Accuracy of natural language processors for patients seeking inguinal hernia information.

BACKGROUND: NLPs such as ChatGPT are novel sources of online healthcare information that are readily accessible and integrated into internet search tools. The accuracy of NLP-generated responses to health information questions is unknown. METHODS: We queried four NLPs (ChatGPT 3.5 and 4, Bard, and Claude 2.0) for responses to simulated patient questions about inguinal hernias and their management. Responses were graded on a Likert scale (1 poor to 5 excellent) for relevance, completeness, and accuracy. Responses were compiled and scored collectively for readability using the Flesch-Kincaid score and for educational quality using the DISCERN instrument, a validated tool for evaluating patient information materials. Responses were also compared to two gold-standard educational materials provided by SAGES and the ACS. Evaluations were performed by six hernia surgeons. RESULTS: The average NLP response scores for relevance, completeness, and accuracy were 4.76 (95% CI 4.70-4.80), 4.11 (95% CI 4.02-4.20), and 4.14 (95% CI 4.03-4.24), respectively. ChatGPT4 received higher accuracy scores (mean 4.43 [95% CI 4.37-4.50]) than Bard (mean 4.06 [95% CI 3.88-4.26]) and Claude 2.0 (mean 3.85 [95% CI 3.63-4.08]). The ACS document received the best scores for reading ease (55.2) and grade level (9.2); however, none of the documents achieved the readibility thresholds recommended by the American Medical Association. The ACS document also received the highest DISCERN score of 63.5 (57.0-70.1), and this was significantly higher compared to ChatGPT 4 (50.8 [95% CI 46.2-55.4]) and Claude 2.0 (48 [95% CI 41.6-54.4]). CONCLUSIONS: The evaluated NLPs provided relevant responses of reasonable accuracy to questions about inguinal hernia. Compiled NLP responses received relatively low readability and DISCERN scores, although results may improve as NLPs evolve or with adjustments in question wording. As surgical patients expand their use of NLPs for healthcare information, surgeons should be aware of the benefits and limitations of NLPs as patient education tools.

The association between gender and industry payments to minimally invasive surgeons.

BACKGROUND: It is unknown if there are differential industry payments to surgeons based on gender. This study aims to examine differences by gender for industry relations with minimally invasive surgeons, using speakers at the SAGES Annual Meeting as a proxy for key thought leaders in minimally invasive surgery. METHODS: We queried the Open Payments Database for payments made to US speakers from the 2023 SAGES meeting. All payments from the prior fiscal year prior were collected. The National Provider Identity (NPI) Registry was cross-referenced to determine surgeon's self-reported gender. Industry sponsors were analyzed based on differences in payments made. RESULTS: A total of 305 speakers were assessed, with 175 (57.4%) males and 130 (42.6%) females. Of the 305 speakers, 246 were listed in the OPD. There were 145/175 (82.8%) males who were received general payments, compared to 101/130 (77.6%) females (p = 0.326). The total amount of industry payments was $2,894,287 for males and $1,539,481 for females. Median payments were 2.8X higher for males ($4657, IQR $422-$15,798) than females ($1651, IQR $299-$9005) (p = 0.05). CONCLUSIONS: Despite efforts to decrease gender bias in surgery, there remains a significant and substantial difference in payments towards male and female surgeons via industry relationships. This has potential downstream effects on career development, consulting and research opportunities, and development of new devices.

A genome-wide meta-analysis of palmoplantar pustulosis implicates TH2 responses and cigarette smoking in disease pathogenesis.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. OBJECTIVES: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. METHODS: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. RESULTS: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 × 10-6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. CONCLUSIONS: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking.

Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.

Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>109) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is open to >80% but, when S4s are deactivated, the gate is open <10-9 of the time. Using noise analysis, we show that the coupling between S4 and the gate is <200 in HCN channels. In addition, using voltage clamp fluorometry, locking the gate open in a Kv channel drastically altered the energetics of S4 movement. In contrast, locking the gate open or decreasing the coupling between S4 and the gate in HCN channels had only minor effects on the energetics of S4 movement, consistent with a weak coupling between S4 and the gate. We propose that this loose coupling is a prerequisite for the reversed voltage gating in HCN channels.

The posterolateral ligament of the elbow: anatomy and clinical relevance.

BACKGROUND: The posterolateral capsule was recognized in the past as an important structure for elbow stability but was later disregarded. Two recent biomechanical studies demonstrated its role in preventing posterolateral instability, and thus it should be identified as a distinct ligament: the posterolateral ligament (PLL). This study includes 2 parts: an anatomic study of the PLL's footprint and a collection of 5 cases of pathologic lesions of the PLL. METHODS: Six cadaveric upper limbs were assessed. The attachments of the PLL were dissected, the footprints were marked and photographed, and the 2-dimensional area and length were measured. RESULTS: The mean proximal attachment dimensions were a length of 13 mm and an area of 101 mm2, and the mean distal attachment dimensions were 19 mm and 111 mm2, respectively. There were 2 cases of posterolateral elbow pain in professional cricket bowlers, diagnosed radiographically as enthesopathy of the PLL's proximal attachment on the posterior capitellum, probably due to repeated forced hyperextension of the elbow. Both patients were treated by débridement of the posterior capitellum and reattachment of the PLL, with complete resolution of symptoms. In addition, there were 3 cases of clinical posterolateral rotatory instability in young patients. Two athletes had an isolated acute tear of the PLL, and on physical examination, both had positive posterior draw test results but negative pivot-shift test results. Both underwent elbow arthroscopy and repair of the PLL with resolution of symptoms. The third patient had long-standing recurrent elbow instability, following a failed lateral ulnar collateral ligament reconstruction, in the presence of an Osborne-Cotterill lesion. He underwent revision lateral ulnar collateral ligament reconstruction, bone grafting of the bony lesion, and reattachment of the PLL, with complete resolution of symptomatic posterolateral rotatory instability. CONCLUSIONS: The PLL of the elbow has a significant role in the elbow's posterolateral stability. Its footprints were described, and its clinical significance was demonstrated in cases of elbow instability caused by acute ligament tears and elbow pain due to ligament enthesopathy. Surgeons should be aware of this structure and potential pathology related to its injury.

Operative vs Nonoperative Management of Acute Cholecystitis During the Different Trimesters of Pregnancy.

Importance: Acute cholecystitis (AC) management during pregnancy requires balancing the risk of pregnancy loss or preterm delivery (adverse pregnancy outcomes [APOs]) with or without surgery. Guidelines recommend cholecystectomy across trimesters; however, trimester-specific evidence on the risks of AC and its management is lacking. Objective: To assess cholecystectomy frequency in pregnant people with AC, compare the rates of APOs in pregnant people with or without AC, and compare the rates of APOs in people with AC who did or did not undergo cholecystectomy. Design, Setting, and Participants: This retrospective, population-based cohort study used data for pregnant people with AC from the IBM MarketScan Commercial Claims and Encounters Database from January 1, 2007, to December 31, 2019, and a propensity score-matched cohort of pregnant people without AC. Trimester status (first [T1], second [T2], and third [T3]), APOs, and cholecystectomy were defined by administrative claims. Data were analyzed from October 2021 to July 2022. Exposures: Pregnant patients with or without AC. Pregnant patients with AC who did or did not receive cholecystectomy. Main Outcomes and Measures: The main outcomes were cholecystectomy during pregnancy and APOs (ie, preterm delivery and pregnancy loss). Pregnant patients with and without AC were compared to assess the association of AC with risk of APOs. Propensity score inverse-probability weighting was used to calculate treatment-associated APO risk among patients with 1-year follow-up. Results: The study included 5759 pregnant patients with AC (mean [SD] age, 30.1 [6.6] years) and 23 036 controls (mean [SD] age, 29.9 [6.7] years) after propensity score matching. Among 3426 pregnant patients with AC and 1-year follow-up, 1182 (34.5%) underwent cholecystectomy during the pregnancy (684 [41.7%] presenting with AC in T1, 404 [40.4%] in T2, and 94 [12.0%] in T3). Acute cholecystitis during pregnancy, irrespective of treatment, was associated with higher odds of APO compared with no AC during pregnancy across all trimesters (odds ratio [OR], 1.69 [95% CI, 1.54-1.85]). Compared with nonoperative management, receipt of surgery was associated with lower odds of APOs across all trimesters (OR, 0.75 [95% CI, 0.63-0.87]), in T1 (OR, 0.81 [95% CI, 0.66-1.00]), in T2 (OR, 0.71 [95% CI, 0.50-1.00]), and in T3 (OR, 0.45 [95% CI, 0.28-0.70]). Conclusions and Relevance: In this study, cholecystectomy was associated with lower risk of APO in patients with AC across all trimesters, with the greatest benefit in T3. However, only 34.5% overall and 12.0% of patients in T3 had a cholecystectomy. These findings support guidelines recommending cholecystectomy during pregnancy and should inform decision-making discussions. Greater guideline adherence and surgery use, especially in T3, may represent an opportunity to improve outcomes for pregnant people with AC.

Laparoscopic Heller myotomy with Toupet fundoplication: revisiting GERD in treated achalasia.

INTRODUCTION: With the advent of the laparoscopic era in the 1990s, laparoscopic Heller myotomy replaced pneumatic dilation as the first-line treatment for achalasia. An advantage of this approach was the addition of a fundoplication to reduce gastroesophageal reflux disease (GERD). More recently, Peroral Endoscopic Myotomy has competed for first-line therapy, but the postoperative GERD may be a weakness. This study leverages our experience to characterize GERD following LHM with Toupet fundoplication (LHM+T ) so that other treatments can be appropriately compared. METHODS: A single-institution retrospective review of adult patients with achalasia who underwent LHM+T from January 2012 to April 2022 was performed. We obtained routine 6-month postoperative pH studies and patient symptom questionnaires. Differences in questionnaires and reflux symptoms in relation to pH study were explored via Kruskal-Wallis test or chi-square tests. RESULTS: Of 170 patients who underwent LHM+T , 51 (30%) had postoperative pH testing and clinical symptoms evaluation. Eleven (22%) had an abnormal pH study; however, upon manual review, 5 of these (45.5%) demonstrated low-frequency, long-duration reflux events, suggesting poor esophageal clearance of gastric refluxate and 6/11 (54.5%) had typical reflux episodes. Of the cohort, 7 (15.6%) patients reported GERD symptoms. The median [IQR] severity was 1/10 [0, 3] and median [IQR] frequency was 0.5/4 [0, 1]. Patients with abnormal pH reported more GERD symptoms than patients with a normal pH study (3/6, 50% vs 5/39, 12.8%, p = 0.033). Those with a poor esophageal clearance pattern (n = 5) reported no concurrent GERD symptoms. CONCLUSION: The incidence of GERD burden after LHM+T is relatively low; however, the nuances relevant to accurate diagnosis in treated achalasia patients must be considered. Symptom correlation to abnormal pH study is unreliable making objective postoperative testing important. Furthermore, manual review of abnormal pH studies is necessary to distinguish GERD from poor esophageal clearance.

Comparing P53 expression and genome-wide transcriptome profiling to Comet assay in lymphocytes from melanoma patients and healthy controls.

This study compared the expression of TP53 in lymphocytes from malignant melanoma (MM) patients with positive sentinel nodes to healthy controls (HCs) following exposure to various doses of UVA radiation. The Lymphocyte Genome Sensitivity (LGS) assay indicated significant differences in DNA damage in lymphocytes between MM patients and HCs. qPCR data demonstrated an overall 3.4-fold increase in TP53 expression in lymphocytes from MM patients compared to healthy controls, following treatment with 0.5 mW/cm2 UVA radiation. Western blotting confirmed that p53 expression was increased in MM lymphocytes following UVA exposure compared to healthy individuals. Genome transcriptome profiling data displayed differences in gene expression between UVA-treated lymphocytes from MM patients and HCs. Peripheral lymphocytes from MM patients are more susceptible to the genotoxic effects of UVA compared to healthy individuals. Our previous studies showed that UVA exposure of various intensities caused significant differences in the levels of DNA damage between lymphocytes from cancer patients compared to HCs through the LGS assay. The present study's results provide further credibility to the LGS assay as a screening test for cancer detection. Peripheral lymphocytes could be a promising blood biopsy biomarker for staging of carcinomas and prevention of carcinoma progression at early stages.

Application of the acquisition of data for outcomes and procedure transfer (ADOPT) method to a hands-on course for teaching extended-view totally extraperitoneal (eTEP) hernia repair to practicing surgeons.

BACKGROUND: After completion of training, practicing surgeons rely on hands-on courses to expand their procedure armamentarium and improve their surgical technique. However, such courses vary in standardized teaching methods. SAGES developed the Acquisition of Data for Outcomes and Procedure Transfer (ADOPT) program as a method of longitudinal instruction utilizing standardized teaching techniques, mentorship, and webinars to cover additional techniques. This study examines the adoption of learned techniques and participant confidence before and after an ADOPT course focused on extended-view totally extraperitoneal (eTEP) hernia repair. METHODS: A hands-on course focused on eTEP hernia repair was conducted with enrollment capped at 10 participants. Pre-course and post-course surveys at 3, 6, and 12 months determined implementation of the learned procedure, case volume, and confidence with eTEP skills. A 5-point Likert scale (1 = not confident at all to 5 = completely confident) assessed confidence levels. Survey responses were summarized using descriptive statistics. RESULTS: Of the 10 participants, 10 (100%) completed the pre-course survey, and 7 (70%) completed at least one post-course survey. Median age was 48.5 years (36,56) with a median of 16 years (2,23) in practice, mostly in the community setting (70%). After the course, 50% had performed an eTEP procedure, and 100% reported considering this technique during surgical planning. Participants reported higher confidence in eTEP-specific skills at three months post-course from pre-course levels. The highest change in confidence was seen for the following skills: accessing the retromuscular/extraperitoneal space for ventral hernia and recognizing when the linea alba has been violated, p < 0.05. CONCLUSION: This study shows that rapid incorporation of learned techniques can be achieved through the ADOPT format. Furthermore, through longitudinal mentorship and a structured hands-on course, the ADOPT course supports practicing surgeons to attain autonomy and confidence even when teaching a relatively technically challenging procedure, such as eTEP.

Chronic alcohol exposure alters action control via hyperactive premotor corticostriatal activity.

Alcohol use disorder (AUD) alters decision-making control over actions, but disruptions to the responsible neural circuit mechanisms are unclear. Premotor corticostriatal circuits are implicated in balancing goal-directed and habitual control over actions and show disruption in disorders with compulsive, inflexible behaviors, including AUD. However, whether there is a causal link between disrupted premotor activity and altered action control is unknown. Here, we find that mice chronically exposed to alcohol (chronic intermittent ethanol [CIE]) showed impaired ability to use recent action information to guide subsequent actions. Prior CIE exposure resulted in aberrant increases in the calcium activity of premotor cortex (M2) neurons that project to the dorsal medial striatum (M2-DMS) during action control. Chemogenetic reduction of this CIE-induced hyperactivity in M2-DMS neurons rescued goal-directed action control. This suggests a direct, causal relationship between chronic alcohol disruption to premotor circuits and decision-making strategy and provides mechanistic support for targeting activity of human premotor regions as a potential treatment in AUD.

Esophageal Motility Patterns in Paraesophageal Hernia Patients Compared to Sliding Hiatal Hernia: Bigger Is Not Better.

BACKGROUND: In patients with paraesophageal hernias (PEH), the course of the esophagus is often altered, which may affect esophageal motility. High-resolution manometry (HRM) is frequently used to evaluate esophageal motor function prior to PEH repair. This study was performed to characterize esophageal motility disorders in patients with PEH as compared to sliding hiatal hernia and to determine how these findings affect operative decision-making. METHODS: Patients referred for HRM to a single institution from 2015 to 2019 were included in a prospectively maintained database. HRM studies were analyzed for the appearance of any esophageal motility disorder using the Chicago classification. PEH patients had confirmation of their diagnosis at the time of surgery, and the type of fundoplication performed was recorded. They were case-matched based on sex, age, and BMI to patients with sliding hiatal hernia who were referred for HRM in the same period. RESULTS: There were 306 patients diagnosed with a PEH who underwent repair. When compared to case-matched sliding hiatal hernia patients, PEH patients had higher rates of ineffective esophageal motility (IEM) (p<.001) and lower rates of absent peristalsis (p=.048). Of those with ineffective motility (n=70), 41 (59%) had a partial or no fundoplication performed during PEH repair. CONCLUSION: PEH patients had higher rates of IEM compared to controls, possibly due to a chronically distorted esophageal lumen. Offering the appropriate operation hinges on understanding the involved anatomy and esophageal function of each individual. HRM is important to obtain preoperatively for optimizing patient and procedure selection in PEH repair.

The environmental impact of surgical telemedicine: life cycle assessment of virtual vs. in-person preoperative evaluations for benign foregut disease.

BACKGROUND: Health care accounts for almost 10% of the United States' greenhouse gas emissions, accounting for a loss of 470,000 disability-adjusted life years based on the health effects of climate change. Telemedicine has the potential to decrease health care's carbon footprint by reducing patient travel and clinic-related emissions. At our institution, telemedicine visits for evaluation of benign foregut disease were implemented for patient care during the COVID-19 pandemic. We aimed to estimate the environmental impact of telemedicine usage for these clinic encounters. METHODS: We used life cycle assessment (LCA) to compare greenhouse gas (GHG) emissions for an in-person and a telemedicine visit. For in-person visits, travel distances to clinic were retrospectively assessed from 2020 visits as a representative sample, and prospective data were gathered on materials and processes related to in-person clinic visits. Prospective data on the length of telemedicine encounters were collected and environmental impact was calculated for equipment and internet usage. Upper and lower bounds scenarios for emissions were generated for each type of visit. RESULTS: For in-person visits, 145 patient travel distances were recorded with a median [IQR] distance travel distance of 29.5 [13.7, 85.1] miles resulting in 38.22-39.61 carbon dioxide equivalents (kgCO2-eq) emitted. For telemedicine visits, the mean (SD) visit time was 40.6 (17.1) min. Telemedicine GHG emissions ranged from 2.26 to 2.99 kgCO2-eq depending on the device used. An in-person visit resulted in 25 times more GHG emissions compared to a telemedicine visit (p < 0.001). CONCLUSION: Telemedicine has the potential to decrease health care's carbon footprint. Policy changes to facilitate telemedicine use are needed, as well as increased awareness of potential disparities of and barriers to telemedicine use. Moving toward telemedicine preoperative evaluations in appropriate surgical populations is a purposeful step toward actively addressing our role in health care's large carbon footprint.

Mapping of glutamate metabolism using 1H FID-MRSI after oral administration of [1-13C]Glc at 9.4 T.

Glutamate is the major excitatory transmitter in the brain and malfunction of the related metabolism is associated with various neurological diseases and disorders. The observation of labeling changes in the spectra after the administration of a 13C labelled tracer is a common tool to gain better insights into the function of the metabolic system. But so far, only a very few studies presenting the labeling effects in more than two voxels to show the spatial dependence of metabolism. In the present work, the labeling effects were measured in a transversal plane in the human brain using ultra-short TE and TR 1H FID-MRSI. The measurement set-up was most simple: The [1-13C]Glc was administered orally instead of intravenous and the spectra were measured with a pure 1H technique without the need of a 13C channel (as Boumezbeur et al. demonstrated in 2004). Thus, metabolic maps and enrichment curves could be obtained for more metabolites and in more voxels than ever before in human brain. Labeling changes could be observed in [4-13C]glutamate, [3-13C]glutamate+glutamine, [2-13C]glutamate+glutamine, [4-13C]glutamine, and [3-13C]aspartate with a high temporal (3.6 min) and spatial resolution (32 × 32 grid with nominal voxel size of 0.33 µL) in five volunteers.

Predicting Wrist Posture during Occupational Tasks Using Inertial Sensors and Convolutional Neural Networks.

Current methods for ergonomic assessment often use video-analysis to estimate wrist postures during occupational tasks. Wearable sensing and machine learning have the potential to automate this tedious task, and in doing so greatly extend the amount of data available to clinicians and researchers. A method of predicting wrist posture from inertial measurement units placed on the wrist and hand via a deep convolutional neural network has been developed. This study has quantified the accuracy and reliability of the postures predicted by this system relative to the gold standard of optoelectronic motion capture. Ten participants performed 3 different simulated occupational tasks on 2 occasions while wearing inertial measurement units on the hand and wrist. Data from the occupational task recordings were used to train a convolutional neural network classifier to estimate wrist posture in flexion/extension, and radial/ulnar deviation. The model was trained and tested in a leave-one-out cross validation format. Agreement between the proposed system and optoelectronic motion capture was 65% with κ = 0.41 in flexion/extension and 60% with κ = 0.48 in radial/ulnar deviation. The proposed system can predict wrist posture in flexion/extension and radial/ulnar deviation with accuracy and reliability congruent with published values for human estimators. This system can estimate wrist posture during occupational tasks in a small fraction of the time it takes a human to perform the same task. This offers opportunity to expand the capabilities of practitioners by eliminating the tedium of manual postural assessment.

Practice Patterns and Outcomes of Patients With Retained Gastric Food Content Encountered During Endoscopy.

INTRODUCTION: Retained gastric food content encountered during upper endoscopy may reduce diagnostic accuracy and increase the risk of aspiration. The aim of this study was to evaluate endoscopists' practice patterns and clinical outcomes in patients with retained gastric food content encountered during endoscopy. METHODS: Consecutive patients with retained gastric food content during first-time endoscopy at Loma Linda University Health (January 2016-March 2021) were identified. Primary endpoints were a complete examination (deep duodenal intubation) and 30-day postprocedural respiratory adverse events. RESULTS: Of 17,868 patients undergoing endoscopy, 629 (3.5%) (mean age 55 ± 17 years) met inclusion criteria. Moderate sedation was performed in 506 (80.4%), anesthesiologist-assisted sedation in 16 (2.5%), and general anesthesia in 107 (17.0%) patients. 534 (84.9%) patients received a complete examination, and endoscopist-specific completion rates varied by quintile among 26 endoscopists (range 70.3%-98.0%, P < 0.0001). Large food gastric content decreased (adjusted odds ratio [aOR] 0.3, 95% confidence interval [CI] 0.2-0.4) while obtaining mucosal biopsies increased (aOR 2.5, 95% CI 1.4-4.7) the likelihood of complete examination after adjusting for endoscopist-specific completion rates. Subsequently, 58 (9.2%) patients required repeat endoscopy within 30 days. During follow-up, 41 (6.5%) patients developed respiratory adverse events including 21 (3.3%) requiring ventilatory support. Hospitalized patients (aOR 37.8, 95% CI 4.9-289.0) compared with outpatients and large compared with small gastric food content (aOR 2.1, 95% CI 1.1-4.2) increased the likelihood of respiratory adverse events. DISCUSSION: Although deep duodenal intubation was achieved in most patients receiving endoscopy, the rate of complete examination varied among individual endoscopists and the extent of food burden. Respiratory adverse events occurred almost exclusively in hospitalized patients and were associated with high morbidity including half developing respiratory failure.

Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 µg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

Detecting subject-specific fatigue-related changes in lifting kinematics using a machine learning approach.

Individual responses to fatigue have been observed in lifting kinematics, suggesting a subject-specific approach is necessary for fatigue identification. One-class support vector machines (OCSVM) may provide an objective method to classify fatigue-related kinematic changes during repetitive lifting. Participants completed a repetitive lifting protocol while motion capture recorded lifting motions. Subject-specific kinematics from participants' first 35% of lifts trained OCSVM decision boundaries. The remaining lifts were separated into test sets and classified against the decision boundary to identify the percentage of outlier lifts within each test set. Spearman's correlation assessed if the test sets' percentage of outlier lifts increased concurrently with participants' rating of perceived exertion (RPE). Significant positive associations were found for participants who demonstrated evidence of fatigue, while no significant associations were found for participants who did not demonstrate evidence of fatigue. These results demonstrate the prospective efficacy of an outlier detection tool for fatigue detection during repetitive lifting.Practitioner Summary: An objective subject-specific fatigue detection method is desired for workplace tasks, such as lifting. An outlier detection machine learning approach was identified when lifting movement patterns changed from baseline throughout a repetitive lifting protocol. Participants who demonstrated an increase in outlier movement patterns had a concurrent increase in self-reported fatigue.

Type II hiatal hernias: do they exist or are they actually parahiatal hernias?

BACKGROUND: Type II hiatal hernias (HH) are characterized by a portion of the gastric fundus located above the esophageal hiatus adjacent to the esophagus while the gastroesophageal junction (GEJ) remains fixed below the esophageal hiatus. This type of HH has been called the "true" paraesophageal hernia (PEH) because the fundus appears to the side of the esophagus. In our experience, Type II HHs are occasionally identified on radiographic testing, however they are rarely, if ever, confirmed intraoperatively. This led to our question: Does Type II HH exist? METHODS: We searched for evidence of type II HH in three locations: 1. Retrospective review of all first-time PEH repairs (excluding Type I HHs and re-operative cases) performed at the University of Washington Medical Center from 1994 to 2021; 2. Operative videos available on YouTube and WebSurg websites; and 3. Abstracts from the SAGES annual meetings from 2005 to 2021. RESULTS: We found no evidence of Type II HH in any of our three searches. We performed 846 PEH repairs: 760 Type III, 75 Type IV, and 11 parahiatal. Upon website video review, we found only one possible type II hernia, though it too was likely a para-hiatal hernia. No video or case presentations of a type II HH were identified within SAGES annual meeting abstracts. CONCLUSION: Type II HHs do not exist as they are currently defined. Although uncommon, parahiatal hernia can easily be misinterpreted as Type II HH. We should consider changing the hiatal hernia classification system to prevent ongoing clinical confusion.

Test-retest reproducibility of human brain multi-slice 1 H FID-MRSI data at 9.4T after optimization of lipid regularization, macromolecular model, and spline baseline stiffness.

PURPOSE: This study analyzes the effects of retrospective lipid suppression, a simulated macromolecular prior knowledge and different spline baseline stiffness values on 9.4T multi-slice proton FID-MRSI data spanning the whole cerebrum of human brain and the reproducibility of respective metabolite ratio to total creatine (/tCr) maps for 10 brain metabolites. METHODS: Measurements were performed twice on 5 volunteers using a short TR and TE FID MRSI 2D sequence at 9.4T. The effects of retrospective lipid L2-regularization, macromolecular spectrum and different LCModel baseline flexibilities on SNR, FWHM, fitting residual, Cramér-Rao lower bound, and metabolite ratio maps were investigated. Intra-subject, inter-session coefficient of variation and the test-retest reproducibility of the mean metabolite ratios (/tCr) of each slice was calculated. RESULTS: Transversal, sagittal, and coronal slices of many metabolite ratio maps correspond to the anatomically expected concentration relations in gray and white matter for the majority of the cerebrum when using a flexible baseline in LCModel fit. Results from the second measurements of the same subjects show that slice positioning and data quality correlate significantly to the first measurement. L2-regularization provided effective suppression of lipid-artifacts, but should be avoided if no artifacts are detected. CONCLUSION: Reproducible concentration ratio maps (/tCr) for 4 metabolites (total choline, N-acetylaspartate, glutamate, and myoinositol) spanning the majority of the cerebrum and 6 metabolites (N-acetylaspartylglutamate, γ-aminobutyric acid, glutathione, taurine, glutamine, and aspartate) covering 32 mm in the upper part of the brain were acquired at 9.4T using multi-slice FID MRSI with retrospective lipid suppression, a macromolecular spectrum and a flexible LCModel baseline.