Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis: A Scoping Review.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but is not routinely used in EoE. We aimed to systematically review and describe current literature evaluating esophageal manometry in EoE. Forty-eight studies meeting the criteria were identified, describing 802 patients. Using standard water swallow protocols, the proportion of abnormalities detected was not dissimilar to other populations, apart from disorders of esophago-gastric outflow, which were found in 5%. Twelve studies described pretreatment and posttreatment manometry, with motility normalization after pharmacological therapy reported in 20%. Early, brief panesophageal pressurization was described in a number of studies and was more prevalent in the few studies utilizing additional provocation testing. Reports in the literature regarding temporal relationships between manometric findings and symptoms are variable. Esophageal manometry may be capable of detecting clinically relevant changes to esophageal function in EoE. Possible mechanisms are altered neuromuscular function because of secretory products of EoE and/or fibroinflammatory processes, manifesting as pressurization because of altered esophageal compliance. Some changes may be reversible with therapy. Drawing strong conclusions from the literature is difficult, with bias toward case reports and retrospective observation. Adaptations to assessment protocols to include provocation testing may provide more robust evaluation and detect clinically relevant, subtle changes in esophageal function, earlier within the patient pathway.

Characterization of Phosphopeptide Positional Isomers on the Transcriptional Co-activator TAZ.

The transcriptional co-activator with the PDZ binding motif (TAZ) is a critical regulator of numerous cellular processes such as cell differentiation, development, proliferation, and cell growth. Aberrant expression and activity of TAZ are also featured in many human malignancies. A hallmark of TAZ biology is its cytoplasmic retention mediated by 14-3-3 isoforms in response to phosphorylation of Ser89 by members of the LATS family of kinases. Following the observation that TAZ is a highly phosphorylated protein even when Ser89 is mutated, high-resolution mass spectrometry employing data-independent acquisition and ion mobility separation was conducted to elucidate additional TAZ phosphorylation sites that may play a role in regulating this critical transcriptional rheostat. Numerous phosphorylation sites on TAZ were identified, including several novel modifications. Of notable interest was the identification of positional phosphoisomers on a phosphopeptide containing Ser89. Optimized use of a so-called wideband enhancement acquisition technique yielded higher-quality fragmentation data that confirmed the detection of Ser93 as the positional phosphoisomer partner of Ser89 and identified diagnostic fragment ions for the phosphorylation events. Functional analysis indicated that Ser93 phosphorylation reduces the level of 14-3-3 association and increases the level of nuclear translocation, indicating this phosphorylation event attenuates the 14-3-3-mediated TAZ cytoplasmic retention mechanism. These findings suggest that the biological activities of TAZ are likely dynamically regulated by multisite phosphorylation.

Interventions to increase engagement with rehabilitation in adults with acquired brain injury: A systematic review.

Rehabilitation in adults with acquired brain injury is often hampered by a lack of client engagement with the rehabilitation process, leading to frustration, withdrawal of services and poorer recovery. Motivation, apathy and awareness are potential mechanisms underlying engagement, but few studies have suggested potential intervention techniques. A systematic review of the literature was carried out to identify and evaluate interventions designed to increase rehabilitation engagement in adults with acquired brain injury. Database searches used the following terms: rehabilitation, brain injury, and compliance/engagement/adherence in PsychInfo, Medline, Cinahl, Embase, AMED, Web of Knowledge, PsycBite, Cochrane clinical trials, and clinicaltrials.org. Hand searches were conducted of reference lists and relevant journals. Fifteen studies were included in the review. Intervention techniques fell into two broad categories: behavioural modification techniques and cognitive/meta-cognitive skills. Contingent reward techniques were most effective at increasing adherence and compliance, while interventions enabling clients' active participation in rehabilitation appeared to increase engagement and motivation. The review highlighted methodological and measurement inconsistencies in the field and suggested that interventions should be tailored to clients' abilities and circumstances.

Rehabilitation treatment taxonomy and the international classification of health interventions.

This commentary provides some reactions to the rehabilitation treatment taxonomy project in relation to work already underway to develop an International Classification of Health Interventions. This commentary also includes some comments in response to questions posed by the authors.

A complex case of dysphagia with dual aetiology.

A woman in her early 60s was referred with dysphagia and chest pain to a tertiary referral centre specialising in oesophageal disorders. Cardiac symptom origin and sinister oesophageal pathology had been excluded at her local hospital in NHS Scotland. Under multidisciplinary team oversight, reinvestigation of mucosal pathology and oesophageal motility ultimately uncovered both Type III achalasia and eosinophilic oesophagitis. This case demonstrates the benefit of including provocative testing during high-resolution manometry to reproduce relevant dysphagia and the importance of stopping proton-pump inhibitors long enough to uncover excessive eosinophils which could otherwise be masked. Ultimately, tailored management for both conditions separately was required to achieve symptoms resolution.

5α-Tetrahydrocorticosterone: A topical anti-inflammatory glucocorticoid with an improved therapeutic index in a murine model of dermatitis.

BACKGROUND AND PURPOSE: Glucocorticoids are powerful anti-inflammatory drugs, but are associated with many side-effects. Topical application in atopic dermatitis leads to skin thinning, metabolic changes, and adrenal suppression. 5α-Tetrahydrocorticosterone (5αTHB) is a potential selective anti-inflammatory with reduced metabolic effects. Here, the efficacy and side-effect profile of 5αTHB were compared with hydrocortisone in preclinical models of irritant dermatitis. EXPERIMENTAL APPROACH: Acute irritant dermatitis was invoked in ear skin of male C57BL/6 mice with a single topical application of croton oil. Inflammation was assessed as oedema via ear weight following treatment with 5αTHB and hydrocortisone. Side-effects of 5αTHB and hydrocortisone were assessed following chronic topical steroid treatment (28 days) to non-irritated skin. Skin thinning was quantified longitudinally by caliper measurements and summarily by qPCR for transcripts for genes involved in extracellular matrix homeostasis; systemic effects of topical steroid administration also were assessed. Clearance of 5αTHB and hydrocortisone were measured following intravenous and oral administration. KEY RESULTS: 5αTHB suppressed ear swelling in mice, with ED50 similar to hydrocortisone (23 µg vs. 13 µg). Chronic application of 5αTHB did not cause skin thinning, adrenal atrophy, weight loss, thymic involution, or raised insulin levels, all of which were observed with topical hydrocortisone. Transcripts for genes involved in collagen synthesis and stability were adversely affected by all doses of hydrocortisone, but only by the highest dose of 5αTHB (8× ED50 ). 5αTHB was rapidly cleared from the systemic circulation. CONCLUSIONS AND IMPLICATIONS: Topical 5αTHB has potential to treat inflammatory skin conditions, particularly in areas of delicate skin.

Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

Mephedrone (4-methylmethcathinone) is a ß-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity.

Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity.

Neuropsychiatric disorders characterized by behavioral disinhibition, including disorders of compulsivity (e.g. obsessive-compulsive disorder; OCD) and impulse-control (e.g. impulsive aggression), are severe, highly prevalent and chronically disabling. Treatment options for these diseases are extremely limited. The pathophysiological bases of disorders of behavioral disinhibition are poorly understood but it has been suggested that serotonin dysfunction may play a role. Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2-/-), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays that are well known for their utility in modeling human neuropsychiatric diseases. Mice lacking Tph2 (and brain 5HT) show intense compulsive and impulsive behaviors to include extreme aggression. The impulsivity is motor in form and not cognitive because Tph2-/- mice show normal acquisition and reversal learning on a spatial learning task. Restoration of 5HT levels by treatment of Tph2-/- mice with its immediate precursor 5-hydroxytryptophan attenuated compulsive and impulsive-aggressive behaviors. Surprisingly, in Tph2-/- mice, the lack of 5HT was not associated with anxiety-like behaviors. The results indicate that 5HT mediates behavioral disinhibition in the mammalian brain independent of anxiogenesis.

Expanding on the use of The International Classification of Functioning, Disability and Health: Examples and resources.

Most physiotherapists today are familiar with the abbreviation ICF and know that it stands for the International Classification of Functioning, Disability and Health; the title of the World Health Organization's international standard for describing health and health related states. Most universities in South Africa and globally have adopted the framework of the ICF in their curricula especially in promoting clinical reasoning, however, translating that knowledge for recording and monitoring has been slow in coming. Less well known, is how the ICF is and can be used and how it can inform physiotherapy practice, research, education and administration. Our article outlines the importance of the ICF to physiotherapy and recommends resources to facilitate expanded ICF use by physiotherapists. Examples are given of how to use coding and the importance of aggregating data and concluding with resources that can assist with the expanded use. Sufficient evidence and resources are available to support the expanded use of the ICF for data collection and clinical coding. Clinical implications: The aggregation of data can be used for the monitoring of universal health coverage especially in the context of National Health Insurance implementation.

Inter-rater agreement when linking stroke interventions to the extended international classification of functioning, disability and health core set for stroke.

PURPOSE: To uncover the factors that influence inter-rater agreement when extracting stroke interventions from patient records and linking them to the relevant categories in the Extended International Classification of Functioning, Disability and Health Core Set for Stroke. METHOD: Using 10 patient files, two linkers independently extracted interventions and linked the target of the intervention to relevant functions in the ICF. The percentage agreement of extracted interventions and the ICF codes was calculated. Non-matching interventions and codes were further analysed to determine the reasons for poor agreement. RESULTS: A total of 518 interventions were extracted, with 44.01% agreement between the two linkers. Of the non-agree codes and interventions, 43.79% were due to mismatched ICF codes and 56.20% were due to mismatched interventions. Differences were due to linkers (a) extracting interventions from different parts of the patient note (b) differences in interpreting the target of the intervention, and (c) choosing a different code with similar meaning. CONCLUSION: Greater reliability when linking interventions to ICF codes can be achieved by; health services using a consistent progress note that uses ICF language, recording the intervention aim, linkers knowing the aims of each discipline's interventions and using multiple reliability checks and analysis to inform the linking method.Implications for rehabilitationLinking intervention targets to the ICF and to the ICHI is an emerging research field.Development of trustworthy inter-rater reliability methods is needed to achieve its potential to demonstrate the equity, quality and effectiveness of interventions.Independent linking of patient notes to the ICF can identify factors that impact inter-rater reliability.When writing patient notes, health professionals should use a consistent format that identifies the functional target of the intervention using ICF terms.

20 Years of ICF-International Classification of Functioning, Disability and Health: Uses and Applications around the World.

The International Classification of Functioning Disability and Health (ICF) was approved in 2001 and, since then, several studies reported the increased interest about its use in different sectors. A recent overview that summarizes its applications is lacking. This study aims to provide an updated overview about 20 years of ICF application through an international online questionnaire, developed by the byline authors, and sent to each World Health Organization Collaborating Centers of the Family of International Classifications (WHO-FIC CCs). Data was collected during October 2020 and December 2021 and descriptive content analyses were used to report main results. Results show how, in most of the respondent countries represented by WHO-FIC CCs, ICF was mainly used in clinical practice, policy development and social policy, and in education areas. Despite its applications in different sectors, ICF use is not mandatory in most countries but, where used, it provides a biopsychosocial framework for policy development in health, functioning and disability. The study provides information about the needs related to ICF applications, that can be useful to organize targeted intervention plans. Furthermore, this survey methodology can be re-proposed periodically to monitor the use of the ICF in the future.

Tryptophan hydroxylase 2 aggregates through disulfide cross-linking upon oxidation: possible link to serotonin deficits and non-motor symptoms in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine neurons of the nigrostriatal system, resulting in severe motor disturbances. Although much less appreciated, non-motor symptoms are also very common in PD and many can be traced to serotonin neuronal deficits. Tryptophan hydroxylase (TPH) 2, the rate-limiting enzyme in the serotonin biosynthesis, is a phenotypic marker for serotonin neurons and is known to be extremely labile to oxidation. Therefore, the oxidative processes that prevail in PD could cause TPH2 misfolding and modify serotonin neuronal function much as is seen in dopamine neurons. Oxidation of TPH2 inhibits enzyme activity and leads to the formation of high molecular weight aggregates in a dithiothreitol-reversible manner. Cysteine-scanning mutagenesis shows that as long as a single cysteine residue (out of a total of 13 per monomer) remains in TPH2, it cross-links upon oxidation and only cysteine-less mutants are resistant to this effect. The effects of oxidants on TPH2 catalytic function and cross-linking are also observed in intact TPH2-expressing HEK293 cells. Oxidation shifts TPH2 from the soluble compartment into membrane fractions and large inclusion bodies. Sequential non-reducing/reducing 2-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting confirmed that TPH2 was one of a small number of cytosolic proteins that form disulfide-bonded aggregates. The propensity of TPH2 to misfold upon oxidation of its cysteine residues is responsible for its catalytic lability and may be related to loss of serotonin neuronal function in PD and the emergence of non-motor (psychiatric) symptoms.

Managing the psychosocial aspects of heart failure: a case study.

BACKGROUND: Depression is common in patients who have heart failure. This article presents a brief psychological intervention that could be useful for heart failure patients with depression that is likely to be precipitated by heart failure. METHOD: A brief intervention was designed to help heart failure patients. It was delivered in an outpatient setting as an adjunct to a nurse consultant-led clinic. A case study of 'Albert', who completed measures at 1 month on the waiting list before the intervention, and at 6 months after completion of the intervention is presented. RESULTS: The impact of the intervention was limited but it did show that the patient's scores on the emotional items of the Minnesota Living with Heart Failure Questionnaire had improved. The patient also used more active coping skills after the intervention. The patient self-reported an improvement in his loneliness, depression and sleep problems. The nurse consultant involved in his care reported an improvement in his anxiety about his condition. CONCLUSIONS: This brief intervention showed some benefits for Albert. Ideally, more follow-up sessions should be provided. However, the patient stated that he felt that the intervention had helped him to start managing his heart failure.

Remodeling of the ICF: A commentary.

Since its publication in 2001 the International Classification of Functioning, Disability and Health (ICF) has attracted debate about the content and the model presented. After almost 20 years use, regular updating since 2008 and with the prospect of a new edition in 2020 there is increasing interest in the ICF as a tool to meet contemporary information requirements. Information on functioning is important across not only health systems, but all areas where change in functioning is important: education, employment, and social welfare for example. This commentary responds to the issues raised in a commentary by Mitra & Shakespeare in 2019 and supports review of the ICF in the current context by informing users and providers of data on human functioning how they might engage in the maintenance, updating, and modernisation of the ICF.

Toward a Harmonized WHO Family of International Classifications Content Model.

An overarching WHO-FIC Content Model will allow uniform modeling of classifications in the WHO Family of International Classifications (WHO-FIC) and promote their joint use. We provide an initial conceptualization of such a model.

Avoiding the Banality of Evil in Times of COVID-19: Thinking Differently with a Biopsychosocial Perspective for Future Health and Social Policies Development.

The COVID-19 pandemic provides the opportunity to re-think health policies and health systems approaches by the adoption of a biopsychosocial perspective, thus acting on environmental factors so as to increase facilitators and diminish barriers. Specifically, vulnerable people should not face discrimination because of their vulnerability in the allocation of care or life-sustaining treatments. Adoption of biopsychosocial model helps to identify key elements where to act to diminish effects of the pandemics. The pandemic showed us that barriers in health care organization affect mostly those that are vulnerable and can suffer discrimination not because of severity of diseases but just because of their vulnerability, be this age or disability and this can be avoided by biopsychosocial planning in health and social policies. It is possible to avoid the banality of evil, intended as lack of thinking on what we do when we do, by using the emergence of the emergency of COVID-19 as a Trojan horse to achieve some of the sustainable development goals such as universal health coverage and equity in access, thus acting on environmental factors is the key for global health improvement.

Psychosocial interventions for carers of survivors of stroke: a systematic review of interventions based on psychological principles and theoretical frameworks.

PURPOSE: Most stroke survivors are cared for at home by informal carers, usually their partners or children. The chronic burden of meeting these care needs can have a significant impact on the psychological well-being of the carer. The aim of this review is to analyse interventions that target psychosocial functioning in carers of stroke survivors to understand how such interventions can reduce the burden of caring. METHOD: Seven studies that reported on randomized controlled trials of psychosocial interventions for informal adult carers of a survivor of stroke, which reported validated measures of psychological health outcome and met a satisfactory rating of quality were included in this systematic review. RESULTS: A forest plot of two studies that used education and counselling as the intervention for patients and spouses indicate a more favourable outcome for the intervention on the global family functioning scale. The Clarke, Rubenach, and Winsor (2003) study showed that patients were more likely to benefit from an intervention consisting of counselling and education than spouses. CONCLUSIONS: It is noted that there are relatively few studies investigating the impact of psychologically based interventions for carers of stroke survivors and the quality of evidence is varied. However, there is evidence of good quality to show that stroke patients benefit from a counselling combined with education intervention. The clinical implications of this review suggests, according to current available evidence, that those working with survivors of stroke and their families should consider providing counselling and education interventions to patients in the first instance. More research is needed to determine the effectiveness of interventions aimed at improving the psychosocial functioning of carers of survivors of stroke.

Effective learner-centered strategies for teaching adults: using visual media to engage the adult learner.

This article offers practical guidance for educators as they prepare specialists to enhance the lives and communities of older persons through the strategic use of visual media in age-related courses. Advantages and disadvantages of this learning innovation are provided as well as seven approaches for enriching instruction. Resources are included for locating effective visual media, matching course content with video resources, determining fair use of copyrighted media, and inserting video clips into PowerPoint presentations. Strategies for accessing assistive services for implementing visual media in the classroom are also addressed. This article promotes the use of visual media for the purpose of enriching gerontological and geriatrics instruction for the adult learner.

A systematic review of computer-based softwares for educating patients with coronary heart disease.

OBJECTIVE: To evaluate the use of computer-based softwares for educating patients with coronary heart disease. METHODS: A systematic electronic search for randomised controlled trials and comparison studies published from 1999 to the end of 2005 using the MEDLINE (1999-2005), EMBASE (1999-2005) and CINAHL (1999-2005) was carried out. Articles including the reference lists in the following journals were hand-searched: Patient Education and Counselling and Patient Counselling and Health Education. RESULTS: A total of 487 articles were identified. Based on a review of abstracts, five studies fulfilled the inclusion criteria of the review. A scoring sheet was used to assess the papers' quality. All studies reported significantly increased knowledge in patients using the educational software when compared to standard education. The difference in knowledge between the intervention and control groups remained high even at 6 months follow up. Furthermore, patients reported high satisfaction with the educational programs. CONCLUSION: Despite there only being five studies that met the inclusion criteria, this review supports the successful use of computer software to increase knowledge in patients with coronary heart disease. The reviewed articles reveal that computer-based education has an important role in increasing patients' knowledge about their condition. PRACTICAL IMPLICATIONS: It is commonly reported that patients want more information about their illness. This study shows that computer-based education can be a useful, acceptable to patients and effective way to deliver education about coronary heart disease.