Obg-like ATPase 1 exacerbated gemcitabine drug resistance of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis due to inefficient diagnosis and tenacious drug resistance. Obg-like ATPase 1 (OLA1) is overexpressed in many malignant tumors. The molecular mechanism of OLA1 underlying gemcitabine (GEM)-induced drug resistance was investigated in this study. An enhanced expression of OLA1 was observed in a GEM acquired resistant pancreatic cancer cell lines and in patients with pancreatic cancer. Overexpressed OLA1 showed poor overall survival rates in patients with pancreatic cancer. Dysregulation of the OLA1 reduced expression of CD44+/CD133+, and improved the sensitivity of pancreatic cancer cells to GEM. OLA1 highly expression facilitated the formation of the OLA1/Sonic Hedgehog (SHH)/Hedgehog-interacting protein (HHIP) complex in nuclei, resulting in the inhibition of negative feedback of Hedgehog signaling induced by HHIP. This study suggests that OLA1 may be developed as an innovative drug target for an effective therapy of pancreatic cancer.

The Impact of the COVID-19 Pandemic on Geographic Placement of Applicants to General Surgery Residency Programs.

OBJECTIVE: COVID-19 greatly influenced medical education and the residency match. As new guidelines were established to promote safety, travel was restricted, visiting rotations discontinued, and residency interviews turned virtual. The purpose of this study is to assess the geographic trends in distribution of successfully matched General Surgery applicants prior to and after the implementation of pandemic guidelines, and what we can learn from them as we move forward. DESIGN: This was a retrospective review of 129 Accreditation Council for Graduate Medical Education (ACGME) accredited, academic General Surgery Residency Programs across 46 states and the District of Columbia. Categorically matched residents' medical schools (i.e., home institutions), medical school states, and medical school regions as defined per the Association of American Medical Colleges (AAMC), were compared to the same geographic datapoints as their residency program. Preliminary residents were excluded. Residents in the 2018, 2019, and 2020 cycles were sub-categorized into the "pre-COVID" group and residents in the 2021 and 2022 applications cycles were sub-categorized into the "post-COVID" group. The percentages of residents who matched at their home institution, in-state, and in-region were examined. SETTING: Multiple ACGME-accredited, university-affiliated General Surgery Residency Programs across the United States of America. PARTICIPANTS: A total of 4033 categorical General Surgery residents were included. RESULTS: Of 4033 categorical residents who matched between 2018 and 2022, 56.1% (n = 2,263) were in the pre-COVID group and 43.9% (n = 1770) were in the post-COVID group. In the pre-COVID group 14.4% (n = 325) of residents remained in-home (IH), 24.4% (n = 553) in-state (IS), and 37.0% (n = 837) in- region (IR), compared to 18.8% IH (n = 333), 27.8% IS (n = 492), and 39.9% IR (n = 706) in the post-COVID group, respectively. Significant increases for IH and IS resident matching at 4.5% and 3.4%, respectively, were noted in the post-COVID period (p < 0.05). CONCLUSION: The COVID-19 pandemic, and the ensuing changes adopted to promote safety, significantly impacted medical student opportunities and the General Surgery residency application process. General Surgery match data over the last 5 years reveals a statistically significant increase in the percentage of applicants matching at in-home and in-state institutions after the pandemic.

RNA structural probing of guanine and uracil nucleotides in yeast.

RNA structure can be essential for its cellular function. Therefore, methods to investigate the structure of RNA in vivo are of great importance for understanding the role of cellular RNAs. RNA structure probing is an indirect method to asess the three-dimensional structure of RNA by analyzing the reactivity of different nucleotides to chemical modifications. Dimethyl sulfate (DMS) is a well-established compound that reports on base pairing context of adenine (A) and cytidine (C) in-vitro and in-vivo, but is not reactive to guanine (G) or uracil (U). Recently, new compounds were used to modify Gs and Us in plant, bacteria, and human cells. To complement the scope of RNA structural probing by chemical modifications in the model organism yeast, we analyze the effectiveness of guanine modification by the glyoxal family in Saccharomyces cerevisiae and Candida albicans. We show that within glyoxal family of compounds, phenylglyoxal (PGO) is the best guanine probe for structural probing in S. cerevisiae and C. albicans. Further, we show that PGO treatment does not affect the processing of different RNA species in the cell and is not toxic for the cells under the conditions we have established for RNA structural probing. We also explore the effectiveness of uracil modification by Cyclohexyl-3-(2-Morpholinoethyl) Carbodiimide metho-p-Toluenesulfonate (CMCT) in vivo and demonstrate that uracils can be modified by CMCT in S. cerevisiae in vivo. Our results provide the conditions for in vivo probing the reactivity of guanine and uracil nucleotides in RNA structures in yeast and offer a valuable tool for studying RNA structure and function in two widely used yeast model systems.

Evaluating YouTube videos on sialendoscopy as an educational resource for patients.

Objectives: Patients are increasingly relying on YouTube for health information. We objectively evaluated the quality and comprehensiveness of sialendoscopy YouTube videos available to patients. We further investigated the relationship between video content and video popularity. Methods: We identified 150 videos using the search term "sialendoscopy." Videos were excluded if they were lectures for medical professionals, operating room (OR) recordings, unrelated, non-English, or non-audio. Video quality and comprehensiveness were evaluated using modified DISCERN criterion (range: 5-25) and novel sialendoscopy criterion (NSC, range: 0-7), respectively. Secondary outcomes included standard video metrics and Video Power Index to measure popularity. Videos were classified binarily by uploader type as from an academic medical center or from other sources. Results: Twenty-two (14.7%) of 150 videos were included for review, with 7 (31.8%) uploaded from academic medical institutions. One hundred-nine (72.7%) videos were excluded as lectures for medical professionals or OR recordings. Overall mean modified DISCERN (13.45 ± 3.42) and NSC (3.05 ± 0.96) scores were low; however, videos uploaded by academic medical institutions were significantly more comprehensive (NSC mean difference = 0.98, 95% CI: 0.16-1.80, p = .02). There were no significant correlations between video popularity and objective measures of quality or comprehensiveness. Conclusions: This study highlights the paucity and low quality of sialendoscopy videos for patients. More popular videos are not higher quality, and most videos are targeted more toward physicians rather than patients. As YouTube becomes increasingly used by patients, there is opportunity for otolaryngologists to produce more informative videos for patients while implementing targeted strategies to increase viewership. Level of Evidence: NA.

Evaluating YouTube Videos on Facelift Surgery for Facial Rejuvenation as a Resource for Patients.

OBJECTIVES: This study evaluated the content and patient educational quality of YouTube videos on facelift surgery for facial rejuvenation. This study investigated the relationship between education quality compared to video content, video metrics, and popularity. METHODS: Two hundred videos were identified across 4 search terms: "facelift surgery," "facelift surgery what to expect," "facelift surgery patient education," and "what is facelift surgery." Unrelated videos, operating room recordings, medical professional lectures, non-English, non-audio, and testimonials were excluded from review. Video quality was assessed using the Global Quality Score (GQS) (range: 1-5), modified DISCERN score (range: 5-25), and JAMA Benchmark Criteria (range: 0-4). Secondary outcomes included upload source, video metrics (views, likes, dislikes, duration, days since upload, comments), and Video Power Indexto measure popularity. The first 10 comments on videos were characterized as positive, neutral, or negative. RESULTS: One hundred forty-three videos were excluded (43 did not meet criteria, 100 duplicates), and 57 videos were included. Fifty-five videos (96.5%) were uploaded by private medical practices. Overall video quality was poor across all 3 scoring systems: GQS (2.92 ± 1.14), modified DISCERN (13.03 ± 3.64), and JAMA Benchmark Criteria (1.78 ± 0.52). Popularity positively correlated with JAMA Benchmark Criteria (R = .49, P < .05) but did not correlate with other quality criteria. CONCLUSIONS: For patients undergoing facelift surgery, there are limited educational videos on YouTube with few videos detailing indications, alternatives, complications, and the postoperative course. YouTube is a growing resource for patient education and opportunities exist for medical institutions to produce higher-quality videos for prospective patients.

Nasopharyngectomy Without Maxillary Swing via a Combined Open Lateral and Endoscopic Approach.

Nasopharyngeal tumors in the proximity of the internal carotid artery are often difficult to dissect. Here, we describe a combined transcervical and endoscopic endonasal approach that provides improved internal carotid artery protection and confident tumor resection. Laryngoscope, 133:105-108, 2023.

Euglycemic diabetic ketoacidosis (EDKA) after pancreaticoduodenectomy: An under-recognized metabolic abnormality with outcome implications.

BACKGROUND: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy. METHODS: A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge. RESULTS: Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P < .05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P < .001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P < .05). CONCLUSION: This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner.

Recurrence of premalignant oral cavity and oropharynx lesions after pulsed diode laser treatment.

PURPOSE: Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser. MATERIALS AND METHODS: Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment. RESULTS: Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain. CONCLUSIONS: Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Risk Factors for 30-day and 90-day Readmission After Lumbar Decompression.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess readmission rates and risk factors for 30-day and 90-day readmission after elective lumbar decompression at a single institution. SUMMARY OF BACKGROUND DATA: Hospital readmission is an undesirable aspect of interventional treatment. Studies evaluating readmissions after elective lumbar decompression typically analyze national databases, and therefore have several drawbacks inherent to their macroscopic nature that limit their clinical utility. METHODS: Patients undergoing primary one- to four-level lumbar decompression surgery were retrospectively identified. Demographic, surgical, and readmission data within "30-days" (0-30 days) and "90-days" (31-90 days) postoperatively were extracted from electronic medical records. Patients were categorized into four groups: (1) no readmission, (2) readmission during the 30-day or 90-day postoperative period, (3) complication related to surgery, and (4) Emergency Department (ED)/Observational (OBs)/Urgent (UC) care. RESULTS: A total of 2635 patients were included. Seventy-six (2.9%) were readmitted at some point within the 30- (2.3%) or 90-day (0.3%) postoperative periods. Patients in the pooled readmitted group were older (63.1 yr, P  < 0.001), had a higher American Society of Anesthesiologists (ASA) grade (31.2% with ASA of 3, P = 0.03), and more often had liver disease (8.1%, P = 0.004) or rheumatoid arthritis (12.0%, P = 0.02) than other cohorts. A greater proportion of 90-day readmissions and complications had surgical-related diagnoses or a diagnosis of recurrent disc herniation than 30-day readmissions and complications (66.7% vs. 44.5%, P = 0.04 and 33.3% vs. 5.5%, P < 0.001, respectively). Age (Odds ratio [OR]: 1.02, P = 0.01), current smoking status (OR: 2.38, P < 0.001), longer length of stay (OR: 1.14, P < 0.001), and a history of renal failure (OR: 2.59, P = 0.03) were independently associated with readmission or complication. CONCLUSION: Increased age, current smoking status, hospital length of stay, and a history of renal failure were found to be significant independent predictors of inpatient readmission or complication after lumbar decompression.

Evaluating YouTube Videos on Hypoglossal Nerve Stimulation as a Resource for Patients.

OBJECTIVES/HYPOTHESIS: This study evaluated the quality and comprehensiveness of YouTube videos on hypoglossal nerve stimulation (HNS) for patients. This study also investigated the relationship between video content, video metrics, and popularity. STUDY DESIGN: Cross-sectional study. METHODS: We identified 150 videos using three search terms: "inspire sleep apnea," "hypoglossal nerve stimulation," and "upper airway stimulation." Videos that were unrelated to the use of HNS for obstructive sleep apnea in adults, operating room recordings, lectures for medical professionals, non-English, or non-audio were excluded. Video quality and comprehensiveness were assessed using modified DISCERN criterion (range: 5-25) and novel content criterion (range: 0-12), respectively. Secondary outcomes included video metrics (views, likes, dislikes, comments, and days since upload) and Video Power Index to measure popularity. Outcomes were stratified by video uploader source (medical institutions, medical companies, individual users, other). RESULTS: Users searched YouTube for "inspire sleep apnea" 2.48 times more in 2020 than in 2018. We identified 67 videos for review, with the majority coming from medical institutions (70.2%). Overall, the average-modified DISCERN (13.65 ± 4.88) and novel content (3.87 ± 2.09) scores were low and did not differ between medical institutions or other uploader sources. Higher quality and more comprehensive video content did not correlate with popularity. CONCLUSION: Overall quality and comprehensiveness of information of HNS YouTube videos was low. Given the high demand for information on HNS, there is opportunity for medical institutions to implement new strategies to improve both video content and visibility to patients. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2827-E2832, 2021.

Small, low-grade ampullary neuroendocrine tumor presenting with metastasis and multiple synchronous tumors in a patient with neurofibromatosis type 1: a case report with literature review.

Neurofibromatosis type 1 (NF1) is a tumor syndrome and one of the most common genetic disorders. Patients have an increased risk of developing neurologic and gastrointestinal (GI) neoplasms, but GI lesions are often underrecognized since most cases are asymptomatic. It is extremely rare to see multiple types of abdominal tumors synchronously in NF1. In this case, we describe a patient presenting with a small, low-grade periampullary neuroendocrine tumor (NET) that underwent endoscopic submucosal dissection and later pancreaticoduodenectomy (Whipple procedure). This led to findings of lymph node and distant metastasis of her NET, and the incidental discovery of gastrointestinal stromal tumors, extensive pancreatic intraepithelial neoplasia, and main duct and side branch intraductal pancreatic mucinous neoplasm. The synchronous presence of these lesions has not been reported in the literature.

Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFß/SMAD2 axis in vitro.

BACKGROUND: The human Obg-like ATPase 1 (OLA1) protein has been reported to play an important role in cancer cell proliferation. The molecular mechanism underlying OLA1 regulated oral metastasis is still unknown. We investigated in this study the regulatory role of OLA1 playing in oral squamous cell metastasis. RESULTS: A series of in vitro assays were performed in the cells with RNAi-mediated knockdown or overexpression to expound the regulatory function of OLA1 in oral cancer. We found that the endogenous level of OLA1 in a highly metastatic oral squamous cell line was significantly lower than that in low metastatic oral cells as well as in normal oral cells. Escalated expression of OLA1 resulted in a reduced ability of metastasis in highly metastatic cells, and enhanced its sensitivity to the paclitaxel treatment. Further analysis of the EMT markers showed that Snail, Slug, N-cadherin were up-expressed significantly. Meanwhile, E-cadherin was significantly down-regulated in the oral cancer cells with OLA1-knocked down, suggesting that OLA1 inactivated EMT process. Furthermore, we found that OLA1 suppressed oral squamous cell metastasis by suppressing the activity of a TGFß/SMAD2/EMT pathway. CONCLUSION: Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.

Augmented reality experimentation on oxygen gas generation from hydrogen peroxide and bleach reaction.

The appreciation and understanding of gas generation through processes is vital in biochemical education. In this work, an augmented reality tool is reported to depict the redox reaction between hydrogen peroxide and sodium hypochlorite solutions, two ubiquitous oxidizing agents, to create oxygen, a combustible gas. As it operates out of smartphones or tablets, students are able to conduct the exercise collaboratively, respond in a manner similar to an actual physical experiment, and able to depict the oxygen volume changes in relation to the volume of hydrogen peroxide of different concentrations used. The tool offers to help students acquire bench skills by limiting handing risks and to mitigate possible student anxiety on handling chemical materials and implements in the laboratory. The feedback received from Year 11 and 12 high school student participants in an outreach exercise indicate the overall effectiveness of this tool. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):245-252, 2018.

Advance in microRNA as a potential biomarker for early detection of pancreatic cancer.

Pancreatic cancer is characterized as a disease with low survival and high mortality because of no effective diagnostic and therapeutic strategies available in clinic. Conventional clinical diagnostic methods including serum markers and radiological imaging (CT, MRI, EUS, etc.) often fail to detect precancerous or early stage lesions. Development of effective biomarkers is unmet for reduction of mortality of pancreatic cancer. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs playing roles in regulation of cell physiology including tumorigenesis, apoptotic escape, proliferation, invasion, epithelial-mesenchymal transition (EMT), metastasis and chemoresistance. Various altered signaling pathways involving in molecular pathogenesis of pancreatic cancer are mediated by miRNAs as a role of either oncogenes or tumor suppressors. Among biomarkers developed including protein, metabolites, DNA, RNA, epigenetic mutation, miRNAs are superior because of its unique chemical property. Recent study suggests that miRNAs may be promising biomarkers used for early detection of pancreatic cancer. This review will update the progression made in early detection of pancreatic cancer.

Recurrent Primary Cardiac Sarcoma Managed With Radical Cardiac Resection and Pneumonectomy.

Primary cardiac tumors are extremely rare. Although complete surgical resection of malignant primary cardiac tumors results in an improved survival compared with no intervention, the overall prognosis is generally poor, with treatable recurrent primary cardiac sarcomas being extremely rare. We report a patient with a recurrent primary cardiac sarcoma obstructing the left atrium managed with radical cardiac resection, including right pneumonectomy, with 21-month postprocedural survival.