In vitro inflammatory multi-cellular model of osteoarthritis.

Objective: Osteoarthritis (OA) is a chronic joint disease, with limited treatment options, characterized by inflammation and matrix degradation, and resulting in severe pain or disability. Progressive inflammatory interaction among key cell types, including chondrocytes and macrophages, leads to a cascade of intra- and inter-cellular events which culminate in OA induction. In order to investigate these interactions, we developed a multi-cellular in vitro OA model, to characterize OA progression, and identify and evaluate potential OA therapeutics in response to mediators representing graded levels of inflammatory severity. Methods: We compared macrophages, chondrocytes and their co-culture responses to "low" Interleukin-1 (IL-1) or "high" IL-1/tumor necrosis factor (IL-1/TNF) levels of inflammation. We also investigated response changes following the administration of dexamethasone (DEX) or mesenchymal stromal cell (MSC) treatment via a combination of gene expression and secretory changes, reflecting not only inflammation, but also chondrocyte function. Results: Inflamed chondrocytes presented an osteoarthritic-like phenotype characterized by high gene expression of pro-inflammatory cytokines and chemokines, up-regulation of ECM degrading proteases, and down-regulation of chondrogenic genes. Our results indicate that while MSC treatment attenuates macrophage inflammation directly, it does not reduce chondrocyte inflammatory responses, unless macrophages are present as well. DEX however, can directly attenuate chondrocyte inflammation. Conclusions: Our results highlight the importance of considering multi-cellular interactions when studying complex systems such as the articular joint. In addition, our approach, using a panel of both inflammatory and chondrocyte functional genes, provides a more comprehensive approach to investigate disease biomarkers, and responses to treatment.

Magnetic Levitation System Isolates and Purifies Airborne Viruses.

Detection of viable viruses in the air is critical in order to determine the level of risk associated with the airborne diffusion of viruses. Different methods have been developed for the isolation, purification, and detection of viable airborne viruses, but they require an extensive processing time and often present limitations including low physical efficiency (i.e., the amount of collected viruses), low biological efficiency (i.e., the number of viable viruses), or a combination of all. To mitigate such limitations, we have employed an efficient technique based on the magnetic levitation (Maglev) technique with a paramagnetic solution and successfully identified distinct variations in levitation and density characteristics among bacteria (Escherichia coli), phages (MS2), and human viruses (SARS-CoV-2 and influenza H1N1). Notably, the Maglev approach enabled a significant enrichment of viable airborne viruses in air samples. Furthermore, the enriched viruses obtained through Maglev exhibited high purity, rendering them suitable for direct utilization in subsequent analyses such as reverse transcription-polymerase chain reaction (RT-PCR) or colorimetric assays. The system is portable, easy to use, and cost-efficient and can potentially provide proactive surveillance data for monitoring future outbreaks of airborne infectious diseases and allow for the induction of various preventative and mitigative measures.

Mohs Surgeons Dominate Cutaneous Reconstructions in Cosmetically and Functionally Sensitive Sites: Medicare Trends From 2013 to 2019.

BACKGROUND: Although dermatologists perform more cutaneous reconstructions than any other specialists for the Medicare population, the perception of dermatologists as surgeons may not be as fully recognized. Mohs surgeons are trained in complex reconstructions of cosmetically and functionally sensitive (CFS) sites, although the proportion they account for is unknown. OBJECTIVE: To quantify the proportion of cutaneous reconstructions in CFS sites performed by Mohs surgeons compared with other specialists, and to identify trends from 2013 to 2019. METHODS: A cross-sectional analysis was performed using the Medicare Public Use Files for 2013 to 2019. Data were stratified by physician specialty, with dermatologists further subdivided into Mohs surgeons and non-Mohs dermatologists. RESULTS: Mohs surgeons performed 75.3% of all reconstructions in 2019, a significant increase from 2013 ( p < .0001). Mohs surgeons dominated nearly every type of CFS cutaneous reconstruction, with significant increases in proportion ( p < .0001) from 2013 to 2019 for every category except interpolation flaps. Complex repairs were the most commonly performed cutaneous reconstruction type. CONCLUSION: Mohs surgeons perform far more cutaneous reconstructive surgeries in CFS sites than any other specialty for the Medicare population, with significant increases in their lead over the study period.

Emotional journey of Asian mothers of premature infants who received pasteurised donor human milk: a qualitative study.

OBJECTIVE: To explore the effect of donor human milk usage on the emotional experience of mothers with premature infants in a multiracial Asian population. DESIGN: A qualitative descriptive study. Semistructured individual interviews were audio-recorded, transcribed and analysed using Braun and Clarke's process of thematic analysis. SETTING AND PATIENTS: Seventeen mothers whose premature infants received donor human milk in a level III neonatal intensive care unit. MAIN OUTCOME MEASURES: Perceptions of mothers whose premature infants received donor human milk. RESULTS: Mothers described their experience as a journey of acceptance with three sequential themes. 'Resistance to receiving somebody else's milk' was a process of overcoming initial hesitation and concerns. 'Recognising maternal limitations and baby's needs' depicted the mothers' struggles in reconciling their infant's milk demand and their low milk supply. 'Embracing benefits of donor human milk and acceptance with gratitude' illustrated the mothers' joy and gratitude to milk donors as they embraced benefits of donor human milk usage. Although participants had agreed to use of donor human milk after counselling, many still struggled with negative emotions of anxiety and guilt. Mothers of Muslim faith had additional concerns about milk kinship and religious permissibility of donor human milk. CONCLUSION: Mothers undergo a spectrum of complex emotions from initial hesitation to acceptance with gratitude, when their premature infants receive donor human milk. Some continue to struggle with negative emotions and require more support. By recognising their emotional responses, healthcare providers can support mothers in their breastfeeding journey with targeted counselling.

Dental dams in dermatology: An underutilized barrier method of protection.

Dental dams are a barrier method of protection, which may help prevent the spread of sexually transmitted infections during oral-vaginal or oral-anal sex. Despite their relative simplicity of use, data on dental dams are limited and patients infrequently utilize this method of barrier protection because of the lack of awareness, perceived barriers to procurement and accessibility, and unfamiliarity on the part of health educators. Nevertheless, increased knowledge of dental dams may be beneficial especially in high-risk populations, where sexually transmitted infections are more common and remain a significant cause for morbidity. This article aims to increase awareness and knowledge of dental dams, as well as provide an informational guide on their procurement and use that may be helpful to dermatologists when counseling patients.

Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians: Results of a Modified Delphi Survey of Pigmented Lesion Experts.

Importance: Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know. Objectives: To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency. Design, Setting, and Participants: A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys-diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software. Main Outcomes and Measures: Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians. Results: Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists. Conclusions and Relevance: Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.

Real-world outcomes of melanoma surveillance using the MoleMap NZ telemedicine platform.

BACKGROUND: MoleMap NZ is a novel New Zealand-based store-and-forward telemedicine service to detect melanoma. It uses expert review of total body photography and close-up and dermoscopic images of skin lesions that are suspicious for malignancy. OBJECTIVE: The purpose of this study was to assess the effectiveness of MoleMap NZ as a melanoma early detection program. METHODS: We conducted a review of 2108 melanocytic lesions recommended for biopsy/excision by MoleMap NZ dermoscopists between January 2015 and December 2016. RESULTS: Pathologic diagnoses were available for 1571 lesions. Of these, 1303 (83%) lesions were benign and 260 (17%) lesions were diagnosed as melanoma, for a melanoma-specific benign:malignant ratio of 5.0:1. The number needed to biopsy to obtain 1 melanoma was 6. Among melanomas with available tumor thickness data (n = 137), 92% were <0.8 mm (range in situ to 3.1 mm), with in situ melanomas comprising 74%. LIMITATIONS: Only lesions recommended for excision were analyzed. Pathology results were available for 75% of these cases. Tumor thickness data were available for 53% of melanomas diagnosed. CONCLUSIONS: This real-world study of MoleMap NZ, a community-based teledermoscopy program, suggests that it has the potential to increase patients' access to specialist expertise via telemedicine. Additional studies are needed to more accurately define its efficacy.

Technological advances for the detection of melanoma: Advances in molecular techniques.

The growth of molecular technologies analyzing skin cells and inherited genetic variations has the potential to address current gaps in both diagnostic accuracy and prognostication in patients with melanoma or in individuals who are at risk for developing melanoma. In the second article in this continuing medical education series, novel molecular technologies are reviewed. These have been developed as adjunct tools for melanoma management and include the Pigmented Lesion Assay, myPath Melanoma, and DecisionDx-Melanoma tests, and genetic testing in patients with a strong familial melanoma history. These tests are commercially available and marketed as ancillary tools for clinical decision-making, diagnosis, and prognosis. We review fundamental principles behind each test, discuss peer-reviewed literature assessing their performance, and highlight the utility and limitations of each assay. The goal of this article is to provide a comprehensive, evidence-based foundation for clinicians regarding the management of patients with difficult pigmented lesions.

Technological advances for the detection of melanoma: Advances in diagnostic techniques.

Managing the balance between accurately identifying early stage melanomas while avoiding obtaining biopsy specimens of benign lesions (ie, overbiopsy) is the major challenge of melanoma detection. Decision making can be especially difficult in patients with extensive atypical nevi. Recognizing that the primary screening modality for melanoma is subjective examination, studies have shown a tendency toward overbiopsy. Even low-risk routine surgical procedures are associated with morbidity, mounting health care costs, and patient anxiety. Recent advancements in noninvasive diagnostic modalities have helped improve diagnostic accuracy, especially when managing melanocytic lesions of uncertain diagnosis. Breakthroughs in artificial intelligence have also shown exciting potential in changing the landscape of melanoma detection. In the first article in this continuing medical education series, we review novel diagnostic technologies, such as automated 2- and 3-dimensional total body imaging with sequential digital dermoscopic imaging, reflectance confocal microscopy, and electrical impedance spectroscopy, and we explore the logistics and implications of potentially integrating artificial intelligence into existing melanoma management paradigms.

Pulsed electromagnetic fields promote repair of focal articular cartilage defects with engineered osteochondral constructs.

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue-engineered cartilage grafts in a direction-dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p = .026) and control (p = .012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p = .010 and .028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3-month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p = .051) and proteoglycan (OR: 5.0, p = .013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p < .05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low-cost, low-risk, noninvasive treatment modality for expediting early cartilage repair.

Sustained low-dose dexamethasone delivery via a PLGA microsphere-embedded agarose implant for enhanced osteochondral repair.

Articular cartilage defects are a common source of joint pain and dysfunction. We hypothesized that sustained low-dose dexamethasone (DEX) delivery via an acellular osteochondral implant would have a dual pro-anabolic and anti-catabolic effect, both supporting the functional integrity of adjacent graft and host tissue while also attenuating inflammation caused by iatrogenic injury. An acellular agarose hydrogel carrier with embedded DEX-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (DLMS) was developed to provide sustained release for at least 99 days. The DLMS implant was first evaluated in an in vitro pro-inflammatory model of cartilage degradation. The implant was chondroprotective, as indicated by maintenance of Young's modulus (EY) (p = 0.92) and GAG content (p = 1.0) in the presence of interleukin-1ß insult. In a subsequent preliminary in vivo experiment, an osteochondral autograft transfer was performed using a pre-clinical canine model. DLMS implants were press-fit into the autograft donor site and compared to intra-articular DEX injection (INJ) or no DEX (CTL). Functional scores for DLMS animals returned to baseline (p = 0.39), whereas CTL and INJ remained significantly worse at 6 months (p < 0.05). DLMS knees were significantly more likely to have improved OARSI scores for proteoglycan, chondrocyte, and collagen pathology (p < 0.05). However, no significant improvements in synovial fluid cytokine content were observed. In conclusion, utilizing a targeted DLMS implant, we observed in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes. These improved outcomes were correlated with superior histological scores but not necessarily a dampened inflammatory response, suggesting a primarily pro-anabolic effect. STATEMENT OF SIGNIFICANCE: Articular cartilage defects are a common source of joint pain and dysfunction. Effective treatment of these injuries may prevent the progression of osteoarthritis and reduce the need for total joint replacement. Dexamethasone, a potent glucocorticoid with concomitant anti-catabolic and pro-anabolic effects on cartilage, may serve as an adjuvant for a variety of repair strategies. Utilizing a dexamethasone-loaded osteochondral implant with controlled release characteristics, we demonstrated in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes following osteochondral repair. These improved outcomes were correlated with superior histological cartilage scores and minimal-to-no comorbidity, which is a risk with high dose dexamethasone injections. Using this model of cartilage restoration, we have for the first time shown the application of targeted, low-dose dexamethasone for improved healing in a preclinical model of focal defect repair.

Health Professionals' and Postpartum Women's Perspectives on Digital Health Interventions for Lifestyle Management in the Postpartum Period: A Systematic Review of Qualitative Studies.

Objective: To explore postpartum women and health professionals' perspectives of digital health interventions (DHIs) for lifestyle management in postpartum women. Design: A systematic review and thematic synthesis of peer-reviewed qualitative studies. Relevant databases were searched from 1990 to 2019. Study quality was appraised using the Critical Appraisal Skills Programme (CASP) Qualitative Checklist. Setting and participants: Studies describing postpartum women's or health professionals' views regarding DHIs for lifestyle management in postpartum women. Findings: Nine studies with postpartum women were included in the thematic synthesis. Four common themes emerged: "personal facilitators and barriers to lifestyle modification," "intervention-related strategies for lifestyle modification," "user experience of the technology," "suggestions for improvement." The review indicated that DHIs are highly acceptable among postpartum women. Postpartum women valued behavior change strategies that were delivered through DHIs including goal-setting and self-monitoring, however personal barriers such as lack of motivation or childcare priorities were cited. Key conclusions and implications for practice: DHIs should be considered for lifestyle management in postpartum women. The development of DHIs should focus on delivering behavior change strategies and addressing practical barriers faced by postpartum women.