Skin-derived stem cells for wound treatment using cultured epidermal autografts : clinical applications and challenges

The human skin fulfills important barrier, sensory, and immune functions—all of which contribute significantly to health and organism integrity. Widespread skin damage requires immediate treatment and coverage because massive skin loss fosters the invasion of pathogens, causes critical fluid loss, and may ultimately lead to death. Since the skin is a highly immunocompetent organ, autologous transplants are the only viable approach to permanently close a widespread skin wound. Despite the development of tissue-saving autologous transplantation techniques such as mesh and Meek grafts, treatment options for extensive skin damage remain severely limited. Yet, the skin is also a rich source of stem and progenitor cells. These cells promote wound healing under physiological conditions and are potential sources for tissue engineering approaches aiming to augment transplantable tissue by generating cultured epidermal autografts (CEAs). Here, we review autologous tissue engineering strategies as well as transplantation products based on skin-derived stem cells. We further provide an overview of clinical trial activities in the field and discuss relevant translational and clinical challenges associated with the use of these products

Increased hippocampal shape asymmetry and volumetric ventricular asymmetry in autism spectrum disorder

Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD

A Scoping Review Exploring the Feasibility of Virtual Reality Technology Use with Individuals Living with Dementia

The existing evidence base in relation to the feasibility of using Virtual Reality technology systems with individuals living with a dementia appeared limited and was therefore explored. The research was collected and reviewed in terms of the different types of Virtual Reality systems (equipment and levels of immersion) and feasibility of the technology within different stages of demen- tia as well as the methodological limitations. A systematic search of the literature was conducted using the healthcare databases advanced search (Medline, PsychINFO, and EMBASE) and snowballing methods. The participants had a dementia diagnosis and the feasibility of Virtual Reality in terms of its acceptability and practicality was discussed. Only five articles met the eligibility criteria. Four included semi-immersive Virtual Reality with participants in the early stages of dementia. One included fully- immersive Virtual Reality where dementia stage ranged from ‘mild’ to ‘severe’. Based on available demographic information, study participants resided in residential care homes, alone in the community or with their spouse. The existing literature sug- gests that both semi and fully-immersive Virtual Reality technology use can be feasible amongst individuals living within the ear- lier stages of dementia outside of a hospital environment, with it being viewed as a welcomed distraction that increased alert- ness and pleasure. However, Virtual Reality was also found to increase fear and anxiety in one study, raising important ethical implications around the safety of the user. The current evidence-base leaves a predominant gap in Virtual Reality technology system use for people within the moderate to later stages of dementia and those living in a hospital environment

Composition of the immune microenvironment differs between carcinomas metastatic to the lungs and primary lung carcinomas.

Lungs are among the most common sites for development of both primary and metastatic carcinomas. Tumor cells expression (TC) of PD-L1 is an important predictor of the of response to immune check-point inhibition in NSCLC, while the composition of the immune cells (IC) in the tumor microenvironment including PD-L1+ cells is believed to predict responses in tumors of some other primary sites. Total mutational load (TML) and microsatellite instability (MSI) also play a role in response to the immune checkpoint blockade. We investigated immune microenvironment characteristics (PD-1, PD-L1, CD8) of 257 lung biopsies including 81 primary (NSCLC) and 176 metastatic tumors to the lungs. TML and MSI were calculated from massively parallel sequencing (592-gene panel). TC expression of PD-L1 was more common in NSCLC than in metastatic carcinomas (28% vs. 10%, p=0.009), while PD-L1-positive IC were present at relevant percentages (1-5%) exclusively in metastatic carcinomas (31% IC positive vs. 0%, p<0.001). Metastatic carcinomas carried significantly lower TML in comparison with the NSCLCs (6.6 mutations on average vs. 10, p=0.01). All primary NSCLC were microsatellite stable, and only 2 metastatic carcinomas exhibited MSI-H status. The number of PD-1+ and CD8+ tumor infiltrating lymphocytes did not differ significantly between the primary and metastatic carcinomas. Our study revealed significant differences in tumor immune microenvironment (PD-L1 in IC and TC), and its relationship to TML between NSCLC and metastatic cancers. These differences could determine the choice of a predictive biomarker test and subsequently effect(s) of the immune therapy treatments in various advanced cancers

Bringing the outside in: The feasibility of virtual reality with people with dementia in an inpatient psychiatric care setting

Background and objectives: Emerging research supports virtual reality use with people with dementia in the community, but is limited to this area, warranting further investigation in different care settings. The feasibility of virtual reality within an inpatient psychiatric care setting was therefore explored. Research design and methods: Eight people with dementia and 16 caregivers were recruited in January and February 2018 from a UK hospital specialising in progressive neurological conditions. A mixed methods design measured affect and behaviour using the Observed Emotion Rating Scale, Overt Aggression Scale-Modified for Neurorehabilitation and St Andrew’s Sexual Behaviour Assessment. Thematic analysis was conducted following semi-structured interviews. Caregivers who worked at the hospital supported people with dementia throughout the process and were interviewed for their views on Head Mounted Display-Virtual Reality (HMD-VR) use with people with dementia. Results: HMD-VR was tried and accepted by people with dementia. Participants viewed HMD-VR positively as a ‘change in environment’ and would use it again. People with dementia experienced more pleasure during and after HMD-VR compared to before exposure, as well as increased alertness after. Three core themes emerged: ‘Virtual Reality Experiences’, ‘Impact of Virtual Reality’ and ‘Experiences within the Virtual Environment’. Caregivers discussed preconceptions about virtual reality use and how these changed. Discussion and implications: This is the first study to explore the feasibility of HMD-VR with people with mild to moderately severe dementia in hospital and found that overall HMD-VR is viable. Findings evidence the clinical feasibility of HMD-VR implementation in this environment and inform future research

The assessment of tumor-infiltrating lymphocytes in invasive apocrine carcinoma of the breast in relation to the HER2 status.

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER-/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/-, AR+/-). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P = 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median 5%, range 0%-50%). TIL levels were significantly higher in ALC than in PAC (P = 0.02). HER2 status had no impact on TIL distribution (P = 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody-drug conjugates (ADCs) for HER2-low breast cancers

The assessment of tumor-infiltrating lymphocytes in invasive apocrine carcinoma of the breast in relation to the HER2 status

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P = 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P = 0.02). HER2 status had no impact on TIL distribution (P = 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers

Bring the Outside In: Providing Accessible Experiences Through VR for People with Dementia in Locked Psychiatric Hospitals

Many people with dementia (PWD) residing in long-term care may face barriers in accessing experiences beyond their physical premises; this may be due to location, mobility constraints, legal mental health act restrictions, or offence-related restrictions. In recent years, there have been research interests towards designing non-pharmacological interventions aiming to improve the Quality of Life (QoL) for PWD within long-term care. We explored the use of Virtual Reality (VR) as a tool to provide 360°-video based experiences for individuals with moderate to severe dementia residing in a locked psychiatric hospital. We discuss at depth the appeal of using VR for PWD, and the observed impact of such interaction. We also present the design opportunities, pitfalls, and recommendations for future deployment in healthcare services. This paper demonstrates the potential of VR as a virtual alternative to experiences that may be difficult to reach for PWD residing within locked setting

Social emotional competence, learning outcomes, emotional and behavioral difficulties of preschool children : parent and teacher evaluations

This paper addresses the role of social emotional competence in the emotional and behavioral problems and learning outcomes of preschool children based on their parents’ and teachers’ evaluations. In this study, we compared the perceptions of teachers and parents when evaluating the same child using the multi-informant assessment. First, the associations and differences between both the informant evaluations were investigated. Second, the correlation of the social emotional competence and emotional, and behavioral difficulties among preschool children was analyzed, separately addressing their parents’ and teachers’ evaluations. Third, the role of the preschool children’s social emotional competence in their emotional and behavioral problems, and learning outcomes was investigated building the regression and mediation models. The sample consisted of 507 preschool children (3–6 years, mean age 4.85 years, SD 0.82) and their parents and teachers. Both informants completed the Strengths and Difficulties Questionnaire and Social Skills Improvement System Social-Emotional Learning Brief Scales, and teachers reported on each child’s learning outcomes (by completing a three-item Learning outcomes measure). When comparing both informants’ evaluations, positive associations were found between teacher and parental evaluations of prosocial behavior and emotional, and behavioral difficulties of preschool children, as well as self-management. Parents evaluated their children higher than teachers in conduct problems, hyperactivity, prosocial behavior, and total difficulty, while teachers evaluated children higher than parents in social emotional competence. According to teachers, the social emotional competence of preschool children was negatively correlated to all difficulty scales, and positively related to the prosocial behavior scale. The demographic variables, as well as parental socioeconomic status and children’s belonging to a vulnerable group were not found to be significantly associated with the preschool children’s learning outcomes. However, social emotional competence remains a significant variable in teacher-rated learning outcomes of preschool children even if sociodemographic variables are controlled. Our findings indicate that a higher level of social emotional competence and lower levels of social, emotional, and behavioral difficulties are related to a higher preschoolers’ academic learning in their teachers’ evaluation. This suggests the importance of early facilitation of social emotional competence as a key factor for academic success and more positive behavioral outcomes.peer-reviewe

MIRA/LOOK Exhibition

This exhibition produced for the Wistariahurst Museum in Holyoke and displayed in September and October of 2008, highlights community planning and design initiatives that promote cultural expression and community visions for Holyoke. The designs were created by Professor Joseph Krupczynski and students from the Architecture + Design program at the University of Massachusetts Amherst