Human keratin matrices promote wound healing by modulating skin cell expression of cytokines and growth factors.

A wide variety of biomaterials has been developed to assist in wound healing, including acellular animal and human-derived protein matrices. However, millions of patients worldwide still suffer from non-healing chronic wounds, demonstrating a need for further innovation in wound care. To address this need, a novel biomaterial, the human keratin matrix (HKM), was developed, characterised, and tested in vitro and in vivo. HKM was found to be degradation-resistant, and a proteomics analysis showed it to be greater than 99% human keratin proteins. PCR revealed adult human epidermal keratinocytes (HEKa) grown in contact with HKM showed increased gene expression of keratinocyte activations markers such as Epidermal Growth Factor (EGF). Additionally, a cytokine microarray demonstrated culture on HKM increased the release of cytokines involved in wound inflammatory modulation by both HEKa cells and adult human dermal fibroblasts (HDFa). Finally, in a murine chronic wound model, full-thickness wounds treated weekly with HKM were smaller through the healing process than those treated with human amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS). HKM-treated wounds also closed significantly faster than AM- and SIS-treated wounds. These data suggest that HKM is an effective novel treatment for chronic wounds.

Optomechanically Actuated Hydrogel Platform for Cell Stimulation with Spatial and Temporal Resolution.

Cells exist in the body in mechanically dynamic environments, yet the vast majority of in vitro cell culture is conducted on static materials such as plastic dishes and gels. To address this limitation, we report an approach to transition widely used hydrogels into mechanically active substrates by doping optomechanical actuator (OMA) nanoparticles within the polymer matrix. OMAs are composed of gold nanorods surrounded by a thermoresponsive polymer shell that rapidly collapses upon near-infrared (NIR) illumination. As a proof of concept, we crosslinked OMAs into laminin-gelatin hydrogels, generating up to 5 µm deformations triggered by NIR pulsing. This response was tunable by NIR intensity and OMA density within the gel and is generalizable to other hydrogel materials. Hydrogel mechanical stimulation enhanced myogenesis in C2C12 myoblasts as evidenced by ERK signaling, myocyte fusion, and sarcomeric myosin expression. We also demonstrate rescued differentiation in a chronic inflammation model as a result of mechanical stimulation. This work establishes OMA-actuated biomaterials as a powerful tool for in vitro mechanical manipulation with broad applications in the field of mechanobiology.

Intention to Initiate HIV Pre-exposure Prophylaxis Among Cisgender Women in a High HIV Prevalence U.S. City.

OBJECTIVE: Our objective was to identify the individual, interpersonal, community, health-system, and structural factors that influence HIV pre-exposure prophylaxis (PrEP) initiation among cisgender women seeking sexual and reproductive health care in a high HIV prevalence community to inform future clinic-based PrEP interventions. METHODS: We collected anonymous, tablet-based questionnaires from a convenience sample of cisgender women in family planning and sexual health clinics in the District of Columbia. The survey used the lens of the socio-ecological model to measure individual, interpersonal, community, institutional, and structural factors surrounding intention to initiate PrEP. The survey queried demographics, behavioral exposure to HIV, perceived risk of HIV acquisition, a priori awareness of PrEP, intention to initiate PrEP, and factors influencing intention to initiate PrEP. RESULTS: A total of 1437 cisgender women completed the survey. By socio-ecological level, intention to initiate PrEP was associated with positive attitudes toward PrEP (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.13-2.15) and higher self-efficacy (OR, 1.32; 95% CI, 1.02-1.72) on the individual level, perceived future utilization of PrEP among peers and low fear of shame/stigma (OR, 1.65; 95% CI, 1.33-2.04) on the community level, and having discussed PrEP with a provider (OR. 2.39; 95% CI, 1.20-4.75) on the institutional level. CONCLUSION: Our findings highlight the importance of multilevel, clinic-based interventions for cisgender women, which promote sex-positive and preventive PrEP messaging, peer navigation to destigmatize PrEP, and education and support for women's health medical providers in the provision of PrEP services for cisgender women.

Beyond arrival: safeguarding unaccompanied asylum-seeking children in the UK.

Unaccompanied children (also called unaccompanied minors) are children who have been separated from both parents and other relatives and are not being cared for by an adult who, by law or custom, is responsible for doing so. From 2010 to 2020, unaccompanied minors accounted on average for 15.4% of the total number of first-time asylum applicants aged less than 18 years in the UK. These young people risk their lives and undergo traumatic journeys in search of a better life. However, when they arrive in the UK, they are vulnerable to significant ongoing traumatic experiences.In this review, we look at the reasons young people are forced to flee their countries, how they make their journey, and the risks and dangers they face along the way. We examine safety and victimisation risks faced by children and young people after arrival in the UK, which mechanisms and processes exist to safeguard these individuals, and examine the data available on outcomes of unaccompanied asylum-seeking child (UASC. Finally, we share two case examples that represent both the strengths and weaknesses of existing processes for UASC.

Screening for neglected tropical diseases and other infections in refugee and asylum-seeker populations in the United Kingdom.

Asylum-seekers and refugees have an increased burden of infections compared with the general population. This has been widely recognised by countries welcoming those fleeing conflict and persecution; however, there are no screening standardised guidelines and regulatory processes. Identification of certain neglected tropical diseases (NTDs) and other infections is important for the health and well-being of the individual in addition to public health and biosecurity. In the United Kingdom, screening for infections at port of entry or after arrival is not mandatory. Those on refugee resettlement programmes will have infection screening as part of their pre-entry health assessment, but no such system exists for those claiming asylum in the United Kingdom. In this article, we have reviewed published, peer-reviewed articles looking at the approaches to screening for NTDs and infectious diseases in the United Kingdom. In addition to this, we have reviewed the literature looking at the acceptability, barriers and facilitators of these screening practices. We found that there is a heterogeneous approach to screening practices in the United Kingdom and a paucity of data to support a single 'best practice' approach. Based on our findings, we have made recommendations and consideration for NTD screening strategies and highlighted important areas for future research.

Factors Associated with Intention to Initiate Pre-exposure Prophylaxis in Cisgender Women at High Behavioral Risk for HIV in Washington, D.C.

Pre-exposure prophylaxis (PrEP) for HIV prevention is underutilized by cisgender women at risk for HIV in the USA. Published research on PrEP initiation among cisgender women at risk for HIV focuses on identifying barriers and facilitators associated with intention to initiate, but few apply a behavioral theoretical lens to understand the relative importance of these diverse factors. This study provides a theoretically grounded view of the relative importance of factors associated with intention to initiate PrEP. We conducted an anonymous, cross-sectional survey of 1437 cisgender women seeking care at family planning and sexual health clinics to evaluate hypothesized barriers and facilitators of PrEP initiation. We categorized cisgender women with ≥ 3 behavioral risk-factors as "high-risk" for HIV acquisition; 26.9% (N = 387) met high-risk criterion. Among cisgender women in the high-risk sample, the majority were Black and single. Perceived risk of HIV acquisition was low and 13.7% reported intention to initiate PrEP. Positive attitudes toward PrEP, self-efficacy, perceived support from medical providers and social networks, and prior discussion about PrEP with medical providers were associated with intention to initiate PrEP; stigma was negatively associated. Background characteristics (other than age), risk factors for HIV acquisition, prior awareness of PrEP, and perceived risk of HIV were not associated with uptake intention. These findings support interventions that center on the role of providers in the provision of PrEP and on social networks in destigmatization of PrEP use.

Description and evaluation of a pathway for unaccompanied asylum-seeking children.

OBJECTIVE: (1) To describe a novel integrated pathway for unaccompanied asylum-seeking children (UASC).(2) To evaluate a population engaged with this service. DESIGN: Description of the integrated pathway (objective 1) and retrospective evaluation, using data from community paediatrics, infectious diseases (IDs) screening and a sexual health (SH) service (objective 2). SETTING: Unlinked data were collected from three services across three National Health Service (NHS) trusts in London. PATIENTS: All Camden UASC engaged with the service from 01 January 2016 to 30 March 2019. INTERVENTIONS: A multidisciplinary approach prioritising the health needs of UASC including a childre and adolescent mental health service (CAMHS) clinican and a health improvement practitioner. There are low thresholds for onward referral and universal asymptomatic screening of UASC for ID. MAIN OUTCOME MEASURES: Data on demographics, unmet health needs and known outcomes. RESULTS: Data were available for 101 UASC, 16% female, median age 16 years (range 14-17). Physical assault/abuse was reported in 67% and 13% disclosed sexual assault/abuse, including 38% of female UASC. Mental health symptoms were documented in 77%. IDs warranting treatment were identified in 41% including latent tuberculosis (25%) and schistosomiasis (13%). Interpreters were required for 97% and initial non-attendance rates at follow-up were 40% (ID) and 49% (SH). CONCLUSIONS: These data demonstrate high rates of historical physical and sexual assault/abuse, unmet physical, mental and emotional health needs among UASC and significant barriers to engaging with services. An integrated pathway has been successfully implemented and shown to deliver appropriate, joined-up care for UASC, consistent with current recommendations, with the potential to improve outcomes.

A Whole-child, whole-family approach to health assessments for asylum-seeking children.

In 2020, 21% of people who sought asylum in the UK were children. This population has complex interconnecting health and social needs. Assessment requires a holistic approach, with consideration of physical and mental health in addition to social and developmental well-being, within the whole family group. A trauma-informed life-cycle and intergenerational care approach is important. This article, aimed at all health professionals who may work with asylum-seeking families, outlines the best practice principles for undertaking health assessments in migrant children and young people.

Programmable Mechanically Active Hydrogel-Based Materials.

Programmable mechanically active materials (MAMs) are defined as materials that can sense and transduce external stimuli into mechanical outputs or conversely that can detect mechanical stimuli and respond through an optical change or other change in the appearance of the material. Programmable MAMs are a subset of responsive materials and offer potential in next generation robotics and smart systems. This review specifically focuses on hydrogel-based MAMs because of their mechanical compliance, programmability, biocompatibility, and cost-efficiency. First, the composition of hydrogel MAMs along with the top-down and bottom-up approaches used for programming these materials are discussed. Next, the fundamental principles for engineering responsivity in MAMS, which includes optical, thermal, magnetic, electrical, chemical, and mechanical stimuli, are considered. Some advantages and disadvantages of different responsivities are compared. Then, to conclude, the emerging applications of hydrogel-based MAMs from recently published literature, as well as the future outlook of MAM studies, are summarized.

Mechanical Stimulation of Adhesion Receptors Using Light-Responsive Nanoparticle Actuators Enhances Myogenesis.

The application of cyclic strain is known to enhance myoblast differentiation and muscle growth in vitro and in vivo. However, current techniques apply strain to full tissues or cell monolayers, making it difficult to evaluate whether mechanical stimulation at the subcellular or single-cell scales would drive myoblast differentiation. Here, we report the use of optomechanical actuator (OMA) particles, comprised of a ∼0.6 µm responsive hydrogel coating a gold nanorod (100 × 20 nm) core, to mechanically stimulate the integrin receptors in myoblasts. When illuminated with near-infrared (NIR) light, OMA nanoparticles rapidly collapse, exerting mechanical forces to cell receptors bound to immobilized particles. Using a pulsed illumination pattern, we applied cyclic integrin forces to C2C12 myoblasts cultured on a monolayer of OMA particles and then measured the cellular response. We found that 20 min of OMA actuation resulted in cellular elongation in the direction of the stimulus and enhancement of nuclear YAP1 accumulation, an effector of ERK phosphorylation. Cellular response was dependent on direct conjugation of RGD peptides to the OMA particles. Repeated OMA mechanical stimulation for 5 days led to enhanced myogenesis as quantified using cell alignment, fusion, and sarcomeric myosin expression in myotubes. OMA-mediated myogenesis was sensitive to the geometry of stimulation but not to MEK1/2 inhibition. Finally, we found that OMA stimulation in regions proximal to the nucleus resulted in localization of the transcription activator YAP-1 to the nucleus, further suggesting the role of YAP1 in mechanotransduction in C2C12 cells. These findings demonstrate OMAs as a novel tool for studying the role of spatially localized forces in influencing myogenesis.

Unaccompanied asylum-seeking children and young people - Understanding their journeys towards improved physical and emotional health.

In 2018, approximately 20,000 unaccompanied children and young people applied for asylum in a European Union country. Unaccompanied asylum-seeking children present with significant emotional and physical health needs. These needs are likely the result of the situation that led them to leave their home, the difficult journeys they make to reach safety and their living circumstances after arriving at their destination. Maintaining engagement with both screening and therapeutic health services is challenging. A stepwise approach to delivery of services is recommended so as not to overwhelm them. Case studies and personal practical experience are used to highlight key learning points.

Screening for infection in unaccompanied asylum-seeking children and young people.

We aimed to evaluate a screening programme for infection in unaccompanied asylum seeking children and young people against national guidance and to described the rates of identified infection in the cohort. The audit was conducted by retrospective case note review of routinely collected, anonymised patient data from all UASC referred between January 2016 and December 2018 in two paediatric infectious diseases clinics.There were 252 individuals from 19 countries included in the study, of these 88% were male, and the median age was 17 years (range 11-18). Individuals from Afghanistan, Eritrea and Albania constituted the majority of those seen. Median time between arriving in the UK and infection screening was 6 months (IQR 4-10 months, data available on 197 UASC). There were 94% (238/252) of cases tested for tuberculosis (TB), of whom 23% (55/238) were positive, including three young people with TB disease. Of those tested for hepatitis B, 4.8% (10/210) were positive, 0.5% (1/121) were positive for hepatitis C and of 252 tested, none were positive for HIV. Of the 163 individuals who were tested for schistosomiasis, 27 were positive (16%).The majority of patients were appropriately tested for infections with a high rate of identification of treatable asymptomatic infection. Infections were of both individual and public health significance. Our findings of clinically significant rates of treatable infections in UASC highlight the importance of infection screening for all in this vulnerable patient group.

Cross-country comparison of victimisation-related injury admission in children and adolescents in England and Western Australia.

BACKGROUND: A single, standardised measure of victimisation-related (VR) injury admission in hospital administrative datasets could allow monitoring of preventive and response strategies and international comparisons of policy. Consistency of risk factors and incidence rates for a measure of victimisation-related injury in different countries with similar access to healthcare services would provide indirect evidence for measure validity. METHODS: Cohorts were derived from hospital administrative data for children aged less than 18 years who were admitted for acute injury to hospitals in England or Western Australia (WA) in 2000 to 2008. We compared the effects of age, sex and deprivation on the annual incidence of acute admission for VR injury defined by a cluster of ICD-10 codes reflecting characteristics that should alert clinicians to consider victimisation as a cause of injury. Four subcategories comprised codes specifically indicating child maltreatment, assault, undetermined cause, or adverse social circumstances. RESULTS: The incidence of VR injury followed a similar 'J'-shaped association with age in both countries with increasing rates from 10 years onwards and peaks in infancy and in 16-17 year-olds. In both countries, rates increased with deprivation. Girls had lower rates than boys except in the 11-15 age group where girls had higher rates than boys in WA but not in England. Adjusted incidence rates were similar in both countries for children aged 3 to 15 years old, but were higher in WA compared with England in children under 3 years old and in those aged 16-17 years. Higher rates in WA in 16-17 year-olds were explained by more admissions coded for the subcategories of adverse social circumstances, and to a lesser extent, assault, than in England. Children less than 3 years old were more often coded specifically for maltreatment in WA than in England. CONCLUSIONS: The similarities in risk factors and in the adjusted rates of victimisation-related injury admission in both countries suggest that the VR cluster of ICD-10 codes is measuring a similar underlying problem. Differential use of coding subcategories highlights the need to use the entire VR cluster for comparisons across settings.