The Common Sense Model in Raynaud's Phenomenon:Do illness perceptions account for variance in symptom severity and quality of life?

People with Raynaud’s phenomenon (RP) experience poorer mental health and quality of life than the general population, and there is limited evidence for treatment options in RP. The Common Sense Model of illness representations (CSM) is a well-established theoretical model, which has not yet been robustly investigated in RP, but may provide potential avenues for psychological interventions with the ability to explore perceptions and beliefs, such as cognitive behavioural therapy (CBT). The study aims were to investigate illness perceptions and examine the relationship between illness perceptions and symptom severity and quality of life in RP to explore a theoretical basis for potential treatment avenues. A cross-sectional online questionnaire design was employed and 169 adults with RP (primary or secondary) were analysed. Illness perceptions significantly differed between primary and secondary RP types on all but one domain (p &lt; .05). Hierarchical multiple regressions indicated that illness perception subscales made a significant unique contribution to the models explaining 65% variance in symptom severity (R2 = .65, p &lt; .001) and 30% variance in quality of life (R2 = .30, p &lt; .001). This novel study provides preliminary evidence regarding the applicability of the CSM to RP in a clinically meaningful way. CBT, which can specifically target illness perceptions within a wider psychological formulation, may be helpful for individuals with RP who are experiencing psychological distress in relation to symptom severity. Further work is needed to develop outcome measures specific to RP and tailor interventions to manage distress and impaired quality of life.<br/

The Common Sense Model in Raynaud's Phenomenon:Do illness perceptions account for variance in symptom severity and quality of life?

People with Raynaud’s phenomenon (RP) experience poorer mental health and quality of life than the general population, and there is limited evidence for treatment options in RP. The Common Sense Model of illness representations (CSM) is a well-established theoretical model, which has not yet been robustly investigated in RP, but may provide potential avenues for psychological interventions with the ability to explore perceptions and beliefs, such as cognitive behavioural therapy (CBT). The study aims were to investigate illness perceptions and examine the relationship between illness perceptions and symptom severity and quality of life in RP to explore a theoretical basis for potential treatment avenues. A cross-sectional online questionnaire design was employed and 169 adults with RP (primary or secondary) were analysed. Illness perceptions significantly differed between primary and secondary RP types on all but one domain (p &lt; .05). Hierarchical multiple regressions indicated that illness perception subscales made a significant unique contribution to the models explaining 65% variance in symptom severity (R2 = .65, p &lt; .001) and 30% variance in quality of life (R2 = .30, p &lt; .001). This novel study provides preliminary evidence regarding the applicability of the CSM to RP in a clinically meaningful way. CBT, which can specifically target illness perceptions within a wider psychological formulation, may be helpful for individuals with RP who are experiencing psychological distress in relation to symptom severity. Further work is needed to develop outcome measures specific to RP and tailor interventions to manage distress and impaired quality of life.<br/

Adult patients’ experiences of NHS specialist services for chronic fatigue syndrome (CFS/ME):a qualitative study in England

Abstract Background Few studies have explored patients’ experiences of treatment for CFS/ME. This study aims to fill this gap by capturing the perspective of patients who have been treated by NHS specialist CFS/ME services in England. Methods Semi-structured interviews were conducted during the period June–September 2014 with 16 adults who were completing treatment at one of three outpatient NHS specialist CFS/ME services. Interviews were analysed thematically using constant comparison techniques, with particular attention paid to contrasting views. Results Three themes were identified: ‘Journey to specialist services’; ‘Things that help or hinder treatment’; and ‘Support systems’. Within these themes nine sub-themes were identified. A wide range of factors was evident in forming participants’ experiences, including personal characteristics such as perseverance and optimism, and service factors such as flexibility and positive, supportive relationships with clinicians. Participants described how specialist services played a unique role, which was related to the contested nature of the condition. Many participants had experienced a lack of validation and medical and social support before attending a specialist service. Patients’ experiences of life before referral, and the concerns that they expressed about being discharged, highlighted the hardship and obstacles which people living with CFS/ME continue to experience in our society. Conclusions The experiences of CFS/ME patients in our study showed that NHS specialist CFS/ME services played a vital role in patients’ journeys towards an improved quality of life. This improvement came about through a process which included validation of patients’ experiences, acceptance of change, practical advice and support, and therapeutic outcomes

Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study

The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B

Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study

The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B

Children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME):a systematic review and meta-ethnography of qualitative studies

Objective To synthesis the qualitative studies of children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Design Systematic review and meta-ethnography. Background CFS/ME is an important disabling illness, with uncertain cause and prognosis. As a result, children with CFS/ME can find themselves living with greater uncertainty and stigma, exacerbating the impact of the condition. There is a growing body of qualitative research in CFS/ME, yet there has been no attempt to systematically synthesis the studies involving children. Methods Studies exploring the experiences of children diagnosed with CFS/ME, published or unpublished, using qualitative methods were eligible. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched as well as grey literature, reference lists and contacting authors. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography. Results Ten studies involving 82 children with CFS/ME aged 8–18 were included. Our synthesis describes four third-order constructs within children's experiences: (1) disruption and loss: physical, social and the self; (2) barriers to coping: suspension in uncertainty, problems with diagnosis and disbelief; (3) facilitators to coping: reducing uncertainty, credible illness narratives, diagnosis and supportive relationships and (4) hope, personal growth and recovery. CFS/ME introduces profound biographical disruption through its effects on children's ability to socialise, perform school and therefore how they see their future. Unfamiliarity of the condition, problems with diagnosis and felt stigma prevent children from forming a new illness identity. Children adopt coping strategies such as building credible explanations for their illness. Conclusions Physical, social, emotional and self-dimensions of life should be included when treating and measuring outcomes from healthcare in paediatric CFS/ME. There is a need for greater recognition and diagnosis of childhood CFS/ME, specialist advice on activity management and improved communication between health and education providers to help children cope with their condition

Review of young driver risk taking and its association with other risk taking behaviours

This report documents the investigation of the relationship between risky driving behaviours and other health risk behaviours among youth and young adults, locally and elsewhere. Literature reviews were undertaken of the development of risk taking; young driver behaviour; substance use including alcohol, smoking and illicit drugs; unsafe sex, and self-harm and suicide to identify and compare common risk factors for local youth and those elsewhere. Countermeasures that can be adopted from other risk taking areas and applied to young driver risk taking were also reviewed. A number of recommendations were provided for potential interventions to reduce risk taking on the road as well as others for additional research into the relationship between risk taking on the road and elsewhere for Western Australian youth.Road Safety Council of Western Australiahttp://deepblue.lib.umich.edu/bitstream/2027.42/94210/1/102889.pd

Training the Workforce to Conduct Embedded Pragmatic Clinical Trials to Improve Care for People Living with Dementia and Their Caregivers

The National Institute on Aging IMbedded Pragmatic Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias Clinical Trials (IMPACT) Collaboratory serves as a national resource for the conduct of embedded pragmatic clinical trials to improve the care of people living with dementia (PLWD) in partnership with the healthcare systems that serve them. Inherent in this objective is the need to train and support a cadre of investigators prepared to conduct this work now and in the future. The Training Core of the IMPACT Collaboratory supports the training of investigators to become experts in this field through three objectives: (1) curricula development and dissemination; (2) network generation and navigation; and (3) a career development award program. The innovative approach of the Training Core will require developing content and providing training experiences that recognize the unique challenges of research at the intersection of health systems, pragmatic trials, and PLWD and their caregivers. Ultimately, we seek to build the nation’s capacity to conduct research that bridges the gaps between efficacy studies to effectiveness research to implementation science. Although foundational resources in the methods of each of these areas are already available, few actually focus on pragmatic trials embedded within healthcare systems that focus on PLWD. To bring new interventions for PLWD from efficacy to widespread implementation, researchers must build diffusability, adaptability, heterogeneity, and scalability into the design of the intervention. In achieving these objectives, the Training Core will utilize the network of investigators, institutions, and stakeholders represented in the IMPACT Collaboratory

Dynamic Interaction of TTDA with TFIIH Is Stabilized by Nucleotide Excision Repair in Living Cells

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy