Medium-Term Weight Loss and Remission of Comorbidities Following Endoscopic Sleeve Gastroplasty: a Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to determine the short- and medium-term weight loss outcomes and comorbidity resolution following endoscopic sleeve gastroplasty. Our search identified 35 relevant studies containing data from 7525 patients. Overall, pooled short-term (12 months) total weight loss (TWL) was 16.2% (95% CI 13.1-19.4%) in 23 studies (n = 5659). Pooled medium-term TWL was 15.4% (95% CI 13.7-17.2%) in 10 studies (n = 4040). Diabetes resolution was 55.4% (95% CI 46-64%), hypertension resolution was 62.8% (95% CI 43-82%), dyslipidaemia resolution was 56.3% (95% CI 49-63%), and obstructive sleep apnoea resolution was 51.7% (95% CI 16.2-87.3%) in four studies (n = 480). This pooled analysis demonstrates that ESG can induce durable weight loss and resolution of obesity-associated comorbidities in patients with moderate obesity.

Fungus-derived protein particles as cell-adhesive matrices for cell-cultivated food.

Cell-adhesive factors mediate adhesion of cells to substrates via peptide motifs such as the Arg-Gly-Asp (RGD) sequence. With the onset of sustainability issues, there is a pressing need to find alternatives to animal-derived cell-adhesive factors, especially for cell-cultivated food applications. In this paper, we show how data mining can be a powerful approach toward identifying fungal-derived cell-adhesive proteins and present a method to isolate and utilize these proteins as extracellular matrices (ECM) to support cell adhesion and culture in 3D. Screening of a protein database for fungal and plant proteins uncovered that ~5.5% of the unique reported proteins contain RGD sequences. A plot of fungi species vs RGD percentage revealed that 98% of the species exhibited an RGD percentage > = 1%. We observed the formation of protein particles in crude extracts isolated from basidiomycete fungi, which could be correlated to their stability towards particle aggregation at different temperatures. These protein particles were incorporated in 3D fiber matrices encapsulating mouse myoblast cells, showing a positive effect on cell alignment. We demonstrated a cell traction stress on the protein particles (from Flammulina velutipes) that was comparable to cells on fibronectin. A snapshot of the RGD-containing proteins in the fungal extracts was obtained by combining SDS-PAGE and mass spectrometry of the peptide fragments obtained by enzymatic cleavage. Therefore, a sustainable source of cell-adhesive proteins is widely available in the fungi kingdom. A method has been developed to identify candidate species and produce cell-adhesive matrices, applicable to the cell-cultivated food and healthcare industries.

Interventions for Grieving and Bereaved Informal Caregivers: A Scoping Review of the Canadian Literature.

Background: The palliative approach to care is playing a larger role in the healthcare of older adults in Canada. Within (hospice) palliative care, informal caregivers play a crucial role as part of the interdisciplinary care team. Ensuring high quality palliative care includes providing effective grief and bereavement supports for them. Objective: This study aimed to identify current interventions addressing the grief and bereavement experiences of informal caregivers of geriatric patients in the Canadian (hospice) palliative/end-of-life care realm. Methods: A scoping review was undertaken using Arksey and O'Malley's framework. Seven electronic health and social science databases were searched. In addition, several stakeholder organizations' websites were reviewed to identify grey literature sources. Interventions that took place in Canada, were in English, and explored grief and bereavement supports for informal caregivers in an adult/geriatric (hospice) palliative care setting were included. After full text review, data were extracted and charted. Major themes were established following thematic content analysis. Results: Within a total of 18 sources, three themes were identified: (1) Classification of intervention, (2) Format of intervention, and (3) Intervention target. Method of delivery and type of intervention for grief and bereavement supports were aligned with the international literature. There is a need for large-scale evaluations of interventions and informal caregivers should be engaged in this process. Practitioners should be encouraged to direct bereavement interventions toward grieving caregivers, and to collaborate with them to improve access to these interventions. Policy makers should provide additional funding for grief interventions for informal caregivers. Conclusions: It is important to better understand the needs of informal caregivers experiencing grief and bereavement. Interdisciplinary collaborations will be necessary to develop, evaluate, and scale future interventions.

Xeno-free self-assembling peptide scaffolds for building 3D organotypic skin cultures.

Organotypic skin cultures represent in vitro models of skin which can be used for disease modeling, tissue engineering, and screening applications. Non-human collagen is currently the gold standard material used for the construction of the supporting matrix, however, its clinical applications are limited due to its xenogeneic origin. We have developed a novel peptide hydrogel-based skin construct that shows a pluristratified epidermis, basement membrane, and dermal compartment after 3 weeks of in vitro culture. Peptide-based constructs were compared to collagen-based constructs and stratification marker expression was histologically higher in peptide constructs than in collagen constructs. Transepithelial electrical resistance also showed mature barrier function in peptide constructs. This study presents a novel application of the self-assembling peptide hydrogel in a defined xeno-free in vitro system.

Observations that suggest a contribution of altered dermal papilla mitochondrial function to androgenetic alopecia.

Androgenetic alopecia (AGA) is a prevalent hair loss condition in males that develops due to the influence of androgens and genetic predisposition. With the aim of elucidating genes involved in AGA pathogenesis, we modelled AGA with three-dimensional culture of keratinocyte-surrounded dermal papilla (DP) cells. We co-cultured immortalised balding and non-balding human DP cells (DPCs) derived from male AGA patients with epidermal keratinocyte (NHEK) using multi-interfacial polyelectrolyte complexation technique. We observed up-regulated mitochondria-related gene expression in balding compared with non-balding DP aggregates which indicated altered mitochondria metabolism. Further observation of significantly reduced electron transport chain complex activity (complexes I, IV and V), ATP levels and ability to uptake metabolites for ATP generation demonstrated compromised mitochondria function in balding DPC. Balding DP was also found to be under significantly higher oxidative stress than non-balding DP. Our experiments suggest that application of antioxidants lowers oxidative stress levels and improves metabolite uptake in balding DPC. We postulate that the observed up-regulation of mitochondria-related genes in balding DP aggregates resulted from an over-compensatory effort to rescue decreased mitochondrial function in balding DP through the attempted production of new functional mitochondria. In all, our three-dimensional co-culturing revealed mitochondrial dysfunction in balding DPC, suggesting a metabolic component in the aetiology of AGA.

Support for Informal Caregivers in Canada: A Scoping Review from a Hospice and Palliative/End-of-Life Care Lens.

Objective: Informal caregivers (ICs) providing care for those at the end-of-life face physical, psycho-social, emotional, and/or financial challenges. However, there is a paucity of research towards the effectiveness of available interventions for this vulnerable population. The purpose of this scoping review was to investigate the availability and efficacy of interventions for ICs providing hospice and palliative/end-of-life care in Canada. Methods: Using Arksey and O'Malley's five step framework, a scoping review was conducted in the spring of 2020. Key electronic healthcare, social sciences, and grey literature databases were searched. Relevant publications from 2005 to 2019 were screened for inclusion criteria, and a thematic content analysis was conducted to summarize all key findings. Results: Initial searches yielded 145 results out of which 114 distinct articles were obtained. De-duplication and final screening yielded 28 sources which met inclusion criteria (22 peer-reviewed articles [78%] and 6 grey sources [22%]; 12 qualitative papers [42%]). Through thematic content analysis, four major themes were identified: [1] Direct financial support, [2] Direct psycho-sociospiritual support, [3] Indirect patient information provision/education, and [4] Indirect patient support. Conclusions: Healthcare practitioners should provide information on patient care and financial aid to ICs. Policies should aim to expand eligibility for and access to financial aid, in particular the Compassionate Care Benefits (CCB). Future research should focus on exploring other interventions, such as physical activities, to better support this vulnerable population. The results from this review will help inform and improve the well-being of ICs providing end-of-life care in Canada and beyond.

Informal Caregiving for People With Life-Limiting Illness: Exploring the Knowledge Gaps.

Background: People with life-limiting illness are increasingly having more care provided to them by informal caregivers (ICs) such as family members and friends. Although there is a substantial amount of literature surrounding informal caregiving, there is a paucity of research from a hospice palliative care angle. To address this knowledge gap, this scoping review explored the effects of/challenges to informal caregiving at the end of life in Canada. Methods: Scoping review of the literature following Arksey and O'Malley's framework. Key healthcare and social sciences databases alongside the gray literature were searched. Relevant scholarly and gray literature sources from 2005 to 2019 were screened for inclusion criteria, and a thematic content analysis employed to summarize findings. Results: Of 2,717 initial search results, 257 distinct full text articles were obtained. Following deduplication and screening, 33 met inclusion criteria. Four major themes were identified: (1) Physical health challenges, (2) Psycho-socio-spiritual health challenges, (3) Financial issues, and (4) Health system issues. Gender of ICs was also found to be an important contributor to the differing effects of providing support. Conclusions: This review raises awareness toward ICs regarding the numerous physical, psycho-socio-spiritual, financial, and health system challenges faced during care for people with life-limiting illness. The knowledge gained will inform and advance future practice, policy, and research. Application to interventions (such as caregiver benefits) will assist to improve informal caregiving experiences and outcomes alongside quality of life. Further research is required to understand these unique experiences and the challenges of minority IC populations.

The Grief and Bereavement Experiences of Informal Caregivers: A Scoping Review of the North American Literature.

Background: Informal caregivers are a significant part of the hospice and palliative care landscape as members of the interdisciplinary care team. Despite this, little is known about the impact this responsibility has on informal caregivers' experiences of grief and bereavement. Objective: To address this, a scoping review of the literature was conducted to explore the current state of knowledge toward grief and bereavement of informal caregivers of adult/geriatric patients in the hospice and palliative/end-of-life care realm within North America. Methods: Using Arksey and O'Malley's 5-step framework, key electronic health care and social sciences databases (eg, CINAHL, MEDLINE, ProQuest Sociological Abstracts, PsycINFO) alongside gray literature sources were searched and screened against inclusion and exclusion criteria. A thematic content analysis was used to identify key themes. Results: 29 articles met the final inclusion criteria with 3 central themes emerging: (1) mediators of grief, (2) grief experiences, and (3) types of grief. Discussion: Informal caregivers encounter unique grief and bereavement experiences: The range of psychosocial outcomes, both negative and positive, can be affected by various mediators such as caregiver burden, demographics, disease type of the patient being cared for, etc. Bereavement interventions must be designed with the mediators of grief in mind. Conclusions: Understanding the nuances of informal caregivers' experiences with grief and bereavement will inform and advance practice, policy, and research. Practitioners/clinicians should be further educated on how to properly acknowledge the complexity of grief and bereavement for informal caregivers, specifically paying attention to mediators. Further research needs to consider the role of culture.

Systems for Muscle Cell Differentiation: From Bioengineering to Future Food.

In light of pressing issues, such as sustainability and climate change, future protein sources will increasingly turn from livestock to cell-based production and manufacturing activities. In the case of cell-based or cultured meat a relevant aspect would be the differentiation of muscle cells into mature muscle tissue, as well as how the microsystems that have been developed to date can be developed for larger-scale cultures. To delve into this aspect we review previous research that has been carried out on skeletal muscle tissue engineering and how various biological and physicochemical factors, mechanical and electrical stimuli, affect muscle cell differentiation on an experimental scale. Material aspects such as the different biomaterials used and 3D vs. 2D configurations in the context of muscle cell differentiation will also be discussed. Finally, the ability to translate these systems to more scalable bioreactor configurations and eventually bring them to a commercial scale will be touched upon.

pH-Degradable imidazolium oligomers as antimicrobial materials with tuneable loss of activity.

Antimicrobial resistance (AMR) has become a global public health threat. One of the major causes of AMR development is the accumulation of low levels of antimicrobials in the environment. To tackle this problem, novel antimicrobial agents that do not leave active residues after treatment are needed. In this study, a strategy for synthesizing a series of main-chain imidazolium oligomers that incorporate carbonate, hemiaminal, ester and urea functional groups to serve as degradable linkers is presented. These oligomers exhibit excellent microbicidal activity and kill E. coli at low concentrations in a short time (99% killing efficiency in 2 min). Moreover, the oligomers are self-degradable and biocompatible. The degradation of these oligomers is studied in buffered solutions with different pH. Under basic conditions (pH = 8), carbonate-linked and ester-linked oligomers degrade to inactive and less toxic small molecules within weeks, making it less likely for these oligomers to induce antimicrobial resistance as compared to traditional antibiotics. The application of these oligomers for the in vivo treatment of S. aureus infected wounds is demonstrated in a mouse model. Notably, the oligomers demonstrate antibacterial efficacy and accelerated wound healing comparable to vancomycin, a first-line antibiotic for the treatment of complicated skin infections.

Time of Transfer of Admitted Patients from the ED: A Contributor to ED Boarding in High-Volume Community Hospitals.

The twin challenges of bed boarding and "hallway medicine" have emerged in recent years as key healthcare issues. Many hospitals, challenged with increasing demand and limited resources, have tried to find efficiencies within their operations. One such strategy is that of early morning discharges and expedited bed turnaround times. We conducted a retrospective study within three high-volume hospitals in the Greater Toronto Area looking at discharge times of in-patients and transfer times of admitted, Emergency Department (ED)-boarded patients. We discovered a consistent pattern of late-in-the-day discharges, and even later-in-the-day transfers of boarded ED patients, indicating that this may be a potential source of increased efficiency for overburdened hospitals.

Primitive Cancer Cell States: A Target for Drug Screening?

At present, most drug screening efforts employ bulk cancer cell populations, which may lead to selection of the more drug-resistant cancer stem cells (CSCs). However, drug screening using CSCs has been limited, mainly owing to the difficulty of their isolation. This article discusses how methods of reprogramming cancer cells to primitive cancer cell states, such as transcription factor reprogramming, epithelial-mesenchymal transition (EMT), conditional reprogramming, and hypoxia, may approach the CSC state and thus be relevant for drug screening purposes. This leads to the importance of recapitulating the stem cell niche in drug assays, which is enabled by recent advances in cell culture and tissue engineering. With the advent of these technologies, this article addresses the question of whether the stem cell phenotype should be targeted for drug screening.

Sensitization of Cancer Cells via Non-Viral Delivery of Apoptosis Inducing Proteins Using a Cationic Bolaamphiphile.

Cationic bolaamphiphile polymers had been previously studied as efficient delivery system for the delivery of proteins with relatively low toxicity. Here, the authors investigate the use of a protein delivery system based on a cationic bolaamphiphile to sensitize cancer cells toward apoptosis-inducing drugs as a novel approach for cancer therapy. The authors demonstrates the efficacy of the system by two strategies. The first strategy involves delivery of a survivin antibody to inhibit survivin activity. Sensitization of MCF-7 cells to doxorubicin is observed by survivin inhibition by antibodies. The IC50 of doxorubicin is reduced ≈2.5-fold after delivery of survivin antibodies to breast cancer cells and induction of apoptosis is shown by Western blotting with apoptosis specific antibodies. In a second approach, functional wild type p53 is delivered into p53-null liver cancer (Hep3B) cells, sensitizing the cells toward the p53 pathway drug, Nutlin. Nutlin reduced the viability of Hep3B cells by ≈42% at 15 µM concentration, demonstrating the effectiveness of p53 delivery. The expression of p21, a downstream target of p53 further confirmed the functional status of the delivered protein. In conclusion. The successful delivery of apoptosis inducing proteins and sensitization of cancer cells via cationic bolaamphiphile polymer represents a promising system for cancer therapeutics.

A Chemically Well-Defined, Self-Assembling 3D Substrate for Long-Term Culture of Human Pluripotent Stem Cells.

Clinical applications of human pluripotent stem cells (PSCs) are limited by the lack of chemically well-defined scaffolds for cell expansion, differentiation, and implantation. In this study, we systematically screened various self-assembling hexapeptides to identify the best matrix for long-term 3D PSC culture. Lysine-containing Ac-ILVAGK-NH2 hydrogels maintained best the pluripotency of human embryonic and induced PSCs even after 30 passages. This peptide matrix is also compatible with the use of xeno-free and defined differentiation media. By exploiting its stimuli-responsive sol-gel transition, arrays of encapsulated PSCs can be bioprinted for large-scale cell expansion and derivation of miniaturized organoid cultures for high-throughput screening.

Characterization of Simultaneous Pressure Waves as Biomarkers for Colonic Motility Assessed by High-Resolution Colonic Manometry.

Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, SPWs were often not a pan-colonic event. SPWs and HAPW-SPWs were observed at baseline with SPW amplitudes of 12.0 ± 8.5 mmHg and 20.2 ± 7.2 mmHg respectively. The SPW occurrence and amplitude significantly increased in response to meal, balloon distention and luminal bisacodyl, associated with 50.3% anal sphincter relaxation at baseline, which significantly increased to 59.0% after a meal, and 69.1% after bisacodyl. Often, full relaxation was achieved. The SPWs associated with gas expulsion had a significantly higher amplitude compared to SPWs without gas expulsion. SPWs could be seen to consist of clusters of high frequency pressure waves, likely associated with a cluster of fast propagating, circular muscle contractions. SPWs were occasionally observed in a highly rhythmic pattern at 1.8 ± 1.2 cycles/min. Unlike HAPWs, the SPWs did not obliterate haustral boundaries thereby explaining how gas can be expelled while solid content can remain restrained by the haustral boundaries. In conclusion, the SPW may become a biomarker for normal gas transit, the gastrocolonic reflex and extrinsic neural reflexes. The SPW assessment reveals coordination of activities in the colon, rectum and anal sphincters. SPWs may become of diagnostic value in patients with colonic dysmotility.

Lineage-specific exosomes could override extracellular matrix mediated human mesenchymal stem cell differentiation.

Lineage specification is an essential process in stem cell fate, tissue homeostasis and development. Microenvironmental cues provide direct and selective extrinsic signals to regulate lineage specification of stem cells. Microenvironmental milieu consists of two essential components, one being extracellular matrix (ECM) as the substratum, while the other being cell secreted exosomes and growth factors. ECM of differentiated cells modulates phenotypic expression of stem cells, while their exosomes contain phenotype specific instructive factors (miRNA, RNA and proteins) that control stem cell differentiation. This study demonstrates that osteoblasts-derived (Os-Exo) and adipocytes-derived (Ad-Exo) exosomes contain instructive factors that regulate the lineage specification of human mesenchymal stem cells (hMSCs). Analyses of exosomes revealed the presence of transcription factors in the form of RNA and protein for osteoblasts (RUNX2 and OSX) and adipocytes (C/EBPα and PPARγ). In addition, several miRNAs reported to have osteogenic and adipogenic differentiation potentials are also identified in these exosomes. Kinetic and differentiation analyses indicate that both osteoblast and adipocyte exosomes augment ECM-mediated differentiation of hMSCs into the respective lineage. The combination of osteoblast/adipocyte ECM and exosomes turned-on the lineage specific gene expressions at earlier time points of differentiation compared to the respective ECM or exosomes administered individually. Interestingly, the hMSCs differentiated on osteoblast ECM with adipogenic exosomes showed expression of adipogenic lineage genes, while hMSCs differentiated on adipocyte ECM with osteoblast exosomes showed osteogenic lineage genes. Based on these observations, we conclude that exosomes might override the ECM mediated instructive signals during lineage specification of hMSC.

Synthetic Poly(Vinylalcohol)-Based Membranes for Cartilage Surgery and Repair.

Cell-based therapies for cartilage repair are continually being developed to treat osteoarthritis. The cells are either introduced directly by intra-articular injection or via a cell-seeded matrix scaffold. Here, poly(vinylalcohol)-based membranes are developed to be used for mesenchymal stem cell implantation in cartilage repair procedures, having controllable physicochemical properties such as porosity, mechanical strength, and permeability, and a unique self-sealing property. The membranes possess a bilayer structure with a less porous layer providing mechanical strength and selective permeability, exhibit an elastic modulus of between 0.3 and 0.9 MPa, and are permeable to molecules <40 kDa, which is in the range of cartilage permeability. Three different peptide ligands with the sequences Ac-GCGYGRGDSPG, Ac-GCG(OPG)4REGOFG(OPG)4, and Ac-GCG(OPG)7, respectively, are conjugated to the membranes and subject to in vitro cell adhesion and differentiation assays. Col I/Col II gene expression ratios indicated that the collagen-mimetic peptide, Ac-GCG(OPG)7, best supported mesenchymal stem cell differentiation into the chondrogenic lineage. Although low retention of the membrane is observed in vivo in a rabbit knee model, results suggest that the membrane was able to facilitate mesenchymal stem cell implantation and differentiation to chondrocytes. These PVA-based membranes provide a feasible, synthetic, off-the-shelf material for the delivery of stem cells, and can be modified for other surgical applications.

Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening.

Cardiotoxicity is one of the major reasons for clinical drug attrition. In vitro tissue models that can provide efficient and accurate drug toxicity screening are highly desired for preclinical drug development and personalized therapy. Here, we report the fabrication and characterization of a human cardiac tissue model for high throughput drug toxicity studies. Cardiac tissues were fabricated via cellular self-assembly of human transgene-free induced pluripotent stem cells-derived cardiomyocytes in pre-fabricated polydimethylsiloxane molds. The formed tissue constructs expressed cardiomyocyte-specific proteins, exhibited robust production of extracellular matrix components such as laminin, collagen and fibronectin, aligned sarcomeric organization, and stable spontaneous contractions for up to 2 months. Functional characterization revealed that the cardiac cells cultured in 3D tissues exhibited higher contraction speed and rate, and displayed a significantly different drug response compared to cells cultured in age-matched 2D monolayer. A panel of clinically relevant compounds including antibiotic, antidiabetic and anticancer drugs were tested in this study. Compared to conventional viability assays, our functional contractility-based assays were more sensitive in predicting drug-induced cardiotoxic effects, demonstrating good concordance with clinical observations. Thus, our 3D cardiac tissue model shows great potential to be used for early safety evaluation in drug development and drug efficiency testing for personalized therapy.

Educational strategies for teaching evidence-based practice to undergraduate health students: systematic review.

PURPOSE: The aim of this systematic review was to find best teaching strategies for teaching evidence-based practice (EBP) to undergraduate health students that have been adopted over the last years in healthcare institutions worldwide. METHODS: The authors carried out a systematic, comprehensive bibliographic search using Medline database for the years 2005 to March 2015 (updated in March 2016). Search terms used were chosen from the USNLM Institutes of Health list of MeSH (Medical Subject Headings) and free text key terms were used as well. Selected articles were measured based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, articles relevant to the subject of this review were retrieved in full text. Critical appraisal was done to determine the effects of strategy of teaching evidence-based medicine (EBM). RESULTS: Twenty articles were included in the review. The majority of the studies sampled medical students (n=13) and only few conducted among nursing (n=2), pharmacy (n=2), physiotherapy/therapy (n=1), dentistry (n=1), or mixed disciplines (n=1) students. Studies evaluated a variety of educational interventions of varying duration, frequency and format (lectures, tutorials, workshops, conferences, journal clubs, and online sessions), or combination of these to teach EBP. We categorized interventions into single interventions covering a workshop, conference, lecture, journal club, or e-learning and multifaceted interventions where a combination of strategies had been assessed. Seven studies reported an overall increase to all EBP domains indicating a higher EBP competence and two studies focused on the searching databases skill. CONCLUSION: Followings were deduced from above analysis: multifaceted approach may be best suited when teaching EBM to health students; the use of technology to promote EBP through mobile devices, simulation, and the web is on the rise; and the duration of the interventions varying form some hours to even months was not related to the students' EBP competence.