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International audience; Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

Objectives: To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists. Background: The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures. Methods: A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies. Results: Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow-up evaluation was appraised. Conclusions: Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited. © 2013 Wiley Periodicals, Inc.

A universal anti-Xa assay for the determination of rivaroxaban, apixaban and edoxaban drug concentrations would simplify laboratory procedures and facilitate widespread implementation. Following two pilot studies analysing spiked samples and material from 698 patients, we conducted a prospective multicentre cross-sectional study, including 867 patients treated with rivaroxaban, apixaban or edoxaban in clinical practice to comprehensively evaluate a simple, readily available anti-Xa assay that would accurately measure drug concentrations and correctly predict relevant levels in clinical practice. Anti-Xa activity was measured by an assay calibrated with low-molecular-weight heparin (LMWH) in addition to ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). As an external validation, LMWH-calibrated anti-Xa activity was also determined in nine external laboratories. The LMWH-calibrated anti-Xa activity correlated strongly with rivaroxaban, apixaban or edoxaban drug levels [r s = 0·98, 95% confidence interval (CI) 0·98-0·98]. The sensitivity for the clinically relevant cut-off levels of 30, 50 and 100 µg/l was 96·2% (95% CI 94·4-97·4), 96·4% (95% CI 94·4-97·7) and 96·7% (95% CI 94·3-98·1) respectively. Concordant results were obtained in the external validation study. In conclusion, a universal, LMWH-calibrated anti-Xa assay accurately measured rivaroxaban, apixaban and edoxaban concentrations and correctly predicted relevant drug concentrations in clinical practice.

BACKGROUND: Dietitians play an important role in the intervention and prevention of being overweight and obesity. More and more blended care interventions are being implemented. The present study aimed to evaluate the delivery by Dutch dietitians of a multicomponent, evidence-based weight-loss programme (SMARTsize), including counselling for relapse prevention. The aim of this qualitative study was to identify facilitators and barriers to the delivery of SMARTsize.METHODS: Nine semi-structured interviews were conducted with 10 dietitians who participated in a larger implementation study. Each interview was recorded and transcribed verbatim. Determinants of theory of implementation, including characteristics of the user, the innovation, organisational context and setting, and innovation strategy guided interviews and analysis. Data were coded and analysed using the framework approach.RESULTS: According to dietitians, the SMARTsize intervention had a positive influence on patients. The main implementation facilitators were the availability of implementation materials, such as a manual, training in relapse prevention and social support from other dietitians. The main barriers to implementation were organisation and financial reimbursement of cooking classes, the belief that patients need more individual counselling in the starting phase, and the unsuitability for people with low levels of health literacy.CONCLUSIONS: Most dietitians considered that implementation of the SMARTsize intervention consisting of e-health, written information and cooking classes and face-to-face counselling is challenging but feasible. Further development of the SMARTsize intervention and implementation tools is needed to lower experienced barriers. It is also recommended that a version of the intervention to be developed that is suitable for patients with lower levels of health literacy.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se

BACKGROUND AND PURPOSE Reliable prediction of pro-arrhythmic side effects of novel drug candidates is still a major challenge. Although drug-induced pro-arrhythmia occurs primarily in patients with pre-existing repolarisation disturbances, healthy animals are employed for pro-arrhythmia testing. To improve current safety screening, transgenic long QT (LQTS) rabbit models with impaired repolarisation reserve were generated by overexpressing loss-of-function mutations of human HERG (HERG-G628S, loss of IKr ; LQT2), KCNE1 (KCNE1-G52R, decreased IKs ; LQT5), or both transgenes (LQT2-5) in the heart. EXPERIMENTAL APPROACH Effects of K+ channel blockers on cardiac repolarisation and arrhythmia susceptibility were assessed in healthy wild-type (WT) and LQTS rabbits using in vivo ECG and ex vivo monophasic action potential and ECG recordings in Langendorff-perfused hearts. KEY RESULTS LQTS models reflect patients with clinically "silent" (LQT5) or "manifest" (LQT2 and LQT2-5) impairment in cardiac repolarisation reserve: they were more sensitive in detecting IKr -blocking (LQT5) or IK1 /IKs -blocking (LQT2 and LQT2-5) properties of drugs compared to healthy WT animals. Impaired QT-shortening capacity at fast heart rates was observed due to disturbed IKs function in LQT5 and LQT2-5. Importantly, LQTS models exhibited higher incidence, longer duration, and more malignant types of ex vivo arrhythmias than WT. CONCLUSION AND IMPLICATIONS LQTS models represent patients with reduced repolarisation reserve due to different pathomechanisms. As they demonstrate increased sensitivity to different specific ion channel blockers (IKr blockade in LQT5 and IK1 and IKs blockade in LQT2 and LQT2-5), their combined use could provide more reliable and more thorough prediction of (multichannel-based) pro-arrhythmic potential of novel drug candidates.

This study examined (a) psychosocial health care needs of people with type 2 diabetes from the perspective of patients and diabetes healthcare providers in primary care, in terms of topics, attention in diabetes care and preferences and (b) factors associated with a positive attitude towards specialized psychosocial health care.Qualitative focus group study.Using purposive sampling, participants were selected from general practices. In 2012-2013, three focus groups were conducted in people with type 2 diabetes (N = 20) and three with healthcare providers (N = 18).Opinions differed considerably on whether there was a need for psychosocial health care. Topics focused mainly on diabetes-specific issues ranging from a need for additional diabetes education to attention and support in regular diabetes care. However, not all healthcare providers felt competent enough to address psychosocial problems. Some participants reported a need for specialized psychosocial help. A positive attitude towards specialized psychosocial health care appeared to be influenced by care setting (e.g., in the primary care practice or 'outside' mental health care), care accessibility, proactive discussion of psychosocial issues with and referral by healthcare providers and previous experiences with psychosocial health care.Although only few participants expressed a need for specialized psychosocial care, attention for psychosocial well-being in regular diabetes care was generally appreciated.People with type 2 diabetes generally felt psychosocial care could be provided as part of regular diabetes care. Suggestions for healthcare providers to meet psychosocial health care needs include training and discussion tools.目的: 本研究从初级保健中的患者和糖尿病医疗保健提供者的角度,从话题、对糖尿病护理的关注和偏好方面,审查了(a)II型糖尿病患者的心理社会医疗保健需求,以及(b)与对专业心理社会医疗保健的积极态度相关因素。 设计: 定性焦点小组研究。 方法: 通过采用有目的抽样,从 全科医生中选取了参与者。 在2012至2013年间,对II型糖尿病患者(20名)和医疗保健提供者(18名)进行了三次分组座谈会。 结果: 关于是否需要心理社会医疗保健,意见分歧很大。话题主要关注糖尿病特有的问题,从需要额外的糖尿病教育到常规糖尿病护理的关注和支持。然而,并不是所有的医疗保健提供者都觉得能够解决心理社会问题。一些参与者报告说需要专门的心理社会帮助。对专门心理社会医疗保健的积极态度似乎受到保健环境(例如,初级保健实践或‘外部’心理健康护理)、保健可及性、与医疗保健提供者积极讨论心理社会问题和通过他们进行转诊以及以往心理社会医疗保健经验的影响。 结论: 尽管只有少数参与者表示需要专门的心理社会护理,但在常规糖尿病护理中对心理社会健康的关注还是得到了普遍认可。 影响: II型糖尿病患者通常认为心理社会护理可以作为常规糖尿病护理的一部分。医疗保健提供者满足心理社会医疗保健需求的建议包括培训工具和讨论工具。.

Ligand‐based NMR techniques to study protein–ligand interactions are potent tools in drug design. Saturation transfer difference (STD) NMR spectroscopy stands out as one of the most versatile techniques, allowing screening of fragments libraries and providing structural information on binding modes. Recently, it has been shown that a multi‐frequency STD NMR approach, differential epitope mapping (DEEP)‐STD NMR, can provide additional information on the orientation of small ligands within the binding pocket. Here, the approach is extended to a so‐called DEEP‐STD NMR fingerprinting technique to explore the binding subsites of cholera toxin subunit B (CTB). To that aim, the synthesis of a set of new ligands is presented, which have been subject to a thorough study of their interactions with CTB by weak affinity chromatography (WAC) and NMR spectroscopy. Remarkably, the combination of DEEP‐STD NMR fingerprinting and Hamiltonian replica exchange molecular dynamics has proved to be an excellent approach to explore the geometry, flexibility, and ligand occupancy of multi‐subsite binding pockets. In the particular case of CTB, it allowed the existence of a hitherto unknown binding subsite adjacent to the GM1 binding pocket to be revealed, paving the way to the design of novel leads for inhibition of this relevant toxin., Fingerprinting: A powerful protocol by using NMR spectroscopy and molecular dynamics to study multi‐subsite binding pockets has been developed. For cholera toxin subunit B (CTB), the combination of differential epitope mapping saturation transfer difference (DEEP‐STD) NMR, STD competition experiments, transfer‐NOESY, and Hamiltonian replica exchange molecular dynamics (HREMD) unveiled the presence of a novel subsite adjacent to the known subsites of GM1 on CTB.

BACKGROUND AND PURPOSE: 3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood.EXPERIMENTAL APPROACH: We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mouse in vivo, ex vivo precision cut lung slices (PCLS), and in human in vitro cell models to track the effects of CS exposure.KEY RESULTS: Under fenoterol stimulated conditions, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein upregulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed downregulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways.CONCLUSION AND IMPLICATIONS: We show that CS upregulates expression and activity of both PDE3 and PDE4, which regulate real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology.

The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.

To assess maternal health care service utilisation and associated factors in Somali pastoral communities of eastern Ethiopia.Community-based cross-sectional study complemented by qualitative assessments in Adadle district, Somali region, eastern Ethiopia, among 450 women in six kebeles from August to September 2016. Logistic regression was used to assess factors associated with antenatal care use and skilled delivery care use, controlling for confounders.About 27% [95%CI 22.8-31.2%] of women used antenatal care, and 22.6% [95%CI 18.7-26.5%] received skilled delivery service. None of the respondents reported post-natal care. About 43% reported that they had no knowledge of antenatal care, and 46% did not perceive delivery at a health facility as important. Pastoral lifestyle, husband's educational status, women's attitude towards health care service and financial support from the husband were significantly associated with antenatal care utilisation. Health professionals' attitudes, perceptions of institutional delivery, antenatal care utilisation and information about exemptions from maternal health care fees were associated with skilled delivery service utilisation.Improving community awareness of antenatal care, employing female health professionals and culturally adapted guidelines could improve skilled delivery utilisation. In a patriarchal society, involving male partners in all maternal health issues is essential to increase use of maternal health services and to decrease maternal mortality.Evaluer l'utilisation des services de soins de santé maternelle et les facteurs associés dans les communautés pastorales somaliennes dans l'est de l'Ethiopie. MÉTHODES: Etude transversale basée sur la communauté complétée par des évaluations qualitatives dans le district d'Adadle, région somalienne, dans l'est de l'Ethiopie, portant sur 450 femmes dans six kebeles d'août à septembre 2016. Une régression logistique a été utilisée pour évaluer les facteurs associés à l'utilisation des soins prénatals et à l'accouchement sous soins qualifiés, en ajustant pour les facteurs confusionnels. RÉSULTATS: 27% [IC95%: 22.8-31.2%] des femmes ont utilisé des soins prénatals et 22,6% [IC95%: 18.7-26.5%] ont reçu des services d'accouchement qualifiés. Aucune des répondantes n'a signalé des soins postnatals. 43% ont déclaré qu'elles n'avaient aucune connaissance des soins prénatals et 46% ne percevaient pas l'accouchement dans un établissement de santé comme important. Le mode de vie pastoral, le niveau d'éducation du mari, l'attitude des femmes à l'égard des services de santé et le soutien financier du mari étaient significativement associés à l'utilisation des soins prénatals. Les attitudes des professionnels de la santé, les perceptions de l'accouchement en établissement, l'utilisation des soins prénatals et les informations sur les exemptions des frais de soins de santé maternelle ont été associées à l'utilisation des services d'accouchement qualifiés.Améliorer la sensibilisation de la communauté aux soins prénatals, employer des professionnels de la santé féminins et des directives culturellement adaptées pourrait améliorer l'utilisation de l’accouchement qualifié. Dans une société patriarcale, la participation des partenaires masculins à toutes les questions de santé maternelle est essentielle pour accroître l'utilisation des services de santé maternelle et réduire la mortalité maternelle.

Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age‐related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62‐dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age‐related diseases, including age‐related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies., AGEs are toxic compounds formed by non‐enzymatic reactions between sugars and proteins. AGEs are prone to aggregate. Insoluble AGEs are efficiently removed via p62‐selective autophagy. The autophagic removal of AGEs is a conserved pathway, and the lack of p62 leads to accumulation of toxic AGEs in mouse and worms. Enhanced autophagy is protective against glycation‐derived damage. p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies.

Journal of applied crystallography 52(5), 1144 - 1156 (2019). doi:10.1107/S1600576719010720, Single-crystal elastic constants have been derived by lattice strain measurements using neutron diffraction on polycrystalline Ti-6Al-4V, Ti-6Al-2Sn-4Zr-6Mo and Ti-3Al-8V-6Cr-4Zr-4Mo alloy samples. A variety of model approximations for the grain-to-grain interactions, namely approaches by Voigt, Reuss, Hill, Kroener, de Wit and Matthies, including texture weightings, have been applied and compared. A load-transfer approach for multiphase alloys was also implemented and the results are compared with single-phase data. For the materials under investigation, the results for multiphase alloys agree well with the results for single-phase materials in the corresponding phases. In this respect, all eight elastic constants in the dual-phase Ti-6Al-2Sn-4Zr-6Mo alloy have been derived for the first time., Published by Wiley-Blackwell, [S.l.]

Background: Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted.Methods: Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10 000, 20 000 or 40 000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen- specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season).Results: In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P Conclusions: A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40 000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).

Background: Patient-reported outcome measures (PROMs) are increasingly used to establish the value of health care. In order to reflect value, PROMs should measure outcomes that matter to patients. However, patients are not always involved in the development of PROMs. This study therefore aimed to investigate whether PROMs, which were developed without patient involvement, are relevant to patients and whether the level of importance allocated towards aspects of these PROMs varies between patient groups.Methods: All patients from 20 Dutch hospitals undergoing hip or knee surgery in 2014 were invited to a PROMs survey. Participants were asked to rate the importance of each of the items in the HOOS-Physical Function Short form or the KOOS-Physical Function Short form, the EQ-5D and the NRS pain.Results: Most outcomes were considered important. However, 77.7% of hip surgery patients rated being able to run as unimportant. Being able to kneel (32.7%) or squat (39.6%) was not important to a considerable minority of knee surgery patients. Pain, especially during rest, was considered very important by both hip (68.2%) and knee (66.5%) surgery patients. Patients who were older, male, experienced overall bad health and psychological health considered many items from the PROMs less important than other patients.Discussion: Patients differ in what they consider important. Health-care professionals should explore patients’ preferences and discuss which treatment options best fit patients’ preferences. Additionally, if PROMs are used in performance measurement, further research is needed to look at whether and how variation in patient preferences can be taken into account.KEYWORDShip and knee surgery, importance ratings, patient preferences, patient-reported outcome measures

Purpose To explore the strategies used by older people living in Ireland to obtain information about community health and social services. Methods A qualitative exploratory design was used. Focus groups (n = 3) were conducted with community dwelling older people (n = 17). A series of vignettes were used to guide discussion regarding hypothetical situations that approximated real-life scenarios for older people. Data were transcribed verbatim and analysed using content analysis. Results Obtaining information about community health and social services is an ongoing process that requires continuous commitment by older adults. Key strategies which emerged from the data included (i) taking a proactive stance towards accessing health information, (ii) making use of personal networks in your community and (iii) developing ‘insider’ knowledge. Conclusion Older people in this study had a proactive approach to obtaining health information and identified the importance of taking responsibility for managing their own needs. Despite this, obtaining basic information about community health and social services was a challenging and time-consuming process. Future research should focus on developing health literacy interventions that build upon and expand the strategies currently used by older people.

Background\ud \ud Shunts, the main treatment for hydrocephalus, are problematic as they frequently malfunction. Identifying shunt malfunction requires parents to recognize its symptoms and health professionals to integrate parents' information about the child's symptoms within the clinical assessment to reach a diagnosis.\ud Aim\ud \ud To investigate parent–professional shared decision making during the diagnosis of suspected shunt malfunction in acute hospital admissions.\ud Design and methods\ud \ud A mixed method study involving audio recordings of admission consultations, a shared decision making questionnaire and interviews 1-week post-consultation, was undertaken. Twenty-eight family members and fourteen health professionals participated. The interactions were analysed using conversational analysis, framework approach for the interview data and descriptive statistics for questionnaire responses.\ud Findings\ud \ud Both parents and professionals focussed on establishing a diagnosis and ruling out shunt malfunction when a child with hydrocephalus was ill. Participants' perceived effective collaboration as central to this task: parents wanted to contribute to the process of diagnosis by providing information about the likely cause of symptoms. Professionals were satisfied with the level of involvement by parents, although parent satisfaction was more variable. The challenge for professionals was to integrate parents' expertise of their child's presenting symptoms within clinical decision making processes.\ud Conclusion\ud \ud In this context, both parents' and professionals' perceived their interactions to be about problem-solving, rather than making decisions about treatments. Although the shared decision-making model can help patients to make better decisions between treatment options, it is unclear how best to support collaboration between professionals and parents to ensure a good problem-solving process.

BACKGROUND AND PURPOSE The aggregation of α-synuclein is connected to the pathology of Parkinson's disease and prolyl oligopeptidase (PREP) accelerates the aggregation of α-synuclein in vitro. The aim of this study was to investigate the effects of a PREP inhibitor, KYP-2047, on α-synuclein aggregation in cell lines overexpressing wild-type or A30P/A53T mutant human α-syn and in the brains of two A30P α-synuclein transgenic mouse strains. EXPERIMENTAL APPROACH Cells were exposed to oxidative stress and then incubated with the PREP inhibitor during or after the stress. Wild-type or transgenic mice were treated for 5 days with KYP-2047 (2 × 3 mg·kg−1 a day). Besides immunohistochemistry and thioflavin S staining, soluble and insoluble α-synuclein protein levels were measured by Western blot. α-synuclein mRNA levels were quantified by PCR. The colocalization of PREP and α-synuclein,and the effect of KYP-2047 on cell viability were also investigated. KEY RESULTS In cell lines, oxidative stress induced a robust aggregation of α-synuclein,and low concentrations of KYP-2047 significantly reduced the number of cells with α-synuclein inclusions while abolishing the colocalization of α-synuclein and PREP. KYP-2047 significantly reduced the amount of aggregated α-synuclein,and it had beneficial effects on cell viability. In the transgenic mice, a 5-day treatment with the PREP inhibitor reduced the amount of α-synuclein immunoreactivity and soluble α-synuclein protein in the brain. CONCLUSIONS AND IMPLICATIONS The results suggest that the PREP may play a role in brain accumulation and aggregation of α-synuclein, while KYP-2047 seems to effectively prevent these processes.

In cardiac ventricular myocytes, an imbalance between inward and outward currents may prolong action potential duration. This makes the heart vulnerable to the occurrence of so-called torsade de pointes (TdP) arrhythmias, which are life-threatening ventricular tachycardias that create rapid fluctuations of QRS complexes around the isoelectric line on the human ECG. In patients, there are several independent risk factors or ‘challenges’ for TdP arrhythmias, including hypokalaemia, bradycardia, genetic and drug-induced long QT syndromes and chronic congestive heart failure (CHF) (Roden, 2004). A single ‘challenge’ to cardiac ventricular repolarization, for example, the reduction of a single membrane ion current, usually does not result in repolarization-dependent arrhythmias. Apparently, the heart has a reserve, commonly referred to as ‘repolarization reserve’ (Varro and Baczko, 2011), and multiple challenges are therefore usually required in order to provoke arrhythmia. Often, QT-prolonging drugs associated with TdP arrhythmias are the final challenge that exceeds the reserve, resulting in proarrhythmia. Quantification of the repolarization reserve, however, remains difficult. Although a number of surrogate parameters have been suggested (Thomsen et al., 2006), such as temporal or spatial dispersion of action potential duration, optimal quantification of repolarization reserve still requires testing of susceptibility to arrhythmias, where the cumulative severity of the challenges required to exceed the reserve then provides an estimation of the reserve. Interestingly, some drugs, including those that block the inward L-type calcium current (ICa-L), have been shown to be effective against drug-induced arrhythmias, by counteracting one or more of the predisposing challenges (Oros et al., 2010). Only a few experimental large animal models mimicking CHF have been developed. Currently, the efficacy in which ICa-L inhibition prevents or suppresses early after depolarizations (EAD) and polymorphic ventricular tachycardia in CHF is not clear and difficult to predict since calcium-handling disturbances are apparent in this disease (Janse, 2004). Moreover, in a setting of CHF, this apparent simple antiarrhythmic approach has to deal with conflicting imperatives such as antiarrhythmic action versus haemodynamic tolerance. In this issue of the BJP, Milberg et al. (2012a) report the outcome of ICa-L block by verapamil, a well established antiarrhythmic compound, on arrhythmic end points in a rabbit model of non-ischemic CHF with long-QT characteristics (Milberg et al., 2012a). CHF was generated by continuous right ventricular rapid pacing and, subsequently, Langendorff-perfused sham and CHF hearts were subjected to a number of additional challenges in order to provoke arrhythmias: bradycardia, ectopic ventricular activation, severe hypokalaemia and erythromycin-mediated IKr block. Repolarization was prolonged to some extent in CHF but spatial dispersion was not affected at baseline. Only after IKr block, especially transmural dispersion was increased to a larger extent in CHF. Arrhythmias were observed, but their number in hearts from sham animals (four of 11 hearts; 36%) was not significantly different from rabbit hearts with CHF (eight of 11; 73%; P = NS). Unfortunately, surrogate parameters were only reported for normokalemic circumstances, when the repolarization reserve was challenged less severely and thus could not directly be associated with the arrhythmic end point. Remarkably, the findings of the same group published recently (Frommeyer et al., 2011), in which the rabbit hearts were used to analyse the proarrhythmic effect of the IKr blocker sotalol were in favour of the CHF model used here. In this CHF group, sotalol induced EADs (as estimated from monophasic action potential morphology) and TdP in 16 of 18 (89%) hearts compared with seven of 14 (50%) hearts in the sham group. When we solely compare arrhythmia incidence based on these numbers, a P-value of 0.023 is obtained (two-tailed Fisher exact test). However, in both studies, and yet another [seven of 14 (50%) Milberg et al., 2012b], the pronounced incidence of arrhythmias in the sham hearts represents a potential limitation. Nevertheless, verapamil was demonstrated to be an efficient antiarrhythmic drug in this setting, and importantly, we may thus conclude that effectiveness of ICa-L block as antiarrhythmic treatment persists in an isolated rabbit heart model where CHF is added. The next hurdle will be to reach similar conclusions in an in vivo model where CHF is a more prominent proarrhythmic factor. Mechanisms of the antiarrhythmic potential of verapamil against repolarization-dependent arrhythmias have been ascribed to shortening of the QT interval and decreases in beat-to-beat variability of action potential duration (Oros et al., 2010; Bourgonje et al., 2011), and now Milberg et al. (2012a) show that it counteracts spatial dispersion in a CHF heart too. Promising as it seems, verapamil is contraindicated in CHF, especially in cases with severe systolic dysfunction and reduced fractional shortening (Chew et al., 1981). As verapamil inhibits the systolic calcium flux and, consequently, contractility, it is negatively inotropic, and this makes verapamil probably a poor choice in the clinic; certainly, when considering that the concentration used by Milberg et al. (0.75 µM) was unable to suppress arrhythmias completely. In the in vivo complete atrial-ventricular block dog model, verapamil plasma levels of around 0.5 µM clearly were antiarrhythmic but also lowered left ventricular pressure (Oros et al., 2010). Upon titrating verapamil, antiarrhythmic activity could not be observed without a drop in left ventricular pressure (Bourgonje et al., 2011). Other calcium channel antagonists might be a better option, however, and the authors themselves advocate second-generation ICa-L blockers. Take, for instance, nifedipine that more strongly affects smooth than striated muscle (Millard et al., 1983), where lowering peripheral resistance would compensate for negative inotropy. This may still have a major drawback because, in order to preserve blood pressure where contractility is reduced and vessels are dilated, heart rate must increase, which is also unfavourable for an already weakened heart. Obviously, it would be hard to predict the individual effects on vasodilatation and cardiac contractility, and where they would counterbalance each other in a haemodynamically challenged heart under neurohumoral influence. This should be approached experimentally. Furthermore, while inhibiting systolic calcium may be worrisome, in the case of diastolic dysfunction, calcium channel antagonism might be beneficial by improving coronary flow and muscle relaxation. As answering these questions is beyond the opportunities offered by the model of Milberg et al. (2012a), other models should be employed to address these intriguing possibilities. In conclusion, the study of Milberg et al. (2012a) demonstrates the efficacy of verapamil as an antiarrhythmic agent in the setting of CHF and provides basic science insights into its mechanism of action of reducing spatial dispersion. Further studies are required to pinpoint the contribution of CHF to arrhythmogenesis in this model, to recapitulate the findings in models where CHF is a more pronounced proarrhythmic challenge and to validate the antiarrhythmic efficacy and demonstrate clinical feasibility, of ICa-L block in in vivo models of CHF.

The XendoU family of enzymes includes several proteins displaying high sequence homology. The members characterized so far are endoribonucleases sharing similar biochemical properties and a common architecture in their active sites. Despite their similarities, these proteins are involved in distinct RNA‐processing pathways in different organisms. The amphibian XendoU participates in the biosynthesis of small nucleolar RNAs, the human PP11 is supposed to play specialized roles in placental tissue, and NendoU has critical function in coronavirus replication. Notably, XendoU family members have been implicated in human pathologies such as cancer and respiratory diseases: PP11 is aberrantly expressed in various tumors, while NendoU activity has been associated with respiratory infections by pathogenic coronaviruses. The present study is aimed at identifying small molecules that may selectively interfere with these enzymatic activities. Combining structure‐based virtual screening and experimental approaches, we identified four molecules that specifically inhibited the catalytic activity of XendoU and PP11 in the low micromolar range. Moreover, docking experiments strongly suggested that these compounds might also bind to the active site of NendoU, thus impairing the catalytic activity essential for the coronavirus life cycle. The identified compounds, while allowing deep investigation of the molecular functions of this enzyme family, may also represent leads for the development of new therapeutic tools., Dock, dock, docking! Using a combination of structure‐based and experimental approaches, we identified four inhibitors of the catalytic activity of XendoU RNases, a family of enzymes implicated in a range of diseases. A pharmacophore model is proposed, highlighting the chemical properties potentially required for efficient binding to XendoU.WILEY-VCHThis article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

Bodur, Sait (Balikesir Author), The aim of this study was to investigate impact of central blood pressure (BP) levels and sex on the difference between central and upper arm oscillometric BP values. Oscillometric arterial BP measurements of 675 patients were simultaneously compared with values measured from the ascending aorta. The patients were divided into 3 groups according to systolic BP levels. The upper arm oscillometric device overestimated systolic BP (SBP) at low and medium BP levels but it underestimated SBP at high BP level. As for the effect of sex on differences in central and oscillometric BP, SBP was overestimated to a lesser degree in women than in men at low BP levels, but it was more highly underestimated in women than in men at high BP levels. The difference between oscillometric upper arm BP and aortic BP was directly affected by the patient's central BP level. In addition, the difference between central and oscillometric BP was also affected by sex factor.

WOS: 000287034000178, PubMed ID: 21522985, In the title compound, C16H14N4O4S center dot H2O, the benzene and pyridine rings make a dihedral angle of 85.8 (1)degrees. Both enantiomers of the chiral title compound are statistically disordered over the same position in the unit cell. The methyl and carbonyl group attached to the stereogenic center (C-5 of the thiazolidine ring) were therefore refined with common site-occupation factors of 0.531 (9) and 0.469 (9), respectively, for each stereoisomer. In the crystal, intermolecular N-H center dot center dot center dot O, O-H center dot center dot center dot O and O-H center dot center dot center dot N hydrogen bonds link the molecules, forming a three-dimensional supramolecular network. The crystal structure further shows pi-pi stacking interactions [centroid-centroid distance = 3.5063 (13) angstrom] between the pyridine rings., University Research Fund [F.279], The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund). HD and SO acknowledge the Scientific Research Projects Coordination Unit of Istanbul University (Project number T-3691).

WOS: 000287820000167, PubMed: 21522394, In the crystal structure of the title compound, C20H20OP+center dot Cl-, the cations and anions are linked by intermolecular CH center dot center dot center dot Cl and O-H center dot center dot center dot Cl hydrogen bonds into chains running parallel to the b axis. In the cation, the hydroxyethyl group is disordered over two orientations with site-occupancy factors of 0.554 (4) and 0.446 (4)., BAP Selcuk University in TurkeySelcuk University; University Research Fund [F279], This work was financially supported by the BAP Selcuk University in Turkey. The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant No. F279 of the University Research Fund).

WOS: 000279389400018, PubMed ID: 21587984, The title compound, C(18)H(23)N(2)Si(+)center dot Cl(-)center dot H(2)O, was synthesized from 1-[(trimethylsilyl)methyl]benzimidazole and benzyl chloride in dimethylformamide. The benzimidazole ring system is approximately planar, with a maximum deviation of 0.022 (2) angstrom, and makes an angle of 74.80 (12)degrees with the phenyl ring. The crystal packing is stabilized by O-H center dot center dot center dot Cl, C-H center dot center dot center dot Cl, C-H center dot center dot center dot O and C-H center dot center dot center dot pi interactions between symmetry-related molecules together with pi-pi stacking interactions between the imidazolium and benzene rings [centroid-centroid distance = 3.5690 (15) angstrom] and between the benzene rings [centroid-centroid distance = 3.7223 (14) angstrom]., Ondokuz Mayis University, Turkey [F. 279]; Inonu University Research Fund [BAPB-2008-60], The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F. 279 of the University Research Fund). HK & NS, also thank the Inonu University Research Fund (BAPB-2008-60) for financial support of this study.

J Clin Hypertens (Greenwich). 2010;12:666–677. (©)2010 Wiley Periodicals, Inc. Hypertensive patients with cardiovascular (CV) comorbidities are at increased risk, and cardiologists’ care should put particular emphasis on controlling blood pressure. Data on blood pressure treatment and control and drug utilization on a global scale, however, are scarce. Aiming to resolve this lack of information, the authors analyzed the data of International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients With Hypertension (i‐SEARCH) to gain further insights into national and regional blood pressure control and antihypertensive pharmacotherapy prescribed in cardiology practice. A total of 22,282 patients with hypertension from 26 countries were enrolled in 2005/2006. A total of 18,652 patients were treated (mean age, 63.0±11.4 years; 52.2% male; mean body mass index, 28.9 kg/m(2)). Mean systolic blood pressure was 148.2±19.8 mm Hg and diastolic blood pressure was 86.7±11.6 mm Hg. Blood pressure was controlled in 8.3% of diabetic and 25.3% of nondiabetic patients (21.2% overall), with particularly good control rates in North and Latin America (28.0% and 30.6%, respectively). A total of 31.2% of patients were treated with 1, 39.7% with 2, and 29.1% with ≥3 drugs. β‐Blockers were being used most frequently (47.9%), in both monotherapy and combination therapy despite low numbers of patients with respective compelling indications for their use. The present data illustrate the potential for an improvement of blood pressure treatment and control in daily cardiology practice.

The metabolic syndrome (MS) has been associated with hyperactivity of the renin-angiotensin-aldosterone system (RAAS). To assess the hypothesis that diuretic therapy in MS patients through further stimulation of RAAS would elicit greater potassium (K) depletion, two groups of hypertensive patients with (MS group [MSG]; n=20) and without (control group [CG]; n=19) MS were studied. Plasma renin activity (PRA), aldosterone (PA), and K levels were determined and an oral glucose tolerance test with plasma insulin determinations for calculation of homeostasis model assessment of insulin resistance (HOMA-IR), sensitivity (ISI), and secretion (HOMA-beta) was performed, both before and 12 weeks after hydrochlorothiazide (HCT; 25 mg/d) therapy. At baseline, higher HOMA IR and HOMA-beta and lower ISI and plasma K were found in the MSG than in the CG, with no differences in PA and PRA between groups. With therapy, PRA increased similarly in both groups while PA increased only in the MSG. However, greater reduction in plasma K occurred in the CG, and the 2 groups reached similar final K values. Impairment in glucose tolerance occurred in both groups, with no change in HOMA-beta in the CG and reduction in the MSG, suggesting that diuretic therapy increases insulin resistance and impairs insulin secretion independent of abdominal obesity. These alterations could not be attributed to hyperactivity of RAAS. Universidade Federal de São Paulo, Div Endocrinol, BR-04025011 São Paulo, Brazil Universidade Federal de São Paulo, Div Nephrol, BR-04025011 São Paulo, Brazil Universidade Federal de São Paulo, Div Endocrinol, BR-04025011 São Paulo, Brazil Universidade Federal de São Paulo, Div Nephrol, BR-04025011 São Paulo, Brazil Web of Science

In the crystal structure of the title compound, [WCl(2)(NO)(C(6)H(16)P(2))(2)]Cl, the seven-coordinated tungsten(II) center displays a distorted penta-gonal-bipyramidal geometry with trans nitrosyl and chloride ligands. The NO and Cl ligands are disordered over two positions; the site occupancy factors are 0.6 and 0.4.

The global health crisis due to the pandemic of the SARS‐CoV‐2 is associated with processes of urbanisation and globalisation. Globally well‐connected areas with high population densities are hence expected to be disproportionately affected by COVID‐19. This paper investigates the role of population density within the Netherlands, comparing hospitalisation and mortality related to COVID‐19 across municipalities. The paper finds that infections, hospitalisation and mortality related to COVID‐19 are not clearly correlated with the population density or urbanity of the municipality, also when controlling for age and public health factors. The paper concludes that while the public debate stresses the elevated risk of infections in cities, due to transgressive behaviour, the evidence in this paper suggests that the geography of the epidemic in the Netherlands is more complex. It speculates that the variation in urbanisation in most of the country might just be too small to expect significant differences., This paper investigate the role of population density within the Netherlands, comparing hospitalization and mortality related to COVID‐19 across municipalities. It concludes that while scientific evidence expects an elevated risk of infections in large global cities, and Dutch public debate strongly focuses on lack of compliance with social distancing measures in larger cities, this paper finds no evidence of population density being correlated with the incidence nor the mortality related to COVID‐19 It therefore suggests that, within the highly urbanized context of the Netherlands, the spatial patterns are more socially and politically than epidemiologically relevant.

An initial coin offering (ICO) has become a popular venue for crowdfunding at an early stage in a blockchain project. In the ICO process, a whitepaper may serve as an effective marketing tool to influence investor perception and investor trading behaviour. In this paper, we investigate whether management sentiment, as captured by the disclosure tone of the ICO whitepaper, is seen as a credible signal and capable of affecting price behaviour of the ICO on its first trading day. We document a positive association between management's net positive tone in the whitepaper and ICO first-day return, indicating that management sentiment has a significant impact on investor behaviour. Our findings show, however, that such association is contingent on the presence of causal argument, suggesting that disclosure tone needs a significant extent of causal reasoning support to back up its credibility and make it persuasive. These findings provide incremental evidence on the relationship between management tone and relative asset returns during an ICO process in the cryptocurrency markets. While management may benefit from soft information disclosure in the whitepaper, investors and regulators should be aware of self-serving incentives in whitepaper disclosures.

Prolactin (PRL) is mitogenic for lymphocytes in vitro, but the responsiveness of lymphocytes depends on the in vivo hormonal status of the rats from which the cells were obtained. Lymphocytes from ovariectomized (OVX) rats, but not from rats in oestrus or from male rats, respond to prolactin; administration of oestradiol to OVX rats diminishes the response. In order to determine if a correlation exists between lymphocyte responsiveness to prolactin and levels of cell surface prolactin receptors (PRL‐R) expression, the percentage of splenocytes and each splenocyte subpopulation expressing surface PRL‐R from rats of various hormonal states (OVX, oestradiol‐injected OVX, oestrus and male) was analysed by single‐colour and dual‐colour flow cytometric analysis. We found that approximately 20% of splenocytes expressed surface PRL‐R regardless of hormonal states (n=16). The majority (85%) of PRL‐R positive splenocytes were B lymphocytes whereas 11.1% and 4.8% of splenocytes expressing the PRL‐R were CD4 positive T‐helper (T(H)) and CD8 positive T‐cytotoxic (T(C)) lymphocytes, respectively. B lymphocytes also stained more brightly than T lymphocytes. This distribution of PRL‐R expression did not show significant alterations on total splenocytes or T(H) and T(C) lymphocytes during various hormonal stages. However, the percentage of PRL‐R‐positive B lymphocytes increased markedly in OVX rats (twofold), compared to rats at oestrus. In summary, no correlation was found between the responsiveness to prolactin as a mitogen and levels of PRL‐R expression by lymphocytes from rats at different hormonal states. This result suggests that sex steroid hormones may control prolactin responsiveness of lymphocytes by affecting the signal transduction pathway through PRL‐R rather than by altering the level of the cell surface receptor expression.

Objective:\ud Evidence suggests that people with a learning disability (PwLD) are less likely to attend cancer screening than the general population in the United Kingdom. The aim of this systematic review was to identify and synthesise qualitative studies reporting the attitudes and opinions of PwLD, family carers, and paid care workers towards national cancer screening programmes.\ud \ud Methods:\ud Five electronic and two grey literature databases were searched. Fourteen thousand eight hundred forty-six papers were reviewed against predetermined inclusion criteria. Included papers were critically appraised. Findings were synthesised using meta-aggregation.\ud \ud Results:\ud Eleven papers met the inclusion criteria, all related to cervical and breast screening. No papers were related to colorectal cancer screening. Findings were clustered into four synthesised findings: (1) supporting women with a learning disability (WwLD) to attend screening, (2) WwLD's awareness of screening and their psychophysical experiences, 3) professional practice barriers including the need for multidisciplinary working and an understanding of the needs of WwLD, and (4) approaches to improve the uptake of cervical and breast cancer screening. The synthesis highlights the significance of WwLD having support to understand the importance of screening to be able to make an informed choice about attending.\ud \ud Conclusions:\ud WwLD may not attend cancer screening due to fear, concerns over pain, and the potential influence of family carers and paid care workers. The review identified practical mechanisms which could help WwLD attend screening. Future research should focus on identifying potential barriers and facilitators as a proactive measure to promote colorectal cancer screening.

"This paper investigates the impact of community home-based care (CHBC) on self-management outcomes for chronically ill patients in rural Malawi. A pre- and post-evaluation survey was administered among 140 chronically ill patients with HIV and non-communicable diseases, newly enrolled in four CHBC programmes. We translated, adapted and administered scales from the Stanford Chronic Disease Self-Management Programme to evaluate patient's self-management outcomes (health status and self-efficacy), at four time points over a 12-month period, between April 2016 and May 2017. The patient's drop-out rate was approximately 8%. Data analysis included descriptive statistics, tests of associations, correlations and pairwise comparison of outcome variables between time points, and multivariate regression analysis to explore factors associated with changes in self-efficacy following CHBC interventions. The results indicate a reduction in patient-reported pain, fatigue and illness intrusiveness, while improvements in general health status and quality of life were not statistically significant. At baseline, the self-efficacy mean was 5.91, which dropped to 5.1 after 12\xC2\xA0months. Factors associated with this change included marital status, education, employment and were condition-related; whereby self-efficacy for non-HIV and multimorbid patients was much lower. The odds for self-efficacy improvement were lower for patients with diagnosed conditions of longer duration. CHBC programme support, regularity of contact and proximal location to other services influenced self-efficacy. Programmes maintaining regular home visits had higher patient satisfaction levels. Our findings suggest that there were differential changes in self-management outcomes following CHBC interventions. While self-management support through CHBC programmes was evident, CHBC providers require continuous training, supervision and sustainable funding to strengthen their contribution. Furthermore, sociodemographic and condition-related factors should inform the design of future interventions to optimise outcomes. This study provides a systematic evaluation of self-management outcomes for a heterogeneous chronically ill patient population and highlights the potential and relevant contribution of CHBC programmes in improving chronic care within sub-Saharan Africa."

BackgroundIncreasing the societal participation of people with intellectual disabilities via competitive employment requires a full understanding of what this means to them. This paper aims to provide an in‐depth examination of the lived experiences of people with intellectual disabilities in competitive employment.MethodInterviews were conducted with six participants with mild intellectual disability or borderline functioning and good verbal communication skills. Interviews were analysed according to the guidelines of interpretative phenomenological analysis (IPA). Member checks were conducted.ResultsAnalysis yielded three main themes: (a) Building on my life experiences, (b) My place at work and (c) Being a valuable member of society, like everyone else.ConclusionsCompetitive employment could make a substantial contribution to the sense of belonging to society and quality of life of people with intellectual disabilities. Nevertheless, they must cope with stigma‐related obstacles and feelings of being dependent on others in the work environment.

Research suggests that robotics can provide an engaging learning experience for learners with special educational needs. However, further work is required to explore the impact of robots within the classroom, particularly for learners with intellectual disabilities (ID). This paper seeks to further explore the potential effects of robots on such learners through examining engagement and goal achievement within teaching sessions. Eleven participants with ID were recruited from two countries to take part in the study using an ABAB design where the participants acted as their own controls. An appropriate learning goal for each participant was selected by the teacher and equivalent control sessions designed seeking to achieve the same learning goal but without the robot. Engagement, using eye‐gaze, learning goal achievement with and without help and goals not achieved provided the outcome measures from the sessions. This study found no significant difference between the robot and the control sessions for any of the outcome measures utilized suggesting robots are as effective as teaching tools as traditional methods. Through an increased sample size and a rigorously applied experimental protocol, this study provides new data and methodological considerations for further work based on the techniques applied in this study. Practitioner NotesWhat we already know about this topic Robots can encourage engagement in the learning process for students with intellectual disabilities.There is a lack of work examining the potential use of robots within formal learning.There is a lack of work utilizing experimental protocols to study the use of robots.What this paper adds Knowledge of the impact of robots on learner engagement using eye‐gaze as an outcome measure.Knowledge of the impact of robots on goal achievement in pursuit of structured learning objectives.Knowledge of the experimental protocol and suggestions for refinement of the outcome measures in future trials.Implications for practice and/or policy Robots can be as effective as traditional teaching methods in promoting engagement in learning for students with intellectual disabilities.Robots can be as effective as traditional teaching methods in the pursuit of learning goals for students with intellectual disabilities.The effect of robots on learning appears to be variable depending on individual learner characteristics. [ABSTRACT FROM AUTHOR]

Aim This paper discusses the risk factors and management of paediatric irritable bowel syndrome (IBS), with a focus on the role of the gastrointestinal microbiome. Methods English articles of interest published in PubMed and Google Scholar were searched using subject heading and keywords of interest. Results Only few randomised controlled trials on the management of IBS in children have been published. The vast majority of these intervention trials target to change the composition of the gastrointestinal microbiome. Most studies are underpowered. Major heterogeneities in study designs such as differences in inclusion criteria, including patients with different pain-related functional gastrointestinal disorders and differences in primary outcomes, make it impossible to formulate recommendations. Overall, few adverse events are reported what could indicate safety or point to suboptimal conduction of clinical trials and safety reporting. However, it can also not be excluded that some interventions such as the administration of selected probiotic products may result in benefit. Conclusion There is insufficient evidence to recommend any therapeutic intervention in paediatric IBS, including manipulation of the gastrointestinal tract microbiome, despite the evidence that dysbiosis seems an associated pathophysiologic factor. More designed prospective trials are needed since IBS is not a rare condition during childhood.

The COVID‐19 pandemic has dramatically impacted the lives of consumers across the globe. What guidance can consumer researchers and policymakers provide consumers to elicit adaptive responses that contribute to their life‐satisfaction under these adverse conditions? To this end, we develop and test an adaptive response model and demonstrate its impact on the life‐satisfaction of the consumers experiencing the pandemic in Turkey. Our model suggests that amidst COVID‐19, seeking emotional help triggers the positivity in people, which in turn increases life‐satisfaction. Moreover, turning to religion to deal with the challenges of the pandemic leads to positivity and hope, which in turn positively affect life‐satisfaction. Importantly, “escape” behaviors (such as excessive work or time spent in online shows/games) reduce positivity and hope in consumers, thus negatively impacting life‐satisfaction. The paper discusses the conceptual and public policy implications of the results and offers recommendations for future research., Special issue on Pandemics and Consumer Well‐being

Read the full text\ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud ePDF\ud \ud \ud PDF\ud \ud \ud ePDFPDF\ud \ud PDF\ud \ud Tools\ud \ud \ud \ud \ud \ud Share\ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud \ud Abstract\ud \ud \ud \ud Background\ud \ud Children with new onset type 1 diabetes (T1D) are at risk of developing the life‐threatening condition ketoacidosis if they have a delayed diagnosis. The rate of children presenting in ketoacidosis remains high in a number of countries worldwide. To ensure interventions to raise awareness of symptoms are effective a systematic review was conducted to evaluate previous publicity campaigns. \ud \ud \ud Methods\ud \ud A range of databases was searched using search terms relating to T1D, publicity campaigns, and symptom awareness. Identified articles were checked against the inclusion criteria, ensuring interventions were designed to target individuals prior to diagnosis of T1D. Papers were independently assessed under the criteria specified within the Critical Appraisal Skills Programme checklist. \ud \ud \ud Results\ud \ud The initial search retrieved 1537 papers and following screening 20 were identified for full consideration. Thirteen did not meet the inclusion criteria, leaving 7 to be assessed. Of these 7, 2 observational case‐control studies reported a reduction in the rate of ketoacidosis following a publicity campaign using posters and providing glucose testing equipment to primary healthcare professionals. Four observational cohort studies, utilized posters, and media campaigns; 2 reported a reduction in the rate of ketoacidosis and 2 reported no difference following their interventions. A feasibility study, not designed to evaluate effectiveness, reported some anecdotal evidence of a more timely diagnosis. \ud \ud \ud Conclusion\ud \ud Due to the methodological limitations of the studies identified, it is not possible to make a definitive conclusion on the effectiveness of the interventions reported.

Many individuals affected by cancer who experience emotional distress report not wanting help. This review aims to understand why individuals affected by cancer seek, accept or decline help for emotional distress and what influences these actions. A systematic review and thematic synthesis of the qualitative literature was conducted. Using pre‐defined search terms, four electronic databases were searched from January 2000 to May 2016. Pre‐determined inclusion and exclusion criteria were then applied. Identified papers were quality appraised. In total, 32 papers were included in the synthesis. Four themes emerged from data synthesis: attaining normality—the normality paradox; being emotionally literate; perceptions of help; needs‐support gap. Attaining normality is ideographic, context dependent and temporally situated; some individuals maintain normality by not seeking/declining help whereas others seek/accept help to achieve a new normality. Thus, attaining normality paradoxically functions to explain both why individuals sought/accepted help or did not seek/declined help. Data indicate that a context dependent, systems thinking approach is merited to enhance psychosocial care. In particular, clinicians must actively explore the personal context of an individual's distress to ensure that help desired and help offered are mutually understood. Further research must address the limitations of the current evidence base to advance theoretical understanding.

Research in the health sciences has been highly successful in revealing the aetiologies of many morbidities, particularly those involving the microbiology of communicable disease. This success has helped form a narrative to be found in numerous public health documents, about interventions to reduce the burden of non‐communicable diseases (e.g., obesity or alcohol related pathologies). These focus on tackling the purported pathogenic factors causing the diseases as a means of prevention. In this paper, we argue that this approach has been sub‐optimal. The mechanisms of aetiology and of prevention are sometimes significantly different and failure to make this distinction has hindered efforts at preventing non‐communicable diseases linked to diet, exercise and alcohol consumption. We propose a sociological approach as an alternative based on social practice theory. (A virtual abstract for this paper can be found at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA).

Summary An international consensus clinical practice statement issued in 2011 ranked psychogenic nonepileptic seizures (PNES) among the top three neuropsychiatric problems. An ILAE PNES Task Force was founded and initially charged with summarizing the current state of the art in terms of diagnosis and treatment, resulting in two publications. The first described different levels of diagnostic certainty. The second summarized current knowledge of management approaches. The present paper summarizes an international workshop of the ILAE PNES Task Force that focused on the current understanding and management of PNES around the world. We initially provide a knowledge update about the etiology, epidemiology, and prognosis of PNES—in adults and in special patient groups, such as children, older adults, and those with intellectual disability. We then explore clinical management pathways and obstacles to optimal care for this disorder around the world by focusing on a number of countries with different cultural backgrounds and at very different stages of social and economic development (United Kingdom, U.S.A., Zambia, Georgia, China, and Japan). Although evidence‐based methods for the diagnosis and treatment of PNES have now been described, and much is known about the biopsychosocial underpinnings of this disorder, this paper describes gaps in care (not only in less developed countries) that result in patients with PNES not having adequate access to healthcare provisions. A range of challenges requiring solutions tailored to different healthcare systems emerges. Continued attention to PNES by the ILAE and other national and international neurologic, psychiatric, and health organizations, along with ongoing international collaboration, should ensure that patients with PNES do not lose out as healthcare services evolve around the world.

Leishmaniasis corresponds to a group of neglected tropical diseases caused by flagellated protozoa belonging to the Leishmania genus. This widely spread illness is found in over 90 countries in the tropic and sub-tropic regions and also in southern Europe. As parasites exclusively infect the highly phagocytic cells (macrophages), this aspect can be exploited for targeted delivery making use of nanoparticles. Drug-loaded nanoparticles have been proposed to improve the bioavailability of classical drugs commonly in use as standard leishmania therapy, to overcome parasitic resistance and side effects and improve the treatment efficacy. Infected macrophages are expected to recognize drug-loaded nanoparticles which undergo phagocytosis releasing the drug inside macrophages. This approach can further be exploited for the development of nanovaccines. This paper provides an overview of the current disease status worldwide, its classical pharmacological treatments and how these can be improved by the use of featured nanoparticles specific tailored for such a complex disease. Several types of nanoparticles have been proposed while others have already reached clinical trials. This article is protected by copyright., This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017–2100 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq no. 01/2019) and the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund)., info:eu-repo/semantics/publishedVersion

This paper updates the bruxism management review published by Lobbezoo et al. in 2008 (J Oral Rehabil 2008; 35: 509-23). The review focuses on the most recent literature on management of sleep bruxism (SB) in adults, as diagnosed with polysomnography (PSG) with audio-video (AV) recordings, or with any other approach measuring the sleep-time masticatory muscles' activity, viz., PSG without AV recordings or electromyography (EMG) recorded with portable devices. Fourteen (N = 14) papers were included in the review, of which 12 were randomised controlled trials (RCTs) and 2 were uncontrolled before-after studies. Structured reading of the included articles showed a high variability of topics, designs and findings. On average, the risk of bias for RCTs was low-to-unclear, whilst the before-after studies had several methodological limitations. The studies’ results suggest that (i) almost every type of oral appliance (OA) (seven papers) is somehow effective to reduce SB activity, with a potentially higher decrease for devices providing large extent of mandibular advancement; (ii) all tested pharmacological approaches [i.e. botulinum toxin (two papers), clonazepam (one paper) and clonidine (one paper)] may reduce SB with respect to placebo; (iii) the potential benefit of biofeedback (BF) and cognitive-behavioural (CB) approaches to SB management is not fully supported (two papers); and (iv) the only investigation providing an electrical stimulus to the masseter muscle supports its effectiveness to reduce SB. It can be concluded that there is not enough evidence to define a standard of reference approach for SB treatment, except for the use of OA. Future studies on the indications for SB treatment are recommended.

Background Although heart failure (HF) patients often consider sexual activity as an essential aspect of their quality of life (QoL) and are usually uncertain if it is safe to perform sexual activity, this topic is overall poorly addressed in clinical practice. Aims The aim of this study was to explore the perceptions and practices of Flemish caregivers. Methods Healthcare providers were recruited through convenience sampling and filled in an adapted version of the UNITE Sexual Counselling Instrument. Several relevant network structures in Flanders were used to distribute the questionnaires-online as well as on paper-to healthcare workers being involved in the care to HF patients. Results Results of 180 participants indicated that 51.5% of the healthcare providers have never provided sexual counselling in HF patients. Being male, having a masters' degree, having more than 10 years of experience in cardiovascular disease, working in an ambulatory care department and having more positive attitudes were independently associated with a higher provision of sexual counselling in practice. Conclusion Although healthcare providers perceive it as their responsibility to discuss patients' sexual concerns, these issues are not often addressed in daily practice. Increasing knowledge in healthcare providers and specific practical training in providing information on sexual activity in HF patients are recommended. Further studies are needed to investigate how sexual counselling can be provided in agreement with HF patients' expectations and needs.

While some papers report an increased risk of COVID-19 and worse outcomes1 in oncological patients, others have found no differences2 . We are not aware of studies assessing risk for COVID-19 and clinical outcomes of patients with Primary Cutaneous Lymphomas (PCL).

Vascular malformations (VMs) of the central nervous system (CNS) include a wide range of pathological conditions related to intra and extracranial vessel abnormalities. Although some VMs show typical neuroimaging features, other VMs share and overlap pathological and neuroimaging features that hinder an accurate differentiation between them. Hence, it is not uncommon to misclassify different types of VMs under the general heading of arteriovenous malformations. Thorough knowledge of the imaging findings of each type of VM is mandatory to avoid these inaccuracies. Conventional MRI sequences, including MR angiography, have allowed the evaluation of CNS VMs without using ionizing radiation. Newer MRI techniques, such as susceptibility-weighted imaging, black blood sequences, arterial spin labeling, and 4D flow imaging, have an added value of providing physiopathological data in real time regarding the hemodynamics of VMs. Beyond MR images, new insights using 3D printed models are being incorporated as part of the armamentarium for a noninvasive evaluation of VMs. In this paper, we briefly review the pathophysiology of CNS VMs, focusing on the MRI findings that may be helpful to differentiate them. We discuss the role of each conventional and advanced MRI sequence for VMs assessment and provide some insights about the value of structured reports of 3D printing to evaluate VMs.

Objective: To test the efficacy of a dentifrice containing baking soda (BS), compared with dentifrice without BS for controlling plaque and gingivitis.Materials and methods: MEDLINE‐PubMed and Cochrane‐CENTRAL were searched. The inclusion criteria were randomized controlled clinical trials including healthy participants aged 18 years or older. Studies were selected that compared the effect of toothbrushing with a dentifrice with and without BS on the clinical parameters of plaque and gingivitis. Data were extracted from the selected studies, and a meta‐analysis was performed.Results: The search retrieved 21 eligible publications. Among these papers, 43 comparisons were provided, with 23 involving a single‐use design and 20 being evaluations with a follow‐up. Negative controls were found, or positive controls for which various active ingredients had been used. The included studies showed a moderate overall potential risk of bias and considerable heterogeneity. The meta‐analysis of plaque scores from the single‐brushing experiments showed that BS dentifrice (BS‐DF) was associated with significantly better outcomes than the negative control dentifrices (DiffM −0.20; P < 0.0001; 95% CI: [−0.27; −0.12]) or the positive control dentifrices (DiffM −0.18; P < 0.0001; 95% CI: [−0.24; −0.12]). This finding was only confirmed in studies that used a follow‐up design as compared to a negative control (DiffM −0.19; P = 0.01; 95% CI: [−0.34; −0.04]). The indices of gingival bleeding also improved when the comparison was a negative control (DiffM −0.08; P = 0.02; 95% CI: [−0.16; −0.01] and (DiffM −0.13; P < 0.001; 95% CI: [−0.18; −0.08]. However, for the gingival index scores, the meta‐analysis did not reveal any significant differences.Conclusion: BS‐DF showed promising results with respect to plaque removal in single‐use studies. However, the finding was partially substantiated in follow‐up studies. Studies that assessed bleeding scores indicated that a small reduction can be expected from BS, relative to a control product.

Background Expanded carrier screening (ECS) is aimed at detecting carrier states for autosomal recessive (AR) or X‐linked conditions in couples from the general population planning a pregnancy. ECS is currently usually offered on an individual basis despite the fact that, for AR conditions, only carrier couples are at risk of affected offspring. In this paper, we present a couple‐based ECS test‐offer for AR conditions, where results are offered as couple‐results only, and describe how couples view such an offer. Methods and results An online survey covering attitudes, perceived difficulty, and intention to take up couple‐based ECS was used to examine couples' views. Results show that in 76% of the participating couples there is no objection at all towards receiving couple‐results only. Most couples display similar views. Observed discrepancies usually involved one of the couple members having a positive view, whilst the other was neutral. Although views stayed strikingly stable after discussion, the partner's opinion was regarded as important in deciding whether or not to have testing. Conclusion This study shows that most couples do not object to receiving couple rather than individual ECS results, have similar views towards the offer, and are able to discuss differences in views and intentions., What's already known about this topic? Expanded carrier screening (ECS) has become widely availableECS is usually offered on individual basis, and individual carrier states are reportedViews of potential individual users have been researched What does this study add? A couple‐based ECS test‐offer for autosomal recessive conditions, where results are offered as couple‐results onlyAn examination of couples' views towards this offer: most couples do not object to receiving couple‐results only

Contains fulltext : 198770.pdf (Publisher’s version ) (Open Access) Background: Informal supportive networks of individuals with intellectual disability have become increasingly important. The aim of this paper is to describe how the Family Network Method - Intellectual Disability (FNM-ID) offers a way to gather the perspective of people with mild intellectual disability on their family support. Method: The FNM is designed to explore how individuals define their family contexts, and more specifically how they perceive existing supportive relationships in these contexts. Results: By carefully piloting ways of questioning people with mild intellectual disability, systematic adaptations were made to the original FNM. Data obtained by the FNM-ID can be analysed using social network analysis. Thereby, the FNM-ID provides rich, theoretically significant information on emotional support in the family networks of individuals with mild intellectual disability. Conclusions: The FNM-ID is a useful and successfully adapted tool for other researchers and professionals to systematically explore the family support experiences of individuals with mild intellectual disability. 12 p.