p>The results provided evidence that emotional defensiveness as a coping style tends to differentially affect the mental and the physical component of HRQL in CKD. Clinicians should be aware of the effects of long-term denial and could examine the possibility of screening for defensive coping and depression in recently diagnosed CKD patients with the aim to improve both physical and mental health.</p

Transactional paths between children and parents in pediatric asthma: Associations between family relationships and adaptation

Introduction. The particular challenges posed by pediatric asthma may have a negative impact on the adaptation of children and their parents. From a transactional approach it is important to examine how reciprocal links between children and parents contribute to explain their adaptation and under which conditions these associations occur. This cross-sectional study aimed at examining the direct and indirect links between children’s and parents’ perceptions of family relationships and adaptation, separately (within-subjects) and across participants (cross-lagged effects), and the role of asthma severity in moderating these associations. Method. The sample comprised 257 children with asthma, aged between 8 and 18 years-old, and one of their parents. Both family members completed self-reported questionnaires on family relationships (cohesion and expressiveness) and adaptation indicators (quality of life and psychological functioning). Physicians assessed asthma severity. Structural Equation Modeling was used to test within-subjects and cross-lagged paths between children’s and parents’ family relationships and adaptation. Results. The model explained 47% of children’s and 30% of parents’ adaptation: family relationships were positively associated with adaptation, directly for children and parents, and indirectly across family members. Asthma severity moderated the association between family relationships and health-related quality of life for children: stronger associations were observed in the presence of persistent asthma. Conclusion. These results highlight the need of including psychological interventions in pediatric healthcare focused on family relationships as potential targets for improving children’s and parents’ quality of life and psychological functioning, and identified the children with persistent asthma as a group that would most benefit from family-based interventions.This study was supported by the R&D Unit Institute of Cognitive Psychology, Vocational and Social Development of the University of Coimbra (PEst-OE/PSI/UI0192/2011) and by the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/69885/2010)