Growth Factors to Enhance Nerve Regeneration: Approaching Clinical Translation.

Following nerve injury, growth factors (GFs) are transiently upregulated in injured neurons, proliferating Schwann cells, and denervated muscle and skin. They act on these same cells and tissues to promote nerve regeneration and end-organ reinnervation. Consequently, much attention has been focused on developing GF-based therapeutics. A major barrier to clinical translation of GFs is their short half-life. To provide sustained GF treatment to the affected nerve, muscle, and skin in a safe and practical manner, engineered drug delivery systems are needed. This review highlights recent advancements in GF-based therapeutics and discusses the remaining hurdles for clinical translation.

An improved synthesis of guanosine TNA phosphoramidite for oligonucleotide synthesis.

The chemical synthesis of guanosine nucleosides generates both the N9 and N7 regioisomers, which require careful separation to obtain the desired N9 isomer. To preferentially obtain the N9 isomer, a bulky diphenylcarbamoyl (DPC) group can be installed at the O6 position of guanine. However, installation of the DPC group presents a challenging task due to low solubility of the N-acetyl protected guanine. Here we report the usage of commercially available 2-amino-6-chloro purine as a new strategy that offers a more efficient route to the synthesis of the guanine phosphoramidite of threose nucleic acid (TNA).

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

FACE-Q for Measuring Patient-reported Outcomes after Facial Skin Cancer Surgery: Cross-cultural Validation.

Background: Facial skin cancer and its surgical treatment can affect health-related quality of life. The FACE-Q Skin Cancer Module is a patient-reported outcome measure that measures different aspects of health-related quality of life and has recently been translated into Dutch. This study aimed to evaluate the performance of the translated version in a Dutch cohort using modern psychometric measurement theory (Rasch). Methods: Dutch participants with facial skin cancer were prospectively recruited and asked to complete the translated FACE-Q Skin Cancer Module. The following assumptions of the Rasch model were tested: unidimensionality, local independence, and monotonicity. Response thresholds, fit statistics, internal consistency, floor and ceiling effects, and targeting were assessed for all scales and items within the scales. Responsiveness was tested for the "cancer worry" scale. Results: In total, 259 patients completed the preoperative questionnaire and were included in the analysis. All five scales assessed showed a good or sufficient fit to the Rasch model. Unidimensionality and monotonicity were present for all scales. Some items showed a local dependency. Most of the scales demonstrate ordered item thresholds and appropriate fit statistics. Conclusions: The FACE-Q Skin Cancer Module is a well-designed patient-reported outcome measure that shows psychometric validity for the translated version in a Dutch cohort, using classical and modern test theory.

The diagnostic difficulties of juvenile vulvar pemphigoid.

Mucous membrane pemphigoid is a rare autoimmune disease affecting mucosal surfaces. Pediatric cases are exceptionally rare, one subtype being vulvar pemphigoid. Juvenile vulvar pemphigoid can be challenging to diagnose due to its rarity and subtle initial symptoms. We present a case of an 8-year-old girl successfully diagnosed early in the disease course via histopathology, and immunofluorescence. Detecting MMP can be complex due to variations in epitope binding typically not included in commercial ELISA assays, necessitating comprehensive workup. Missed diagnosis may lead to progression to systemic involvement with severe consequences; thus, timely diagnosis and treatment are crucial.

Exploring trainee perspectives on barriers and facilitators in serious mental illness doctoral training.

Although there have been momentous and critical advancements in serious mental illness (SMI) psychology doctoral training models and competencies, there is still much systemic change needed to increase access to evidence-based SMI training for psychologists. In the last decade, there has been little to no growth or expansion of SMI training opportunities in clinical psychology doctoral programs in the United States, and psychologists are underrepresented in serving clients with SMI. As trainees and trainers committed to careers in SMI, the contributors aimed to identify barriers and facilitators throughout each stage of the SMI doctoral training pathway, including pregraduate school, graduate school, and internship to reflect critically on systemic issues that have impeded trainees from accessing the appropriate tools for SMI training. This conceptual article reviews the existing literature on barriers and facilitators to accessing SMI training. In centering trainee perspectives, the contributors also reflect on their own experiences through brief narratives illustrating the barriers and facilitators they have faced across training stages with existing empirical research. Recommendations made by the contributors include increasing access to financial support and mechanisms, diversifying departments and practicum sites to include SMI-focused training, and people in positions of power advocating for and centering trainee voices in departmental training decisions and development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Diversity in online resources for breast reconstruction: What do patients see?

BACKGROUND: Online resources are commonly used by patients to obtain information on breast reconstruction. Despite the key role of these resources in patient decision-making, their visual content has not yet been evaluated. This study sought to 1) characterize the presence and content of visual aids in online patient education breast reconstruction resources and 2) determine if the women represented in these visual aids reflect the breast reconstruction patient population in the United States. METHODS: The top 10 Google websites and the first 400 Google Images containing photographs/graphics depicting human skin for the search phrase "breast reconstruction" were analyzed. Images were categorized by content as "Before/After," "Surgical/Anatomical," "Step-by-Step," or "Breast-Centric Stock Images." Image subjects were classified by skin tone into "White" or "Non-White" using the Fitzpatrick scale and by body type into "Lean" or "Full-Figured." RESULTS: In total, 471 images were analyzed. These were predominantly "Before/After" images (43.9%), followed by "Breast-Centric Stock Images" (27.4%), "Surgical/Anatomical" (24.2%), and "Step-by-Step" (4.5%). The majority of all images depicted "White" skin types (90.7%) and "Lean" body types (73.0%). "Before/After" images were more likely to show "Full-Figured" women than the other content categories (p < 0.0001) and had the highest percentage of "Non-White" skin types (35.3%). CONCLUSIONS: Our findings demonstrate that breast reconstruction online resources are not reflective of the patient population seeking reconstruction. Improving the diversity of online image resources can both better represent our diverse patient population as well as better align patient expectations with postoperative outcomes, likely improving patient satisfaction.

Patient Satisfaction Following Primary Closure or Second Intention Healing After Conventional Nasal Skin Cancer Excision: A Cross-sectional Cohort Study.

BACKGROUND: Nasal reconstruction after conventional surgical excision (CSE) of nonmelanoma skin cancer (NMSC) can be challenging. After excision and before the pathologic report, a simple reconstruction is favored. Yet, little is known about patient satisfaction after primary closure and second intention healing. OBJECTIVE: Patient satisfaction after nasal defect reconstruction with primary closure or second intention healing, using the FACE-Q Skin Cancer. METHODS: All patients who underwent CSE of nasal NMSC with immediate primary closure or second intention healing between March 2018 and March 2020 at Máxima Medisch Centrum Veldhoven were identified and asked to complete the FACE-Q Skin Cancer. RESULTS: Of 183 patients, 140 patients completed the questionnaire. Fifty-five defects were closed by primary closure (38.5%) and 88 by second intention healing (61.5%). Thirty-one complications were reported (16.7%), of which 87.1% ( n = 27) after second intention healing ( p = .004). Both groups experienced high facial and scar satisfaction, low appearance-related distress, and no to minimal adverse effects. Second intention healing had 2.7 higher odds of achieving the maximum scar satisfaction score ( p = .02). CONCLUSION: This study shows high satisfaction on facial and scar appraisal, low appearance-related distress, and no to minimal adverse effects for second intention healing and primary closure after CSE of nasal NMSC.

Dupilumab-induced psoriasiform dermatitis in two pediatric cardiac transplant patients.

Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.

Family Planning Experiences and Challenges of Mohs Fellowship Trainees.

BACKGROUND: There is a paucity of literature describing family planning challenges faced by Mohs fellows. OBJECTIVE: To characterize perceptions about and experiences with family planning, fertility, lactation, and parental leave and identify ways to support parental health and family planning for Mohs fellows. MATERIALS AND METHODS: A voluntary, anonymous survey was distributed to Mohs surgeons who recently completed fellowship. RESULTS: In total, 116 Mohs surgeons completed the survey. Their mean age was 34.5 years old, and more were female ( n = 81, 69.8%) than male ( n = 35, 30.2%). Most had children before completion of their Mohs training ( n = 73, 62.9%). The most significant barrier to having children during fellowship was "loss of education or training time." Over 20% ( n = 23) of respondents or their partner had experienced infertility. Half of the 20 respondents ( n = 10) who breastfed or pumped did not have a convenient place to do so. CONCLUSION: This study elucidates trainee perceptions and gaps in parental support for Mohs fellowship trainees. In addition, barriers to implementing a universal family planning policy in Mohs surgery are discussed.

Training Psychology and Psychiatry Diversity Dialogue Facilitators.

This article describes a Diversity Dialogue Facilitator Training Program for Trainees, an innovative project that prepares psychology and psychiatry learners to facilitate diversity dialogues with healthcare professionals (i.e., clinical and research faculty, staff, and learners) in academic healthcare settings. Through participating in this program, trainees learn to facilitate discussions in which participants reflect upon oppression, discrimination, and disparities; explore their biases; connect and exchange views with colleagues regarding challenging societal events; and delineate action steps for advancing equity, inclusion, social responsivity, and justice in their professional and personal lives. After outlining contextual factors that informed project development, implementation, and dissemination, the iterative process of creating and implementing the training curriculum is detailed, with the aim of offering a model for other academic health center-based training programs interested in establishing a similar initiative. Lessons learned also are shared with the hope of contributing to future efforts to advance training in diversity dialogue facilitation and expand the role of psychologists in medical settings.

Quality of Life Before and After Radiation Therapy for Early-Stage Keratinocyte Carcinoma: A Longitudinal Analysis.

PURPOSE: Little is known about patient-reported quality of life (QOL) before and after radiotherapy (RT) for early keratinocyte carcinoma (KC). The present study tested the hypothesis that QOL is hypothesized to deteriorate soon after RT, with subsequent improvement of a magnitude similar to other KC treatments. METHODS AND MATERIALS: This observational study assessed prospectively collected longitudinal patient-reported QOL data at a single center. Patients undergoing external beam RT for early-stage (T0-2, <4 cm) KC that completed the Skindex-16 (S16) or Skin Cancer Index (SCI) before and at least once after RT were included. These indices include subscales of symptoms, emotions, and functioning for S16 and emotional, social, and appearance for SCI. RESULTS: 81 patients (median age 79 years) were treated for early KC, most being basal cell carcinomas (87%) on the face (80%) an average of 1.3 cm in diameter. Composite S16 scores and total SCI scores showed significant, clinically meaningful improvements at 3 months and 6 weeks after RT, respectively. QOL declined at 6 weeks after treatment on the S16 symptoms subscale. Concurrently, S16 and SCI emotional subscales significantly improved, and this trend persisted for 2+ years. Improvements in S16 functioning and SCI social and appearance QOL occurred after RT. The magnitude of improvement in QOL 3-12 months after RT was comparable to what has been previously reported after other types of KC treatments, like surgery. CONCLUSIONS: QOL related to symptoms deteriorates during the first 6 weeks after RT for early KC, but it improves by 3 months. QOL related to emotions, functioning, social, and appearance all improve after RT. These changes in QOL are similar to those observed after other treatments of early KC.

Impact of a Teaching Kitchen Curriculum for Health Professional Trainees in Nutrition Knowledge, Confidence, and Skills to Advance Obesity Prevention and Management in Clinical Practice.

Nutrition knowledge, confidence, and skills are thought to be important elements in the role of healthcare professionals in obesity prevention and management. The Upstream Obesity Solutions curriculum goes upstream with a multidisciplinary approach to supplement nutrition education among health professional trainees. Educational strategies of didactics, teaching kitchens, and service-based learning were employed for medical, dental, and nursing students and resident physicians. Pre/post participation surveys assessed knowledge, attitude, and practices; lifestyle habits; and culinary skills among 75 trainees in this cross-sectional descriptive study. There was variability in statistically significant improvement in knowledge, attitudes, and practices about obesity management and nutrition education, lifestyle habits, and culinary skills among learner groups.

Quantitative Benefit of Inpatient Dermatology Services on Hospital Length of Stay in an Academic Hospital.

BACKGROUND: Dermatologic disease has been shown to have high rates of diagnostic and treatment discordance between dermatologists and non-specialists. Inpatient dermatology consultative services have the potential to improve patient care, but there is a paucity of data evaluating the quantitative effects of such services. This study aimed to evaluate the impact a newly established inpatient dermatology service had on quantitative patient care outcomes. METHODS: This retrospective cohort study compared quantitative care measures of dermatologic inpatients during the years both pre- and post-implementation of an academic hospital's dermatology consultative service. The primary outcomes included hospitalization duration, readmission rates, and establishment of outpatient dermatologic care. RESULTS: The study found a 1.04-day reduction in hospital length of stay (p-value = 0.046) after the consultation service establishment. Additionally, there was a significant increase in the rate by which patients sought outpatient dermatology follow-up (6.7% versus 24.4%, p-value <0.001). No significant change in the all-cause readmission rate was identified. CONCLUSION: The reduction of hospitalization duration supports inpatient dermatology services as a viable means to provide improved patient care and reduce health systems costs. Hospitals that do not have a consulting service for cutaneous conditions provided by a dermatology specialist should strongly consider establishing such a department.

Stability and mechanism of threose nucleic acid toward acid-mediated degradation.

Xeno-nucleic acids (XNAs) have gained significant interest as synthetic genetic polymers for practical applications in biomedicine, but very little is known about their biophysical properties. Here, we compare the stability and mechanism of acid-mediated degradation of α-l-threose nucleic acid (TNA) to that of natural DNA and RNA. Under acidic conditions and elevated temperature (pH 3.3 at 90°C), TNA was found to be significantly more resistant to acid-mediated degradation than DNA and RNA. Mechanistic insights gained by reverse-phase HPLC and mass spectrometry indicate that the resilience of TNA toward low pH environments is due to a slower rate of depurination caused by induction of the 2'-phosphodiester linkage. Similar results observed for 2',5'-linked DNA and 2'-O-methoxy-RNA implicate the position of the phosphodiester group as a key factor in destabilizing the formation of the oxocarbenium intermediate responsible for depurination and strand cleavage of TNA. Biochemical analysis indicates that strand cleavage occurs by ß-elimination of the 2'-phosphodiester linkage to produce an upstream cleavage product with a 2'-threose sugar and a downstream cleavage product with a 3' terminal phosphate. This work highlights the unique physicochemical properties available to evolvable non-natural genetic polymers currently in development for biomedical applications.