The Domain of Social Work: What is It

Cast within a framework derived from general systems theory, the authors examine the domain of the social work profession. Domain is first defined as having several components. These are specified and fully expanded as Claimed Domain, Domain Competition, Emerging Domain and Unclaimed Domain. This elaboration is followed by a discussion of some of the constraints that impinge upon the profession\u27s ability to define and to choose its domain

Dietary L-Tryptophan Consumption Determines the Number of Colonic Regulatory T cells and Susceptibility to Colitis via GPR15

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3+ regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15+ Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3–4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15+ Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer\u27s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that leads to a progressive decline in a person’s memory and ability to communicate and carry out daily activities. The brain pathology in AD is characterized by extensive neuronal loss, particularly of cholinergic neurons, intracellular neurofibrillary tangles composed of the tau protein (NFTs) and extracellular deposition of plaques composed of β-amyloid (Aβ), a cleavage product of the amyloid precursor protein (APP). These two insoluble protein aggregates are accompanied by a chronic inflammatory response and extensive oxidative damage. Whereas dys-regulation of APP expression or processing appears to be important for the familial, early-onset form of AD, controversy exists between the “Baptists” (in favour of Aβ) and the “Tauists” (in favour of tau) as to which of these two protein dysfunctions occur at the earliest stages or are the most important contributors to the disease process in sporadic AD. However, more and more “non-amyloid” and “non-tau” causes have been proposed, including, glycation, inflammation, oxidative stress and dys-regulation of the cell cycle. However, to get an insight into the ultimate cause of AD, and to prove that any drug target is valuable in AD, disease-relevant models giving insight into the pathogenic processes in AD are urgently needed. In the absence of a good animal model for sporadic AD, we propose in this review that induced pluripotent stem cells, derived from dermal fibroblasts of AD patients, and differentiated into cholinergic neurons, might be a promising novel tool for disease modelling and drug discovery for the sporadic form of AD

Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer\u27s disease

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models; however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model

Monitoring neurointerventional radiation doses using dose-tracking software: implications for the establishment of local diagnostic reference levels

Objectives: There is potential for high radiation exposure during neurointerventional procedures. Increasing regulatory requirements mandate dose monitoring of patients and staff, and justification of high levels of radiation exposure. This paper demonstrates the potential to use radiation dose-tracking software to establish local diagnostic reference levels. Methods: Consecutive neurointerventional procedures, performed in a single institution within a one-year period, were retrospectively studied. Dose area product (DAP) data were collected using dose-tracking software and clinical data obtained from a prospectively generated patient treatment database. Results: Two hundred and sixty-four procedures met the selection criteria. Median DAP was 100 Gy.cm2 for aneurysm coiling procedures, 259 Gy.cm2 for arteriovenous malformation (AVM) embolisation procedures, 87 Gy.cm2 for stroke thrombolysis/thrombectomy, and 74 Gy.cm2 for four-vessel angiography. One hundred and nine aneurysm coiling procedures were further studied. Six significant variables were assessed using stepwise regression analysis to determine effect on DAP. Aneurysm location (anterior vs posterior circulation) had the single biggest effect (p = 0.004). Conclusions: This paper confirms variable radiation exposures during neurointerventional procedures. The 75th percentile (used to define diagnostic reference levels) of DAP measurements represents a reasonable guidance metric for monitoring purposes. Results indicate that aneurysm location has the greatest impact on dose during coiling procedures and that anterior and posterior circulation coiling procedures should have separate diagnostic reference levels. Key Points: Dose-tracking software is useful for monitoring patient radiation dose during neurointerventional procedures; This paper provides a template for methodology applicable to any interventional suite; Local diagnostic reference levels were defined by using the 75th percentile of DAP as per International Commission on Radiological Protection recommendations; Aneurysm location is the biggest determinant of radiation dose during coiling procedures.; Anterior and posterior circulation coiling procedures should have separate diagnostic reference levels

Embolic activity subsequent to injection of the internal mammary artery with papaverine hydrochloride.

BACKGROUND: Neurologic injury is a rare yet devastating outcome of coronary artery bypass grafting surgery. Mechanisms producing both focal and global neurologic injuries include embolization, cerebral hypoperfusion, and hypotension. In this present study, we report an association between variations in the treatment of the internal mammary artery with the detection of cerebral embolic signals. METHODS: An intensive intraoperative neurologic and physiologic monitoring approach was implemented to associate discrete processes of clinical care with the concurrent detection of cerebral embolic signals, cerebral hypoperfusion, and hypotension. The method of treating the left internal mammary artery was tracked among 68 patients undergoing isolated coronary artery bypass grafting. Cerebral embolic signals were counted within 3 minutes of the treatment of the left internal mammary artery. RESULTS: Among a series of 68 patients undergoing isolated coronary artery bypass grafting, 22 were not treated with papaverine. Of those treated, 12 received injection intraluminally and 28 had a topical application. Embolic signals were noted concurrently among 7 patients receiving injection of papaverine. No embolic signals were noted among patients who were treated topically. CONCLUSIONS: We report an association between the injection of papaverine hydrochloride and cerebral embolic signals. Our findings suggest that adoption of topical applications of papaverine hydrochloride may offer opportunities to reduce a portion of cerebral embolic signals in the setting of coronary artery bypass grafting

The Need for New Care Strategies to Prevent A1c Relapse

Background/Aims: The principle treatment strategy for glycemic management in most care settings is reactive; monitor A1c levels and then react with treatment intensification when the A1c exceeds the recommended optimal care goal. Our goal was to assess the potential to improve diabetes performance measures through preventive strategies directed at patients who are at A1c goal but at high risk for disease progression and A1c relapse. Methods: Patients not meeting optimal care goals were partitioned into one of three different A1c trajectories: (a) FLAT –– those who are consistently above optimal A1c goal, (b) Negative slope –– those patients who are on an improvement trajectory, and (c) Positive slope –– those who have previously been meeting A1c goals but who have relapsed (often due to medical issues, comorbidities, psychosocial stress, behavioral or medication adherence, or disease progression). We quantified the proportion of patients with diabetes who contribute to the relapse vector by identifying patients with diabetes and A1c tests in the last two years (9/1/2012–8/31/2014) and quantifying the proportion of patients who relapsed in year 2, stratified by A1c range and pharmacologic treatment in year 1. Results: We identified 29,321 patients with at least two diabetes diagnoses in years 1 and 2, with median A1c of 7.4%. Of these, 8,889 (30%) had an A1c \u3e 8% in year 2. Of 6,321 patients with A1c of 7–7.9% in year 1, 2,332 (36.9%) relapsed to \u3e 8% in year 2. Relapse was higher (43.2%) for patients medicated with sulfonylurea or insulin. Only 689/10,202 (6.7%) patients with A1c \u3c 7% in year 1 relapsed to A1c \u3e 8% in year 2. Discussion: We estimate that the phenomenon of A1c relapse accounts for one-third of all adults identified as having uncontrolled glucose on quality measures. Proactive care strategies in high-risk patients close to goal (A1c 7–7.9%) to help them sustain control could reduce the proportion of patients not meeting optimal A1c goals. More systematic use of patient-reported self-monitored blood glucose data could further help to identify patients who are relapsing or progressing. Further research is needed to test these hypotheses

Evaluation of Provider Experience With an Electronic Health Record-Based Clinical Decision Support Tool

Background/Aims: Our goal was to evaluate provider experience with an electronic health record (EHR)-based clinical decision support (CDS) tool called CV Wizard implemented as part of a large randomized trial with 80% use rates for eligible patients. The tool included a quantitative “provider” form with prioritized treatment suggestions and a simpler visual companion “patient” form to efficiently elicit treatment preferences. Methods: Two focus groups were held outside of clinic hours with a meal and $250 compensation. Twelve providers participated and were asked to comment on open-ended questions including a) what goes into their decision to use the tool, b) the implementation process, c) how patients reacted to it, d) how it could be improved, and e) how effective it was. The discussions were audio-taped and transcribed verbatim and examined by the study team to identify themes. Results: Providers were enthusiastic about the tool and found it valuable. They were happy that the nurse printed it for them before visits, and commented that it helped set the visit agenda and organized cardiovascular (CV) risk information. They were more likely to discuss CV risk with patients, and indicated that they took additional time to use it with patients. There was general consensus that it was time well spent. They said the tool reinforced their treatment suggestions. Variability was noted with how nurses and providers were using the tools. For conversations with patients, some providers preferred to use the provider form over the patient form, and vice versa. The patient form was intended to be given to the patient while waiting to be seen by the provider, but this was often not happening. Providers had several suggestions for improving the use process, and asked for better documentation tools for results (smart phrases). Discussion: A clinical decision support tool designed to help providers and patients engage in shared decision-making for CV risk reduction was well received and perceived as time well spent with patients. Overcoming some problems associated with workflow and adding easier ways to document use of the tool for patient discussions would add to the existing value