Awareness and usage of evidence-based learning strategies among health professions students and faculty.

Introduction: Learning is essential and life-long for faculty and students. Often students and teachers use ineffective learning strategies and are not aware of evidence-based strategies.Methods: A multicenter, international, cross-sectional, online survey-based assessment of awareness of evidence-based learning strategies among health professions students (n = 679) and faculty (n = 205).Results: Students endorsed many study habits which violate evidence-based principles, including studying whatever is due soonest (389/679, 57%), failing to return to course material once a course has ended (465/679, 68%), and re-reading underlined or highlighted notes (298.679, 44%). While the majority of faculty surveyed (125/157, 80%) reported recommending effective study strategies for their students, most students (558/679, 82%) said they did not study the way they do because of instruction from faculty. The majority of faculty (142/156, 91%) and students (347/661, 53%) believe students have different learning styles.Discussion: The results of this study demonstrate health professions students continue to use many ineffective study strategies, and both students and faculty hold misconceptions about evidence-based learning. While planning a curriculum, medical educators should focus on teaching students how to learn and use higher order thinking procedures in addition to teaching content.

Chronic ulcerative stomatitis: Case series of an under-recognized entity.

Chronic ulcerative stomatitis (CUS) is a mucocutaneous condition characterized by chronic relapsing and remitting oral ulcers and erosions. This condition remains under-recognized among dermatopathologists, possibly because of common misdiagnosis as oral erosive lichen planus (LP). We report five cases of CUS in order to raise awareness of this uncommon condition. All patients presented with desquamative gingivitis and/or oral erosions, with biopsies showing lichenoid mucositis and epithelial nuclear IgG deposition on direct immunofluorescence. Recognition of the characteristic direct immunofluorescence findings allows for distinction of chronic ulcerative stomatitis from oral LP and appropriate therapy.

Endothelial cell-derived interleukin-6 regulates tumor growth.

BACKGROUND: Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. METHODS: Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. RESULTS: We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. CONCLUSIONS: Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells.

Can peer feedback substitute for faculty feedback in predoctoral dental education?

PURPOSE/OBJECTIVES: The ability to give and receive feedback is a key skill to develop during predoctoral dental education, and the use of peer feedback specifically offers distinct benefits including a different understanding of material due to peers' proximity of knowledge development and assisting with overburdened instructors. However, it is unclear if peer feedback offers similar quality to instructor feedback. METHODS: Dental students in two different graduation years provided quantitative and qualitative peer feedback on a case-based oral and maxillofacial pathology simulation. The data from these exercises were aggregated and analyzed to compare the quality of qualitative feedback to course examination scores. Student perceptions of peer feedback were also recorded. RESULTS: The mean quality of feedback was not correlated with course examination scores, though the number of times students gave high-quality feedback and received high-quality feedback was correlated with course examination scores. Student feedback overall had a lower quality than instructor feedback, though there was no significant difference between instructor feedback quality and the maximum student feedback quality received. Student perceptions of the utility of feedback were positive. CONCLUSION: While instructor feedback is more reliable and consistent, our findings suggest that in most instances, at least one peer in moderate-sized groups is able to approximate the quality of instructor feedback on case-based assignments.

Oral health educators' reflections on teaching 2022 and beyond.

INTRODUCTION: The global pandemic prompted changes in health science education affecting both teaching and learning. This multi-institutional study assesses the near-term implications of these changes on faculty and faculty development. The project goals were to: (1) describe faculty experiences of teaching during the pandemic; (2) identify ways to sustain new pedagogical approaches, (3) describe the types of support faculty members need, and (4) offer recommendations to enhance oral health professions education. METHODS: A mixed-method approach using exploratory sequential design was conducted in two phases collecting qualitative and quantitative data. Focus group participants included didactic, pre-clinical, and clinical faculty in dental school (DMD/DDS), dental hygiene and dental therapy programs, and also faculty members serving in administrative roles in these programs (N = 37). One hundred forty-four faculty participated in the multi-institutional follow-up survey. RESULTS: Focus group and survey results led to 14 recommendations (nine structural and five individual) for oral health profession institutions and educators. CONCLUSION: Oral health profession education faculty were dramatically impacted by the pandemic and new faculty development needs were identified. Traditional faculty development topics and practices may be no longer applicable in the post-COVID-19 environment. Additionally, the pandemic stimulated creative approaches for curriculum design, teaching, and assessment in oral health profession education. Strategies need to be implemented to sustain these innovations.

Small ubiquitin-like modifier (SUMO) modification mediates function of the inhibitory domains of developmental regulators FOXC1 and FOXC2.

FOXC1 and FOXC2 are forkhead transcription factors that play essential roles during development and physiology. Despite their critical role, the mechanisms that regulate the function of these factors remain poorly understood. We have identified conserved motifs within a previously defined N-terminal negative regulatory region of FOXC1/C2 that conforms to the definition of synergy control or SC motifs. Because such motifs inhibit the activity of transcription factors by serving as sites of post-translational modification by small ubiquitin-like modifier (SUMO), we have examined whether FOXC1/C2 are targets of SUMOylation and probed the functional significance of this modification. We find that endogenous FOXC1 forms modified by SUMO2/3 can be detected. Moreover, in cell culture, all three SUMO isoforms are readily conjugated to FOXC1 and FOXC2. The modification can be reconstituted in vitro with purified components and can be reversed in vitro by treatment with the SUMO protease SENP2. SUMOylation of FOXC1 and FOXC2 occurs primarily on one consensus synergy control motif with minor contributions of a second, more degenerate site. Notably, although FOXC1 is also phosphorylated at multiple sites, disruption of sites immediately downstream of the SC motifs does not influence SUMOylation. Consistent with a negative functional role, SUMOylation-deficient mutants displayed higher transcriptional activity when compared with wild type forms despite comparable protein levels and subcellular localization. Thus, the findings demonstrate that SC motifs mediate the inhibitory function of this region by serving as sites for SUMOylation and reveal a novel mechanism for acute and reversible regulation of FOXC1/C2 function.

Pediatric extranodal marginal zone B-cell lymphoma presenting as amyloidosis in minor salivary glands: a case report and review of the literature.

We report an unusual case of an extranodal marginal zone B-cell lymphoma (EMZL) arising in the labial minor salivary gland in an immunocompetent 11-year-old boy. The initial histopathologic review favored localized amyloidosis. However, further evaluation supported the diagnosis of low-grade B-cell lymphoma with plasmacytic differentiation, surrounded by deposits of AL κ-type amyloid. Clinical management consisted of excision with no recurrence at 1-year follow-up. This case demonstrates that a diagnosis of lymphoma must be considered in cases of amyloidosis associated with minor salivary gland involvement, even in children. In addition, we provide a literature review of extranodal marginal zone B-cell lymphoma arising in salivary glands.

The basic helix loop helix transcription factor Twist1 is a novel regulator of ATF4 in osteoblasts.

Parathyroid hormone (PTH) is an essential regulator of endochondral bone formation and an important anabolic agent for the reversal of bone loss. PTH mediates its functions in part by regulating binding of the bone-related activating transcription factor 4 (ATF4) to the osteoblast-specific gene, osteocalcin. The basic helix-loop-helix (bHLH) factors Twist1 and Twist2 also regulate osteocalcin transcription in part through the interaction of the C-terminal "box" domain in these factors and Runx2. In this study, we discovered a novel function of PTH: its ability to dramatically decrease Twist1 transcription. Since ATF4 is a major regulator of the PTH response in osteoblasts, we assessed the mutual regulation between these factors and determined that Twist proteins and ATF4 physically interact in a manner that affects ATF4 DNA binding function. We mapped the interaction domain of Twist proteins to the C-terminal "box" domain and of ATF4, to the N-terminus. Furthermore, we demonstrate that Twist1 overexpression in osteoblasts attenuates ATF4 binding to the osteocalcin promoter in response to PTH. This study thus identifies Twist proteins as novel inhibitory binding partners of ATF4 and explores the functional significance of this interaction.

Entrustable professional activities framework for assessment of patient handoffs in dentistry.

PURPOSE/OBJECTIVES: The aim of this study is to report data on the lack of a proper patient handoff system in dentistry and dental education and to present a possible solution to integrate this into curriculum using the "entrustable professional activities" (EPAs) framework. METHODS: Delphi participants from seven US dental schools provided feedback on a preliminary definition of handoff, a mnemonic and an assessment rubric. 2019 American Dental Education Association Commission on Change and Innovation in Dental Education (ADEA CCI) participants further evaluated the handoff EPA using the EQual rubric for EPA quality and structure. RESULTS: Delphi participants identified points of transition in dentistry, selected the D-PASS as a mnemonic, and agreed with the evaluation rubric. The ADEA CCI participants agreed the handoff EPA describes work that is essential for the profession and suitable for entrustment. CONCLUSION: The D-PASS rubric is an effective way to assess patient handoffs.

Oxidative stress drives disulfide bond formation between basic helix-loop-helix transcription factors.

Basic helix-loop-helix (bHLH) transcription factors including Twist1 and E2a proteins regulate essential processes. These factors bind DNA as homo- or heterodimers and the choice of binding partners determines their functional output. To investigate potential regulators of bHLH dimerization, cells were exposed to the oxidative agent hydrogen peroxide (H(2)O(2)). Western blot analysis in the presence or absence of reducing agents, revealed that H(2)O(2) induces the rapid formation of an intermolecular disulfide bond between Twist1 homodimers and Twist/E2a proteins heterodimers. The disulfide bond is first observed between Twist1 homodimers at 25 mM H(2)O(2) and between Twist1 heterodimers at 75 mM H(2)O(2). This response is dependent upon cell density as H(2)O(2) did not induce disulfide bridge formation between bHLH proteins in cells seeded at high density. In the presence of E proteins, the formation of Twist1/E2a proteins heterodimers is favored over Twist1 homodimers, identifying an oxidative stimulus as an important factor in modulating binding partner specificity. We further demonstrated that a cysteine residue located at the C-terminus of Twist1 and E2a proteins is involved in this response. Disulfide bond formation between Twist1 homodimers significantly reduced its ability to interact with two of its binding partners, Runx2 and HDAC4, indicating that disulfide dimerization in response to H(2)O(2) has functional significance. These data support the conclusion that disulfide bond formation in response to an oxidative stimulus contributes to Twist1 homo- and heterodimerization and raises the possibility that the redox status of a cell may represent an important step in bHLH transcriptional regulation.

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study.

BACKGROUND: To quantify pain severity in patients and the efficacy treatments, researchers and clinicians apply tools such as the traditional visual analog scale (VAS) that leads to inaccurate interpretation of the main sensory pain. OBJECTIVE: This study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain. METHODS: Patients with temporomandibular disorder (TMD) were assessed using GeoPain measures in comparison to VAS and positive and negative affect schedule (PANAS), pain and mood scales, respectively. Principal component analysis (PCA), scatter score analysis, Pearson methods, and effect size were used to determine the correlation between GeoPain and VAS measures. RESULTS: The PCA resulted in two main orthogonal components: first principal component (PC1) and second principal component (PC2). PC1 comprises a combination score of all GeoPain measures, which had a high internal consistency and clustered together in TMD pain. PC2 included VAS and PANAS. All loading coefficients for GeoPain measures in PC1 were above 0.70, with low loadings for VAS and PANAS. Meanwhile, PC2 was dominated by a VAS and PANAS coefficient >0.4. Repeated measure analysis revealed a strong correlation between the VAS and mood scores from PANAS over time, which might be related to the subjectivity of the VAS measure, whereas sensory-discriminative GeoPain measures, not VAS, demonstrated an association between chronicity and TMD pain in locations spread away from the most commonly reported area or pain epicenter (P=.01). Analysis using VAS did not detect an association at baseline between TMD and chronic pain. The long-term reliability (lag >1 day) was consistently high for the pain area and intensity number summation (PAINS) with lag autocorrelations averaging between 0.7 and 0.8, and greater than the autocorrelations for VAS averaging between 0.3 and 0.6. The combination of higher reliability for PAINS and its objectivity, displayed by the lack of association with PANAS as compared with VAS, indicated that PAINS has better sensitivity and reliability for measuring treatment effect over time for sensory-discriminative pain. The effect sizes for PAINS were larger than those for VAS, consequently requiring smaller sample sizes to assess the analgesic efficacy of treatment if PAINS was used versus VAS. The PAINS effect size was 0.51 SD for both facial sides and 0.60 SD for the right side versus 0.35 SD for VAS. Therefore, the sample size required to detect such effect sizes with 80% power would be n=125 per group for VAS, but as low as n=44 per group for PAINS, which is almost a third of the sample size needed by VAS. CONCLUSIONS: GeoPain demonstrates precision and reliability as a 3D mobile interface for measuring and analyzing sensory-discriminative aspects of subregional pain in terms of its severity and response to treatment, without being influenced by mood variations from patients.

Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer.

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, ß, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p < 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous µ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.

Calcium regulates the PI3K-Akt pathway in stretched osteoblasts.

Mechanical loading plays a vital role in maintaining bone architecture. The process by which osteoblasts convert mechanical signals into biochemical responses leading to bone remodeling is not fully understood. The earliest cellular response detected in mechanically stimulated osteoblasts is an increase in intracellular calcium concentration ([Ca(2+)](i)). In this study, we used the clonal mouse osteoblast cell line MC3T3-E1 to show that uniaxial cyclic stretch induces: (1) an immediate increase in [Ca(2+)](i), and (2) the phosphorylation of critical osteoblast proteins that are implicated in cell proliferation, gene regulation, and cell survival. Our data suggest that cyclic stretch activates the phosphoinositide 3-kinase (PI3K) pathway including: PI3K, Akt, FKHR, and AFX. Moreover, cyclic stretch also causes the phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase. Attenuation in the level of phosphorylation of these proteins was observed by stretching cells in Ca(2+)-free medium, using intra- (BAPTA-AM) and extracellular (BAPTA) calcium chelators, or gadolinium, suggesting that influx of extracellular calcium plays a significant role in the early response of osteoblasts to mechanical stimuli.

Small cell carcinoma in the parotid harboring Merkel cell polyomavirus.

OBJECTIVE: This study aimed to document three new cases of primary small cell carcinoma (SmCC) of the parotid and examine immunohistochemical and quantitative real-time polymerase chain reaction (qPCR) data of the recently developed Merkel cell polyomavirus (MCPyV) within these tumors. STUDY DESIGN: Immunohistochemistry for neuroendocrine markers (chromogranin A, CD56, CD57, neuron-specific enolase [NSE], thyroid transcription factor 1 [TTF-1]), epithelial markers (CK20, CK7, CAM 5.2), and MCPyV large T antigen (LTAg) were examined. qPCR and Sanger sequencing were performed to confirm the presence of the MCPyV LTAg gene. RESULTS: Two males and one female, average age 76 years, presented with left parotid masses. Clinical examinations, histories, and imaging studies were negative for cutaneous Merkel cell carcinoma (MCC), pulmonary and extrapulmonary SmCC, or any other malignancy. Immunohistochemical analysis demonstrated positive immunoreactivity for CK20 in a perinuclear dotlike pattern (3/3), CAM 5.2 (3/3), (2/3), NSE (3/3), CD56 (2/3), and CD57 (3/3). Two cases stained positive for MCPyV, showing moderate to strong, diffuse positivity, confirmed with qPCR. PCR-Sanger sequencing of LTAg exon 2 showed greater than 97% similarity to the MCPyV reference genome in both cases. CONCLUSION: Our findings expand the number of reported cases classified as primary parotid SmCC that harbors MCPyV and underscore the similarity between cutaneous MCC and parotid SmCC. Further investigation is needed to determine whether immune-based therapeutic strategies targeting MCPyV in MCC are also effective in the setting of parotid SmCC harboring MCPyV.