Patient Opinions and Side Effects Before and After General Anesthesia for Surgery.

As the number of surgical procedures performed the world over continues to increase, so does the number of anesthetic procedures needed for those surgeries to occur. While much thought and research has been focused on the perspective of the anesthesiologist, little has been explored from the perspective of the patient receiving anesthesia. The purpose of this study was to explore the general public's opinions and experiences of general anesthesia, as well as any change in their perception after having undergone a procedure requiring it. We decided that further inquiry into the subject was warranted, and we decided to run an online Qualtrics survey in order to make that inquiry. The key takeaway from our online anonymous survey shows that there is a significant amount of anxiety related to anesthesia, but that most people specify a large decrease in said anxiety after having undergone the procedure. Noticeably, people were made more comfortable by discussing anesthesia with people who had lived through the experience, and people believed they would be significantly comforted by the presence of therapy animals prior to beginning their procedures. We hope that our exploratory research will promote future research into this topic in order to improve the healthcare outcomes of a significant number of patients. We believe that this data has opened up many potential avenues for further exploration and research, as well as potentially being able to guide surgical practice.

Characterization of Research Mentorship During Medical School for Future Radiation Oncology Trainees.

Purpose: Medical student access to radiation oncology (RO) research opportunities is important for stimulating interest in the specialty. The purpose of this study was to assess the publication record during medical school of students who ultimately matched in RO, to characterize the source(s) of their RO mentorship relative to other specialties. Methods and Materials: We performed web-based searches to identify manuscripts published during medical school (defined as being published from January 2016 to December 2019) for all RO residents with postgraduate year 2 status in 2020 to 2021. Students with a PhD degree and international graduates were excluded. Characteristics of these publications, the student, and the primary mentor, were assessed. Results: A total of 435 publications were authored by the 148 included residents. In total, 115 (78%) attended a medical school with an affiliated RO residency program. The median number of publications per student was 2 (interquartile range, 1-4), and students' median byline author position was 2 (interquartile range, 1-4). In total, 351 publications (80.7%) were on a cancer-related topic, with 234 (53.8%) published in oncology-oriented journal, and 96 (22.0%) published in RO-oriented journals. There were 294 unique mentors, with 70 mentors (24%) on 2 or more student publications. Most mentors (n = 187, 64%) shared the same institution as the student. Mentors were most commonly radiation oncologists/radiation biologists/medical physicists (n = 153, 52.6%), surgical subspecialists (n = 53, 21%), and medical oncologists (n = 18, 6.2%). Students working with primary RO mentors were more likely to publish in an oncology-oriented journal (79.1% vs 18.2%, P < .01) or RO-oriented journal (36.2% vs 2.2%, P < .01), compared with students working with non-RO mentors, respectively. A higher percentage of publications with RO mentors occurred in the last 2 years of medical school compared with the first 2 years (64.0% vs 40.9%, respectively, P < .01). Conclusions: Approximately one-half of student publications among future RO residents are published in nononcology journals, and result from mentoring relationships with non-RO physicians.

Assessment of Medical Student Research Mentorship in Radiation Oncology.

Purpose: Mentored medical student (MS) research opportunities in radiation oncology (RO) provide in-depth exposure to the specialty and may promote greater interest in a career in RO. Many radiation oncologists conduct research; however, the extent to which they directly engage MSs in their research is unknown. The purpose of this study was to characterize MS authorship in American Society for Radiation Oncology (ASTRO) journals. Methods and Materials: The byline and abstract of all scientific articles (ie, clinical, basic science, training/education) and case reports published from 2019 to 2021 in the International Journal of Radiation Oncology, Biology, and Physics; Practical Radiation Oncology; and Advances in Radiation Oncology were reviewed. Characteristics of MSs and senior authors are reported. Results: A total of 105 of 1785 articles (5.8%) included an MS author, among which 72 (68.6%) were clinical, 13 training/education (12.4%), 12 case reports (11.4%), and 8 basic science (7.6%). MS authors were more common for publications in Advances in Radiation Oncology (9.0%) than Practical Radiation Oncology (6.4%) or the International Journal of Radiation Oncology, Biology, and Physics (4.2%; P = .002). There were 125 unique MS authors from 72 institutions, among which 40 were first author (32.0%), 28 second author (22.4%), and 57 third (or higher) author (45.6%). There were 88 unique senior authors from 55 institutions, among which 10 (11.3%) were on 2 or more MS publications, and 57 (64.7%) shared the same institution as the MS. The median number of articles per mentor institution was 1 (interquartile range, 1-2), and the mentor institutions in the upper quartile in terms of number of MS publications accounted for 53 (50.5%) of all MS publications. Conclusions: Few publications in American Society for Radiation Oncology journals include MS authors with mentorship disproportionately from a small number of academic faculty at select institutions. These findings suggest that there is great potential for radiation oncologists to proactively engage more students in their work.

Analysis of Research Productivity of Orthopedic Surgery Residency Applicants.

Background Orthopedic surgery has become an increasingly competitive specialty. With a pass-fail Step 1, an even greater emphasis on research has been placed to allow candidates to better distinguish themselves. This study analyzes the scholarly activity of accepted orthopedic residency applicants during medical school, assessing what factors, including the novel altmetric attention score, may be associated with greater research productivity. Methods A list of orthopedic residency programs was obtained from the Electronic Residency Application Service (ERAS). A total of 688 orthopedic residents from 180 programs who matriculated in 2020 from allopathic medical schools were identified. Resident demographic information and bibliometric data (total publications, orthopedic-related publications, h-index, and altmetric score) of publications published from July 1, 2016, to September 1, 2020, were collected. Descriptive statistics were calculated. Kruskal-Wallis tests analyzed the association between medical school characteristics and research productivity using Stata® 17.0 (StataCorp LLC, College Station, Texas). Results Postgraduate-Year-3 orthopedic residents (N=688) published 2,600 articles during medical school, averaging 3.8 articles per resident. The residents from a top 25 medical school for research had publication counts, altmetric scores, and h-indices, on average, that were higher than those from non-top 25 medical schools for research. Over 150 residents had no publications, and ~10 residents had more than 30 publications. Conclusions The results illustrate that medical school research status influences the research productivity of applicants. Also, given the average number of publications, most research listed on applications are abstracts and presentations. Utilization of the altmetric score may not yet be the best way of examining research experience because orthopedic applicants do not appear to use social networks for academic research.

A Patient With Pelizaeus-Merzbacher Disease Caused by a c.67G>A Mutation in the PLP1 Gene.

Pelizaeus-Merzbacher disease is a tremendously rare genetic disorder caused by a mutation on the X chromosome. The mutation affects a gene critical to white matter myelination and results in significant neurological issues. Here, we present one such case of a child diagnosed with Pelizaeus-Merzbacher disease. A relatively normal gestation and birth belied the underlying issue until he presented to the emergency department a month after birth with seizure-like activity and failure to thrive. After intensive evaluation and treatment, the patient was diagnosed with the illness and received surgery to place a tracheostomy and a gastrostomy tube to treat the stridor and failure to thrive caused by his illness. After approximately a month and a half of inpatient treatment, the patient was able to be discharged home in stable condition.

Intraoperative Complications During Orthopaedic Spinal Surgery in a Polypharmacy Patient With Multiple Comorbidities.

Orthopedic spinal surgeries, such as laminectomies or decompressions, have the potential to significantly increase quality of life for patients suffering from a spectrum of health issues ranging from neuropathy to chronic pain. Patients suffering from neurological symptoms such as weakness or neuropathy may lose significant function and become unable to perform the activities of daily living, however these delicate surgical interventions also come with significant risks to the health and well-being of those same patients. This is especially true with patients who have predisposing health conditions. Here, we discuss the effects of surgery on a patient with severe obesity, multiple confounding pre-existing conditions, and significant polypharmacy. An initially unremarkable spinal laminectomy and decompression surgery resulted in severe intraoperative complications that necessitated direct admission to the intensive care unit for significant post-operative management before he was able to be discharged safely. Although not a case of incredible rarity, we hope it can contribute to the growing body of data about the role of predisposing health conditions and polypharmacy in calculating and understanding the risks of orthopaedic surgery.

Rheumatoid Arthritis-Linked Artificial Joint Infections Leading to Amputations.

Rheumatoid arthritis (RA) is a common autoimmune condition that can rarely cause more serious complications, such as permanent joint damage or infection, and may pose a significant additional risk during certain routine procedures. One major consequence of RA is that it can lead to serious and permanent joint damage requiring arthroplasty. Additionally, RA is a known cause of infection, with orthopedic prosthetic joint infections (PJIs) being documented. We explore one such serious case of a patient with long-term RA and a left knee joint replacement who presented to the emergency room with a serious PJI. History revealed that he repeatedly was affected by infections and had an extensive and severe clinical course, including nine revision surgeries. After a physical examination, imaging was performed, which further supported the diagnosis of joint infection. Considering the extensive number of attempts to salvage the joint, clinicians decided an above-knee amputation was necessary. This case highlights the fact that RA both increases the need for orthopedic arthroplasties and the risk of complications from these procedures, complicating clinical decision-making for physicians. Additionally, this patient had other underlying medical conditions and social habits that may have contributed to his severe clinical course, and we hope to explore these, discuss possible methods of modifying them, and assist clinicians in not only better treating similar patients but also emphasizing the importance of further developing standardized predictive algorithms and scoring tools.

Trends in Residency Academic Productivity of Ophthalmic Plastic and Reconstructive Surgery Fellows Between 2012 and 2019.

PURPOSE: To characterize research productivity of ophthalmic plastic and reconstructive surgery (OPRS) fellows during residency. METHODS: A database was compiled of OPRS fellows listed on the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Annual Fall Scientific Symposium program books who began their fellowship between 2012 and 2019. PubMed was searched for all publications published between July 1st of the year they began residency and September 30th of the year they began fellowship training. Bibliometric variables captured for each fellow included: the number of publications, first-author publications, and ophthalmology-related publications. RESULTS: A total of 197 OPRS fellows who began their fellowship training between 2012 and 2019 published a mean (± SD) of 2.42 ± 2.80 publications, 1.43 ± 1.85 first-author publications, and 2.33 ± 2.74 ophthalmology-related publications during residency. Linear regression revealed that the number of publications ( P < 0.001), first-author publications ( P < 0.001), and ophthalmology-related publications ( P < 0.001) that OPRS fellows published during residency have all significantly increased over the time assessed. CONCLUSIONS: The academic productivity of OPRS fellows during residency was quantified through bibliometric analysis to establish a national benchmark for the benefit of both prospective applicants and program directors. Residency research output of OPRS fellows has significantly increased between 2012 and 2019. Since ASOPRS program requirements necessitate academic productivity and thesis completion, publication records and involvement in research become valuable considerations when evaluating fellowship applicants. The knowledge of what accepted fellows have published provides the opportunity to make historical comparisons and may prove useful in the evaluation of the competitiveness of a given year's applicant pool.

Necrotizing Fasciitis Presenting as Generalized Weakness, Malaise, and Acute Kidney Injury.

Necrotizing fasciitis (NF) is a surgical emergency that must be diagnosed promptly in order to avoid serious consequences or death. Additionally, symptoms of this condition are similar to less severe skin and soft tissue infections such as cellulitis or erysipelas and can be easily confused. In this case, the patient presented to the emergency department with systemic symptoms, notably malaise and generalized weakness. A cutaneous complaint, a "labial cyst", was only elicited after more specific questioning. Laboratory investigations revealed abnormal renal function tests (RFTs), suggestive of an acute kidney injury. An abdominal/pelvic computed tomography (CT) showed gas in the subcutaneous tissue. These findings led to clinical suspicion of NF, prompting a general surgery consultation. The surgeon proceeded to perform extensive debridement following the discovery of necrotic tissue. The prompt diagnosis and treatment of this condition resulted in patient survival and expected recovery. It is, therefore, critical to keep this condition in mind when diagnosing apparent skin and soft tissue infections presenting with abnormal RFTs due to the possibility of rapid decline and death if the NF is left untreated. Additionally, this is a case of less frequent Fournier's gangrene in a non-diabetic female. Finally, it underlines the importance of eliciting additional symptoms, even those that may seem unrelated, or less concerning, to the patient's initial complaint.

Analyzing the Role of Research in the Radiation Oncology Match.

PURPOSE: Program directors consider scholarly output to be integral in matching applicants with radiation oncology residencies. However, applicants' research productivity can be quantified in several ways, and the results can be misleading for both applicants and program directors. We conducted a bibliometric analysis to quantify the research productivity of applicants who had successfully matched to radiation oncology residencies and to test for associations between research productivity and residency program rankings. METHODS AND MATERIALS: We identified U.S. radiation oncology residency programs from the Accreditation Council for Graduate Medical Education website and sorted the findings into 4 tiers based on the programs' reputation and research output per Doximity's Residency Navigator. First-year (post-graduate year-2) radiation oncology residents starting in 2020 were identified on residency program websites. Residents' research productivity was estimated by identifying peer-reviewed research articles (published before the residency applications began) via PubMed, Scopus, and Google Scholar for each resident. Bibliometric variables were analyzed for potential association with matching to higher-tier residencies. RESULTS: We identified 187 first-year residents in 83 U.S. residency programs. The mean number of National Resident Matching Program publications (which was self-reported and included presentations and abstracts) was 18.3 per applicant; the mean (± standard deviation) peer-reviewed publications was 2.47 (±2.88) per resident. Multivariate analysis showed that number of first-author publications was associated with matching to a higher-tier program, based on the program's reputation (P = .019) and research output (P = .010); numbers of radiation oncology-specific publications (P = .039) and h-index (P = .024) correlated with matching to a higher-tier residency based on the program's research output. CONCLUSIONS: The number of first-author publications was significantly associated with matriculating into a higher-tier residency ranked by both reputation and research output. Significant correlations were also found for number of radiation oncology-specific publications and h-index. Applicants may find publishing meaningful radiation oncology articles, especially as first author, to be more valuable than meeting National Resident Matching Program numbers.

EIN2-directed histone acetylation requires EIN3-mediated positive feedback regulation in response to ethylene.

Ethylene is an important phytohormone with pleotropic roles in plant growth, development, and stress responses. ETHYLENE INSENSITIVE2 (EIN2) mediates the transduction of the ethylene signal from the endoplasmic reticulum membrane to the nucleus, where its C-terminus (EIN2-C) regulates histone acetylation to mediate transcriptional regulation by EIN3. However, no direct interaction between EIN2-C and EIN3 has been detected. To determine how EIN2-C and EIN3 act together, we followed a synthetic approach and engineered a chimeric EIN2-C with EIN3 DNA-binding activity but lacking its transactivation activity (EIN2C-EIN3DB). The overexpression of EIN2C-EIN3DB in either wild-type or in the ethylene-insensitive mutant ein3-1 eil1-1 led to a partial constitutive ethylene response. Chromatin immunoprecipitation sequencing showed that EIN2C-EIN3DB has DNA-binding activity, indicating that EIN3DB is functional in EIN2C-EIN3DB. Furthermore, native EIN3 protein levels determine EIN2C-EIN3DB binding activity and binding targets in a positive feedback loop by interacting with EIN2C-EIN3DB to form a heterodimer. Additionally, although EIN3 does not direct affect histone acetylation levels in the absence of EIN2, it is required for the ethylene-induced elevation of H3K14Ac and H3K23Ac in the presence of EIN2. Together, we reveal efficient and specific DNA-binding by dimerized EIN3 in the presence of ethylene to mediate positive feedback regulation, which is required for EIN2-directed elevation of histone acetylation to integrate into an EIN3-dependent transcriptional activation.

A novel pattern of germ cell divisions in the production of hymenopteran insect eggs.

Egg development is a defining process of reproduction in higher eukaryotes. In the fruit fly, Drosophila melanogaster, this process begins with four mitotic divisions starting from a single germ cell, producing a cyst of 16 cystocytes; one of these cells will become the oocyte and the others supporting nurse cells. These mitotic divisions are exceptional because cytokinesis is incomplete, resulting in the formation of cytoplasmic bridges known as ring canals that interconnect the cystocytes. This organization allows all cystocytes to divide synchronously during each mitotic round, resulting in a final, power-of-2 number of germ cells. Given that numerous insects obey this power-of-2 rule, we investigated if strict cell doubling is a universal, underlying cause. Using confocal microscopy, we found striking departures from this paradigm in three different power-of-2 insects belonging to the Apocrita suborder (ants, bees and wasps). In these insects, the earliest-formed cystocytes cease to divide during the latter mitotic cycles while their descendants undergo further division, thereby producing a 'radial' direction of division activity. Such cystocyte division patterns that depart from strict cell doubling may be 'fine-tuned' in order to maintain a final, power-of-2 germ cell number.

Molecular Profiling of Ulcerative Colitis Subjects from the TURANDOT Trial Reveals Novel Pharmacodynamic/Efficacy Biomarkers.

BACKGROUND AND AIMS: To define pharmacodynamic and efficacy biomarkers in ulcerative colitis [UC] patients treated with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody, in the TURANDOT study. METHODS: Transcriptome, proteome and immunohistochemistry data were generated in peripheral blood and intestinal biopsies from 357 subjects in the TURANDOT study. RESULTS: In peripheral blood, C-C motif chemokine receptor 9 [CCR9] gene expression demonstrated a dose-dependent increase relative to placebo, but in inflamed intestinal biopsies CCR9 gene expression decreased with increasing PF-00547659 dose. Statistical models incorporating the full RNA transcriptome in inflamed intestinal biopsies showed significant ability to assess response and remission status. Oncostatin M [OSM] gene expression in inflamed intestinal biopsies demonstrated significant associations with, and good accuracy for, efficacy, and this observation was confirmed in independent published studies in which UC patients were treated with infliximab or vedolizumab. Compared with the placebo group, intestinal T-regulatory cells demonstrated a significant increase in the intermediate 22.5-mg dose cohort, but not in the 225-mg cohort. CONCLUSIONS: CCR9 and OSM are implicated as novel pharmacodynamic and efficacy biomarkers. These findings occur amid coordinated transcriptional changes that enable the definition of surrogate efficacy biomarkers based on inflamed biopsy or blood transcriptomics data.ClinicalTrials.gov identifierNCT01620255.

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis.

One of the obstacles for cancer immunotherapy is the inefficiency of CD8(+) T-cell recruitment to tumors. STAT3 has been shown to suppress CD8(+) T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8(+) T cells. However, the underlying molecular mechanism by which STAT3 in CD8(+) T cells inhibits their accumulation in tumors remains to be defined. Here, we show that STAT3 signaling in CD8(+) T cells inhibits chemokine CXCL10 production by tumor-associated myeloid cells by reducing IFNγ expression by T cells. We further demonstrate that ablating STAT3 in T cells allows expression of CXCR3, the receptor of CXCL10, on CD8(+) T cells, resulting in efficient accumulation of CD8(+) T cells at tumor sites. Blocking IFNγ or CXCR3 impairs the accumulation of STAT3-deficient CD8(+) T cells in tumor and their antitumor effects. Together, our study reveals a negative regulation by STAT3 signaling in T cells on cross-talk between myeloid cells and T cells through IFNγ/CXCR3/CXCL10, which is important for CD8(+) T cells homing to tumors. Our results thus provide new insights applicable to cancer immunotherapy and adoptive T-cell strategies.

An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium.

The mechanical landscape in biological systems can be complex and dynamic, with contrasting sustained and fluctuating loads regularly superposed within the same tissue. How resident cells discriminate between these scenarios to respond accordingly remains largely unknown. Here, we show that a step increase in compressive stress of physiological magnitude shrinks the lateral intercellular space between bronchial epithelial cells, but does so with strikingly slow exponential kinetics (time constant approximately 110 s). We confirm that epidermal growth factor (EGF)-family ligands are constitutively shed into the intercellular space and demonstrate that a step increase in compressive stress enhances EGF receptor (EGFR) phosphorylation with magnitude and onset kinetics closely matching those predicted by constant-rate ligand shedding in a slowly shrinking intercellular geometry. Despite the modest degree and slow nature of EGFR activation evoked by compressive stress, we find that the majority of transcriptomic responses to sustained mechanical loading require ongoing activity of this autocrine loop, indicating a dominant role for mechanotransduction through autocrine EGFR signaling in this context. A slow deformation response to a step increase in loading, accompanied by synchronous increases in ligand concentration and EGFR activation, provides one means for cells to mount a selective and context-appropriate response to a sustained change in mechanical environment.

Quantification of three-dimensional dynamics of intercellular geometry under mechanical loading using a weighted directional adaptive-threshold method.

Capturing and quantifying dynamic changes in three-dimensional cellular geometries on fast time scales is a challenge because of mechanical limitations of imaging systems as well as of the inherent tradeoffs between temporal resolution and image quality. We have combined a custom high-speed two-photon microscopy approach with a novel image segmentation method, the weighted directional adaptive-threshold (WDAT), to quantify the dimensions of intercellular spaces of cells under compressive stress on timescales previously inaccessible. The adaptation of a high-speed two-photon microscope addressed the need to capture events occurring on short timescales, while the WDAT method was developed to address artifacts of standard intensity-based analysis methods when applied to this system. Our novel approach is demonstrated by the enhanced temporal analysis of the three-dimensional cellular and extracellular deformations that accompany compressive loading of airway epithelial cells.

Conformational sampling with implicit solvent models: application to the PHF6 peptide in tau protein.

Implicit solvent models approximate the effects of solvent through a potential of mean force and therefore make solvated simulations computationally efficient. Yet despite their computational efficiency, the inherent approximations made by implicit solvent models can sometimes lead to inaccurate results. To test the accuracy of a number of popular implicit solvent models, we determined whether implicit solvent simulations can reproduce the set of potential energy minima obtained from explicit solvent simulations. For these studies, we focus on a six-residue amino-acid sequence, referred to as the paired helical filament 6 (PHF6), which may play an important role in the formation of intracellular aggregates in patients with Alzheimer's disease. Several implicit solvent models form the basis of this work--two based on the generalized Born formalism, and one based on a Gaussian solvent-exclusion model. All three implicit solvent models generate minima that are in good agreement with minima obtained from simulations with explicit solvent. Moreover, free-energy profiles generated with each implicit solvent model agree with free-energy profiles obtained with explicit solvent. For the Gaussian solvent-exclusion model, we demonstrate that a straightforward ranking of the relative stability of each minimum suggests that the most stable structure is extended, a result in excellent agreement with the free-energy profiles. Overall, our data demonstrate that for some peptides like PHF6, implicit solvent can accurately reproduce the set of local energy minimum arising from quenched dynamics simulations with explicit solvent. More importantly, all solvent models predict that PHF6 forms extended beta-structures in solution, a finding consistent with the notion that PHF6 initiates neurofibrillary tangle formation in patients with Alzheimer's disease.