Design, synthesis, and anti-cancer evaluation of C-14 arylcarbamate derivatives of andrographolide.

In this study, we explored a concise and mild synthetic route to produce novel C-14 arylcarbamate derivatives of andrographolide, a known anti-inflammatory and anticancer natural product. Upon assessing their anti-cancer efficacy against pancreatic ductal adenocarcinoma (PDAC) cells, some derivatives showed stronger cytotoxicity against PANC-1 cells than andrographolide. In addition, we demonstrated one derivative, compound 3m, effectively reduced the expression of oncogenic p53 mutant proteins (p53R273H and p53R248W), proliferation, and migration in PDAC lines, PANC-1 and MIA PaCa-2. Accordingly, the novel derivative holds promise as an anti-cancer agent against pancreatic cancer. In summary, our study broadens the derivative library of andrographolide and develops an arylcarbamate derivative of andrographolide with promising anticancer activity against PDAC.

[Applying Team Resource Management to Reduce the Urinary Catheter Usage Rate in Our Intensive Care Unit].

BACKGROUND & PROBLEMS: According to the literature, 74%-84% of patients in adult critical care units have an indwelling catheter. The majority of medical and healthcare infections are urinary tract infections, which are related to urinary catheter usage. Furthermore, critical infections may cause bacteremia, which increases the risk of mortality. Prior to this project, over three-quarters (78.7%) of patients in our unit used a urinary catheter, which is a rate that is higher than all other intensive care units of our hospital's internal medicine department. Due to Foley placement, removal and care of catheters requires collaboration of teamwork. Thus, the concept of team resource management may be applied to improve the situation. PURPOSE: The aim of this study was to reduce the urinary catheter usage rate in our intensive care unit to less than 69.3%. RESOLUTIONS: This project summarized the reasons for the high catheter usage rate in this unit on 2017/1/3 and implemented several approaches to improve the situation from 2017/2/1 to 2017/6/30. These approaches included affixing reminder labels to indwelling catheters, using an ultrasound bladder scanner as a substitute for intermittent catheterization, evaluating indwelling catheters, establishing flow planning for post-catheter removal, holding cross-team meetings, and adopting a reward system. During the improvement period, we held collaborative conference meetings weekly to discuss solutions, evaluate end-of-the-month progress, and set reward policies. RESULTS: We lowered the average urinary catheter usage rate from 78.7% on 2017/3/1 to 57.8% on 2017/6/30, achieving a 26.5% reduction in catheter usage. CONCLUSIONS: This project both effectively reduced the unnecessary use of urinary catheters and significantly strengthened team spirit in our unit, thus improving the quality of medical care provided.

Early Developmental Exposure to General Anesthetic Agents in Primary Neuron Culture Disrupts Synapse Formation via Actions on the mTOR Pathway.

Human epidemiologic studies and laboratory investigations in animal models suggest that exposure to general anesthetic agents (GAs) have harmful effects on brain development. The mechanism underlying this putative iatrogenic condition is not clear and there are currently no accepted strategies for prophylaxis or treatment. Recent evidence suggests that anesthetics might cause persistent deficits in synaptogenesis by disrupting key events in neurodevelopment. Using an in vitro model consisting of dissociated primary cultured mouse neurons, we demonstrate abnormal pre- and post-synaptic marker expression after a clinically-relevant isoflurane anesthesia exposure is conducted during neuron development. We find that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway can reverse the observed changes. Isoflurane exposure increases expression of phospho-S6, a marker of mTOR pathway activity, in a concentration-dependent fashion and this effect occurs throughout neuronal development. The mTOR 1 complex (mTORC1) and the mTOR 2 complex (mTORC2) branches of the pathway are both activated by isoflurane exposure and this is reversible with branch-specific inhibitors. Upregulation of mTOR is also seen with sevoflurane and propofol exposure, suggesting that this mechanism of developmental anesthetic neurotoxicity may occur with all the commonly used GAs in pediatric practice. We conclude that GAs disrupt the development of neurons during development by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.

Traumatic Triceps and Medial Ulnar Collateral Ligament Rupture in an Adolescent Mogul Skier: A Case Report.

Triceps tendon ruptures are uncommon injuries that account for less than 1% of all upper extremity tendon injuries. Medial ulnar collateral ligament injury (mUCL), while common in overhead athletes as a result of valgus forces during the throwing mechanics, has scarcely been reported in non-overhead, throwing individuals. Traumatic assault to the elbow may result in the rupture of the triceps tendon with concomitant mUCL injury. As such an injury pattern typically presents in middle-aged males, weightlifters, or American football players from eccentric overloading of the elbow. We present an adolescent, elite-level, competitive skier with traumatic onset distal triceps rupture with concomitant medial ulnar collateral ligament rupture suffered via a fall on an outstretched hand (FOOSH) mechanism. Magnetic resonance imaging (MRI) showed acute full-thickness avulsion of the distal triceps tendon occurring at the olecranon enthesis. An open tendon repair was performed, and the patient was able to report significant symptom resolution over the course of six months postoperatively and successfully return to elite-level competition. This was a unique and rare case of triceps tendon rupture with concomitant mUCL injury in an adolescent via a non-contact, high-velocity injury mechanism. While a rare injury combination, this case nevertheless identifies an area of research not currently extensively covered-trampoline training and associated injuries in adolescents. This case, therefore, not only adds a novel dimension to the understanding of triceps and mUCL injuries in young athletes but also underscores the need for heightened awareness and specific safety protocols in sports training involving equipment like trampolines.

Popliteal Cyst Compressive Tibial Neuropathy and Venous Insufficiency: A Case Report.

Popliteal cysts are a collection of synovial fluid found in the popliteal fossa that typically form in adults in association with traumatic injuries, degenerative conditions, or inflammatory arthritis of the knee. While often asymptomatic, popliteal cysts may become problematic as enlarging and ruptured cysts may compress surrounding neurovascular structures, resulting in lower extremity edema or peripheral neuropathy. We report a unique case of a symptomatic popliteal cyst in a patient with both compressive neuropathy and venous congestion in the setting of a non-ruptured popliteal cyst after a surgically repaired intraarticular injury. Magnetic resonance imaging (MRI) showed a synovial cyst abutting the posterior neurovascular bundle and evidence of avascular necrosis. An open posterior cyst decompression was done, and the patient was able to report significant symptomatic improvement over the course of two weeks postoperatively. The previously noted varicose veins also demonstrated noticeable resolution. While relatively common, popliteal cysts may require prompt surgical decompression in order to provide effective symptomatic relief.

Return to Sport After Fasciotomy for Chronic Exertional Compartment Syndrome of the Forearm: A Systematic Review.

BACKGROUND: Forearm chronic exertional compartment syndrome (CECS) can represent considerable functional impairment in certain active populations, particularly motorcycle racers. Patients with forearm CECS frequently require fasciotomy to relieve symptoms and return to sport (RTS). PURPOSE: To evaluate the rate at which athletes RTS after fasciotomy for forearm CECS and to compare RTS outcomes between fasciotomy techniques. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review of the PubMed, Scopus, and Cochrane databases was performed from database inception to December 2022 to identify all published reports of forearm CECS managed with fasciotomy. Included studies were analyzed for demographic information, surgical approaches, rehabilitation parameters, RTS rates, time from surgery at which athletes resumed sport, complications, and recurrence. RESULTS: A total of 38 studies (15 level 4 case series, 23 case reports) accounting for 500 patients (831 forearms) who underwent open fasciotomy (112 patients), minimally invasive fasciotomy (166 patients), and endoscopically assisted fasciotomy (222 patients) satisfied inclusion criteria. Most patients (88.0%) were motorcycle racers. The overall RTS rate at any level (RTS-A) was 94.2% (97.3%, 92.2%, and 98.5% for the open fasciotomy, minimally invasive fasciotomy, and endoscopically assisted fasciotomy groups, respectively; P = .010), and the overall RTS at preinjury level or higher was 86.8% (95.9%, 85.6%, and 95.2% for the open fasciotomy, minimally invasive fasciotomy, and endoscopically assisted fasciotomy groups, respectively; P = .132). There was a significant difference in RTS-A between the minimally invasive fasciotomy and endoscopically assisted fasciotomy groups (P = .004). The overall RTS time was 5.1 ± 2.3 weeks, patient satisfaction was 85.1%, and the recurrence rate was 2.4%, and there were no significant differences between fasciotomy approach groups (P = .456, P = .886, and P = .487, respectively). CONCLUSION: Patients who underwent fasciotomy for forearm CECS had high rates of RTS, quick RTS time, high levels of satisfaction, and low rates of recurrence. Outcomes were largely similar between the 3 fasciotomy approaches.

Ankle ligament reconstruction-return to sport after injury scale and return to sports after ankle ligament reconstruction or repair-A systematic review.

Purpose: To systematically review existing literature regarding the ankle ligament reconstruction-return to sport after injury (ALR-RSI) scale and to assess its correlation with Return to sport and functional outcomes as well as feasibility, reliability and consistency. Methods: A systematic review of the literature based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) was conducted using PubMed, Embase and Cochrane Library. Studies that evaluated psychological readiness to return to sport after ankle ligament reconstruction or repair for the treatment of chronic lateral ankle instability using the ALR-RSI scale were included. The results from each study were pooled, and weighted means and overall rates were calculated. Results: In total, 157 patients (53.2% male, mean age: 34.2 years) from three articles were included. Overall, 85.0% of patients reported successful return to sport, but only 48.9% of patients returned to the preoperative sporting level. All studies reported a significant difference in psychological scores between patients who returned to sport and those who did not. Pooled mean patient-reported outcome measures, reported as the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS, three studies) Score and Karlsson-Peterson Score (three studies), were 82.7 (range: 29-100) and 81.7 (range: 25-100), respectively. The ALR-RSI scale demonstrated strong correlations with the AOFAS Score and Karlsson-Peterson Score. Conclusion: Patients who returned to sport after ankle ligament reconstruction or repair exhibited higher psychological readiness compared to those who did not. The ALR-RSI scale showed strong correlations with ankle function. Evaluation of psychological readiness using the ALR-RSI scale may provide an additional tool in the assessment of patients who underwent ankle ligament reconstruction or repair. Level of Evidence: Level III, systematic review.

Hypoglycemic effects of dracorhodin and dragon blood crude extract from Daemonorops draco.

BACKGROUND: Dragon blood is a red fruit resin from the palm tree Daemonorops draco and is a herbal ingredient used in the traditional Chinese medicine, "Jinchuang Ointment," which is used to treat non-healing diabetic wounds. According to the Taiwan Herbal Pharmacopeia, the dracorhodin content in dragon blood should exceed 1.0%. RESULTS: Our findings indicate that dracorhodin and dragon blood crude extracts can stimulate glucose uptake in mouse muscle cells (C2C12) and primary rat aortic smooth muscle cells (RSMC). Dracorhodin is not the only active compound in dragon blood crude extracts from D. draco. Next, we orally administered crude dragon blood extracts to male B6 mice. The experimental group displayed a decreasing trend in fasting blood glucose levels from the second to tenth week. In summary, crude extracts of dragon blood from D. draco demonstrated in vivo hypoglycemic effects in B6 male mice. CONCLUSIONS: We provide a scientific basis "Jinchuang ointment" in treating non-healing wounds in patients with diabetes.

Anesthetics disrupt growth cone guidance cue sensing through actions on the GABAA α2 receptor mediated by the immature chloride gradient.

BACKGROUND: General anesthetics (GAs) may exert harmful effects on the developing brain by disrupting neuronal circuit formation. Anesthetics that act on γ-aminobutyric acid (GABA) receptors can interfere with axonal growth cone guidance, a critical process in the assembly of neuronal circuitry. Here we investigate the mechanism by which isoflurane prevents sensing of the repulsive guidance cue, Semaphorin 3A (Sema3A). METHODS: Growth cone sensing was assayed by measuring growth cone collapse in dissociated neocortical cultures exposed to recombinant Sema3A in the presence or absence of isoflurane and/or a panel of reagents with specific actions on components of the GABA receptor and chloride ion systems. RESULTS: Isoflurane exposure prevents Sema3A induced growth cone collapse. A GABAA α2 specific agonist replicates this effect (36.83 ±â€¯3.417% vs 70.82 ±â€¯2.941%, in the Sema3A induced control group, p < 0.0001), but an α1-specific agonist does not. Both a Na-K-Cl cotransporter 1 antagonism (bumetanide, BUM) and a chloride ionophore (IONO) prevent isoflurane from disrupting growth cone sensing of Sema3A. (65.67 ±â€¯3.775% in Iso + BUM group vs 67.45 ±â€¯3.624% in Sema3A induced control group, 65.34 ±â€¯1.678% in Iso + IONO group vs 68.71 ±â€¯2.071% in Sema3A induced control group, no significant difference) (n = 96 growth cones per group). CONCLUSION: Our data suggest that the effects of isoflurane on growth cone sensing are mediated by the α2 subunit of the GABAA receptor and also that they are dependent on the developmental chloride gradient, in which Cl- exhibits a depolarizing effect. These findings provide a rationale for why immature neurons are particularly susceptible to anesthetic toxicity.

Comparing functional analysis and paired-choice assessment results in classroom settings.

The results of a functional analysis of problem behavior and a paired-choice assessment were compared to determine whether the same social reinforcers were identified for problem behavior and an appropriate response (time allocation). The two assessments were conducted in classroom settings with 4 adolescents with mental retardation who engaged in severe problem behavior. Each student's classroom teacher served as the therapist for all phases of assessment. The two assessment procedures identified the same social reinforcers for problem and appropriate behavior for 3 of 4 participants.

Visible-absorption spectroscopy as a biomarker to predict treatment response and prognosis of surgically resected esophageal cancer.

The application of optical absorption spectra in prognostic prediction has hardly been investigated. We developed and evaluated a novel two dimensional absorption spectrum measurement system (TDAS) for use in early diagnosis, evaluating response to chemoradiation, and making prognostic prediction. The absorption spectra of 120 sets of normal and tumor tissues from esophageal cancer patients were analyzed with TDAS ex-vivo. We demonstrated the cancerous tissue, the tissue from patients with a poor concurrent chemoradiotherapy (CCRT) response, and the tissue from patients with an early disease progression each had a readily identifiable common spectral signature. Principal component analysis (PCA) classified tissue spectra into distinct groups, demonstrating the feasibility of using absorption spectra in differentiating normal and tumor tissues, and in predicting CCRT response, poor survival and tumor recurrence (efficiencies of 75%, 100% and 85.7% respectively). Multivariate analysis revealed that patients identified as having poor-response, poor-survival and recurrence spectral signatures were correlated with increased risk of poor response to CCRT (P = 0.012), increased risk of death (P = 0.111) and increased risk of recurrence (P = 0.030) respectively. Our findings suggest that optical absorption microscopy has great potential to be a useful tool for pre-operative diagnosis and prognostic prediction of esophageal cancer.

Validating efficacy of shea nut oil extract in knee osteoarthritis patients.

Objectives. To examine and investigate the efficacy of shea nut oil extract (SheaFlex75) in relation to knee osteoarthritis (OA). Methods. Thirty-three patients (age 63.6 ± 5.8 years) with knee OA were recruited. Real-time ultrasound imaging and surface electromyography were used to objectively assess the morphological changes and the activity of vastus medialis oblique (VMO) muscles during a 16-week intervention of SheaFlex75. The intraclass correlation coefficient (ICC) was calculated to examine the reliability of the interscans. A paired-sample t-test was used to compare the findings in different stages. The Spearman's rank correlation coefficient was used to examine the relationship between the relevant variables of OA and percentage of thickness change of VMO at different contraction levels. Results. The baseline findings showed strong correlation, suggesting that the reliability of interscans at pretest was high. The ability to contract the muscles of the knee to a 30% contraction level showed significant change between the baseline and after 16-week testing, both in terms of morphological changes and muscle activity. Pain scale reported a significant decrease at the 16th week. Conclusion. The results suggest that SheaFlex75 can relieve the symptoms of knee OA and can result in improvement of muscle control of the knee.