U-Rate-UE; Measuring Perceived Recovery of the Affected Upper Extremity in Adults Post-stroke.

OBJECTIVE: To establish initial validity of "U-Rate-UE", a single-question scale regarding perceived recovery of the stroke affected upper extremity (UE). DESIGN: A retrospective longitudinal study of data collected at rehabilitation admission, 6 weeks, and 6 months since stroke. SETTING: Stroke rehabilitation and community-based. PARTICIPANTS: A convenience sample of 87 individuals, median (interquartile range) age 71.5 (65-80) years, 15.0 (12-20) days post-stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The affected UE was assessed using the Fugl-Meyer Motor Assessment, grip strength, Action Research Arm Test, the Box and Block Test (BBT), and The Rating of Everyday Arm-Use in the Community and Home. Participants also rated how much they perceive that their affected UE recovered from the stroke using U-Rate-UE; 0-100 (no to full recovery). Longitudinal changes in U-Rate-UE ratings were assessed. In addition, at 6 weeks and 6 months post-stroke, the change in BBT was calculated and participants were grouped into achieved/did not achieve the minimal detectable change (MDC). Correlations between U-Rate-UE to the other UE assessments were assessed at all 3 timepoints. RESULTS: Significant changes in U-Rate-UE were seen over time (P<.05). At 6 weeks and 6 months, participants who achieved BBT-MDC rated their recovery significantly higher than participants who did not. U-Rate-UE was moderately-strongly significantly correlated to UE assessments (rho=.61-.85, P<.001). CONCLUSIONS: The U-Rate-UE is supported for use with UE assessments contributing to comprehensive clinical understanding of the recovery of the affected UE in adults post-stroke.

Comparison of Upper Extremity Function and Daily Use in Individuals with and without Post Stroke Depression.

BACKGROUND: Post-stroke depression (PSD) is a frequent psychiatric complication, however very few studies have investigated its relation to the affected upper extremity (UE) post-stroke. Objective. To compare the affected UE in terms of motor impairment, functional ability, and daily-use in individuals with and without PSD during the first 6 months post-stroke. METHODS: This study analyzed data from a previous cohort; participants were assessed at rehabilitation admission (T1), 6 weeks (T2), and 6 months (T3) post-stroke. At each time point we compared between participants with and without PSD (Geriatric Depression Scale score ≥ 5). The Fugl-Meyer Motor Assessment assessed motor impairment, Action Research Arm Test assessed functional ability, and the Rating of Everyday Arm-Use in the Community and Home assessed daily-use. Independence in daily activities and cognition were also assessed. RESULTS: A total of 116 participants were recruited, 38% had PSD at T1. No significant differences were found between groups at T1 and T2. However, significant differences (z = -5.23 to -2.66, p < .01) were found between groups for all UE measures at T3; participants with PSD had lower motor and functional ability and less daily hand-use than participants without PSD. At T3 participants with PSD were also less independent in daily-living. CONCLUSIONS: PSD is associated with greater UE motor, functional, and daily-use disability at 6 months post-stroke. Our findings underscore the negative impact of PSD on UE during the crucial transition period when individuals return home and integrate back into the community. Further research is needed to delineate the effect of change in PSD status on UE outcomes post stroke.

M2OR: a database of olfactory receptor-odorant pairs for understanding the molecular mechanisms of olfaction.

Mammalian sense of smell is triggered by interaction between odorant molecules and a class of proteins, called olfactory receptors (ORs). These receptors, expressed at the surface of olfactory sensory neurons, encode myriad of distinct odors via a sophisticated activation pattern. However, determining the molecular recognition spectrum of ORs remains a major challenge. The Molecule to Olfactory Receptor database (M2OR, https://m2or.chemsensim.fr/) provides curated data that allows an easy exploration of the current state of the research on OR-molecule interaction. We have gathered a database of 75,050 bioassay experiments for 51 395 distinct OR-molecule pairs. Drawn from published literature and public databases, M2OR contains information about OR responses to molecules and their mixtures, receptor sequences and experimental details. Users can obtain information on the activity of a chosen molecule or a group of molecules, or search for agonists for a specific OR or a group of ORs. Advanced search allows for fine-grained queries using various metadata such as species or experimental assay system, and the database can be queried by multiple inputs via a batch search. Finally, for a given search query, users can access and download a curated aggregation of the experimental data into a binarized combinatorial code of olfaction.

Intersite brain MRI volumetric biases persist even in a harmonized multisubject study of multiple sclerosis.

BACKGROUND AND PURPOSE: Multicenter study designs involving a variety of MRI scanners have become increasingly common. However, these present the issue of biases in image-based measures due to scanner or site differences. To assess these biases, we imaged 11 volunteers with multiple sclerosis (MS) with scan and rescan data at four sites. METHODS: Images were acquired on Siemens or Philips scanners at 3 Tesla. Automated white matter lesion detection and whole-brain, gray and white matter, and thalamic volumetry were performed, as well as expert manual delineations of T1 magnetization-prepared rapid acquisition gradient echo and T2 fluid-attenuated inversion recovery lesions. Random-effect and permutation-based nonparametric modeling was performed to assess differences in estimated volumes within and across sites. RESULTS: Random-effect modeling demonstrated model assumption violations for most comparisons of interest. Nonparametric modeling indicated that site explained >50% of the variation for most estimated volumes. This expanded to >75% when data from both Siemens and Philips scanners were included. Permutation tests revealed significant differences between average inter- and intrasite differences in most estimated brain volumes (P < .05). The automatic activation of spine coil elements during some acquisitions resulted in a shading artifact in these images. Permutation tests revealed significant differences between thalamic volume measurements from acquisitions with and without this artifact. CONCLUSION: Differences in brain volumetry persisted across MR scanners despite protocol harmonization. These differences were not well explained by variance component modeling; however, statistical innovations for mitigating intersite differences show promise in reducing biases in multicenter studies of MS.

Annular Lichenoid Dermatitis of Youth: Its Pathogenesis, Diagnosis, and Management.

Annular lichenoid dermatitis of youth (ALDY) is a newly described controversial benign lichenoid inflammatory cutaneous disorder often characterized by annular patches with hypopigmented center and surrounding erythematous border. Primarily, it affects the trunk and groin of young patients. Since its first description in 2003, additional patients have been reported, leading to better characterization of the entity; nevertheless, the pathogenesis is still unclear, and several hypotheses have been provided about possible triggering or causative factors. It tends to follow a chronic course, with some lesions spontaneously remitting, while others may be persistent or recur post-treatment. No standard validated treatment has been indicated so far for this disorder. Commonly prescribed topical treatment includes corticosteroids and calcineurin inhibitors with variable response.

Erosive Pustular Dermatosis of the Scalp.

Erosive pustular dermatosis (EPD) is a rare entity, but it is generally overlooked or missed, rather than rarely encountered. It presents with erosions and shallow ulcers, accompanied by delayed healing and associated with cutaneous atrophy, rather than pustules. It exhibits predominance for women, with a predilection for a chronically sun-damaged scalp and, less commonly, the extremities, particularly the legs, as well as the face and mucosal surfaces. The role of infection, actinic damage, trauma, hormones, autoimmune disease, cutaneous atrophy, and genetics in the pathogenesis of EPD has been described in literature. Increased awareness and a high index of suspicion permit prompt treatment with topical corticosteroids, with or without oral zinc, followed by maintenance therapy with topical calcineurin inhibitors. Prevention, prior recognition, and prompt treatment are required for addressing this complex condition. (SKINmed. 2023;21:12-19).

Deconfounded Dimension Reduction via Partial Embeddings.

Dimension reduction tools preserving similarity and graph structure such as t-SNE and UMAP can capture complex biological patterns in high-dimensional data. However, these tools typically are not designed to separate effects of interest from unwanted effects due to confounders. We introduce the partial embedding (PARE) framework, which enables removal of confounders from any distance-based dimension reduction method. We then develop partial t-SNE and partial UMAP and apply these methods to genomic and neuroimaging data. Our results show that the PARE framework can remove batch effects in single-cell sequencing data as well as separate clinical and technical variability in neuroimaging measures. We demonstrate that the PARE framework extends dimension reduction methods to highlight biological patterns of interest while effectively removing confounding effects.

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). DESIGN/METHODS: We studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. RESULTS: During the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). CONCLUSIONS: In this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.

Synthesis of a Novel Unexpected Cu(II)-Thiazolidine Complex-X-ray Structure, Hirshfeld Surface Analysis, and Biological Studies.

An unexpected trinuclear Cu(II)-thiazolidine complex has been synthesized by mixing CuCl2·2H2O with the Schiff base ligand, 1-(((4,5-dihydrothiazol-2-yl)ethylidene)hydrazono)methyl)phenol L, in ethanol. Unexpectedly, the reaction proceeded via the hydrolysis of the Schiff base L, followed by cyclization to afford 3-methyl-5,6-dihydrothiazolo[3,2-c][1,2,3]triazole (La), then complexation with the Cu(II) salt, forming the trinuclear [Cu3(La)4(Cl)6] complex. The complex was characterized by means of FTIR spectra, elemental analysis, and X-ray crystallography. In the trinuclear [Cu3(La)4(Cl)6] complex, there are two crystallographically independent hexa- and penta-coordinated Cu(II) sites, where the thiazolidine ligand La units act as a monodentate ligand and a linker between the Cu(II) centers. The crystal packing of the [Cu3(La)4(Cl)6] complex is primarily affected by the weak non-covalent C-H∙∙∙Cl interactions. In accordance with Hirshfeld surface analysis, the Cl∙∙∙H, H∙∙∙H, S∙∙∙H, and N∙∙∙H percentages are 31.9%, 27.2%, 13.5%, and 9.9%, respectively. X-ray photoelectron spectroscopy confirmed the oxidation state of copper as Cu(II), as well as the presence of two different coordination environments around copper centers. The complex showed interesting antibacterial activity against the Gram-positive bacteria S. subtilis, with MIC = 9.7 µg/mL compared to MIC = 4.8 µg/mL for the control, gentamycin. Moreover, the Cu(II) complex showed an equal MIC (312.5 µg/mL) against C. albicans compared to ketoconazole. It also exhibits a very promising inhibitory activity against colon carcinoma (IC50 = 3.75 ± 0.43 µg/mL).

Red scrotum syndrome: An update on clinicopathologic features, pathogenesis, diagnosis, and management.

The genital skin may be affected by a variety of dermatoses, be it inflammatory, infectious, malignant, idiopathic, or others. The red scrotum syndrome is characterized by persistent erythema of the scrotum associated with a burning sensation, hyperalgesia, and itching. Its cause is unknown, but proposed mechanisms include rebound vasodilation after prolonged topical corticosteroid use and localized erythromelalgia. The condition is chronic, and treatment is often difficult. Here we review the etiology, the physical and histopathologic findings, and the management of this condition. We also describe related conditions such as red scalp syndrome, red ear syndrome, and red vulva syndrome. Finally, we summarize the different cases reported in the literature and discuss the features that help in the differentiation of red scrotum syndrome from its mimickers.

Genodermatoses with hearing impairment.

Hearing loss is a prominent feature in multiple genodermatoses. Underappreciation of auditory deficits can misdirect proper diagnosis by the treating dermatologist. This review reviews the anatomic, developmental, and embryologic aspects that characterize the ear and summarizes genodermatoses that have aberrant auditory findings. The latter are classified into neural crest, metabolic, pigmentary, craniofacial, and a miscellaneous category of disorders lacking specific cutaneous findings. The algorithms provided in this review enable treating dermatologists to better recognize and manage genodermatoses with ear involvement.

Diagnostic utility of plasmacytoid dendritic cells in dermatopathology.

Differentiating cutaneous diseases that mimic each other clinically and histopathologically can at times be a challenging task for the dermatopathologist. At the same time, differentiation of entities with overlapping features may be crucial for patient management. Although not seen in normal skin, plasmacytoid dendritic cells usually infiltrate the skin in several infectious, inflammatory/autoimmune and neoplastic entities. Plasmacytoid dendritic cells can be identified in tissue using specific markers such as CD123 and/or blood-derived dendritic cell antigen-2. Plasmacytoid dendritic cells are the most potent producers of type I interferons and their activity may therefore be assessed indirectly in tissue using human myxovirus resistance protein A, a surrogate marker for type I interferon production. In recent years, accumulating evidence has established the utility of evaluating for specific plasmacytoid dendritic cell-related parameters (plasmacytoid dendritic cell content, distribution and clustering and/ or human myxovirus resistance protein A expression) as a diagnostic tool in differentiating cutaneous diseases with overlapping features such as the alopecias, lupus and its mimics, and neoplastic entities. In this review, we provide an update on the current evidence on this topic and on the contexts where this can be a useful adjunct to reach the histopathological diagnosis.

Comparative characterization of sun exposed and sun protected skin-derived mesenchymal-like stem cells in variegate porphyria and healthy individuals.

BACKGROUND AND PURPOSE: We hypothesized that upon sun exposure, a sub-population of primary skin-derived mesenchymal-like cells is deleteriously affected and thus contribute to the chronic inflammatory state in autosomal recessive variegate porphyria patients. The aim of this study was to isolate and characterize the mesenchymal-like stem cells from different areas of the skin in a porphyria patient (sun exposed, SE, and sun protected, SP) and to compare them with cells from a healthy individual. METHODS: The proliferation rate and the migration ability of SE and SP cells were evaluated in the presence of an antioxidant compound, N-acetylcysteine. A co-culture of SE-damaged cells with the conditioned medium from the enriched mesenchymal cell-like SP population was performed in order to regenerate the dermal injured tissue after sun exposure in patients. RESULTS: Results showed that the percentage of CD105+ cells varies between 3.9% in SP and 5% in SE of the healthy individual and between 3.6% and 1.4% in SP and SE in the porphyria patient, respectively. The osteogenic differentiation potential was lower in the porphyria patient when compared to the control. Furthermore, the expression of stem cell markers was more pronounced in SE than in SP cells of both control and porphyria. The use of N-acetyl cysteine did not show any beneficial effects on porphyria SE cells. Treatment with SP-conditioned medium slightly increased the expression of stem cell markers in SE of porphyria patient. CONCLUSION: In conclusion, the pool of mesenchymal stem-like SE cells is affected in variegate porphyria patient along with modification of their self-renewal and differentiation properties.

A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.

Discoid lupus erythematosus (DLE) is an autoimmune disorder with a poorly defined etiology. Despite epidemiologic gender and ethnic biases, a clear genetic basis for DLE remains elusive. In this study, we used exome and RNA sequencing technologies to characterize a consanguineous Lebanese family with four affected individuals who presented with classical scalp DLE and generalized folliculitis. Our results unraveled a novel biallelic variant c.1313C > A leading to a missense substitution p.(Thr438Asn) in TRAF3IP2(NM_147200.3). Expression studies in cultured cells revealed mis-localization of the mutated protein. Functional characterization of the mutated protein showed significant reduction in the physical interaction with the interleukin 17-A receptor (IL17RA), while interaction with TRAF6 was unaffected. By conducting a differential genome-wide transcriptomics analysis between affected and non-affected individuals, we showed that the hair follicle differentiation pathway is drastically suppressed, whereas cytokine and inflammation responses are significantly upregulated. Furthermore, our results were highly concordant with molecular signatures in patients with DLE from a public dataset. In conclusion, this is the first report on a new putative role for TRAF3IP2 in the etiology of DLE. The identified molecular features associated with this gene could pave the way for better DLE-targeted treatment.

Genodermatoses with teeth abnormalities.

Many genodermatoses exhibit abnormal teeth findings. Studies examining these entities are scarce and narrow in their scope. This paper reviews the evolution, development, and structure of the tooth and provides a summary of genodermatoses with aberrant dental findings. The latter are classified according to the abnormal dental findings: periodontal disease, anodontia/oligodontia/hypodontia, polydontia, enamel hypoplasia, natal teeth, dental pits, and others. Finally, we provide an algorithm that dermatologists and dentists can follow to better recognize genodermatoses with dental involvement.

Tissue-resident memory T cells in the skin.

PURPOSE: Tissue-resident memory T (TRM) cells are a newly described subset of memory T cells. The best characterized TRM cells are CD8+ and express CD103 and CD69. These cells are non-recirculating and persist long term in tissues, providing immediate protection against invading pathogens. However, their inappropriate activation might contribute to the pathogenesis of autoimmune and inflammatory disorders. In the skin, these cells have been described in psoriasis, vitiligo, and melanoma among other diseases. METHODS: Literature review was done to highlight what is currently known on the phenotype and function of TRM cells and summarizes the available data describing their role in various cutaneous conditions. RESULTS: Resolved psoriatic skin and disease-naïve non-lesional skin contain a population of IL-17-producing TRM cells with shared receptor sequences that recognize common antigens and likely contribute to disease recurrence after cessation of therapy. In vitiligo, TRM cells produce perforin, granzyme B, and interferon-γ following stimulation by interleukin-15 and collaborate with recirculating memory T cells to maintain disease. In melanoma, increased accumulation of TRM cells was recently shown to correlate with improved survival in patients undergoing therapy with immune checkpoint inhibitors.

Efficacy of ethyl-EPA as a treatment for Huntington disease: a systematic review and meta-analysis.

OBJECTIVE: After MRI studies suggested the efficacy of ethyl-EPA in reducing the progressive brain atrophy in Huntington disease (HD), trials were conducted to test its efficacy as a treatment for HD. Trials that continued for 6 months did not find any significant improvement, urging discontinuation of the drug. However, trials that continued for 12 months indicated improvement of motor functions in these patients. METHODS: We searched 12 electronic databases to find randomised clinical trials relevant to our inclusion criteria. After screening, only five papers were included. Continuous and binary variables were analysed to compute the pooled mean difference (MD) and risk ratio (RR), respectively. Quality effect model meta-analysis was used as a post hoc analysis for studies at 12 months. FINDINGS: Meta-analysis indicated that ethyl-eicosapentaenoic acid (EPA) has no significant effect on any scale of HD at 6 months. At 12 months, two studies suggested significant improvements of the Total Motor Score and Total Motor Score-4 in both fixed and quality effect models [MD = -2.720, 95% CI (-4.76, -.68), p = 0.009; MD = -2.225, 95% CI (-3.842, -0.607), p = 0.007], respectively. Maximal chorea score showed significant results [MD = -1.013, 95% CI (-1.793, -0.233), p = 0.011] in only fixed-effect model, while no improvement was detected for Stroop colour naming test or symbol digit modality. CONCLUSION: Meta-analysis indicated a significant improvement of motor scores only after 12 months. These results should be interpreted cautiously because only two studies had assessed the efficacy of ethyl-EPA after 12 months with one of them having a 6-month open-label phase.

Use of Topical Glycolic Acid Plus a Lovastatin-Cholesterol Combination Cream for the Treatment of Autosomal Recessive Congenital Ichthyoses.

Importance: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders caused by defects in signaling pathways involved in epidermal proliferation and differentiation, leading to a wide range of skin manifestations. Therapeutic options are limited and often unsatisfactory. Topical cholesterol and statin as a combined formulation has proven successful in the treatment of patients with CHILD syndrome (congenital hemidysplasia ichthyosis and limb defects). Objective: To assess change in disease severity score after a 3-month therapeutic regimen consisting of a glycolic acid, 10% to 20%, cream and a combination cream of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. Design, Setting, and Participants: This case series of 15 patients with ARCI was conducted at the American University of Beirut, a referral center in the Middle East region for genodermatoses, between May 2017 and January 2018. No age groups were excluded; all patients were from the Middle East area; and all were initially not responsive to treatment with hydrating creams in combination with urea creams, 30% to 40%, or glycolic acid, 10% to 20%. Excluded were patients who had been taking systemic retinoids within 3 months before the start of the study. Interventions: A 3-month therapeutic regimen of glycolic acid, 10% to 20%, cream and a combination of lovastatin, 2%, with cholesterol, 2%, cream. Main Outcomes and Measures: Percentage change in disease severity scores following 2 and 3 months of study treatment. Results: Of the 15 patients included in the study, 10 were male (mean age, 11.2 years; age range, 2-38 years). The average percentage reduction in the disease severity score was 33.7% at 2 months (from 60.8 to 40.2) and 57.5% at 3 months (from 60.8 to 21.9). Adverse effects were mild and consisted mainly of irritation and burning. Conclusions and Relevance: These findings suggest a benefit from a treatment regimen consisting of glycolic acid, 10% to 20%, and a combination of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. This combination of creams might also prove to be beneficial in other types of ichthyoses and other dermatological diseases with a defective skin barrier.

Structured Educational Intervention Leads to Better Infant Positioning in the NICU.

PURPOSE: The purpose is to test the effectiveness of an educational intervention in improving infant positioning because positioning may interfere with neuromotor development. METHODS: A quality improvement (QI) project was initiated to increase knowledge and improve the compliance of nurses and physicians in infant positioning using the Infant Positioning Assessment Tool (IPAT). The project was part of Neonatal Individualized Developmental Care Assessment Program (NIDCAP) training. It included informal discussion and practice about infant positions. MAIN OUTCOME VARIABLES: Staff knowledge, IPAT score. RESULTS: Fifty-two pediatric residents and 39 NICU nurses participated in this project. The mean knowledge assessment test score improved significantly for both nurses (p < .0001) and residents (p < .0001) postintervention; IPAT scores increased significantly from 3.4 (±2. 5) to 8.1 (±2.7) (p < .001). CONCLUSION: Nurses' education with hands-on practice improved infant positioning in the NICU; this may lead to fewer positional deformities and possibly an improved developmental outcome.