Access, acceptance and adherence to cancer prehabilitation: a mixed-methods systematic review.

PURPOSE: The purpose of this systematic review is to better understand access to, acceptance of and adherence to cancer prehabilitation. METHODS: MEDLINE, CINAHL, PsychINFO, Embase, Physiotherapy Evidence Database, ProQuest Medical Library, Cochrane Library, Web of Science and grey literature were systematically searched for quantitative, qualitative and mixed-methods studies published in English between January 2017 and June 2023. Screening, data extraction and critical appraisal were conducted by two reviewers independently using Covidence™ systematic review software. Data were analysed and synthesised thematically to address the question 'What do we know about access, acceptance and adherence to cancer prehabilitation, particularly among socially deprived and minority ethnic groups?' The protocol is published on PROSPERO CRD42023403776 RESULTS: Searches identified 11,715 records, and 56 studies of variable methodological quality were included: 32 quantitative, 15 qualitative and nine mixed-methods. Analysis identified facilitators and barriers at individual and structural levels, and with interpersonal connections important for prehabilitation access, acceptance and adherence. No study reported analysis of facilitators and barriers to prehabilitation specific to people from ethnic minority communities. One study described health literacy as a barrier to access for people from socioeconomically deprived communities. CONCLUSIONS: There is limited empirical research of barriers and facilitators to inform improvement in equity of access to cancer prehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: To enhance the inclusivity of cancer prehabilitation, adjustments may be needed to accommodate individual characteristics and attention given to structural factors, such as staff training. Interpersonal connections are proposed as a fundamental ingredient for successful prehabilitation.

Assessing a digital technology-supported community child health programme in India using the Social Return on Investment framework.

An estimated 5.0 million children aged under 5 years died in 2020, with 82% of these deaths occurring in sub-Saharan Africa and southern Asia. Over one-third of Mumbai's population has limited access to healthcare, and child health outcomes are particularly grave among the urban poor. We describe the implementation of a digital technology-based child health programme in Mumbai and evaluate its holistic impact. Using an artificial intelligence (AI)-powered mobile health platform, we developed a programme for community-based management of child health. Leveraging an existing workforce, community health workers (CHW), the programme was designed to strengthen triage and referral, improve access to healthcare in the community, and reduce dependence on hospitals. A Social Return on Investment (SROI) framework is used to evaluate holistic impact. The programme increased the proportion of illness episodes treated in the community from 4% to 76%, subsequently reducing hospitalisations and out-of-pocket expenditure on private healthcare providers. For the total investment of Indian Rupee (INR) 2,632,271, the social return was INR 34,435,827, delivering an SROI ratio of 13. The annual cost of the programme per child was INR 625. Upskilling an existing workforce such as CHWs, with the help of AI-driven decision- support tools, has the potential to extend capacity for critical health services into community settings. This study provides a blueprint for evaluating the holistic impact of health technologies using evidence-based tools like SROI. These findings have applicability across income settings, offering clear rationale for the promotion of technology-supported interventions that strengthen healthcare delivery.

Mesenchymal stem cell-derived rapid drug screening system for Alzheimer's disease for the identification of novel drugs.

A reliable and efficient in vitro model is needed to screen drugs for Alzheimer's disease (AD), as many drugs are currently in the developmental stage. To address this, we developed an in vitro model using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) to screen novel drugs for AD. We differentiated AM-MSCs into neurons and degenerated them using beta amyloid1-42 (Aß). We then tested AD drugs, which are commercially available such as donepezil, rivastigmine, memantine, citicoline, and two novel drugs, that is, probucol, an anti-hyperlipidaemic drug, and NMJ-2, a cinnamic acid analogue for their potential to protect the cells against neurodegeneration. We used gene expression and immunofluorescence staining to assess the neuroprotective ability of these drugs. We also measured the ability of these drugs to reduce lactate dehydrogenase, reactive oxygen species, and nitric oxide levels, as well as their ability to stabilize the mitochondrial membrane potential and increase acetylcholine (ACh) levels. The AD drugs and novel drugs reduced cytotoxicity and oxidative stress, stabilized mitochondrial membrane potential, and restored ACh levels. Furthermore, they reduced BACE1 expression, with a concomitant increase in the expression of cholinergic markers. This AM-MSCs-based AD-like model has immense potential to be an accurate human model and an alternative to animal models for testing a large number of lead compounds in a short time. Our results also suggest that the novel drugs probucol and NMJ-2 may protect against Aß-induced neurodegeneration.

Design and implementation of a community-based mother-to-mother peer support programme for the follow-up of low birthweight infants in rural western Kenya.

Background: Globally, low birthweight (LBW) infants (<2,500 g) have the highest risk of mortality during the first year of life. Those who survive often have adverse health outcomes. Post-discharge outcomes of LBW infants in impoverished communities in Africa are largely unknown. This paper describes the design and implementation of a mother-to-mother peer training and mentoring programme for the follow-up of LBW infants in rural Kenya. Methods: Key informant interviews were conducted with 10 mothers of neonates (infants <28 days) from two rural communities in western Kenya. These data informed the identification of key characteristics required for mother-to-mother peer supporters (peer mothers) following up LBW infants post discharge. Forty potential peer mothers were invited to attend a 5-day training programme that focused on three main themes: supportive care using appropriate communication, identification of severe illness, and recommended care strategies for LBW infants. Sixteen peer mothers were mentored to conduct seven community follow-up visits to each mother-LBW infant pair with fifteen completing all the visits over a 6-month period. A mixed methods approach was used to evaluate the implementation of the programme. Quantitative data of peer mother socio-demographic characteristics, recruitment, and retention was collected. Two post-training focus group discussions were conducted with the peer mothers to explore their experiences of the programme. Descriptive statistics were generated from the quantitative data and the qualitative data was analysed using a thematic framework. Results: The median age of the peer mothers was 26 years (range 21-43). From March-August 2019, each peer mother conducted a median of 28 visits (range 7-77) with fourteen (88%) completing all their assigned follow-up visits. Post training, our interviews suggest that peer mothers felt empowered to promote appropriate infant feeding practices. They gave multiple examples of improved health seeking behaviours as a result of the peer mother training programme. Conclusion: Our peer mother training programme equipped peer mothers with the knowledge and skills for the post-discharge follow-up of LBW infants in this rural community in Kenya. Community-based interventions for LBW infants, delivered by appropriately trained peer mothers, have the potential to address the current gaps in post-discharge care for these infants.

Identification of a Novel Wnt Antagonist Based Therapeutic and Diagnostic Target for Alzheimer's Disease Using a Stem Cell-Derived Model.

Currently, all the existing treatments for Alzheimer's disease (AD) fail to stall progression due to longer duration of time between onset of the symptoms and diagnosis of the disease, raising the necessity of effective diagnostics and novel treatment. Specific molecular regulation of the onset and progression of disease is not yet elucidated. This warranted investigation of the role of Wnt signaling regulators which are thought to be involved in neurogenesis. The AD model was established using amyloid beta (Aß) in human mesenchymal stem cells derived from amniotic membranes which were differentiated into neuronal cell types. In vivo studies were carried out with Aß or a Wnt antagonist, AD201, belonging to the sFRP family. We further created an AD201-knockdown in vitro model to determine the role of Wnt antagonism. BACE1 upregulation, ChAT and α7nAChR downregulation with synapse and functionality loss with increases in ROS confirmed the neurodegeneration. Reduced ß-catenin and increased AD201 expression indicated Wnt/canonical pathway inhibition. Similar results were exhibited in the in vivo study along with AD-associated behavioural and molecular changes. AD201-knockdown rescued neurons from Aß-induced toxicity. We demonstrated for the first time a role of AD201 in Alzheimer's disease manifestation, which indicates a promising disease target and biomarker.

Designing precision medicine panels for drug refractory cancers targeting cancer stemness traits.

Cancer is one amongst the major causes of death today and cancer biology is one of the most well researched fields in medicine. The driving force behind cancer is considered to be a minor subpopulation of cells, the cancer stem cells (CSCs). Similar to other stem cells, these cells are self-renewing and proliferating but CSCs are also difficult to target by chemo- or radio-therapies. Cancer stem cells are known to be present in most of the cancer subgroups such as carcinoma, sarcoma, myeloma, leukemia, lymphomas and mixed cancer types. There is a wide gamut of factors attributed to the stemness of cancers, ranging from dysregulated signaling pathways, and activation of enzymes aiding immune evasion, to conducive tumor microenvironment, to name a few. The defining outcome of the increased presence of CSCs is tumor metastasis and relapse. Predictive medicine approach based on the plethora of CSC markers would be a move towards precision medicine to specifically identify CSC-rich tumors. In this review, we discuss the cancer subtypes and the role of different CSC specific markers in these varying subtypes. We also categorize the CSC markers based their defining trait contributing to stemness. This review thus provides a comprehensive approach to catalogue a predictive set of markers to identify the resistant and refractory cancer stem cell population within different tumor subtypes, so as to facilitate better prognosis and targeted therapeutic strategies.

'Sometimes you are forced to play God ': a qualitative study of healthcare worker experiences of using continuous positive airway pressure in newborn care in Kenya.

​OBJECTIVE: To explore the experiences of using continuous positive airway pressure (CPAP) in newborn care among healthcare workers in Kenya, and to identify factors that would promote successful scale-up. ​DESIGN AND SETTING: A qualitative study using key informant interviews and focus group discussions, based at secondary and tertiary level hospitals in Kenya. ​PARTICIPANTS: Healthcare workers in the newborn units providing CPAP. ​PRIMARY AND SECONDARY OUTCOME MEASURE: Facilitators and barriers of CPAP use in newborn care in Kenya. ​RESULTS: 16 key informant interviews and 15 focus group discussions were conducted across 19 hospitals from September 2017 to February 2018. Main barriers reported were: (1) inadequate infrastructure to support the effective delivery of CPAP, (2) shortage of skilled staff rendering it difficult for the available staff to initiate or monitor infants on CPAP and (3) inadequate knowledge and training of staff that inhibited the safe care of infants on CPAP. Key facilitators reported were positive patient outcomes after CPAP use that increased staff confidence and partnership with caregivers in the management of newborns on CPAP. Healthcare workers in private/mission hospitals had more positive experiences of using CPAP in newborn care as the relevant support and infrastructure were available. ​CONCLUSION: CPAP use in newborn care is valued by healthcare workers in Kenya. However, we identified key challenges that threaten its safe use and sustainability. Further scale-up of CPAP in newborn care should ensure that staff members have ready access to optimal training on CPAP and that there are enough resources and infrastructure to support its use. ETHICS: This study was approved through the appropriate ethics committees in Kenya and the UK (see in text) with written informed consent for each participant.

Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma.

BACKGROUND: Chemotherapeutic resistance of glioblastoma has been attributed to a self-renewing subpopulation, the glioma stem cells (GSCs), which is known to be maintained by the Wnt ß-catenin pathway. Our previous findings demonstrated that exogeneous addition of the Wnt antagonist, secreted fizzled-related protein 4 (sFRP4) hampered stem cell properties in GSCs. METHODS: To understand the molecular mechanism of sFRP4, we overexpressed sFRP4 (sFRP4 OE) in three human glioblastoma cell lines U87MG, U138MG, and U373MG. We also performed chromatin immunoprecipitation (ChIP) sequencing of sFRP4 OE and RNA sequencing of sFRP4 OE and sFRP4 knocked down U87 cells. RESULTS: We observed nuclear localization of sFRP4, suggesting an unknown nuclear role. ChIP-sequencing of sFRP4 pulldown DNA revealed a homeobox Cphx1, related to the senescence regulator ETS proto-oncogene 2 (ETS2). Furthermore, miRNA885, a p53-mediated apoptosis inducer, was upregulated in sFRP4 OE cells. RNA sequencing analysis suggested that sFRP4-mediated apoptosis is via the Fas-p53 pathway by activating the Wnt calcium and reactive oxygen species pathways. Interestingly, sFRP4 OE cells had decreased stemness, but when knocked down in multipotent mesenchymal stem cells, pluripotentiality was induced and the Wnt ß-catenin pathway was upregulated. CONCLUSIONS: This study unveils a novel nuclear role for sFRP4 to promote apoptosis by a possible activation of DNA damage machinery in glioblastoma.