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IntroductionThe majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages – usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired.MethodsHere, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier’s microabscesses) were profiled for further assessment.Results and discussionInterestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier’s microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

Abstract Psoriasis is a chronic inflammatory skin disease, in which molecular and cellular changes retain following clinical resolution of psoriatic lesions, a form of disease memory (‘molecular scar’) that may reestablish the psoriatic inflammation. The increasing evidence of the benefits from early intervention in other immune‐mediated diseases prompts the question of whether early systemic intervention, such as biologics, in new‐onset cutaneous psoriasis may lead to improved clinical response and sustained remission by averting an inflammatory disease memory. Herein, we review the current evidence on early intervention and disease memory in psoriasis. The evidence is sparse and inconsistent, although an early intervention within 2 years of disease‐onset may provide a more favourable long‐term prognosis in psoriasis. However, ongoing randomised clinical trials will explore whether early intervention with biologics in new‐onset psoriasis will be an effective treatment strategy, and whether it prevents the molecular and cellular changes potentially underlying the inflammatory disease memory.

Immunohistochemical quantification of inflammatory cells in skin biopsies is a valuable tool for diagnosing skin diseases and assessing treatment response. The quantification of individual cells in biopsies is time-consuming, tedious, and difficult. In this study, we presented and compared two methods for the quantification of CD8+ T cells in skin biopsies from patients with psoriasis using both commercial software (Adobe Photoshop) and open-source software (Qupath). In addition, we provided a detailed, step-by-step description of both methods. The methods are scalable by replacing the CD8 antibody with other antibodies to target different cells. Moreover, we investigated the correlation between quantifying CD8+ cells normalized to area or epidermal length and cell classifications, compared cell classifications in QuPath with threshold classifications in Photoshop, and analyzed the impact of data normalization to epidermal length or area on inflammatory cell densities in skin biopsies from patients with psoriasis. We found a satisfactory correlation between normalizing data to epidermal length and area for psoriasis skin. However, when non-lesional and lesional skin samples were compared, a significant underestimation of inflammatory cell density was found when data were normalized to area instead of epidermal length. Finally, Bland–Altman plots comparing Qupath and Photoshop to quantify inflammatory cell density demonstrated a good agreement between the two methods.

Objective: Women of Color (WoC) experiencing intimate partner violence (IPV) have elevated rates of posttraumatic stress disorder (PTSD) and alcohol use and related harm (e.g., increased alcohol use and negative consequences). This secondary data analysis assessed the role of racial microaggressions in the association between PTSD and alcohol use and related harm among WoC experiencing IPV. Methods: Participants were 103 WoC currently experiencing IPV and using substances (Mage=40.39, 51.5% Black) who were recruited from the community and completed assessments of PTSD, racial microaggressions, and alcohol use and related harm. Results: Assumptions of Inferiority (e.g., intelligence; B = 1.44, SE = 0.90, 95% CI [0.10, 3.54]) and Environmental Microaggressions (e.g., portrayal in media; B = 1.88, SE = 1.03, 95% CI [0.28, 4.30]) explained the association between PTSD and alcohol use and related harm. Conclusions: Findings underscore the influence of specific microaggressions in the relation between PTSD and alcohol use and related harm among WoC experiencing IPV. [ABSTRACT FROM AUTHOR]

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility. [ABSTRACT FROM AUTHOR]

The article evaluates the implementation of opt-out HIV screening in the University of Miami Health Tower Emergency Department to enhance HIV detection and linkage to care. Topics discussed include the effectiveness of opt-out testing in increasing screening rates, the demographic disparities observed in HIV-positive results, and the integration of opt-out testing into routine emergency department workflows.

Depression is a common consequence of sexual victimisation. Although religious coping has been previously studied within the context of sexual victimisation, there is a dearth of research examining the potential reciprocal relationships between religious coping and depression among adults with a history of sexual victimisation at the daily level. The current study addresses this important gap by leveraging an intensive longitudinal design and data analysis to explore bidirectional daily relations between religious coping and depression symptoms in a community sample of adults with a history of sexual victimisation. Participants were 84 individuals with a history of sexual assault who self-identified as religious (Mage = 37.43, 67.5% women, 83.1% White). Cross-lagged models showed that prior-day religious coping positively predicted next-day depression symptoms, whereas prior-day depression did not predict next-day religious coping. Findings underscore the potential utility of religious coping in the detection and treatment of depression in this population. [ABSTRACT FROM AUTHOR]

Quantification of osteoclasts to assess bone resorption is a time-consuming and tedious process. Since the inception of bone histomorphometry and manual counting of osteoclasts using bright-field microscopy, several approaches have been proposed to accelerate the counting process using both free and commercially available software. However, most of the present alternatives depend on manual or semi-automatic color segmentation and do not take advantage of artificial intelligence (AI). The present study directly compare estimates of osteoclast-covered surfaces (Oc.S/BS) obtained by the conventional manual method using a bright-field microscope to that obtained by a new AI-assisted method. We present a detailed step-by-step guide for the AI-based method. Tibiae from Wistar rats were either enzymatically stained for TRAP or immunostained for cathepsin K to identify osteoclasts. We found that estimation of Oc.S/BS by the new AI-assisted method was considerably less time-consuming, while still providing similar results to the conventional manual method. In addition, the retrainable AI-module used in the present study allows for fully automated overnight batch processing of multiple annotated sections. • Bone histomorphometry • AI-assisted osteoclast identification • TRAP and cathepsin K

Purpose: Thiazide diuretics (TD) may play a role in preventing osteoporosis. The objective was to investigate the effects of bendroflumethiazide in combination with bisphosphonates on bone mineral density, selected blood parameters, blood pressure, pulse, and muscle function. Methods: Double-blinded, randomized, placebo-controlled interventional study in postmenopausal osteoporotic women over the age of 50 years consisting of four arms: 1) 24 weeks with bendroflumethiazide +24 weeks of washout, 2) 24 weeks with placebo +24 weeks of washout, 3) 48 weeks with bendroflumethiazide, or 4) 48 weeks with placebo. At inclusion, participants were on oral bisphosphonates. Intervention consisted of either bendroflumethiazide or placebo. Dual energy X-ray absorptiometry (DXA), vertebral fracture assessment (VFA), quantitative CT (QCT) and selected blood parameters were acquired at baseline and at 48 weeks and Timed-Up-and-Go, handgrip strength, blood pressure, pulse and balance additionally at 24 weeks. Results: 139 postmenopausal Caucasian women over 50 years were randomized (mean age 64.7 years (SEM 0.6, range 51–79)). 109 (78%) completed the study. No difference in the effect of bendroflumethiazide on DXA, VFA, QCT, biochemistry or muscle function were found between the treatment arms. Conclusion: Bendroflumethiazide for 24- or 48 weeks in combination with bisphosphonates does not improve bone mineral density, selected blood parameters or muscle function compared to placebo combined with bisphosphonates. Studies with longer treatment periods and more patients are needed to further characterize the effects of bendroflumethiazide on bone and subpopulations that might benefit from the treatment.

A prognostic 3-miRNA classifier for early-stage mycosis fungoides has been developed recently, with miR-106b providing the strongest prognostic power. The aim of this study was to investigate the molecular function of miR-106b in mycosis fungoides disease progression. The cellular localization of miR-106b in mycosis fungoides skin biopsies was determined by in situ hybridization. The regulatory role of miR-106b was assessed by transient miR-106b inhibitor/mimic transfection of 2 mycosis fungoides derived cell lines, followed by quantitative real-time PCR (RT-qPCR), western blotting and a proliferation assay. MiR-106b was found to be expressed by dermal T-lymphocytes in mycosis fungoides skin lesions, and miR-106b expression increased with advancing mycosis fungoides stage. Transfection of miR-106b in 2 mycosis fungoides derived cell lines showed that miR-106b represses the tumour suppressors cyclin-dependent kinase inhibitor 1 (p21) and thioredoxin-interacting protein (TXNIP) and promotes mycosis fungoides tumour cell proliferation. In conclusion, these results substantiate that miR-106b has both a functional and prognostic role in progression of mycosis fungoides.

Background: Dead Sea climatotherapy (DSC) is a treatment option for psoriasis in Denmark. However, the response to DSC has not been particularly well studied.Aim: We sought to determine effectiveness and response duration of DSC on psoriasis-related outcome parameters.Methods: Eighteen patients participated in a 4-week treatment program in Ein Gedi in Israel. Treatment, consisting of sun exposure and bathing, was individualized.Results: DSC was associated with a mean 13.0-point reduction (88%) in Psoriasis Area and Severity Index and a mean reduction of 2.3 (76.7%) on the 5-point Investigator's Global Assessment Scale. Furthermore, patients' quality of life improved measured by the Dermatology Quality of Life Index and EuroQol 5D index values. The mean time from treatment end to reappearance of visible skin symptoms was 93.8 days (SD: 62.5, range: 31–219 days).Conclusions: Our results confirm that DSC has an immediate effect on skin manifestations and improves quality of life, but long-term disease control is not observed.

Nike Art Gallery is a legacy handcraft that comprises numerous displays of art and culture developed with the intention of establishing and nurturing an atmosphere conducive to the growth of art in Africa. Despite its presence for approximately 30 years, a paucity in empirical research has occurred on its activities. To address this concern, this study evaluates the patronage patterns and management strategies implemented by Nike Art Gallery in other to know the contribution of the gallery to tourism development. A semi-structured interview was conducted with the two directors of the Gallery with secondary data on influx and revenue. The result revealed that the Gallery receives many visitors for educational, recreational, and other purposes. Students on group excursions paid nominal fees ranging from N300 to N500 per group with average weekly and monthly earnings for the Gallery reaching N10250 and N30000, respectively. The administration of the Gallery is focused on tourism promotion, sales and marketing, and staff training. Nike Art Gallery was found to be a significant heritage treasure that promotes people empowerment and growth but with little tourism impact. Thus, efforts should be exerted to improve its tourism value and, consequently, its socioeconomic contribution to the community. [ABSTRACT FROM AUTHOR]

In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.