Facile Fabrication of Multifunctional Hydrogel Nanoweb Coating Using Carboxymethyl Chitosan-Based Short Nanofibers for Blood-Contacting Medical Devices.

Blood-contacting medical devices (BCDs) require antithrombotic, antibacterial, and low-friction surfaces. Incorporating a nanostructured surface with the functional hydrogel onto BCD surfaces can enhance the performances; however, their fabrication remains challenging. Here, we introduce a straightforward method to fabricate a multifunctional hydrogel-based nanostructure on BCD surfaces using O-carboxymethyl chitosan-based short nanofibers (CMC-SNFs). CMC-SNFs, fabricated via electrospinning and cutting processes, are easily sprayed and entangled onto the BCD surface. The deposited CMC-SNFs form a robust nanoweb layer via fusion at the contact area of the nanofiber interfaces. The superhydrophilic CMS-SNF nanoweb surface creates a water-bound layer that effectively prevents the nonspecific adhesion of bacteria and blood cells, thereby enhancing both antimicrobial and antithrombotic performances. Furthermore, the CMC-SNF nanoweb exhibits excellent lubricity and durability on the bovine aorta. The demonstration results of the CMC-SNF coating on catheters and sheaths provide evidence of its capability to apply multifunctional surfaces simply for diverse BCDs.

Evaluation of machine learning approach for surgical results of Ahmed valve implantation in patients with glaucoma.

BACKGROUND: Ahmed valve implantation demonstrated an increasing proportion in glaucoma surgery, but predicting the successful maintenance of target intraocular pressure remains a challenging task. This study aimed to evaluate the performance of machine learning (ML) in predicting surgical outcomes after Ahmed valve implantation and to assess potential risk factors associated with surgical failure to contribute to improving the success rate. METHODS: This study used preoperative data of patients who underwent Ahmed valve implantation from 2017 to 2021 at Ajou University Hospital. These datasets included demographic and ophthalmic parameters (dataset A), systemic medical records excluding psychiatric records (dataset B), and psychiatric medications (dataset C). Logistic regression, extreme gradient boosting (XGBoost), and support vector machines were first evaluated using only dataset A. The algorithm with the best performance was selected based on the area under the receiver operating characteristics curve (AUROC). Finally, three additional prediction models were developed using the best performance algorithm, incorporating combinations of multiple datasets to predict surgical outcomes at 1 year. RESULTS: Among 153 eyes of 133 patients, 131 (85.6%) and 22 (14.4%) eyes were categorized as the success and failure groups, respectively. The XGBoost was shown as the best-performance model with an AUROC value of 0.684, using only dataset A. The final three further prediction models were developed based on the combination of multiple datasets using the XGBoost model. All datasets combinations demonstrated the best performances in terms of AUROC (dataset A + B: 0.782; A + C: 0.773; A + B + C: 0.801). Furthermore, advancing age was a risk factor associated with a higher surgical failure incidence. CONCLUSIONS: ML provides some predictive value in predicting the outcomes of Ahmed valve implantation at 1 year. ML evaluation revealed advancing age as a common risk factor for surgical failure.

Variables affecting new drug prices in South Korea's pricing system.

Objective: The price of pharmaceuticals is important from the economic and industrial perspectives but as well as patients' access to treatment. This study aimed to analyze the variables affecting the prices of new drugs in South Korea's pricing system. Methods: Data on 192 new drugs listed in South Korea from 2012 to 2022 were collected from the official website of the Health Insurance Review and Assessment Service. The independent variables included drugs for severe diseases, alternatives, number of patients, number of advanced 7 countries listed, budget impact, and listing period. The dependent variables included annual treatment cost and the price ratio to the advanced 7 country's average adjusted price. Descriptive statistics of variables, linear correlations between quantitative independent and dependent variables, and associations between independent and dependent variables were analyzed. Results: The mean annual treatment cost and price ratio to the advanced 7 country's average adjusted price were higher for drugs for severe diseases and those with no alternatives. Annual treatment cost and price ratio to the advanced 7 country's average adjusted price were negatively correlated with the number of patients and positively correlated with the number of advanced 7 countries listed. Annual treatment cost was affected by the variables drugs for severe diseases, alternatives, number of patients, number of advanced 7 countries listed, and budget impact. The price ratio to the advanced 7 country's average adjusted price was affected by drugs for severe diseases, alternatives, and the number of patients. Conclusion: This study revealed the effect of different variables on the prices of new drugs in South Korea, allowing for the development of a more effective assessment system to evaluate the prices of new drugs while ensuring profitability for pharmaceutical companies, sustainability of public insurance, and accessibility to drugs by patients.

Noninvasive ROS imaging and drug delivery monitoring in the tumor microenvironment.

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn2+)-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn2+, which induces T1-weighted MRI signal enhancement. Mn@BRNPs show more rapid and greater MRI signal enhancement in high ROS-producing A549 lung carcinoma cells compared with low ROS-producing DU145 prostate cancer cells. A pseudo three-compartment model devised for the ROS-reactive MRI probe enables mapping of the distribution and concentration of ROS within the tumor. Furthermore, doxorubicin-loaded, cancer-targeting ligand biotin-conjugated Dox/Mn@bt-BRNPs show considerable accumulation in A549 tumors and also effectively inhibit tumor growth without causing body weight loss, suggesting their usefulness as a new theranostic agent. Collectively, these findings suggest that Mn@bt-BRNPs could be used as an imaging probe capable of detecting ROS levels and monitoring drug delivery in the TME with potential applicability to other inflammatory diseases.

Accessory first lumbrical muscle within the carpal tunnel: a case report.

Carpal tunnel syndrome is the most common entrapment neuropathy in the upper extremity. Palmaris longus, flexor digitorum superficialis, and lumbricals have infrequently been reported as causes of nerve compression. During routine Korean cadaver dissection, we incidentally identified an anatomic variant of first lumbrical muscle within the carpal tunnel in both wrists. The aberrant musculature originated from the radial side of the second FDS muscle at distal forearm level, running separately across the wrist beneath the flexor retinaculum. The dissected anomalous muscle was identified as an additional muscle belly of the first lumbrical muscle. Compression of the median nerve at the wrist might rarely be caused by the presence of such a tendon or muscle anomaly found in this study. Surgeons should be aware of possible anatomic variations in the carpal tunnel, and be prepared to modify their surgical plan accordingly.

Association between pre-diagnostic serum uric acid levels in patients with newly diagnosed epilepsy and conversion rate to drug-resistant epilepsy within 5 years: A common data model analysis.

PURPOSE: Drug-resistant epilepsy (DRE) poses a significant challenge in epilepsy management, and reliable biomarkers for identifying patients at risk of DRE are lacking. This study aimed to investigate the association between serum uric acid (UA) levels and the conversion rate to DRE. METHODS: A retrospective cohort study was conducted using a common data model database. The study included patients newly diagnosed with epilepsy, with prediagnostic serum UA levels within a six-month window. Patients were categorized into hyperUA (≥7.0 mg/dL), normoUA (<7.0 and >2.0 mg/dL), and hypoUA (≤2.0 mg/dL) groups based on their prediagnostic UA levels. The outcome was the conversion rate to DRE within five years of epilepsy diagnosis. RESULTS: The study included 5,672 patients with epilepsy and overall conversion rate to DRE was 19.4%. The hyperUA group had a lower DRE conversion rate compared to the normoUA group (HR: 0.81 [95% CI: 0.69-0.96]), while the hypoUA group had a higher conversion rate (HR: 1.88 [95% CI: 1.38-2.55]). CONCLUSIONS: Serum UA levels have the potential to serve as a biomarker for identifying patients at risk of DRE, indicating a potential avenue for novel therapeutic strategies aimed at preventing DRE conversion.

Characterization of sacral chordoma and differential diagnosis from other sacral malignancy using [18F]FDG PET/CT.

2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:F = 6:4, median age = 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:F = 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, P = .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoff ≤ 4.0; sensitivity 100.0%, specificity 58.3%; P = .004), and SUVmax showed the second largest AUC of 0.73 (cutoff ≤ 6.9; sensitivity 80.0%, specificity 66.7%; P = .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.

Clinical characteristics of endometrioma with and without dysmenorrhea diagnosed by laparoscopy: A retrospective cohort study in a tertiary center.

OBJECTIVE: Clinical characteristics of patients with endometrioma without dysmenorrhea have not been well delineated; our goal was to remedy this issue by performing a retrospective cohort study. METHODS: A total of 379 patients who underwent laparoscopic surgery for endometrioma ≥4 cm at a tertiary hospital were included in this retrospective study. Patients were divided into two groups based on the presence of dysmenorrhea at the time of hospital visit; with dysmenorrhea group and without dysmenorrhea group. RESULTS: Patients without dysmenorrhea comprised 9.5% of all surgically confirmed endometriomas. Significant differences were found in the revised American Society for Reproductive Medicine (rASRM) stage, age at surgery, and bilaterality. Patients with rASRM stage IV were more likely to have dysmenorrhea than were subjects with rASRM stage III (odds ratio (OR), 10.58; 95% confidence interval (CI), 4.63-24.21; P < 0.001). Older patients were less likely to have dysmenorrhea (OR, 0.94; 95% CI, 0.88-1.00; P = 0.045), as were patients with bilateral rather than unilateral endometrioma (OR, 0.36; 95% CI, 0.15-0.82; P = 0.015). No significant differences in cyst size, age at menarche, body mass index (BMI), parity, or history of previous ovarian surgery were found between the two groups. CONCLUSION: Patients without dysmenorrhea comprised 9.5% of endometrioma cases and had less advanced rASRM stage, were older at surgery, and had a higher probability of bilateral than unilateral endometrioma than patients with dysmenorrhea.

Security Comparison of Various Surgical Knots Using Nylon Suture.

OBJECTIVE: To evaluate the strengths of various surgical knot techniques, including square knot, surgeon's knot, granny knot, and random knot with the same three throws. METHODS: The authors tested each of the four knot techniques using four different gauges of nylon (polyamide [Ethicon]): 4-0, 5-0, 6-0, and 7-0. Each knot type was tested 20 times per nylon gauge, for a total of 320 knots tested. The authors used a static pull machine to measure elongation at yield and maximal force to break. RESULTS: A comparison of elongation at yield revealed that the surgeon's knot was superior to the square knot, granny knot, and random knots across all gauges of nylons. Further, a comparison of maximal force to break revealed that the surgeon's knot was superior to the square knot, granny knot, and random knots when using 4-0, 5-0, and 6-0 nylon but not when using 7-0 nylon. CONCLUSIONS: The surgeon's knot was the strongest, and random knot was the weakest when the authors used nylon 4-0, 5-0, and 6-0. While handling fine suture materials such as 7-0 nylon, knot failure appears to be unrelated to the knot technique used. This study provides not only fundamental guidance for tying surgical knots using nylon, but also a rational basis for an adequately strong knot choice in various fields of surgery.

Self-Organization via Dewetting in Polymeric Assemblies.

Dewetting is a spontaneous process involving a thin liquid film that minimizes interfacial energy by reducing the surface area via the generation of defects on the film. In industry, dewetting is regarded as a problem that results in defects or a heterogeneous surface; however, in this study, dewetting is intentionally induced to create various patterns at intended positions spontaneously with polymeric materials and nanoparticles. The dewetting-induced patterning process is conducted by controlling the capillary force and evaporation ratio through an evaporative self-assembly system. The linear-polymeric arrays on the substrate played an important role in modifying the surface geometry and treatment for a heterogeneous surface, and an additional patterning process is performed on patterned arrays to create dewetting-induced self-organizing patterns. Here, this method is used to introduce material arrays with specific shapes such as dots, dumbbells, potbellies, Vs, and trapezoids.

Neglected posterior interosseous nerve injury.

Posterior interosseous nerve (PIN) injury is uncommon due to its anatomically deep location. We report a neglected, rare case of PIN injury presenting the loss of extension of thumb, index, and small fingers with weakness of thumb abduction in a 49-year-old male patient. The patient sustained a penetrating injury to his right forearm caused by a kitchen knife that was repaired primarily through an emergency surgery under general anesthesia. During the regular follow-up on the 52nd postoperative day, the patient presented 20° of extension lags in the right thumb and index finger and 30° in the small finger. Wrist extension was intact, and there was no sensory deficit. We explored the wound and traced the PIN completely, identifying a club-shaped neuroma formation at the proximal cut end of the PIN. Delayed nerve repair was performed with a double-strip cable graft. Hand surgeons should be aware of the probable PIN injury in certain situations of forearm-penetrating injury and perform proper preoperative physical examination to rule out neurovascular deficits. Careful exploration and immediate repair of severe PIN are mandatory, even in emergency situations.

Longitudinal Magnetic Resonance Imaging with ROS-Responsive Bilirubin Nanoparticles Enables Monitoring of Nonalcoholic Steatohepatitis Progression to Cirrhosis.

Despite the vital importance of monitoring the progression of nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), an efficient imaging modality that is readily available at hospitals is currently lacking. Here, a new magnetic-resonance-imaging (MRI)-based imaging modality is presented that allows for efficient and longitudinal monitoring of NAFLD and NASH progression. The imaging modality uses manganese-ion (Mn2+)-chelated bilirubin nanoparticles (Mn@BRNPs) as a reactive-oxygen-species (ROS)-responsive MRI imaging probe. Longitudinal T1-weighted MR imaging of NASH model mice is performed after injecting Mn@BRNPs intravenously. The MR signal enhancement in the liver relative to muscle gradually increases up to 8 weeks of NASH progression, but decreases significantly as NASH progresses to the cirrhosis-like stage at weeks 10 and 12. A new dual input pseudo-three-compartment model is developed to provide information on NASH stage with a single MRI scan. It is also demonstrated that the ROS-responsive Mn@BRNPs can be used to monitor the efficacy of potential anti-NASH drugs with conventional MRI. The findings suggest that the ROS-responsive Mn@BRNPs have the potential to serve as an efficient MRI contrast for monitoring NASH progression and its transition to the cirrhosis-like stage.

Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study.

AIMS: Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic. METHODS: By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions. RESULTS: A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021. CONCLUSIONS: Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4+Iba1+, TLR2+Iba1+, and NF-κB+Iba1+ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

Explainable multimodal prediction of treatment-resistance in patients with depression leveraging brain morphometry and natural language processing.

Although 20 % of patients with depression receiving treatment do not achieve remission, predicting treatment-resistant depression (TRD) remains challenging. In this study, we aimed to develop an explainable multimodal prediction model for TRD using structured electronic medical record data, brain morphometry, and natural language processing. In total, 247 patients with a new depressive episode were included. TRD-predictive models were developed based on the combination of following parameters: selected tabular dataset features, independent components-map weightings from brain T1-weighted magnetic resonance imaging (MRI), and topic probabilities from clinical notes. All models applied the extreme gradient boosting (XGBoost) algorithm via five-fold cross-validation. The model using all data sources showed the highest area under the receiver operating characteristic of 0.794, followed by models that used combined brain MRI and structured data, brain MRI and clinical notes, clinical notes and structured data, brain MRI only, structured data only, and clinical notes only (0.770, 0.762, 0.728, 0.703, 0.684, and 0.569, respectively). Classifications of TRD were driven by several predictors, such as previous exposure to antidepressants and antihypertensive medications, sensorimotor network, default mode network, and somatic symptoms. Our findings suggest that a combination of clinical data with neuroimaging and natural language processing variables improves the prediction of TRD.

Enhanced Mechanical Properties of Polylactic Acid/Poly(Butylene Adipate-co-Terephthalate) Modified with Maleic Anhydride.

An increase in plastic waste pollution and the strengthening of global environmental policies have heightened the need for research on biodegradable plastics. In this regard, polylactic acid (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) are notable examples, serving as alternatives to traditional plastics. In this study, the compatibility and mechanical properties of PLA/PBAT blends were improved by the chemical grafting of maleic anhydride (MAH). In addition, qualitative analyses were conducted, dynamic mechanical properties were investigated, and the structure and mechanical characteristics of the blends were analyzed. With an increase in the MAH concentration, the grafting yield of the blends increased, and significantly improved the compatibility of the PLA/PBAT blend, with an ~2 and 2.9 times increase in the tensile strength and elongation at break, respectively. These findings indicate that the modified PLA/PBAT blend demonstrates potential for applications that require sustainable plastic materials, thereby contributing to the development of environmentally friendly alternatives in the plastics industry.

Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases.

Obesity triggers inflammatory responses in the microenvironment of white adipose tissue, resulting in chronic systemic inflammation and the subsequent development of non-communicable diseases, including type 2 diabetes, coronary heart disease, and breast cancer. Current therapy approaches for obesity-induced non-communicable diseases persist in prioritizing symptom remission while frequently overlooking the criticality of targeting and alleviating inflammation at its source. Accordingly, this review highlights the importance of the microenvironment of obese white adipose tissue and the promising potential of employing immunotherapy to target it as an effective therapeutic approach for non-communicable diseases induced by obesity. Additionally, this review discusses the challenges and offers perspective about the immunotherapy targeting the microenvironment of obese white adipose tissue.

Association between Preoperative Glucose Dysregulation and Delirium after Non-Cardiac Surgery.

This study aimed to investigate the association between glucose dysregulation and delirium after non-cardiac surgery. Among a total of 203,787 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, we selected 61,805 with available preoperative blood glucose levels within 24 h before surgery. Patients experiencing glucose dysregulation were divided into three groups: hyperglycemia, hypoglycemia, and both. We compared the incidence of postoperative delirium within 30 days after surgery between exposed and unexposed patients according to the type of glucose dysregulation. The overall incidence of hyperglycemia, hypoglycemia, and both was 5851 (9.5%), 1452 (2.3%), and 145 (0.2%), respectively. The rate of delirium per 100 person-months of the exposed group was higher than that of the unexposed group in all types of glucose dysregulation. After adjustment, the hazard ratios of glucose dysregulation in the development of delirium were 1.35 (95% CI, 1.18-1.56) in hyperglycemia, 1.36 (95% CI, 1.06-1.75) in hypoglycemia, and 3.14 (95% CI, 1.27-7.77) in both. The subgroup analysis showed that exposure to hypoglycemia or both to hypo- and hyperglycemia was not associated with delirium in diabetic patients, but hyperglycemia was consistently associated with postoperative delirium regardless of the presence of diabetes. Preoperative glucose dysregulation was associated with increased risk of delirium after non-cardiac surgery. Our findings may be helpful for preventing postoperative delirium, and further investigations are required to verify the association and mechanisms for the effect we observed.