Charitable Trust Research Articles

Social Return on Investment of Musculoskeletal Physiotherapy in the National Health Service.

Social return on investment (SROI) may present a method for demonstrating the social value of healthcare interventions. It has not previously been measured in musculoskeletal (MSK) physiotherapy but is being used in the procurement and performance management of healthcare services. The aim of the study was to measure SROI in one provider of MSK physiotherapy in the United Kingdom's National Health Service (NHS). A retrospective single arm online survey-based service evaluation was carried out to calculate the SROI of an NHS adult MSK physiotherapy service using the Housing Association's Charitable Trust Social Value Calculator. 237 respondents (35.6%) completed the survey and a mean SROI of £4.13 for every £1 invested was demonstrated. There were sub-group variations based on symptom location and discharge location. This is the first time SROI has been calculated in an MSK physiotherapy setting. This service evaluation raises new questions about the variations observed in subgroups and the applicability of this methodology in individuals with MSK conditions who receive physiotherapy. MSK physiotherapy is an intervention which offers a positive SROI across a range of MSK conditions and contributes towards improved wellbeing. This is the first study to use the HACT Social Value Calculator when evaluating a physiotherapy service and further research is required to validate the results.

Property not required for its trust purpose—and the concept of ‘general charitable intent’

Abstract This article compares the treatment of various types of trust where the settlor stipulates that trust property is to be used to pursue a particular purpose, but that purpose proves abortive, leaving the relevant property not now needed for the purpose and not otherwise disposed of. It argues that charitable trusts, and in particular the doctrine of ‘general charitable intent’ leading to cy-près application, could perhaps draw a lesson from beneficiary trusts.

An Analysis of Nonprofit Organization Federal Income Tax Avoidance Using Publicly Available Income Tax Return Data

ABSTRACT Nonprofit organizations are subject to an Unrelated Business Income Tax (UBIT) on activities unrelated to their tax exempt purpose. In 2007 nonprofits became the first U.S. federal taxpayers required to publicly disclose their income tax returns. Using this data I find that nonprofits avoid the UBIT by combining losses from some activities to offset the profits of other activities. A provision in the Tax Cut and Jobs Act of 2018 was effective in mitigating the use of loss activities as a UBIT avoidance method. I also find that nonprofits continue to avoid the UBIT by shifting common costs from tax exempt to taxable activities. I find that UBIT avoidance is increasing in tax rates. Finally, tax avoidance is smaller for the set of nonprofits organized as charitable trusts rather than as corporations or associations, and that public donors play a governing role by mitigating UBIT avoidance. Data Availability: Data are available from sources identified in the text. JEL Classifications: H26; L30.

EXAMINING THE CURRENT PRACTICE OF GOVERNANCE IN ZAKAT IN A MUSLIM MINORITY COUNTRY: THE CASE OF SRI LANKA

Zakat constitutes one of the pillars of Islam and religious practice in Islam aimed at supporting those in need. It also plays a major role in contributing to the socioeconomic development of society. To achieve efficient zakat management, institutions must focus on strong governance and proper management practices. This focus is essential due to the institution’s responsibility to manage effectively and provide transparent information to the public. Therefore, to meet stakeholder needs, non-profit organizations must prioritize governance. In Sri Lanka, the absence of specific laws or regulations governing zakat practice such as the Marriage and Divorce (Muslim) Act, the Muslim Intestate Succession Ordinance, and the Muslim Mosques and Charitable Trusts or Wakfs Act has led to a need for examination of current governance practices related to zakat collection and distribution. This study explores these practices and highlights how applying governance principles can help achieve the objectives (Maqasid) of zakat management in Sri Lanka. The research employs a doctrinal analysis of primary and secondary data, including statutes, practices, journals, and reports. Additionally, the study analyzes current zakat management practices through interviews with five respondents, including zakat practitioners and Shari’ah scholars, using thematic analysis. The findings reveal several issues: the causes of inefficient governance in zakat management, theoretical and practical problems with existing practices in Sri Lanka, gaps in the zakat governance framework, and conceptual and management deficiencies within zakat institutions. The study recommends developing a new governance framework for zakat management. This should include modern rules and practices based on Islamic law, staff training in fundamental Islamic knowledge, improved internal and external audit processes, and increased awareness among managers, donors, beneficiaries, and members of society.

International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement

Diagnostic imaging using CT enterography, magnetic resonance enterography, and intestinal ultrasound are important tools in evaluating stricturing Crohn's disease. Definitions of strictures have been developed for CT enterography and magnetic resonance enterography. However, expert recommendations for definitions and treatment response of strictures on intestinal ultrasound are not available. The aim of this study was to standardise definitions, diagnosis, and treatment response criteria in small bowel stricturing Crohn's disease on intestinal ultrasound. Using modified RAND-University of California Los Angeles Appropriateness Method, a diverse expert panel of 13 gastroenterologists, seven radiologists, and two patient representatives was assembled. A total of 466 statements on definitions and response to therapy of stricturing Crohn's disease on intestinal ultrasound were generated from a systematic review and from expert opinion, with subsequent rating for appropriateness. Two rounds of voting with an interposed survey result discussion were performed. Statements were classified as inappropriate, uncertain, or appropriate based on the median panel rating and degree of disagreement. Appropriateness was rated using a nine-point Likert scale (1 being inappropriate, 9 being highly appropriate). A naive or anastomotic small bowel Crohn's disease stricture on intestinal ultrasound is defined by the combination of bowel wall thickening, luminal narrowing, and pre-stenotic dilation. Bowel wall thickness is defined as being more than 3 mm. Luminal narrowing is defined as either a luminal diameter reduction of more than 50% in the narrowest area and relative to a normal adjacent bowel loop, or a luminal diameter of less than 1 cm. Pre-stenotic dilation is defined as more than 2·5 cm or an increase in bowel diameter relative to a normal adjacent bowel loop. Definitions for grading hyperaemia, inflammatory fat, wall stratification, intestinal ultrasound machine technical parameters, and image acquisition were also devised. Treatment response of strictures was defined as reduction in stricture length, bowel wall thickening, luminal narrowing, pre-stenotic dilation, and motility abnormalities. To our knowledge, this is the first intestinal ultrasound appropriateness rating exercise conducted for defining, diagnosing, and measuring response to therapy in small bowel stricturing Crohn's disease and informs future clinical use and intestinal ultrasound index development for clinical trials. Leona M and Harry B Helmsley Charitable Trust.

Taxation on Charitable Trust: Comment on Supreme Administrative Court Judgment No. 227 in 2023

Taxation on Charitable Trust: Comment on Supreme Administrative Court Judgment No. 227 in 2023

Sasa’a le fafao?: Approaches to Return and Reintegration of Criminal Deportees (Returnees) into Samoa

Pacific Island states face high levels of criminal deportations arriving from the United States, Australia and New Zealand—with the expectation that returnees will simply reintegrate. However, reintegration into a country that individuals often do not remember, or know the language or cutural protocols of, can be difficult. Returnees may face social stigma and/or subsequent surveillance and legal requirements on their return: the latter known in scholarly literature as ‘crimmigration creep’. In this article, we examine the case of Samoa, which has taken a unique culture-centric approach to reintegration through the establishment of the quasi-governmental Samoa Returnees Charitable Trust, rejecting external ‘one-size-fits-all’ approaches. We argue that this exertion of Samoa’s agency has led to a delay in crimmigration creep.

Study on the Philanthropic Activities of Chinese Commercial Banks from an Environmental, Social, and Governance (ESG) Perspective

The study aims to investigate the integration of philanthropic responsibility objectives with operational goals within commercial banks, embedding the ethos of financial benevolence into their core business strategies. It seeks to understand how these institutions can capitalize on their inherent advantages and resources to establish distinctive identities in the realm of philanthropy. By examining the 2022 ESG reports of China's six state-owned commercial banks, twelve joint-stock banks, and six city commercial banks, the research delineates the performance of commercial banks in philanthropic projects and expenditures, the development of philanthropic financial products, and the provision of philanthropic services. The analysis reveals three key deficiencies in the current philanthropic practices of commercial banks: the absence of a robust performance accounting mechanism for philanthropic projects and expenditures, the challenge of ensuring the long-term continuity of philanthropic financial products, and the relatively small scale of charitable trusts. The study offers four strategic recommendations for commercial banks: to institute an effective performance accounting mechanism for philanthropic initiatives, to innovate and scale up philanthropic financial products, to enhance the promotion of these products, and to broaden the scope of charitable trust projects. These suggestions are intended to facilitate a more holistic advancement of "charity plus finance" initiatives by commercial banks, thereby enhancing their engagement and impact in the ESG sphere.

Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: insights from the faecal volatome

Irritable bowel syndrome (IBS) is a common and debilitating disorder manifesting with abdominal pain and bowel dysfunction. A mainstay of treatment is dietary modification, including restriction of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). A greater response to a low FODMAP diet has been reported in those with a distinct IBS microbiome termed IBS-P. We investigated whether this is linked to specific changes in the metabolome in IBS-P. Solid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 56 IBS cases (each paired with a non-IBS household control) at baseline, and after four-weeks of a low FODMAP diet (39 pairs). 50% cases had the IBS-P microbial subtype, while the others had a microbiome that more resembled healthy controls (termed IBS-H). Clinical response to restriction of FODMAPs was measured with the IBS-symptom severity scale, from which a pain sub score was calculated. Two distinct metabotypes were identified and mapped onto the microbial subtypes. IBS-P was characterised by a fermentative metabolic profile rich in short chain fatty acids (SCFAs). After FODMAP restriction significant reductions in SCFAs were observed in IBS-P. SCFA levels did not change significantly in the IBS-H group. The magnitude of pain and overall symptom improvement were significantly greater in IBS-P compared to IBS-H (p=0.016 and p=0.026, respectively). Using just five metabolites, a biomarker model could predict microbial subtype with accuracy (AUROC 0.797, sensitivity 78.6% (95% CI: 0.78-0.94), specificity 71.4% (95% CI: 0.55-0.88). A metabotype high in SCFAs can be manipulated by restricting fermentable carbohydrate, and is associated with an enhanced clinical response to this dietary restriction. This implies that SCFAs harbour pro-nociceptive potential when produced in a specific IBS niche. By ascertaining metabotype, microbial subtype can be predicted with accuracy. This could allow targeted FODMAP restriction in those seemingly primed to respond best. This research was co-funded by Addenbrooke's Charitable Trust, Cambridge University Hospitals and the Wellcome Sanger Institute, and supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).

Organisational learning through a charitable trust-initiated project focusing on end-of-life care

PurposeWe identify lessons from a project sponsored by a large charitable trust, which sought to build capability for end-of-life (EOL) care in Hong Kong through interdisciplinary and multi-agency collaboration.Design/methodology/approachAn in-depth case study drawing on 21 in-depth interviews with diverse stakeholders was conducted. Lyman et al.’s (2018) model of organisational learning (OL) in healthcare settings was applied to analyse the relative emphasis on particular contextual factors and mechanisms, and to identify outcomes perceived to have been achieved.FindingsInfrastructure such as materials for assessment and education received the most emphasis among the contextual factors and deliberate learning such as training sessions received the greatest attention among the mechanisms. While perceptions indicated that desired outcomes were being achieved in terms of social impact, there were relatively few mentions of “soft” factors such as enhanced motivation, leadership or OL skills among staff.Originality/valueThis study extends the literature on how to create valuable social impact through OL. While prior studies have examined social impact in terms of solutions for social and environmental problems, ours is one of the few that examines how improvements are made to organisations’ capability to deliver such impacts in the context of healthcare.

THE FORECAST STUDY: FACTORS PREDICTING PAIN PERSISTENCE IN SCIATICA. AN UPDATE ON BASELINE AND PRELIMINARY LONGITUDINAL DATA

BackgroundFORECAST is a prospective longitudinal cohort study exploring mechanism-based prognostic factors for pain persistence in sciatica. Here, we share an update on this largest deeply-phenotyped primary care sciatica cohort.Methods/resultsOur cohort includes 180 people with sciatica (score >4 on Stynes’ Sum Score), aged 18–85, within 3 months of symptom onset. Psychosocial factors, self-reported sensory profiling, clinical examination, quantitative sensory testing (QST), biological samples (blood and skin samples), and Magnetic Resonance Neurography of lumbar nerve roots were collected at baseline. Pain persistence was determined at three and twelve months with the Sciatica Bothersomeness Index (SBI) and a numeric pain rating scale (NRS) as primary outcomes. Recruitment nears completion, with 160 participants enrolled to date. 127 and 96 participants have completed 3 and 12 months follow-up respectively.Overall, 56% of our cohort are female, with a mean age (SD) of 54.14yrs (16.57). Ethnicity data approximates local populations.SBI at baseline was (median [IQR]) 13[10-17], and interim longitudinal data shows stepwise improvement at 3 and 12 months. Baseline ‘average’ pain intensity was 5.56 (2.15) for leg pain, and 4.14(2.82) for low back pain (LBP). Overall, pain scores decreased at 3 and 12 months, with greater reductions in leg pain than LBP at 12 months. However, around 55–80% and 40–65% of people reported persistent pain at 3 and 12 months respectively.ConclusionLeg pain severity was moderate and higher than LBP at baseline. All primary outcome measures demonstrate improvement over time, however 40–65% of patients report persistent pain at 12 months.Conflicts of interestLR: Paid facilitation of post-graduate courses internationally. SK, MT, FP, KM, WS, CP, CR, SC: No conflicts of interest. GC: Editor in Chief of Health Psychology Review. Director of board of directors, MentalCHealth Care setting NoordWestVlaanderen. JF: Copyright holder of ODI (Oswestry Disability Index). Served on a data monitoring committee for a clinical trial of 2 different surgical approaches to cervical disc herniation (FORVAD). Member of HTA Prioritisation Committee B: Inside hospital Care from 2015-February 2019. Member of HTA Interventional Procedures Panel from 2010–2015. Trustee and board member of 3 spine related charities – Back to Back; British Scoliosis Research Foundation and BackCare. Expert instructed by both claimant and defendant solicitors in negligence and person injury cases. GB: Paid consultancy (RNA-seq) with Ivy Farm and Coding.bioABS: Paid post-graduate lecturing internationally. Co-chair NeupSig sciatica working group (unpaid).Sources of fundingThis project is funded by UKRI and Versus Arthritis as part of the UKRI Strategic Priorities Fund (SPF) Advanced Pain Discovery Platform (APDP), a co-funded initiative by UKRI (MRC, BBSRC, ESRC), Versus Arthritis, the Medical Research Foundation and Eli Lilly and Company Ltd (Grant MR/W027003/1). Additional funding has been received from the back to back charity to expand longitudinal components of the study. LR has received support with PhD fees from the CSP charitable trust. ABS is supported by a Wellcome Trust Clinical Career Development Fellowship(222101/Z/20/Z). WS is partly funded through the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. FP is funded by a Dorothy Hodgkin Career Development Fellowship in Chemistry in association with Somerville College. GB is supported by the Wellcome Trust (223149/Z/21/Z) and Diabetes UK (19/0005984). GC and KRM are partly funded by UKRI and Versus Arthritis as part of the Advanced Pain Discovery Platform (APDP) PAINSTORM (MR/W002388/1). The UKRI and Versus Arhthritis (APDP) are the major funders of FORECAST. All other funders provided either some people support, or funded projects with legacy data that we reuse.

Choose the Right Fiduciary for Administration Of Charitable Trusts and Estates

Choose the Right Fiduciary for Administration Of Charitable Trusts and Estates

Addressing plastic pollution and waste flows: Insights from South Africa's experience.

The Pew Charitable Trust's 2020 report 'Breaking the Plastic Wave', indicates that existing technologies could support an 80% reduction in plastic leakage relative to business as usual by 2040. Therefore, South Africa became the first country to work with the Pew Charitable Trust and Oxford University to test and apply 'Pathways', a modelling framework and software tool which stemmed and evolved from the Pew report, at country level. The tool calculates the flows of plastics in the economy and the impact of various strategies to reduce future plastic pollution. The Scenario Builder within the Pathways tool allows the user to optimise flows in the plastics value chain to satisfy a set of defined objectives in order to achieve an optimal solution. Three major findings have emerged from the application of Pathways at country level for South Africa. Firstly, plastic pollution is set to almost double by 2040 if no interventions are implemented. Secondly, meeting the newly legislated extended producer responsibility (EPR) targets set for plastic packaging can avoid 33% of projected total pollution over the period of 2023-2040. Lastly, an optimal system change can avoid 63% of total plastic pollution over the period 2023-2040. Thus, applying Pathways at country level in South Africa has proven to be valuable by setting a baseline against which progress towards reducing plastic pollution can be measured; determining the outcome of meeting the legislated EPR targets over time, and informing policy decisions by allowing users to model different scenarios towards an optimal system change scenario.

The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

359-OR: CGM in Primary Care—Practice Characteristics and Choice of CGM Implementation Strategy in PREPARE 4 CGM

Introduction & Objective: Most diabetes care occurs in primary care (PC). Continuous glucose monitoring (CGM) is associated with clinical and psychosocial benefits. While CGM uptake in PC is rising, understanding models to support CGM use in diverse PC practices is needed. The PREPARE 4 CGM study evaluates strategies to implement CGM in PC. We compared characteristics among practices choosing a practice-led, self-paced CGM implementation plan or referral to a virtual CGM implementation service. Methods: Colorado PC practices interested in implementing CGM were recruited and chose to use the American Academy of Family Physicians CGM implementation modules or refer patients to a virtual CGM initiation and education service with dietitian, pharmacist, diabetes care and education specialist (DCES), and physician. Baseline practice characteristics (staffing, specialty, size, payer mix, etc) were compared across study arms using descriptive statistics (frequencies, means, SDs), chi-square tests, Fisher’s exact tests and independent two sample t-tests, using SAS 9.4 (Cary NC). Associations were considered significant at p<0.05. Results: Of 76 practices, 46 chose self-paced implementation, 16 of which (35%) had a DCES; 30 chose the virtual service, none (0%) of which had a DCES, X2(2, N=62)=11.05, p <.001. Besides having a DCES, no differences in 50 other practice characteristics were seen between groups. Conclusion: PC practices were eager to implement CGM. While other practice characteristics were not associated with implementation strategy choice, having a DCES was highly associated: all practices with a DCES chose to implement CGM on their own. DCESs may have potential as technology champions in PC practices. Referral to virtual CGM implementation service allowed access to a DCES and multidisciplinary team for practices without them. As many practices without a DCES also chose to implement CGM on their own, multiple models may be necessary to foster CGM implementation in PC. Disclosure S. Oser: Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Research Support; Abbott. Advisory Panel; Dexcom, Inc., Jaeb Center for Health Research. K.T. Wiggins: None. T. Hall: None. L. Dickinson: None. K. Crispe: None. P. Dickinson: None. T. Oser: Research Support; Abbott. Advisory Panel; Medscape. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2204-05191)

Can a charitable trust be valid, notwithstanding the existence of non-charitable purposes? The landmark decision of the Royal Court of Jersey In the Matter of the Estate of the Late Constantin Mattas

Abstract In a recent judgment regarding the Jersey moveable estate of a Greek national (In the Matter of the Estate of the Late Constantin Mattas [2024]JRC068), the Royal Court decided several issues of trusts and probate law, some novel, and some which go to the very heart of the question of what constitutes a valid Jersey trust. Most notably, the Court held that, in the present case involving a trust for both charitable and non-charitable purposes, the failure of the non-charitable purpose resulted in the whole of the assets of the Trust being held for the benefit of the charitable purpose, rather than the failure of the trust as a whole.

Elucidating the Role of SYK in the Intestinal Epithelium

Background: Inflammatory Bowel Disease (IBD) involves chronic and recurring inflammation of the gastrointestinal tract. We identified several patients presenting with immune dysregulation and systemic inflammation, including inflammation of the gut. Analysis of Whole Exome Sequencing data from pediatric IBD patients has identified five rare protein coding Spleen Tyrosine Kinase (SYK) variants. Functional studies have demonstrated increased kinase activity implicating them in disease pathophysiology. While the role of SYK is well characterized in immune cells, it is not understood what role it plays in the intestinal epithelium. Aims: The primary aim of this project is to understand the role SYK plays in the intestinal epithelium, what molecular pathways it signals through, and how its dysregulation leads to intestinal disease. Methods: To understand SYKs role in the intestinal epithelium, a BioID screen was used to identify novel SYK interacting proteins. BioID was done with wild type SYK as well as the patient derived variants in HEK293 cells. BioID hits were validated using co-immunoprecipitation (CoIP) and proximity ligation assay (PLA). Further functional analysis was done in Caco2 cells, an intestinal epithelial cell model, with western blot, ELISA, and luciferase assays to assess the effect of SYK activity on downstream inflammatory pathways. Finally, we investigated the effect of small molecule kinase inhibitors to explore possible novel treatment options. Results: The BioID screen revealed several high confidence interactors, with dysregulated interactions in the patient variants. USP25, a ubiquitin specific peptidase that is widely expressed, including in the intestinal epithelium, was identified as one of the strongest hits based on peptide counts. The interaction was validated with CoIP and PLA, and further analysis showed SYK activation decreased USP25 protein levels by up to eight-fold. The secretion of the proinflammatory chemokine, IL-8, in response to lipopolysaccharide (LPS) was found to be almost twice as high in Caco2 cells with patient SYK variants relative to WT. Cells expressing the patient variants of SYK showed increased NFkB and AP1 levels, indicating increased inflammatory gene expression when stimulated with 100ng/mL LPS. NFkB was also active for longer in cells expressing the patient variant of SYK post stimulation, with WT cells returning to baseline in under half an hour, while the patient variant stayed in an inflamed state for 36 to 48 hours after LPS was removed. Conclusions: Increased SYK activity is associated with the degradation of USP25. USP25 is known to cleave ubiquitin off TNF receptor associated factors (TRAFs). TRAFs are activated downstream of innate immune receptors such as TLR4, and need to be ubiquitinated for activation. USP25, which is responsible for the deubiquitination of these TRAFs, acts as a negative regulator of these pathways. The hyperactive SYK variants degrade USP25 and impair the cells’ ability to switch off inflammatory signaling pathways, indicated by the cells elongated period in an inflamed state. This research is funded by grants from Canadian Institute for Health Research (CIHR) and the Leona M. and Harry B. Helmsley Charitable Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pioneering contributions of Vaidyaraj Atmaram Waman Datar Shastri in Panchabhautik Chikitsa of Ayurveda

Abstract The resemblance between the universe and the human body is defined by five constituents, viz. earth, water, fire, air, and space are called Panchamahabhuta in Ayurveda. This fundamental concept of Panchamahabhuta is popularized by its application in diagnosis, prognosis, and treatment by Vaidya Atmaram Waman Datar Shastri, known as a pacesetter for Panchabhautik Chikitsa across India. He wrote six books on this concept. For his significant contribution to the clinical examination of Agni Samstha (seat of Agni/digestive system) and preparation of medicines, he was felicitated with “Brihattrayeeratna” by Arya Vaidya Pharmacy, Coimbatore. He founded a charitable trust in Sangli, Maharashtra. After his demise on December 25, 1995, his legacy is being carried forward by students in various ways. This study aims to delve into the life and works of Vaidya Atmaram Waman Datar Shastri. It sheds light on his invaluable contributions to the field and the enduring relevance of Panchabhautik Chikitsa in Ayurvedic practice.

Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Insulin Therapy in Ossabaw Miniature Swine with Type 1 Diabetes

Background: Therapy for type 1 diabetes resulting from immunogenic destruction of the insulin-producing pancreatic beta cells has been a challenge for over 100 years. Delivering exogenous insulin to maintain euglycemia is a delicate balance between plasma glucose transport to insulin-responsive tissues, glucose absorption in the gut, and the pharmacodynamics of insulin. The synthesis of short- and long-acting insulins and use of insulin pumps have made great strides in the standard of diabetes care. Despite advances, hypoglycemia is a major limitation. There is no approved therapy that offers glucose-responsive insulin function. Toward this end we engineered a nanoscale complex combining both electrostatic and dynamic-covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high-affnity glucose-binding motif. Hypothesis: This insulin nanocomplex will yield an injectable insulin depot providing both glucose-sensitive and long-lasting insulin availability in a translation preclinical model. Methods: Ossabaw minature swine (41-59 kg; N=6) were made diabetic with alloxan, which was confirmed by stable hyperglycemia (228±43 mg/dL). Oral glucose tolerance tests (OGTT) were conducted at the diabetic baseline and each of the following 6 days after one subcutaneous injection of the insulin nanocomplex. Results: The basline OGTT elicted blood glucose of 350-450 mg/dL for 90 min of the 150 min OGTT, while serum insulin remained at ~5 μU/mL, nearly the detection limit. In contrast, 3 h after injection of insulin nanocomplex (~0.8-0.9 mg/kg) blood glucose decreased to 71±12 mg/dL. Subsequent OGTTs on days 1-6 increased blood glucose from normoglycemia to ~200 mg/dL and serum insulin increased to ~60-220 μU/mL, followed by return to nearly normolgycemia hours after the OGTT. Hypoglycemia was avoided in all pigs. Conclusions: The subcutaneous nanocomplex of a modified insulin and a synthetic dendrimer carrier produced a glucose-responsive insulin depot for week-long glycemic control following a single routine injection. These findings offer great promise for overcoming the hypoglycemia risk of intensive glucose control. Future studies should include additional physiological challenges of exercise and nutritional states. Support: Juvenile Diabetes Research Foundation 5-CDA-2020-947-A-N, Helmsley Charitable Trust 2019PG-T1D016 and 2102-04994, American Diabetes Association Pathway 1-19-ACE-31, National Science Foundation BMAT1944875, European Union-Next Generation EU LX22NPO5104, Czech Academy of Sciences RVO 6138963. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Exercise Intensity on Cardiovascular Disease in a Rat Model of Hypertension: A Systematic Review and Meta-Analysis

Objective: Hypertension increases the risk of morbidity and mortality including stroke, myocardial infarction, and other serious complications. To prevent these events, regular exercise has been recommended as a nonpharmacological intervention for hypertensive patients, but the optimal exercise intensity, in response to the variation of the condition, remains a subject of investigation. Therefore, our study investigates the impact of exercise training on the disease progression in spontaneously hypertensive rats (SHR), a well-established rat model of hypertension. Specifically, we aim to perform a meta-analysis that measures the effects of low, moderate, and high-intensity exercise on at least one of the following cardiovascular variables: systolic blood pressure (SBP), mean arterial pressure (MAP), and resting heart rate (RHR). Hypothesis: We hypothesize that the meta-analysis findings will determine that treadmill training at low and moderate intensities will significantly improve SBP, MAP, and RHR in SHRs. We also anticipate that we will find that high intensity will produce less benefit due to its stress-inducing effects. Methods: We performed a meta-analysis adhering to the PRISMA guidelines. A systematic search for scientific studies was conducted in the CINAHL, EMBASE, SPORTDiscus, and SciFinder databases using the following key words: “spontaneously hypertensive rat,” and “exercise” yielded 900+ research articles. Subsequent selection of articles included studies that comprised of only treadmill running, more than 45 minutes of exercise per day during the training period, at least five days of training per week, and a duration of at least four weeks. Finally, eligible studies included at least one of the three cardiovascular parameters. Each study was categorized into low, moderate, or high intensity based on either treadmill speed or VO2 max, or both. Quantitative SBP, MAP, and RHR data were extracted from the included studies. Results: A total of 90 studies are included in this qualitative analysis, 9.6% of which include female rats. Preliminary data analysis evaluating means for each intensity determined that all levels of intensity significantly benefited the measured cardiovascular parameters. However, the degree of benefit was greater in the low and moderate intensities as compared to the high intensity. Conclusion: All levels of intensity exercise had a beneficial response to lowering cardiovascular parameters in SHR, however, low and moderate levels of intensity produced the greatest effects. The failure of high-intensity exercise to improve cardiovascular outcomes may suggest a role played by oxidative stress and merits further investigation. Further subgroup analysis based on sex, age, and duration of exercise will be conducted to determine if these confounding variables play role in modulating these benefits. This research was supported by the MJ Murdock charitable trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.