Changing Perceptions About the Dermatology Residency Application Process Among Applicants and Program Directors: 2020-2022.

Importance Over the last two years, dermatology has undergone significant reforms in the residency application process in efforts to reduce applicant stress, increase equity, and due to the COVID-19 pandemic.  Objective We aimed to determine applicant and program director (PD) perspectives in implementing these changes over the last two application cycles.  Design, setting, and participants Anonymous online surveys were administered by the Association of American Medical Colleges (AAMC) to PDs and applicants from the 2021-2022 dermatology residency application cycle.

Drug patch testing in Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review.

Background: The data on patch testing (PT) to identify culprit medications in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are limited to scattered case reports and small case series, without analysis of overall trends to inform clinicians of its utility, methodology, and safety.

Objective: To conduct a systematic review of the practice of PT in SJS/TEN, quantify the positivity rate of common drug classes, and assess safety during testing.

Methods: PubMed was searched from inception to 2021.

Treatment Options for Juvenile Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris represents a group of familial and acquired disorders of cornification that affect both adult and pediatric patients. Treatment options are difficult to assess through clinical trials, given the rarity of the disorder and its tendency for spontaneous remission. Case reports and case series are therefore the primary means of assessment.

Can Atopic Dermatitis and Allergic Contact Dermatitis Coexist?

Due to their seemingly divergent immune pathways, it previously was thought that atopic dermatitis (AD) and allergic contact dermatitis (ACD) could not occur together. However, novel research suggests that the 2 conditions may be more closely related than previously understood. Herein, we discuss the overlapping relationship between AD and ACD and review the evidence for their coexistence.

Aluminum: The 2022 American Contact Dermatitis Society Allergen of the Year.

Aluminum recently was selected as the 2022 Allergen of the Year by the American Contact Dermatitis Society. Aluminum contact allergy, which most often is related to its use as an adjuvant in select vaccines and allergen-specific immunotherapies, tends to present with pruritic subcutaneous nodules at the injection site. Allergy to aluminum-containing antiperspirants manifests as axillary vault dermatitis.

Oncogenic Mutations in the DNA-Binding Domain of FOXO1 that Disrupt Folding: Quantitative Insights from Experiments and Molecular Simulations.

FOXO1, a member of the family of winged-helix motif Forkhead box (FOX) transcription factors, is the most abundantly expressed FOXO member in mature B cells. Sequencing of diffuse large B-cell lymphoma (DLBCL) tumors and cell lines identified specific mutations in the forkhead domain linked to loss of function. Differential scanning calorimetry and thermal shift assays were used to characterize how eight of these mutations affect the stability of the FOX domain.

Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice.

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)-for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development.

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum.

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.

The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant.

Predictors of medical students' ethical decision-making: A pilot study using the Theory of Interpersonal Behavior.

Objective: To understand medical students' (MS) ethical decision-making using the Theory of Interpersonal Behavior (TIB).

Methods: We conducted two rounds of focus groups to develop a TIB-based questionnaire by eliciting students' perspectives on an ethical dilemma they will encounter in a standardized patient (SP) station, in which an SP "surgeon" asked them to intubate a sedated patient whom the student knew had requested no student involvement. We administrated questionnaires to 241 third-year MS following this SP station, asking for their decisions in the SP station and if a surgeon made the same request in their clerkship.

Communication skills teaching in Brazilian medical schools: What lessons can be learned?

Objective: To assess current practices in communication skills (CS) teaching in Brazilian medical schools (MS), looking for similarities and differences with other countries.

Methods: This study was performed with 162 out of the 237 accredited Brazilian MS (68.35%).

Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases.

Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment.

Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation.

The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products of extracellular matrix. Since some DAMPs confer tissue-specific activation of the inflammasomes, we tested the hypothesis that bone matrix components function as DAMPs for the NLRP3 inflammasome and regulate osteoclast differentiation. Indeed, bone particles cause exuberant osteoclastogenesis in the presence of RANKL, a response that correlates with NLRP3 abundance and the state of inflammasome activation.

Inflammatory osteolysis: a conspiracy against bone.

There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone.

Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy.

The goal of breast-conserving surgery is to completely remove all of the cancer. Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen, which results in 20 to 60% of patients undergoing second surgeries to achieve clear margins. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment.

Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms.

RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB-inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic.

Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis.

Background: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies.

Methods: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis.

Pulsed low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis.

A number of studies in model animal systems and in the clinic have established that RANKL promotes bone resorption. Paradoxically, we found that pulsing ovariectomized mice with low-dose RANKL suppressed bone resorption, decreased the levels of proinflammatory effector T cells and led to increased bone mass. This effect of RANKL is mediated through the induction of FoxP3CD25 regulatory CD8 T cells (Tc) by osteoclasts.

Skeletal Fluorosis Due To Inhalation Abuse of a Difluoroethane-Containing Computer Cleaner.

Skeletal fluorosis (SF) is endemic in many countries and millions of people are affected worldwide, whereas in the United States SF is rare with occasional descriptions of unique cases. We report a 28-year-old American man who was healthy until 2 years earlier when he gradually experienced difficulty walking and an abnormal gait, left hip pain, loss of mobility in his right wrist and forearm, and progressive deformities including enlargement of the digits of both hands. Dual-energy X-ray absorptiometry (DXA) of his lumbar spine, femoral neck, total hip, and the one-third forearm revealed bone mineral density (BMD) Z-scores of +6.

Novel ERα positive breast cancer model with estrogen independent growth in the bone microenvironment.

Despite successful therapeutic options for estrogen receptor-α (ERα)+ breast cancer, resistance to endocrine therapy frequently occurs leading to tumor recurrence. In addition to intrinsic changes in the cancer cells, herein we demonstrate that tumor cell-microenvironment interactions can drive recurrence at specific sites. By using two ERα+ cell lines derived from spontaneous mammary carcinomas in STAT1-/- mice (SSM2, SSM3), we establish that the bone microenvironment offers growth advantage over primary site or lung in the absence of ovarian hormones.