Transcriptomic studies unravel the molecular and cellular complexity of systemic lupus erythematosus: A review.

Transcriptomic analysis plays a vital role in investigating Systemic Lupus Erythematosus (SLE), a complex autoimmune disease characterized by diverse clinical manifestations. This approach has yielded valuable insights into gene expression patterns and molecular regulatory mechanisms involved in SLE pathogenesis. Notably, interferon-stimulated gene (ISG) signatures are significantly upregulated in immune cells, skin, and kidney. Although a correlation with serological parameters and clinical symptoms has been proposed, the association with global disease activities remains controversial. Key findings in the field include an upregulated plasmablast signature, which positively correlates with disease activity; a neutrophil signature associated with lupus nephritis; and a decreased lymphocyte signature, reflecting lymphopenia. Tissue-level studies highlight the critical role of infiltrating immune cells in organ damage. Future research should leverage advanced technologies and integrate multi-omics data to deepen our understanding of SLE's molecular underpinnings, facilitating the development of targeted therapies.

Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans.

In photoaged human skin, type I collagen fragmentation impairs dermal extracellular matrix (ECM) integrity, resulting in collapsed/contracted fibroblasts with reduced type I procollagen synthesis. Injections of cross-linked hyaluronic acid (CL-HA) reverse these deleterious changes. To investigate the time course and effects of biochemical changes induced by injected CL-HA, particularly whether fibroblast activation leads to accumulation/deposition of dermal collagen, we injected CL-HA into photoaged skin of human participants over 60 years-old and performed biochemical/microscopic analyses of skin samples. Beginning 1 week post-injection and lasting 6-9 months, fibroblasts exhibited activation, including increased immunostaining and gene expression of markers of type I collagen synthesis, such as heat shock protein 47 and components of the transforming growth factor-ß pathway. At 1 week post-injection, multiphoton microscopy revealed elongation/stretching of fibroblasts, indicating enhanced dermal mechanical support. At 4 weeks, second-harmonic generation microscopy revealed thick collagen bundles densely packed around pools of injected CL-HA. At 12 months, accumulation of thick collagen bundles was observed and injected CL-HA remained present in substantial amounts. Thus, by occupying space in the dermal ECM, injected CL-HA rapidly and durably enhances mechanical support, stimulating fibroblast elongation and activation, which results in thick, densely packed type I collagen bundles accumulating as early as 4 weeks post-injection and continuing for at least a year. These observations indicate that early and prolonged clinical improvement following CL-HA injection results from space-filling and collagen deposition. As type I collagen has an estimated half-life of 15 years, our data provide the foundations for optimizing the timing/frequency of repeat CL-HA injections.

Long-term care planning and the influencing factors among sexual minority older women: A qualitative study.

AIMS: The aim of the study was to explore plans, considerations and factors influencing long-term care among older sexual minority (SM) women. DESIGN: Qualitative interview study. METHODS: Semi-structured in-depth interviews were conducted with 37 older Taiwanese SM women between May and September 2019. This study analysed interview data using a socio-ecological model and constant comparative analysis. RESULTS: The most frequently reported long-term care plans were housing and institutions, private medical or long-term care insurance, financial planning and medical decisions. Factors associated with women's long-term care plans were categorized using the socio-ecological model level: (1) intrapersonal factors: current physical and mental health status, ageing signs and women's attitudes towards ageing; (2) interpersonal-level factors: receiving support from partners, child(ren), siblings or significant others, concerns about being a caregiver for parents and worries regarding social isolation; (3) community-level factors: receiving support from lesbian, gay, bisexual and transgender (LGBT) organizations; private lesbian online groups; or religious groups; (4) societal-level factors: concerns about negative social environments, concerns about the healthcare system and healthcare providers, inappropriate policies and insufficient resources. CONCLUSION: This study identified multi-level factors related to long-term care plans and concerns among older Taiwanese SM women. Recommendations for nurses, managers of long-term care and healthcare settings, policymakers, and governments have been provided to diminish health disparities and reduce anxiety among older SM women. IMPACT: This study assists nurses in understanding older SM women's long-term care concerns and worries when accessing long-term care and healthcare services and helps nurses provide SM-sensitive services and care for women. PATIENT OR PUBLIC CONTRIBUTION: SM older women were recruited from LGBT organizations, LGBT-friendly bookstores, restaurants, coffee shops and LGBT online chatrooms using purposive and snowball sampling.

Cutaneous malakoplakia arising on the ankle of a patient with pyoderma gangrenosum.

Malakoplakia is a rare chronic inflammatory condition that most commonly involves the urogenital tract. Cutaneous malakoplakia is extremely rare and many patients diagnosed with skin involvement are immunosuppressed. While the clinical presentation of cutaneous malakoplakia is variable, the histopathologic features are quite distinct and include sheets of closely packed dermal histiocytes with foamy-appearing cytoplasm and Michaelis-Gutmann bodies that are positive with certain immunohistochemical stains. While the exact pathogenesis of malakoplakia is unknown, it has been associated with certain bacterial infections. Treatment generally involves a combination of surgery and antimicrobial agents and/or modulation of immunosuppressant therapy if appropriate. Herein, the authors report a unique case of cutaneous malakoplakia arising in a patient on chronic immunosuppressive therapy for the management of pyoderma gangrenosum.

Positive Perceptions Towards Virtual Didactics During The COVID-19 Pandemic: A Survey Assessment of Dermatology Residents.

BACKGROUND: During the COVID-19 pandemic, resident didactics at many institutions, including ours, were transitioned from in-person to virtual. OBJECTIVES: We aimed to assess dermatology residents' satisfaction, impression of effectiveness, and preference for virtual didactics, and factors correlating with these sentiments. METHODS: Questionnaire administered to dermatology residents at our institution 3-6 months following transition to virtual didactics. RESULTS: Response rate was 26/31 residents (83.9%), with 20/26 (76.9%) expressing satisfaction, 15/26 (57.7%) effectiveness, and 12/26 (46.2%) preference towards virtual didactics. Factors associated with satisfaction included feeling that virtual didactics positively impacted learning retention, represented time well spent, and utilized high-quality images. Perception of effectiveness correlated with using high-quality images, baseline preference for online instruction, and feeling engaged. Factors associated with preference for virtual didactics included having opportunities for critical thinking, using high-quality images, and utilizing images applicable to teledermatology care. Advantages to virtual didactics included convenience, decreased commuting, and easily hosting guest lecturers. Disadvantages included distractions/decreased focus, reduced social interaction, and difficulty with communication. CONCLUSIONS: Residents expressed satisfaction, effectiveness, and some preference towards virtual didactics, which correlated with numerous factors. Our findings suggest that it is reasonable to maintain a virtual didactic component as part of dermatology resident education. Furthermore, our data provide insights into strategies that residency program directors and educators may consider when/if integrating virtual didactics into future educational curricula.

A striking presentation of pustular Sweet syndrome induced by trimethoprim-sulfamethoxazole.

We describe a strikingly robust presentation of trimethoprim-sulfamethoxazole (TMP-SMX)-induced pustular Sweet syndrome and discuss how to distinguish it from iododerma and other neutrophil-rich conditions. A review of the literature indicates that TMP-SMX-induced Sweet syndrome (SS) may have higher rates of neutrophilia and greater ocular, mucosal, and musculoskeletal involvement compared to SS from other drugs. Recognizing these features and identifying the offending agent are critical for correctly diagnosing TMP-SMX-induced SS in a timely manner.

Dermatology residency preparation curriculum: a model for initiating new residents into dermatology clinical care.

Entering dermatology residency is an immersive experience requiring new specialty-specific skills. There is no standard Accreditation Council for Graduate Medical Education (ACGME) protocol for orienting new dermatology residents. We aimed to design, develop, and evaluate a curriculum for incoming first-year dermatology residents focusing on practical introduction to dermatologic clinical care emphasizing ACGME dermatology milestones. A concentrated 8-hour residency preparation course for first-year dermatology residents was designed and developed by faculty. The course encompassed clinical competencies, procedural techniques, and professionalism and collegiality principles. Teaching methods included lectures, video demonstrations, simulated patient experiences, and one-on-one practical instruction. Surveys were distributed before, immediately after, and 6-months following the course from 2016-2018 to assess participants' skill-based confidence level and perceived usefulness of the course. A total of 24 first-year dermatology residents participated in the residency preparation course over 3 years from 2016-2018. Residents' confidence levels in performing dermatology-specific skills immediately increased following the course and continued to increase 6 months into training. The majority of first-year residents "agreed" or "strongly agreed" that the course was helpful for improving clinical competence. Our residency preparation course increased first-year residents' confidence and perceived competence in performing clinical skills related to ACGME dermatology milestones.

Cutaneous microsporidiosis in an immunosuppressed patient.

Microsporidia are a group of obligate intracellular parasites that naturally infect domestic and wild animals. Human microsporidiosis is an increasingly recognized multisystem opportunistic infection. The clinical manifestations are diverse with diarrhea being the most common presenting symptom. We present a 52-year-old woman with a history of amyopathic dermatomyositis complicated by interstitial lung disease managed with mycophenolate mofetil and hydroxychloroquine who presented with a 7-month history of recurrent subcutaneous nodules as well as intermittent diarrhea and chronic sinusitis. A punch biopsy showed superficial and deep lymphocytic and granulomatous dermatitis with focal necrosis. Tissue stains for microorganisms revealed oval 1 to 3 µm spores within the necrotic areas in multiple tissue stains. Additional studies at the Centers for Disease Control and Prevention confirmed cutaneous microsporidiosis. This case is one of very few confirmed examples of cutaneous microsporidiosis reported in the literature.

A Diaphragmatic Hernia and Pericardial Rupture Caused by Blunt Injury of the Chest: A Case Review.

Blunt traumatic diaphragmatic hernias are most commonly seen in combination with other injuries. Right diaphragmatic ruptures with serious pericardium ruptures are relatively rare. The diagnosis of diaphragmatic hernias is not difficult; however, prior to surgery, it is difficult to judge whether pericardium damage has occurred, particularly on the right side. This injury may occur in a critical pathological state in which cardiac tissue is outside the pericardium due to the pericardial defect. Severe hemodynamic disorders or even death may occur if the patient's condition is not diagnosed and treated in a timely manner. The transportation of patients with severe trauma must be performed with extreme caution. It is necessary to weigh a wide range of differential diagnoses in a serious and thorough initial investigation.