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Background: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. Methods: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. Results: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21–7.49) in the OA cohort and 1.44 (95% CI 1.38–1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54–4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. Conclusions: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS. [ABSTRACT FROM AUTHOR]

Background: Pediatric oncology patients undergoing cancer treatment can often have numerous and recalcitrant cutaneous warts due to their underlying immunosuppression. There are little published data on the optimal management of warts in pediatric oncology patients undergoing active cancer treatment compared to patients having completed treatment. Our objective was to analyze the clinical course of warts treated within this patient population at Boston Children's Hospital over a 10‐year period. Methods: This was a single‐institution retrospective study of 72 pediatric oncology patients from 1 September 2011 to 1 September 2021 who were treated for warts at Boston Children's Hospital. All patients had a diagnosis of cutaneous warts with at least one follow‐up visit and were receiving active treatment for cancer either during or after concurrent treatment of their warts. We examined the modality and effectiveness of wart treatments while both on and offactive treatment of their cancer. Results: The median age was 12 years (range 4–18). Fifty‐four percent of patients were documented to have plantar warts. Sixty percent of patients with a documented number of warts had more than five warts at presentation. For cases in which outcomes were specified, treatment resulted in complete resolution of warts in only 24.0% of patients undergoing active cancer treatment compared to 63.3% of patients not on active treatment. Warts persisted or worsened in 56.0% of patients undergoing active cancer treatment compared to only 13.4% of patients not on active treatment. Conclusion: These data may help guide clinicians in evaluating and treating warts in pediatric oncology patients. [ABSTRACT FROM AUTHOR]

Human epidermal melanocytes play a central role in sensing the environment and protecting the skin from the drastic effects of solar ultraviolet radiation and other environmental toxins or inflammatory agents. Melanocytes survive in the epidermis for decades, which subjects them to chronic environmental insults. Melanocytes have a poor self‐renewal capacity; therefore, it is critical to ensure their survival with genomic stability. The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes and dermal fibroblasts. A symbiotic relationship exists between epidermal melanocytes and keratinocytes on the one hand, and between melanocytes and dermal fibroblasts on the other hand. Melanocytes protect epidermal keratinocytes and dermal fibroblasts from the damaging effects of solar radiation, and the latter cells synthesize biochemical mediators that maintain the homeostasis, and regulate the stress response of melanocytes. Disruption of the paracrine network results in pigmentary disorders, due to abnormal regulation of melanin synthesis, and compromise of melanocyte survival or genomic stability. This review provides an update of the current knowledge of keratinocyte‐ and fibroblast‐derived paracrine factors and their contribution to melanocyte physiology, and how their abnormal production is involved in the pathogenesis of common pigmentary disorders. [ABSTRACT FROM AUTHOR]

A better understanding of what skin conditions are most commonly diagnosed in different pediatric racial and ethnic groups in outpatient dermatology clinics could help guide the development of pediatric dermatology educational initiatives for primary care providers and general dermatologists who have limited access to pediatric dermatologists. Using a nationally representative dataset, we evaluated the most common diagnoses in patients younger than 15 years of age (children) and 15‐24 years of age (youth) who present to outpatient dermatology clinics, stratified by race and ethnicity. While acne and dermatitis were among the top ten most common diagnoses in all racial and ethnic groups studied, Black children were also commonly diagnosed with dermatophytosis and impetigo, and Black and Hispanic children were often diagnosed with seborrheic dermatitis; pigmentary disorders were among the top three most common diagnoses in Black, Asian, and Hispanic youth. Training more physicians how to evaluate and treat common skin conditions in children and youth of diverse racial and ethnic backgrounds may improve access to care for skin disease in the United States. [ABSTRACT FROM AUTHOR]

Porokeratosis ptychotropica is an unusual variant of porokeratosis characterized by papules and plaques located on the buttocks and gluteal cleft and showing multiple coronoid lamellae on histology. In this case report, we present the longitudinal clinical course of porokeratosis ptychotropica in a pediatric patient with individual red‐brown hyperkeratotic lesions that enlarged and became confluent prior to surgical intervention. We also discuss the etiology of porokeratosis ptychotropica and review current as well as future treatment options for the disease. [ABSTRACT FROM AUTHOR]

Cutaneous small-vessel vasculitis ( CSVV) is an infrequent manifestation of pediatric inflammatory bowel disease ( IBD). We report two cases of CSVV associated with ulcerative colitis, review the literature, and discuss the diagnostic evaluation of children who present with CSVV and abdominal pain. After excluding more common causes of CSVV and abdominal pain in children, including immunoglobulin A vasculitis (previously Henoch-Schönlein purpura), infectious colitis, and drug-induced vasculitis, alternative diagnoses such as CSVV secondary to IBD or systemic vasculitis with gastrointestinal involvement must be considered. [ABSTRACT FROM AUTHOR]

The nummular phenotype of atopic dermatitis is clinically characterized by pruritic, coin‐shaped plaques that are frequently recalcitrant to treatment. In this study, a retrospective chart review was conducted to evaluate the effectiveness and safety of dupilumab in children with nummular lesions of dermatitis. Twelve out of 14 patients demonstrated significant clinical improvement at a median time of 2.5 months (interquartile range, 1–4) after dupilumab initiation. A single case of paradoxical psoriasiform eruption was the only side effect reported in our cohort. [ABSTRACT FROM AUTHOR]

The formation of functional amyloid must be carefully regulated to prevent the accumulation of potentially toxic products. Premelanosome protein (PMEL) forms non-toxic functional amyloid fibrils that assemble into sheets upon which melanins ultimately are deposited within the melanosomes of pigment cells. PMEL is synthesized in the endoplasmic reticulum but forms amyloid only within post-Golgi melanosome precursors; thus, PMEL must traverse the secretory pathway in a non-amyloid form. Here, we identified two pre-amyloid PMEL intermediates that likely regulate the timing of fibril formation. Analyses by non-reducing SDS-PAGE, size exclusion chromatography, and sedimentation velocity revealed two native high Mr disulfide-bonded species that contain Golgi-modified forms of PMEL. These species correspond to disulfide bond-containing dimeric and monomeric PMEL isoforms that contain no other proteins as judged by two-dimensional PAGE of metabolically labeled/immunoprecipitated PMEL and by mass spectrometry of affinity-purified complexes. Metabolic pulse-chase analyses, small molecule inhibitor treatments, and evaluation of site-directed mutants suggest that the PMEL dimer forms around the time of endoplasmic reticulum exit and is resolved by disulfide bond rearrangement into a monomeric form within the late Golgi or a post-Golgi compartment. Mutagenesis of individual cysteine residues within the non-amyloid cysteine-rich Kringle-like domain stabilizes the disulfide-bonded dimer and impairs fibril formation as determined by electronmicroscopy. Our data show that the Kringle-like domain facilitates the resolution of disulfide-bonded PMEL dimers and promotes PMEL functional amyloid formation, thereby suggesting that PMEL dimers must be resolved tomonomers to generate functional amyloid fibrils. [ABSTRACT FROM AUTHOR]

Vitiligo is the most common acquired pigmentary disorder, which afflicts 0.5%–1% of the world population, and is characterized by depigmented skin patches resulting from melanocyte loss. Vitiligo has a complex etiology and varies in its manifestations, progression, and response to treatment. It presents as an autoimmune disease, evidenced by circulating melanocyte‐specific antibodies, and association with other autoimmune diseases. However, autoimmunity may be secondary to the high oxidative stress in vitiligo skin and to intrinsic defects in melanocytes and their microenvironment, which contribute to aberrant stress response, neo‐antigenicity, and susceptibility of melanocytes to immune attack and apoptosis. There is also a genetic predisposition to vitiligo, which sensitizes melanocytes to environmental agents, such as phenolic compounds. Currently, there are different treatment modalities for re‐pigmenting vitiligo skin. However, when repigmentation is achieved, the major challenge is maintaining the pigmentation, which is lost in 40% of cases. In this review, we present an overview of the clinical aspects of vitiligo, its pathophysiology, the intrinsic defects in melanocytes and their microenvironment, and treatment strategies. Based on lessons from the biology of human melanocytes, we present our perspective of how repigmentation of vitiligo skin can be achieved and sustained. [ABSTRACT FROM AUTHOR]

Urticaria in infants can cause significant anxiety in parents, especially if a trigger cannot be identified. In a retrospective study of 246 infants seen for urticaria of unknown etiology at Boston Children's Hospital, 88.2% had resolution of urticaria within 6 weeks. The etiology of urticaria was ultimately established in 62.6% (72/115) of acute urticaria and 12.5% (2/16) of chronic urticaria cases with follow‐up data. Pediatric healthcare providers can counsel families that while etiology of urticaria is never determined in over 40% of infants, symptoms are most likely to resolve spontaneously. [ABSTRACT FROM AUTHOR]

Purpose: To provide a holistic and complete comparison of the five most advanced AI models in the augmentation of low-dose 18F-FDG PET data over the entire dose reduction spectrum. Methods: In this multicenter study, five AI models were investigated for restoring low-count whole-body PET/MRI, covering convolutional benchmarks — U-Net, enhanced deep super-resolution network (EDSR), generative adversarial network (GAN) — and the most cutting-edge image reconstruction transformer models in computer vision to date — Swin transformer image restoration network (SwinIR) and EDSR-ViT (vision transformer). The models were evaluated against six groups of count levels representing the simulated 75%, 50%, 25%, 12.5%, 6.25%, and 1% (extremely ultra-low-count) of the clinical standard 3 MBq/kg 18F-FDG dose. The comparisons were performed upon two independent cohorts — (1) a primary cohort from Stanford University and (2) a cross-continental external validation cohort from Tübingen University — in order to ensure the findings are generalizable. A total of 476 original count and simulated low-count whole-body PET/MRI scans were incorporated into this analysis. Results: For low-count PET restoration on the primary cohort, the mean structural similarity index (SSIM) scores for dose 6.25% were 0.898 (95% CI, 0.887–0.910) for EDSR, 0.893 (0.881–0.905) for EDSR-ViT, 0.873 (0.859–0.887) for GAN, 0.885 (0.873–0.898) for U-Net, and 0.910 (0.900–0.920) for SwinIR. In continuation, SwinIR and U-Net's performances were also discreetly evaluated at each simulated radiotracer dose levels. Using the primary Stanford cohort, the mean diagnostic image quality (DIQ; 5-point Likert scale) scores of SwinIR restoration were 5 (SD, 0) for dose 75%, 4.50 (0.535) for dose 50%, 3.75 (0.463) for dose 25%, 3.25 (0.463) for dose 12.5%, 4 (0.926) for dose 6.25%, and 2.5 (0.534) for dose 1%. Conclusion: Compared to low-count PET images, with near-to or nondiagnostic images at higher dose reduction levels (up to 6.25%), both SwinIR and U-Net significantly improve the diagnostic quality of PET images. A radiotracer dose reduction to 1% of the current clinical standard radiotracer dose is out of scope for current AI techniques. [ABSTRACT FROM AUTHOR]

The formation of a dynamic, actin-rich immunological synapse (IS) and the polarization of cytolytic granules toward target cells are essential to the cytotoxic function of NK cells. Following polarization, lytic granules navigate through the pervasive actin network at the IS to degranulate and secrete their toxic contents onto target cells. We examined lytic granule motility and persistence at the cell cortex of activated human NK cells, using high-resolution total internal reflection microscopy and highly quantitative analysis techniques. We illustrate that lytic granules are dynamic and observe substantial motility at the plane of the cell cortex prior to, but not after, degranulation. We also show that there is no significant change in granule motility in the presence of Latrunculin A (which induces actin depolymerization), when added after granule polarization, but that there is a significant decrease in lytic granule persistence subsequent to degranulation. Thus, we show that lytic granules are highly dynamic at the cytolytic human NK cell IS prior to degranulation and that the persistence of granules at the cortex following exocytosis requires the integrity of the synaptic actin network. [ABSTRACT FROM AUTHOR]

Background and Purpose: Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed.Experimental Approach: Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules.Key Results: RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC(50) values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased.Conclusions and Implications: RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological importance: The root of Rehmannia glutinosa (Rehmanniae Radix (RR)) is clinically used as a wound-healing agent in traditional Chinese medicine. Angiogenesis acts crucially in the pathogenesis of chronic wound healing. The present study investigated the angiogenesis effect and its underlying mechanism of RR through zebrafish sprout angiogenesis guided-fractionation. Materials and methods: The in vivo angiogenesis effect was studied by analyzing the number of ectopic sprouts formed upon sub-intestinal vessel of transgenic TG(fli1:EGFP)y1/+(AB) zebrafish embryos by fluorescence microscopy. Quantitative real-time PCR gene expression of the zebrafish embryos was further performed using a panel of 30 angiogenesis-associated genes designed for zebrafish sprout angiogenesis. Classical in vitro angiogenesis assays using human microvascular endothelial cells (HMEC-1) was accompanied. Results: We demonstrated that among all RR sub-fractions tested, C1-1 treated-zebrafish embryos possessed the most potent angiogenesis activities (from 190 to 780ng/ml, p<0.001) in sprout formation in the zebrafish model. Quantitative gene expression of the treated embryos demonstrated significant up-regulation in MMP-9 (p<0.05), ANGPT1 (p<0.05), EGFR (p<0.05), EPHB4 (p<0.01), and significant down-regulation in Ephrin B2 (p<0.05), Flt-1 (p<0.05) and Ets-1 (p<0.05). C1-1 treatment could also significantly (p<0.001–0.05) stimulate HMEC-1 cell migration in scratch assay. Significant increase (p<0.05) in mean tubule length was observed in the C1-1-treated HMEC-1 cells in the tubule formation assay. Conclusions: Our zebrafish sprout angiogenesis model-guided fractionation revealed that C1-1 possessed the most potent angiogenesis effect in RR. The design of the panel with 30 tailor-made angiogenesis-associated genes exhibited in zebrafish gene expression analysis showed that C1-1 could trigger differential expression of various angiogenesis-associated genes, such as VEGFR3 and MMP9, which played key role in angiogenesis. The pro-angiogenic activity of C1-1 was further confirmed in the translated study in motogenic and tubule-inducing effect using HMEC-1. [ABSTRACT FROM AUTHOR]