Engineering Analysis and Control of Transport Across the Intenstinal Mucosal Barrier

Transport phenomena in the intestinal lumen are highly significant to effective oral drug delivery, nutrient absorption, and interactions between microbes and intestinal tissue. Our laboratory is studying the impact of ingested materials, such as lipids in drug delivery systems or food, on transport and overall absorption of orally delivered compounds. Our approach includes mechanistic studies paired with systems-based models of processes key to overall oral absorption, including dissolution and permeation through intestinal membranes. Quantitative mechanistic understanding of transport phenomena in the drug delivery environment is critical to rational design of drug delivery systems enabling oral delivery of agents that may otherwise require injection. One aspect of permeation through the intestinal membrane, transport through mucus, is being investigated in detail. Results to date highlight the dependence of mucosal permeation on physical and chemical properties of penetrating material (drug, particle, microbe) as well as the significance of intestinal lumen contents in altering the mucus barrier. Our findings suggest that mild stimuli, such as those presented by food, can modulate the intestinal barrier, for example to impact oral drug delivery or microbial invasion

Parental divorce among young and adult children: a long-term quantitative analysis of mental health and family solidarity

Journal ArticleIn 2008, it was estimated that 40 percent of all marriages ended in divorce (U.S. Census, 2004) . Research has long suggested that the consequences of divorce can be profound for the children of divorced families (Amato, 2000). For example, children who experienced parental divorce were 50 percent more likely to develop health problems than children from intact two parent families (Angel, 1988; Tucker et al., 1997; Strohschei 2005). Similarly, children from divorced families also exhibit poorer academic performance (Astone & McLanahan, 1991; Wolfinger, 2003), delayed psychological development (Kurdek, Fine, & Sinclair,1994), strained relationships with family members (Hurre, 2006; Portman 2009), and poorer mental health (Ängarne-Lindberg, 2009). Some research has focused on the consequences of parental divorce as immediate or short-term consequences that are faced by the children - this is often referred to as a "crisis model"- whereas other research has documented the long-term effects of divorce - this is often referred to as the "chronic strain" model-, those consequences that persist for many years after parental divorce (Amato, 2000). Furthermore, scant research has attempted to isolate the potentially differential experiences of adult children (those who experience parental divorce as adults) compared to those who experience parental divorce earlier in the life course. About 20 percent of divorces occur in couples married over 15 years (Cooney, 1994), suggesting that parental divorce is not isolated to young children only. The purpose of this analysis is to identify whether children exhibited different types of consequences based on the age at which their parents divorced. Specifically, we explore whether the timing of parental divorce has long-term consequences on two distinct outcomes: the child's perceptions of family-solidarity and their mental health status later in life. These two outcomes were chosen because they represent a range of consequences involving both personal mental health and subsequent relationships with family

Interphotoreceptor matrix-poly(ϵ-caprolactone) composite scaffolds for human photoreceptor differentiation

Tissue engineering has been widely applied in different areas of regenerative medicine, including retinal regeneration. Typically, artificial biopolymers require additional surface modification (e.g. with arginine–glycine–aspartate-containing peptides or adsorption of protein, such as fibronectin), before cell seeding. Here, we describe an alternative approach for scaffold design: the manufacture of hybrid interphotoreceptor matrix-poly (ϵ-caprolactone) scaffolds, in which the insoluble extracellular matrix of the retina is incorporated into a biodegradable polymer well suited for transplantation. The incorporation of interphotoreceptor matrix did not change the topography of polycaprolactone film, although it led to a slight increase in hydrophilic properties (water contact angle measurements). This hybrid scaffold provided sufficient stimuli for human retinal progenitor cell adhesion and inhibited proliferation, leading to differentiation toward photoreceptor cells (expression of Crx, Nrl, rhodopsin, ROM1). This scaffold may be used for transplantation of retinal progenitor cells and their progeny to treat retinal degenerative disorders

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

<p>Abstract</p> <p>Background</p> <p>Potential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.</p> <p>Results</p> <p>Commercially available CdSe QDs, which have a ZnS shell and poly-ethylene glycol (PEG) coating, and in-house prepared surfactant coated CdSe QDs were dosed to Caco-2 cells. Cell viability and attachment were studied after 24 hours of incubation. It was found that cytotoxicity of CdSe QDs was modulated by surface coating, as PEG coated CdSe QDs had less of an effect on Caco-2 cell viability and attachment. Acid treatment increased the toxicity of PEG coated QDs, most likely due to damage or removal of the surface coating and exposure of CdSe core material. Incubation with un-dialyzed in-house prepared CdSe QD preparations, which contained an excess amount of free Cd²⁺, resulted in dramatically reduced cell viability.</p> <p>Conclusion</p> <p>Exposure to CdSe QDs resulted in cultured intestinal cell detachment and death; cytotoxicity depended largely, however, on the QD coating and treatment (e.g. acid treatment, dialysis). Experimental results generally indicated that Caco-2 cell viability correlated with concentration of free Cd²⁺ions present in cell culture medium. Exposure to low (gastric) pH affected cytotoxicity of CdSe QDs, indicating that route of exposure may be an important factor in QD cytotoxicity.</p

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

<p>Abstract</p> <p>Background</p> <p>Potential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.</p> <p>Results</p> <p>Commercially available CdSe QDs, which have a ZnS shell and poly-ethylene glycol (PEG) coating, and in-house prepared surfactant coated CdSe QDs were dosed to Caco-2 cells. Cell viability and attachment were studied after 24 hours of incubation. It was found that cytotoxicity of CdSe QDs was modulated by surface coating, as PEG coated CdSe QDs had less of an effect on Caco-2 cell viability and attachment. Acid treatment increased the toxicity of PEG coated QDs, most likely due to damage or removal of the surface coating and exposure of CdSe core material. Incubation with un-dialyzed in-house prepared CdSe QD preparations, which contained an excess amount of free Cd²⁺, resulted in dramatically reduced cell viability.</p> <p>Conclusion</p> <p>Exposure to CdSe QDs resulted in cultured intestinal cell detachment and death; cytotoxicity depended largely, however, on the QD coating and treatment (e.g. acid treatment, dialysis). Experimental results generally indicated that Caco-2 cell viability correlated with concentration of free Cd²⁺ions present in cell culture medium. Exposure to low (gastric) pH affected cytotoxicity of CdSe QDs, indicating that route of exposure may be an important factor in QD cytotoxicity.</p

A rapid review of strategies to support learning and wellbeing among 16-19 year old learners who have experienced significant disruption in their education as a result of the COVID-19 pandemic

The COVID-19 pandemic has caused a significant disruption to all levels of education, especially pupils from disadvantaged and vulnerable groups. Students aged 16-19 years are at a crucial time in their lives as they transition into further study or employment. The pandemic has brought together a unique set of conditions, not only involving disruption to education, but also to environmental, economic, social and emotional areas of young people’s and their families’ lives. This rapid review investigated strategies to support learning and wellbeing among 16-19 years old learners engaged in full time education within a college or school setting who have experienced significant gaps in their education as a result of the COVID-19 pandemic

What innovations (including return to practice) would help attract, recruit, or retain NHS clinical staff? A rapid evidence map

National Health Service (NHS) waiting times have significantly increased over the past couple of years, particularly since the emergence of COVID-19. The NHS is currently experiencing an acute workforce shortage, which hampers the ability to deal with increasing waiting times and clearing the backlog resulting from the pandemic. Plans to increase the workforce, by recruiting new staff, retaining the existing NHS clinical workforce, and making return to clinical practice more attractive will require a number of approaches. This Rapid Evidence Map aimed to describe the extent and nature of the available evidence base for innovations (including return to practice) that could help attract, recruit, or retain NHS clinical staff, in order to identify the priorities and actions for a rapid review. Three options were proposed for a subsequent focused Rapid Review and discussed with stakeholders: (1) review of primary studies that have evaluated return to practice schemes; (2) review of reviews of factors that influence retention; (3) review of reviews of interventions for supporting recruitment and retention. A decision was made that option 3 would be useful to inform practice and a rapid review will be undertaken

A rapid review of the effectiveness of interventions and innovations relevant to the Welsh NHS context to support recruitment and retention of clinical staff.

The National Health Service (NHS) is experiencing an acute workforce shortage in every discipline, at a time when waiting times are at a record high and there is a growing backlog resulting from the COVID-19 pandemic. This Rapid Review aimed to explore the effectiveness of interventions or innovations relevant to the Welsh NHS context to support recruitment and retention of clinical staff. The review is based on the findings of existing reviews supplemented by a more in-depth evaluation of included primary studies conducted in the UK or Europe. The review identifies a range of interventions that can be used for enhancing recruitment and retention in Wales, particular in rural areas, and supports multiple-component interventions. The findings highlight the importance of providing and locating undergraduate and post graduate training in rural locations. The findings also corroborate the use of bursary schemes for training, such as those already available for Nursing in Wales. Further, more robust evaluations, based on comparative studies, are required to assess the effectiveness of interventions to support recruitment and retention of clinical staff. There was limited evidence on interventions aimed at allied health professionals. Most of the primary studies included in the reviews used cohort (pre-post test) or cross-sectional designs. Most studies lacked a comparison group and did not use statistical analysis