A photoaging smartphone application to promote sun safety behaviors among youth in late childhood and adolescence.

BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.

Altered reward processing underpins emotional apathy in dementia.

INTRODUCTION: While apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, and their common neural correlates, has not been directly examined. METHODS: Sixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer's disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes. RESULTS: HEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy. DISCUSSION: Our results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.

Void Volume Fraction of Granular Scaffolds.

Void volume fraction (VVF) is a global measurement frequently used to characterize the void space of granular scaffolds, yet there is no gold standard by which to measure VVF in practice. To study the relationship  between VVF and particles of varying size, form, and composition, a library of 3D simulated scaffolds is used. Results reveal that relative to particle count, VVF is a less predictable metric across replicate scaffolds. Simulated scaffolds are used to explores the relationship between microscope magnification and VVF, and recommendations are offered for optimizing the accuracy of approximating VVF using 2D microscope images. Lastly, VVF of hydrogel granular scaffolds is measured while varying four input parameters: image quality, magnification, analysis software, and intensity threshold. Results show that VVF is highly sensitive to these parameters. Overall, random packing produces variation in VVF among granular scaffolds comprising the same particle populations. Furthermore, while VVF is used to compare the porosity of granular materials within a study, VVF is a less reliable metric across studies that use different input parameters. VVF, a global measurement, cannot describe the dimensions of porosity within granular scaffolds, and the work supports the notion that more descriptors are necessary to sufficiently characterize void space.

Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes.

PURPOSE: Estrogen-receptor (ER) and progesterone-receptor (PR) expression levels in breast cancer, which have been principally compared via binomial descriptors, can vary widely across tumors. We sought to characterize ER and PR expression levels using semi-quantitative analyses of receptor staining in germline pathogenic variant (PV) carriers of cancer predisposition genes. METHODS: We conducted a retrospective chart review of patients who underwent germline genetic testing for cancer predisposition genes at a tertiary cancer center genetics clinic. We performed comparisons of semi-quantitative ER and PR percentage staining levels across carriers and non-carriers of cancer predisposition genes. RESULTS: Breast cancers from BRCA1 PV carriers expressed significantly lower ER (15.2% vs 78.2%, p < 0.001) and lower PR (6.8% vs 41.1%, p < 0.001) staining compared to non-PV carriers. Similarly, breast cancers of BRCA2 (66.7% vs 78.2%, p = 0.005) and TP53 (50.6% vs 78.2%, p = 0.015) PV tumors also displayed moderate decreases in ER staining. Conversely, CHEK2 tumors displayed higher ER (93.1% vs 78.2%, p = 0.005) and PR (72% vs 48.8%, p = 0.001) staining when compared to non-PV carriers. We observed a wide range of dispersion across the ER and PR staining levels of the carriers and noncarriers. ER and PR ranges of dispersion of CHEK2 tumors were uniquely narrower than all other groups. CONCLUSION: The findings of our study suggest that precise expression levels of ER and PR in breast cancers can vary widely. These differences are further augmented when comparing expression staining across PV and non-PV carriers, suggesting potentially unique tumorigenesis and progression pathways influenced by germline cancer predisposition genes.

Improving dermal level images from reflectance confocal microscopy using wavelet-based transformations and adaptive histogram equalization.

OBJECTIVES: Reflectance confocal microscopy (RCM) generates scalar image data from serial depths in the skin, allowing in vivo examination of cellular features. The maximum imaging depth of RCM is approximately 250 µm, to the papillary dermis, or upper reticular dermis. Frequently, important diagnostic features are present in the dermis, hence improved visualization of deeper levels is advantageous. METHODS: Low contrast and noise in dermal images were improved by employing a combination of wavelet-based transformations and contrast-limited adaptive histogram equalization. RESULTS: Preserved details, noise reduction, increased contrast, and feature enhancement were observed in the resulting processed images. CONCLUSIONS: Complex and combined wavelet-based enhancement approaches for dermal level images yielded reconstructions of higher quality than less sophisticated histogram-based strategies. Image optimization may improve the diagnostic accuracy of RCM, especially for entities with dermal findings.

Impact of mind-body treatment interventions on quality of life in neurofibromatosis patients: A systematic review and meta-analysis.

Individuals with neurofibromatosis (NF) experience poorer quality of life (QoL), in part contributed by the clinical manifestations of NF, such as functional disability, chronic pain, and altered physical appearance. Mind-body therapies (MBTs) tailored to NF have been developed, and have demonstrated promising potential to improve QoL in this population. We sought to systematically review current evidence on the effectiveness of MBTs in addressing QoL deficits in NF patients. Databases were reviewed between the date of inception and June 2020, using search terms: neurofibromatosis, schwannomatosis, psychotherapy, mind-body, mindfulness, meditation, resiliency, and behavioral therapy. Quality appraisal was assessed using the Cochrane Risk of Bias Tools and National Institutes of Health Study Quality Assessment Tools. We conducted a meta-analysis of mean differences and reported aggregate effect estimates with 95% confidence intervals. A total of 10 articles, including randomized-controlled trials and pre-post studies, were identified. Meta-analytic results of randomized-controlled trial data from six citations demonstrated MBTs were associated with improved physical (MD = 13.63, 95%CI 6.95-20.30, P < .0001, I2 = 24%), psychological (MD = 14.11, 95%CI 6.44-21.78, P = .0003, I2 = 38%), social (MD = 9.63, 95%CI 2.93-16.33, P = .005, I2 = 0%), and environmental QoL (MD = 14.14, 95%CI 8.28-20.00, P < .00001. I2 = 0%) in NF patients. These associations were maintained at 6-months follow-up for physical, psychological, and environmental QoL (P < .05). Our findings suggest that NF-adapted MBT strategies are associated with improving QoL in diverse NF populations, including NF2 patients experiencing deafness and youth NF patients. Providers and caregivers for NF should be aware of the potential benefits of MBT in chronic NF management.

Neurophysiological correlates of visuospatial attention and the social dynamics of gaze processing.

The reflexive orienting response triggered by nonpredictive gaze cues is thought to be driven by a dedicated social neural network responsible for directing attention toward socially salient information. However, atypical processing of eye gaze using concomitant perceptual features has been proposed to underlie attentional orienting in groups with impairments in social cognition. Here, we examined the neurophysiological indices of visuospatial attention during a spatial cueing task, considering individual variability in social cognition in typically developing individuals, and the relative salience of social gaze and perceptual motion cues. We found enhanced neural activation to incongruent cues, wherein modulation of the N2b serves as a marker of the allocation of attention in the spatial domain. Our findings suggest the social gaze cue is less salient for those with greater autistic traits. An attentional bias toward perceptual motion cues correlated with greater social anxiety and alexithymia, and thus may reflect reduced sensitivity to social stimuli. These results provide evidence for likely neurophysiological mechanisms underlying gaze cueing and offer insight into the use of qualitatively different cognitive mechanisms used to access social information. Such paradigms provide potential insight into normative orienting responses reported in atypical groups and would benefit investigations of gaze following abilities in clinical populations.

Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.

Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFB1-10) from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns that were, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, T brachyury, GDF15 and active ß-catenin revealed differential expression among blastomeres of 8- to 10-cell human embryos. The UCSFB lines formed derivatives of the three germ layers and CDX2-positive progeny, from which we derived the first human trophoblast stem cell line. Our data suggest heterogeneity among early-stage blastomeres and that the UCSFB lines have unique properties, indicative of a more immature state than conventional lines.

Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.

Pluripotent stem cells are derived from culture of early embryos or the germline and can be induced by reprogramming of somatic cells. Barriers to reprogramming that stabilize the differentiated state and have tumor suppression functions are expected to exist. However, we have a limited understanding of what such barriers might be. To find novel barriers to reprogramming to pluripotency, we compared the transcriptional profiles of the mouse germline with pluripotent and somatic cells, in vivo and in vitro. There is a remarkable global expression of the transcriptional program for pluripotency in primordial germ cells (PGCs). We identify parallels between PGC reprogramming to pluripotency and human germ cell tumorigenesis, including the loss of LATS2, a tumor suppressor kinase of the Hippo pathway. We show that knockdown of LATS2 increases the efficiency of induction of pluripotency in human cells. LATS2 RNAi, unlike p53 RNAi, specifically enhances the generation of fully reprogrammed iPS cells without accelerating cell proliferation. We further show that LATS2 represses reprogramming in human cells by post-transcriptionally antagonizing TAZ but not YAP, two downstream effectors of the Hippo pathway. These results reveal transcriptional parallels between germ cell transformation and the generation of iPS cells and indicate that the Hippo pathway constitutes a barrier to cellular reprogramming.

Examining the propensity and nature of criminal risk behaviours in frontotemporal dementia syndromes and Alzheimer's disease.

INTRODUCTION: Some people with dementia develop changes in behaviour and cognition that may lead to interactions with police or the legal system. However, large, prospective case-control studies examining these behaviours are lacking. METHODS: One hundred and forty-four people with dementia and 53 controls completed the Misdemeanours and Transgressions Screener. RESULTS: Criminal risk behaviours were reported in: 65.6% of behavioural-variant frontotemporal dementia, 46.2% of right-lateralised semantic dementia, and 27.0% of Alzheimer's disease patients. In 19.1% of patients these behaviours led to contact with police or authority figures. Compared to controls, people with dementia showed higher rates of physical assault (p = 0.024), financial/professional recklessness (p = 0.009), and inappropriate behaviours (p  = 0.052). DISCUSSION: Criminal risk behaviours are common across dementia subtypes and may be one of the first clinical signs of frontotemporal dementia. Further research to understand how to balance risk minimisation with an individual's liberties as well as the inappropriate criminalisation of people with dementia is needed. Highlights: The Misdemeanours and Transgressions Screener is a new tool to assess criminal risk behaviours.Forty-seven percent of patients with dementia show criminal risk behaviour after dementia onset.Behaviours included verbal abuse, traffic violations, physical assault.New onset of criminal risk behaviours >50 years is a clinical sign for frontotemporal dementia.

mRNA isoform diversity can obscure detection of miRNA-mediated control of translation.

Reporter-based studies support inhibition of translation at the level of initiation as a substantial component of the miRNA mechanism, yet recent global analyses have suggested that they predominantly act through decreasing target mRNA stability. Cells commonly coexpress several processing isoforms of an mRNA, which may also differ in their regulatory untranslated regions (UTR). In particular, cancer cells are known to express high levels of short 3' UTR isoforms that evade miRNA-mediated regulation, whereas longer 3' UTRs predominate in nontransformed cells. To test whether mRNA isoform diversity can obscure detection of miRNA-mediated control at the level of translation, we assayed the responses of 11 endogenous let-7 targets to inactivation of this miRNA in HeLa cells, an intensively studied model system. We show that translational regulation in many cases appears to be modest when measuring the composite polysome profile of all extant isoforms of a given mRNA by density ultracentrifugation. In contrast, we saw clear effects at the level of translation initiation for multiple examples when selectively profiling mRNA isoforms carrying the 5' or 3' untranslated regions that were actually permissive to let-7 action, or when let-7 and a second targeting miRNA were jointly manipulated. Altogether, these results highlight a caveat to the mechanistic interpretation of data from global miRNA target analyses in transformed cells. Importantly, they reaffirm the importance of translational control as part of the miRNA mechanism in animal cells.

A Psychosocial Intervention for Carers of Individuals Diagnosed with Dementia in Social Isolation.

Introduction: Growing research has shown the negative impact of social isolation on the health and psychological well-being of individuals with dementia and their carers. This study investigated the effectiveness of a psychosocial intervention for dementia carers during a lockdown period of the COVID-19 pandemic. Methods: Twenty-three family carers of individuals diagnosed with dementia living in the community were recruited and provided with an online psychoeducation toolkit that aims to improve health literacy, management of social and behavioural symptoms in dementia, carer social engagement, and coping skills. Carers were divided into "mild" or "moderate" groups based on the disease severity of the person with dementia they cared for. Outcome measures including distress and severity of neuropsychiatric symptoms, carer self-efficacy and burden, social network, and feelings of loneliness were assessed at baseline and 2 weeks later. Results: Carers in the moderate group reported higher levels of distress (p = 0.001) and severity (p < 0.001) of neuropsychiatric symptoms and greater carer burden (p = 0.003) than carers in the mild group. Following the intervention, both groups reported increased social networks (p = 0.001). In addition, carers in the moderate group reported significantly reduced distress for neuropsychiatric symptoms (p = 0.013), enhanced carer self-efficacy for controlling upsetting thoughts (p = 0.040), and decreased loneliness (p = 0.023). Conclusions: This study demonstrated that psychosocial interventions improve outcomes for carers of individuals with dementia, particularly those caring for individuals with greater disease severity. Findings from this study will inform the development of support services that meet the evolving needs of individuals with dementia and their carers in social isolation, during and in a post-pandemic context.

Perspectives on and Quality of Life in Skin of Color Patients With Mycosis Fungoides/Sézary Syndrome: A Qualitative Analysis.

Background Prior quantitative studies have described the diminished health-related quality of life (HRQoL) faced by the overall mycosis fungoides (MF)/Sézary syndrome (SS) population; yet, little is known about how the disease affects HRQoL in skin of color (SOC) patients. This qualitative study sought to explore the lived experiences of SOC patients with MF/SS and gain deeper insights into the impact the disease has on various facets of HRQoL.  Methodology Interviews with SOC patients with MF/SS ≥18 were recruited from a cutaneous lymphoma clinic. A thematic analysis was performed to identify overarching themes. Results Ten patients were invited to participate from July to September 2021. One patient with SS and seven patients with MF (four in the early stage and four in the advanced stage), with a median age of 60.5 years, agreed to participate. Emerging themes included diagnostic and therapeutic delays frequently due to initial misdiagnoses with other skin conditions. Physical and functional burdens significantly hindered participants' abilities to carry out daily responsibilities and maintain employment, and impacts on physical appearance (e.g., darkened skin) led to increased self-consciousness and lack of social acceptance. Participants regarded family and faith as main sources of support in addition to developing healthy coping strategies, such as self-acceptance and adaptability. All participants reported feeling satisfied with their access to healthcare information and the quality of care received. Conclusions Our findings provide greater insights into how HRQoL is impacted across SOC patients with MF/SS, which can help raise awareness among healthcare providers and assist with creating interdisciplinary healthcare approaches to better support the needs of this population.

Impact of Gut Bacterial Metabolites on Psoriasis and Psoriatic Arthritis: Current Status and Future Perspectives.

There is growing evidence that supports a role of gut dysbiosis in the pathogenesis of psoriasis (Pso). Thus, probiotic supplementation and fecal microbiota transplantation may serve as promising preventive and therapeutic strategies for patients with Pso. One of the basic mechanisms through which the gut microbiota interacts with the host is through bacteria-derived metabolites, usually intermediate or end products produced by microbial metabolism. In this study, we provide an up-to-date review of the most recent literature on microbial-derived metabolites and highlight their roles in the immune system, with a special focus on Pso and one of its most common comorbidities, psoriatic arthritis.

A modified ELISA assay differentiates CCL20 locked dimers from wild-type monomers.

A novel engineered CCL20 locked dimer (CCL20LD) is nearly identical to the naturally occurring chemokine CCL20 but blocks CCR6-mediated chemotaxis and offers a new approach to treat the diseases of psoriasis and psoriatic arthritis. Methods for quantifying CCL20LD serum levels are needed to assess pharmacokinetics parameters and evaluate drug delivery, metabolism, and toxicity. Existing ELISA kits fail to discriminate between CCL20LD and the natural chemokine, CCL20WT (the wild type monomer). Herein, we tested several available CCL20 monoclonal antibodies to be able to identify one clone that can be used both as a capture and a detection antibody (with biotin-labeling) to specifically detect CCL20LD with high specificity. After validation using recombinant proteins, the CCL20LD-selective ELISA was used to analyze blood samples from CCL20LD treated mice, demonstrating the utility of this novel assay for preclinical development of a biopharmaceutical lead compound for psoriatic disease.