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Abstract Bone and teeth are comprised of carbonate-substituted apatites with cationic substitutions, like sodium and potassium. Cations substitute for calcium in the apatite lattice but it is unclear whether they substitute for Ca(1) or Ca(2). Additionally, although we know that anionic substitutions affect the mineral mechanics, it is unclear how cationic substitutions affect mineral stiffness. Here, a combined experimental and theoretical approach using in situ fluid-mediated hydrostatic loading with synchrotron Wide Angle X-ray Scattering (WAXS) and Density Functional Theory (DFT) is used to elucidate the role of CO3 2− and Na+ or K+ co-substitutions on the atomic structure and mechanics of biomimetic apatites. Comparison of WAXS and DFT results showed that preferential substitutions at the Ca(1) and Ca(2) sites depended on cationic type and concentration, with a preference for Ca(1) at higher levels of co-substitution. Substitution levels and location of the cationic substitution both significantly affected the modulus of the minerals. This presents a new paradigm for the development of biomimetic apatites with multi-property tunability by considering composition and atomic organization.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression.

The use of telehealth, specifically virtual visits, has increased and adoption continues. Providers need effective training for how to communicate with patients to develop a connection during virtual visits. This article describes the implementation and evaluation of a course called Mastering Presence in Virtual Visits . Results show that although providers perceive lack of time, technology issues, and lacking experiential knowledge as barriers to enacting course behaviors, the course was feasible and acceptable. Following the course, providers rated key course behaviors as helpful for practice, and 80.7% of providers were likely to recommend the course to a colleague. The course shifted provider perceptions of the purpose, patient experience, and procedures in virtual visits. Prior to the course, providers perceived virtual visits as fundamentally different than in-person visits. However, after the course, they recognized the importance of connection in virtual visits and how to foster that connection. Providers continue to require support in conducting high-quality virtual visits. Online, asynchronous courses, developed in partnership with providers, are feasible and effective for encouraging behavior change. Key findings: When asked on a needs assessment in 2020, communication strategies to connect with patients in virtual visits were a top provider need. Partnering with providers to create online, communication training content is effective for increasing the acceptability of courses about virtual visits. Asynchronous, online courses can meet provider needs for communication strategies to connect with patients in virtual visits.

Abstract Background and Aim Eosinophilic esophagitis (EoE) is a chronic disease which may progress to a fibro‐stenotic phenotype due to esophageal sub‐epithelial fibrosis. Esophageal wall thickening in patients with EoE has been demonstrated in a few studies using endoscopic ultrasound (EUS). The aim of this study was to longitudinally assess the endoscopic appearance, wall thickness, histology, and dysphagia score of EoE patients. Methods Patients with EoE were recruited and studied between February 2012 and April 2021. Patients were evaluated on two separate occasions at least 12 months apart with endoscopy, EUS, and esophageal mucosal biopsies. The dysphagia score and epidemiology data were also assessed. Results A total of 16 EoE patients were included with a mean follow‐up duration of 2.2 ± 1.2 years. In 14/16 (88%) patients, the total wall thickness of the distal esophagus significantly increased (P = 0.0012) as a result of thickening of the muscularis propria (P = 0.0218). However, only 1/14 (7%) patient had an increase in the dysphagia score, while 8/14 (57%) and 5/14 (36%) had a stable and reduced dysphagia score, respectively. No differences were found in the total thickness of other esophageal regions, dysphagia score, endoscopic appearance, and eosinophil count over time. Conclusion Distal esophageal wall thickness increases with time in EoE patients, independent of the dysphagia score and eosinophil count.

Abstract Background Allopathic medicine faces a daunting challenge of selecting the best applicants because of the very high applicant / matriculant ratio. The quality of graduates ultimately reflects the quality of medical practice. Alarming recent trends in physician burnout, misconduct and suicide raise questions of whether we are selecting the right candidates. The United States (US) lags far behind the United Kingdom (UK) and Europe in the study of non-cognitive tests in medical school admissions. Although more recently, medical schools in both the UK, Europe and the US have begun to use situational judgement tests such as the Computer-Based Assessment for Sampling Personal Characteristics (CASPer) and the situational judgement test (SJT), recently developed by the Association of American Medical Colleges (AAMC) and that these tests are, in a sense non-cognitive in nature, direct personality tests per se have not been utilized. We have historically used, in the admissions process within the US, knowledge, reasoning and exam performance, all of which are largely influenced by intelligence and also improved with practice. Personality, though also undoubtedly influenced by intelligence, is fundamentally different and subject to different kinds of measurements. Methods A popular personality measurement used over the past two decades within the US in business and industry, but not medical school has been the Neo Personality Inventory – Revised (NEO-PI-R) Test. This test has not been utilized regularly in allopathic medicine probably because of the paucity of exploratory retrospective and validating prospective studies. The hypothesis which we tested was whether NEO-PI-R traits exhibited consistency between two institutions and whether their measurements showed probative value in predicting academic performance. Results Our retrospective findings indicated both interinstitutional consistencies and both positive and negative predictive values for certain traits whose correlative strengths exceeded traditional premed metrics: medical college admission test (MCAT) scores, grade point average (GPA), etc. for early academic performance. Conclusions Our exploratory studies should catalyze larger and more detailed confirmatory studies designed to validate the importance of personality traits not only in predicting early medical school performance but also later performance in one’s overall medical career.

Abstract Background This is a time of unprecedented change in healthcare. More physicians are being tasked with stepping into a variety of leadership roles without having received the training needed to be an effective leader. Previous data have demonstrated the effectiveness of both leadership coaching and 360-feedback tools to foster physician well-being and leadership growth. In this proof of concept study, we explore the combined effect of these two tools. The objective of this study was to examine the effect of a brief physician 360 leadership coaching intervention on perception of professional dynamics and acquired leadership skills. Methods Participants completed a tailored 360-feedback tool to gather input on their leadership skills, then engaged in five bi-weekly leadership coaching sessions. We conducted a post-intervention semi-structured qualitative interview. Qualitative data were coded using an inductive thematic analysis approach. Results Twenty-three primary care physicians at an academic medical center engaged in the 360 leadership coaching study. Participants reported that the intervention yielded valuable benefits in five coaching sessions. Two overarching themes emerged: a Shift in leadership awareness and Navigating their environment. Leadership awareness included increased clarity of purpose and role, and recognition that routine feedback is critical to leadership development. Navigating their environment included gaining relationship-building communication, organizational awareness and navigation strategies. Conclusions Combining a tailored 360-feedback tool with a five-session leadership coaching intervention provided physicians with valued support infrastructure for becoming more effective leaders. Physicians described a nuanced understanding of the leadership challenges physicians face, and identified the leadership tools needed to navigate the evolving healthcare delivery landscape. Curricula for physician leadership learning could consider this combination of a customized 360 plus targeted leadership coaching for training physician leaders.

This article offers an overview of some of the major Christian theological themes that have arisen from the concerns of Chinese Catholic and Protestant Christians since the seventeenth century. It explores contextual factors that have shaped competing categories of loyalty, from differing cultural, religious, and philosophical starting points, to socio-political realities of Western imperialism, and Chinese nationalism and politics. The article examines theological themes that are prioritized by Chinese Christians related to the motif of the ‘family’, understandings of the human condition, and the importance of fostering a spirituality of suffering and an expression of public faith. Whilst in no way comprehensive, this article attempts to offer vignettes of how Chinese Christians, primarily from the Chinese mainland, have wrestled with the faith and offered distinctive expressions of what can be termed Chinese Christian theology.

Abstract Background Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren’s syndrome, Behҫet’s disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate. Case presentation In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred. He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy. The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development. Conclusion This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.

Abstract Background and Aim Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) can be difficult to distinguish as many of their clinical and histological features overlap. Preliminary data suggest a potential association between EoE and immunoglobulin G4 (IgG4) but not GERD. This study aimed to examine the role of esophageal mucosal IgG4 staining when differentiating EoE from GERD. Methods Esophageal biopsy specimens from patients with proven EoE and GERD were evaluated, and immunohistochemical staining for IgG4 was performed by an experienced gastrointestinal pathologist blinded to the clinical and endoscopic data. The results on IgG4 staining were then correlated with clinical, endoscopic, and histological features. Results Sixty patients were included in the study, with 30 EoE (38.8 ± 12.8 years, 23 M:7 F) and 30 GERD (50.7 ± 14.3 years, 14 M:16 F) patients. The prevalence of a positive intercellular IgG4 stain was significantly higher in the EoE patients than those with GERD (23/29 vs 2/30; P

Detailed understanding of how cancer cells transition from a drug sensitive to a tolerant state is lacking. Here, using single cell proteomic and metabolic data the authors uncover that isogenic BRAF mutant melanoma cells can take two distinct paths to become tolerant to BRAF inhibition.

ObjectiveTo identify clinical and biochemical characteristics associated with 7- & 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19.Research Design and MethodsWe conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome.ResultsWe analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p < 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (

The hip capsule and acetabular labrum are critical structures that function to protect and stabilize the hip joint. As the use of hip arthroscopy increases, there is increasing interest in the integrity of the hip capsule and labrum in optimizing postoperative function and outcomes. In this report, we describe the surgical technique for capsular reconstruction with dermal allograft and labral augmentation with tibialis anterior allograft for the treatment of gross instability after hip arthroscopy. This technique may be applied in situations with large capsular defects and deficient labral tissue.

The COVID-19 pandemic has mandated the use of virtual interactions in medical school. Although this falls mainly in the area of didactic instruction, of necessity, it has extended to the critical Admissions Process and the Medical School Interview itself. The California University of Science and Medicine (CUSM) with their flipped classroom approach had previously entered a virtual space of instruction even before COVID-19. Because CUSM was, in a sense, already committed to ‘virtual’ education, in the face of the COVID-19 pandemic, CUSM focused not on what it might lose but what it might gain and what their applicants to medical school might gain with the virtual format. The COVID-19 pandemic provided a unique opportunity to initially compare the Virtual Interview with the traditional On-Campus (In-Person) Interview during the hybrid 2020 year when the COVID-19 pandemic began. The Virtual Interview was patterned after the On-Campus Interview with some modifications. The same faculty conducted both interviews. A number of inherent advantages of the Virtual Interview surfaced to these faculty interviewers based on their subjective observations and conclusions. The overall interviewee satisfaction with the Virtual Interview was very positive based on their subjective observations and conclusions. The objective data from the Virtual Interviews compared to the On-Campus Interviews in the hybrid year resulted in a greater percentage of both offers of acceptance (p = .001) and matriculations (p = .001). In order to strengthen our initial observations, we expanded our study to include 2 pre-COVID-19 years (2018, 2019) of exclusively On-Campus interviews (n = 743) and 1 additional COVID-19 year (2021) of exclusively Virtual Interviews (n = 529). In this expanded study, interviewee demographics were not confounding and the Virtual Interview gave rise to overall greater interviewee satisfaction (p = .001), a trend to greater interviewer satisfaction and a greater percentage of both offers of acceptance (p = .047) and matriculations (p = .036).

Receptor Expressed in Lymphoid Tissues (RELT) is a human tumor necrosis factor receptor superfamily member (TNFRSF) that is expressed most prominently in cells and tissues of the hematopoietic system. RELL1 and RELL2 are two homologs that physically interact with RELT and co-localize with RELT at the plasma membrane. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members. The transcription factor MyoD family inhibitor domain-containing (MDFIC) was identified in a yeast two-hybrid genetic screen using RELL1 as bait. MDFIC co-localizes with RELT family members at the plasma membrane; this co-localization was most prominently observed with RELL1 and RELL2. In vitro co-immunoprecipitation (Co-IP) was utilized to demonstrate that MDFIC physically interacts with RELT, RELL1, and RELL2. Co-IP using deletion mutants of MDFIC and RELT identified regions important for physical association between MDFIC and RELT family members and a computational analysis revealed that RELT family members are highly disordered proteins. Immunohistochemistry of normal human lymph nodes revealed RELT staining that was most prominent in macrophages. Interestingly, the level of RELT staining significantly increased progressively in low and high-grade B-cell lymphomas versus normal lymph nodes. RELT co-staining with CD20 was observed in B-cell lymphomas, indicating that RELT is expressed in malignant B cells. Collectively, these results further our understanding of RELT-associated signaling pathways, the protein structure of RELT family members, and provide preliminary evidence indicating an association of RELT with B-cell lymphomas.

Abstract Background Colorectal cancer (CRC) diagnosed at

Objective: Preclinical medical student electives are prevalent at medical schools across the United States, but the range of electives available and their impact on medical student education are not well described in the literature. The objective of this article is to review the literature relating to preclinical medical student electives and their impact on medical student educational outcomes. Methods: We reviewed studies that met the following criteria: English-language articles describing preclinical US-based medical electives. We used PubMed journal databases and limited our search for the time period 1999–2014. We excluded electives based in other countries or electives designed for third or fourth year students. Data abstracted included the topic of the elective, qualitative descriptions of the electives, and any associated surveys or exam data associated with the electives. Data were synthesized using descriptive tables sorting electives by broad topic. Reported outcomes and statistical methods were analyzed to assess study quality. Results: We found a wide range of subjects taught in the form of preclinical medical school electives. We identified electives in clinical skills, the humanities, student lifestyle, specialty-specific electives, and an assortment of other miscellaneous electives. Surveys and exams administered to students showed that the electives were universally well received by students. Of the 37 electives identified, 15 electives used quantitative objective assessments, such as knowledge exams, while the remaining tended to use student self-reported results. Conclusions: Preclinical medical student electives are prevalent at medical schools across the United States and have a significant impact on medical student education.

Episodic memory recall processes in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centres (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits - false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures.