Radiologic myosteatosis predicts major complication risk following esophagectomy for cancer: a multicenter experience.

BACKGROUND: Myosteatosis is a measure of skeletal muscle quality that is readily identifiable on computed tomography (CT). The effect of preoperative myosteatosis on outcomes after radical esophagectomy remains unclear. This study aimed to correlate the presence of myosteatosis on CT scan with perioperative morbidity, mortality, and survival outcomes after esophagectomy in an Australian population across 3 esophageal cancer centers. METHODS: A retrospective analysis was performed for all patients undergoing radical esophagectomy for cancer across 3 centers. Radiologic assessment of preoperative CT images was performed to determine the presence of myosteatosis. The outcomes measured included perioperative complication rate, overall survival (OS), and disease-free survival (DFS). RESULTS: A total of 462 patients were included in the analysis (male patients, 78.4%; median age, 67 years). Moreover, 353 patients (76.4%) had myosteatosis on CT. Compared to patients with normal skeletal muscle attenuation, patients with myosteatosis had a higher rate of major (Clavien-Dindo grade ≥ IIIb) complication (14.7% vs 24.9%, respectively; P = .026) and a higher rate of 30-day mortality (0.0% vs 4.0%, respectively; P = .048). Myosteatosis was associated with a major complication on multivariate analysis (hazard ratio, 1.906; 95% CI, 1.057-3.437; P = .032). There was no difference in OS and DFS between patients with and without myosteatosis (OS: 59 vs 56 months, respectively [P = .465]; DFS: 39 vs 42 months, respectively; P = .172). CONCLUSION: The presence of myosteatosis on radiologic imaging was associated with an increased risk of major complications and 30-day mortality. Identifying myosteatosis can be an adjunct to preoperative nutritional assessment and prognostication, facilitating early recognition of patients at risk of complications.

Fabrication of highly fluorescent graphene quantum dots for quantification of As3+ ion using modified cellulose paper.

Easy, economical, and swift detecting tools are very demanded for assaying various chemical species. The introduction of label-free paper-based read-out devices has significantly reached the demand of analytical science for target analytes assays. Herein, a facile, and disposable inexpensive paper-based sensing tool was fabricated for sensing As3+ ion using graphene quantum dots (GQDs) as a fluorescent reader. The CA-GQDs were synthesized using citric acid (CA) as a precursor via the pyrolysis method, further physisorbed on the cellulose substrate for sensing of As3+ via aggregation-based fluorescence "turn-off" mechanism. The linear range for quantitating As3+ ion is in the range of 0.05-50 µM with a detection limit of 10 nM. The practical application of the CA-GQDs-based analytical platform was verified by assaying As3+ ion in water samples. The CA-GQDs-embedded paper strip can be easily extended for assaying of As3+ ion, which meets the demand for monitoring of As3+ ion in real samples.

Coaxial bioprinting of a stentable and endothelialized human coronary artery-sized in vitro model.

Atherosclerosis accounts for two-thirds of deaths attributed to cardiovascular diseases, which continue to be the leading cause of mortality. Current clinical management strategies for atherosclerosis, such as angioplasty with stenting, face numerous challenges, including restenosis and late thrombosis. Smart stents, integrated with sensors that can monitor cardiovascular health in real-time, are being developed to overcome these limitations. This development necessitates rigorous preclinical trials on either animal models or in vitro models. Despite efforts being made, a suitable human-scale in vitro model compatible with a cardiovascular stent has remained elusive. To address this need, this study utilizes an in-bath bioprinting method to create a human-scale, freestanding in vitro model compatible with cardiovascular stents. Using a coaxial nozzle, a tubular structure of human coronary artery (HCA) size is bioprinted with a collagen-based bioink, ensuring good biocompatibility and suitable rheological properties for printing. We precisely replicated the dimensions of the HCA, including its internal diameter and wall thickness, and simulated the vascular barrier functionality. To simplify post-processing, a pumpless perfusion bioreactor is fabricated to culture a HCA-sized model, eliminating the need for a peristaltic pump and enabling scalability for high-throughput production. This model is expected to accelerate stent development in the future.

Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Online Search Trends Related to Bariatric Surgery and Their Relationship with Utilization in Australia.

PURPOSE: There is an abundance of online information related to bariatric surgery. Patients may prefer a specific type of bariatric surgery based on what they read online. The primary aim of this study was to determine online search trends in bariatric surgery over time in Australia and worldwide. The secondary aim was to establish a relationship between public online search activity and the types of bariatric surgery performed in Australia. MATERIALS AND METHOD: The terms "adjustable gastric band," "sleeve gastrectomy," and "gastric bypass surgery" were submitted for search volume analysis in Australia and worldwide using the Google Trends "Topic" search function. This was compared alongside the numbers of gastric bandings, sleeve gastrectomies, and gastric bypass surgeries performed in Australia over time to determine if there was a relationship between the two. RESULTS: Search trends for "adjustable gastric band" and "sleeve gastrectomy" in Australia were similar to trends seen worldwide. However, search trends for "gastric bypass surgery" differ between Australia and the rest of the world. It took at least a year for online searches to reflect the higher number of sleeve gastrectomies performed relative to gastric bandings. There was a lag time of over four years before online searches reflected the higher number of gastric bypass surgery performed compared to gastric banding. CONCLUSION: Search interests in Australia and worldwide were similar for gastric banding and sleeve gastrectomy but different for gastric bypass surgery. Online search activity did not have a significant association with the types of bariatric surgery being performed in Australia.

The influence of socioeconomic disadvantage on short- and long-term outcomes after oesophagectomy for cancer: an Australian multicentre study.

BACKGROUND: Socioeconomic status (SES) affects outcomes following surgery for various cancers. There are currently no Australian studies that examine the role of socioeconomic disadvantage on outcomes following oesophagectomy for cancer. This study assessed whether SES was associated with short-term perioperative morbidity, long-term survival, and oncological outcomes following oesophagectomy across three tertiary oesophageal cancer centres in Australia. METHODS: A retrospective cohort study was performed comprising all patients who underwent oesophagectomy for cancer across three Australian centres. Patients were stratified into SES groups using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD). Outcomes measured included perioperative complication rates, overall survival, and disease-free survival. RESULTS: The study cohort was 462 patients, 205 in the lower SES and 257 in the higher SES groups. The lower SES group presented with more advanced oesophageal cancer stage, a higher rate of T3 (52.6% versus 42.7%, P = 0.038) and N2 disease (19.6% versus 10.5%, P = 0.006), and had a higher rate of readmission within 30 days (11.2% versus 5.4%, P = 0.023). There was no difference in overall survival or disease-free survival between groups. CONCLUSION: Lower socioeconomic status was associated with more advanced stage and increased risk of early, unplanned readmission following oesophagectomy, but was not associated with a difference in overall or disease-free survival.

Intermittent fasting induced cerebral ischemic tolerance altered gut microbiome and increased levels of short-chain fatty acids to a beneficial phenotype.

Preconditioning-induced cerebral ischemic tolerance is known to be a beneficial adaptation to protect the brain in an unavoidable event of stroke. We currently demonstrate that a short bout (6 weeks) of intermittent fasting (IF; 15 h fast/day) induces similar ischemic tolerance to that of a longer bout (12 weeks) in adult C57BL/6 male mice subjected to transient middle cerebral artery occlusion (MCAO). In addition, the 6 weeks IF regimen induced ischemic tolerance irrespective of age (3 months or 24 months) and sex. Mice subjected to transient MCAO following IF showed improved motor function recovery (rotarod and beam walk tests) between days 1 and 14 of reperfusion and smaller infarcts (T2-MRI) on day 1 of reperfusion compared with age/sex matched ad libitum (AL) controls. Diet influences the gut microbiome composition and stroke is known to promote gut bacterial dysbiosis. We presently show that IF promotes a beneficial phenotype of gut microbiome following transient MCAO compared with AL cohort. Furthermore, post-stroke levels of short-chain fatty acids (SCFAs), which are known to be neuroprotective, are higher in the fecal samples of the IF cohort compared with the AL cohort. Thus, our studies indicate the efficacy of IF in protecting the brain after stroke, irrespective of age and sex, probably by altering gut microbiome and SCFA production.

Photodynamic treatment increases the lifespan and oxidative stress resistance of Caenorhabditis elegans.

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 µM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.

Back-trajectory analyses for evaluating the transboundary transport effect to the aerosol pollution in South Korea.

This study performed a back-trajectory analysis to determine the influence of transboundary transport on the extent of aerosol pollution in South Korea, based on 5-year PM2.5 measurements (2015-2019) in five cities covering South Korea. A transboundary transport case was selected if a back trajectory passed over a dedicated region (BOX 1 and BOX 2) in the Yellow Sea. First, we found that the frequency of transboundary transport largely increases in the high pollution case, and this pattern is almost consistent for all months and all five cities, indicating the importance of investigating the horizontal direction of air mass movement associated with PM2.5, which has been discussed extensively in previous studies. In this study, we also examined the altitude change and straight moving distance (defined as travel distance) of back trajectories regarding the extent of local PM2.5. Consequently, we found that back trajectories in high aerosol pollution showed much lower altitudes and shorter travel differences, implying a significant contribution of surface emissions and stagnant air conditions to severe aerosol pollution. As a result, the local PM2.5 level was not significantly enhanced when the air mass passed over the Yellow Sea if transboundary transport occurred at high altitudes with rapid movement (i.e., high altitude and long travel distance back-trajectory). Based on these results, we suggest utilizing the combined information of the horizontal direction, altitude variation, and length of back trajectories to better evaluate transboundary transport.

How to perform duodenojejunostomy in addition to Roux-en-Y reconstruction following total gastrectomy to facilitate future duodenal surveillance.

We report two cases of total gastrectomy and Roux-en-Y reconstruction that required future endoscopic surveillance of the duodenum. As such, an additional proximal duodenojejunostomy was fashioned to facilitate endoscopic surveillance.

Sarcopenia impacts perioperative and survival outcomes after esophagectomy for cancer: a multicenter study.

BACKGROUND: The impact of sarcopenia on outcomes after esophagectomy is controversial. Most data are currently derived from Asian populations. This study aimed to correlate sarcopenia to short-term perioperative complication rates and long-term survival and recurrence outcomes. METHODS: A retrospective analysis was performed of patients undergoing esophagectomy for cancer from 3 tertiary referral centers in Australia. Sarcopenia was defined using cutoffs for skeletal muscle index (SMI), assessed on preoperative computed tomography images. Outcomes measured included complications, overall survival (OS), and disease-free survival (DFS). RESULTS: Of 462 patients (78.4% male; median age, 67 years), sarcopenia was evident in 276 (59.7%). Patients with sarcopenia had a higher rate of major (Clavien-Dindo ≥ 3b) complications (27.9% vs 14.5%; P < .001), including higher rates of postoperative cardiac arrythmia (16.3% vs 9.7%; P = .042), pneumonia requiring antibiotics (14.5% vs 9.1%; P = .008), and 30-day mortality (5.1% vs 0%; P = .002). In the sarcopenic group, the median OS was lower (37 months [95% CI, 27.1-46.9] vs 114 months [95% CI, 75.8-152.2]; P < .001), as was the median DFS (27 months [95% CI, 18.9-35.1] vs 77 months [95% CI, 36.4-117.6]; P < .001). Sarcopenia was an independent risk factor for lower survival on multivariate analysis (hazard ratio, 1.688; 95% CI, 1.223-2.329; P = .001). CONCLUSION: Patients with preoperative sarcopenia based on analysis of SMI are at a higher risk of major complications and have inferior survival and oncologic outcomes after esophagectomy for esophageal cancer.

Melanin Inhibitory Effect of Tuber himalayense Isolated in Incheon, Korea.

There has been a growing interest in skin beauty and antimelanogenic products. Melanogenesis is the process of melanin synthesis whereby melanocytes are activated by UV light or hormone stimulation to produce melanin. Melanogenesis is mediated by several enzymes, such as tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), and TRP-2. In this study, we investigated the effect of Tuber himalayense extract on melanin synthesis in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 melanoma cells. We confirmed that T. himalayense extract was not toxic to α-MSH-treated B16F10 melanoma cells and exhibited a significant inhibitory effect on melanin synthesis at concentrations of 25, 50, and 100 µg/ml. Additionally, the T. himalayense extract inhibited melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are enzymes involved in melanin synthesis, in a concentration-dependent manner. Furthermore, T. himalayense extract inhibited the mitogen-activated protein kinase (MAPK) pathways, such as extracellular signal-regulated kinase-1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38. Therefore, we hypothesized that various components of T. himalayense extract affect multiple factors involved in melanogenesis in B16F10 cells. Our results indicate that T. himalayense extract could potentially be used as a new material for preparing whitening cosmetics.

Robust blood pressure measurement from facial videos in diverse environments.

Blood pressure (BP) management is important worldwide, and BP monitoring is a crucial aspect of maintaining good health. Traditional BP meter measures BP independently in various situations, such as at home or work, using a cuff to maintain a stable condition. However, these devices can causes a foreign body sensation and discomfort, and are not always practical for periodic monitoring. As a result, studies have been conducted on the use of photoplethysmography (PPG) for measuring BP. However, PPG also has limitations similar to those of traditional BP meters, as it requires the placement of sensors on two regions of the body (fingers or toes). To address this issue, researchers have conducted studies on non-contact methods for measuring BP using face and hand videos. These studies have utilized two cameras to measure PTT and have focused on internal environments, resulting in low accuracy of BP measurement in external environments. We proposes a method for robust BP measurement using pulse wave velocity (PWV) and PTT calculated from facial videos. PTT is estimated by measuring the phase difference between two different regions of interest (ROIs) and PWV is calculated using PTT and the actual distance between two ROIs. In addition, our proposed method extracts the pulse wave from the ROI to measure BP. The actual distance between the ROIs and PTT are estimated using the two extracted pulse waves, and BP is then measured using PWV and PTT. To evaluate the BP measurement performance, the BP calculated from both BP meters and facial videos (in indoor, outdoor, driving car, and flying drone environments) are compared. Our results reveal that the proposed method can robustly measure BP in diverse environments.

Extensive lymphadenectomy may improve survival in node negative oesophageal cancer.

Lymph node metastases are a major prognostic factor in survival of patients with oesophageal cancer. The number of lymph nodes removed during oesophagectomy has been previously proven to be associated with improved survival. The aim of this study was to examine the effect of lymph node harvest on survival specifically in pathologically node negative (pN0) patients with oesophageal cancer. Data were extracted from a prospectively populated single-surgeon database of oesophageal resections for cancer. All consecutive patients with pN0 were included. Patient-specific risk adjusted analysis of overall and disease-free survival was performed to identify the number of lymph nodes associated with improved survival. Inclusion criteria were met by 137 patients (49 squamous cell carcinoma and 88 adenocarcinoma). Adjusted for cancer stage, tumour (histological type, degree of differentiation, lympho-vascular invasion, neo-adjuvant therapy) and patient related factors (age, sex), increased lymph node number was associated with significant improvement in overall (P = 0.045) and disease free (P = 0.030) survival. Lymph node count ≥ 17 was associated with improved overall and disease-free survival. In this cohort of patients with pathologically node-negative oesophageal cancer, lymph node count of 17 or above was associated with significantly improved survival.

Analyzing the effects of helical flow in blood vessels using acoustofluidic-based dynamic flow generator.

The effects of helical flow in a blood vessel are investigated in a dynamic flow generator using surface acoustic wave (SAW) in the microfluidic device. The SAW, generated by an interdigital transducer (IDT), induces acoustic streaming, resulting in a stable and consistent helical flow pattern in microscale channels. This approach allows rapid development of helical flow within the channel without directly contacting the medium. The precise design of the window enables the creation of distinct unidirectional vortices, which can be controlled by adjusting the amplitude of the SAW. Within this device, optimal operational parameters of the dynamic flow generator to preserve the integrity of endothelial cells are found, and in such settings, the actin filaments within the cells are aligned to the desired state. Our findings reveal that intracellular Ca2+ concentrations vary in response to flow conditions. Specifically, comparable maximum intensity and graphical patterns were observed between low-flow rate helical flow and high-flow rate Hagen-Poiseuille flow. These suggest that the cells respond to the helical flow through mechanosensitive ion channels. Finally, adherence of monocytes is effectively reduced under helical flow conditions in an inflammatory environment, highlighting the atheroprotective role of helical flow. STATEMENT OF SIGNIFICANCE: Helical flow in blood vessels is well known to prevent atherosclerosis. However, despite efforts to replicate helical flow in microscale channels, there is still a lack of in vitro models which can generate helical flow for analyzing its effects on the vascular system. In this study, we developed a method for generating steady and constant helical flow in microfluidic channel using acoustofluidic techniques. By utilizing this dynamic flow generator, we were able to observe the atheroprotective aspects of helical flow in vitro, including the enhancement of calcium ion flux and reduction of monocyte adhesion. This study paves the way for an in vitro model of dynamic cell culture and offers advanced investigation into helical flow in our circulatory system.

Elasto-inertial microfluidic separation of microspheres with submicron resolution at high-throughput.

Elasto-inertial microfluidic separation offers many advantages including high throughput and separation resolution. Even though the separation efficiency highly depends on precise control of the flow conditions, no concrete guidelines have been reported yet in elasto-inertial microfluidics. Here, we propose a dimensionless analysis for precise estimation of the microsphere behaviors across the interface of Newtonian and viscoelastic fluids. Reynolds number, modified Weissenberg number, and modified elastic number are used to investigate the balance between inertial and elastic lift forces. Based on the findings, we introduce a new dimensionless number defined as the width of the Newtonian fluid stream divided by microsphere diameter. The proposed dimensionless analysis allows us to predict whether the microspheres migrate across the co-flow interface. The theoretical estimation is found to be in good agreement with the experimental results using 2.1- and 3.2-µm-diameter polystyrene microspheres in a co-flow of water and polyethylene oxide solution. Based on the theoretical estimation, we also realize submicron separation of the microspheres with 2.1 and 2.5 µm in diameter at high throughput, high purity (>95%), and high recovery rate (>97%). The applicability of the proposed method was validated by separation of platelets from similar-sized Escherichia coli (E.coli).

Acoustofluidic separation of prolate and spherical micro-objects.

Most microfluidic separation techniques rely largely on object size as a separation marker. The ability to separate micro-objects based on their shape is crucial in various biomedical and chemical assays. Here, we develop an on-demand, label-free acoustofluidic method to separate prolate ellipsoids from spherical microparticles based on traveling surface acoustic wave-induced acoustic radiation force and torque. The freely rotating non-spherical micro-objects were aligned under the progressive acoustic field by the counterrotating radiation torque, and the major axis of the prolate ellipsoids was parallel to the progressive wave propagation. The specific alignment of the ellipsoidal particles resulted in a reduction in the cross-sectional area perpendicular to the wave propagation. As a consequence, the acoustic backscattering decreased, resulting in a decreased magnitude of the radiation force. Through the variation in radiation force, which depended on the micro-object morphology enabled the acoustofluidic shape-based separation. We conducted numerical simulations for the wave scattering of spherical and prolate objects to elucidate the working mechanism underlying the proposed method. A series of experiments with polystyrene microspheres, prolate ellipsoids, and peanut-shaped microparticles were performed for validation. Through quantitative analysis of the separation efficiency, we confirmed the high purity and high recovery rate of the proposed acoustofluidic shape-based separation of micro-objects. As a bioparticle, we utilize Thalassiosira eccentrica to perform shape-based separation, as the species has a variety of potential applications in drug delivery, biosensing, nanofabrication, bioencapsulation and immunoisolation.

Pharmacokinetics and Food Effect Between a 100-mg Sustained-Release Tablet and a 50-mg Immediate-Release Tablet of Vildagliptin in Healthy Subjects.

Vildagliptin is one of the dipeptidyl peptidase-4 inhibitors. This study aimed to compare vildagliptin exposure between 50-mg immediate-release (IR) and 100-mg new sustained-release (SR) tablets, and evaluate the food effect on the pharmacokinetics (PKs) of vildagliptin. A randomized, open-label, 3-period, 3-treatment, 6-sequence crossover study was conducted on healthy subjects. During each period, subjects received the SR tablet either in the fasted (T1) or high-fat fed (T2) state once a day, or IR tablets administered twice a day in the fasted state (R). Blood samples for PK analysis were obtained serially up to 24 hours after dosing. Thirty-four subjects completed the study. The geometric mean ratios for the Cmax and AUC0-24h of T1 to R were 1.15 and 0.89, respectively. The corresponding values of T2 to T1 were 0.94 and 1.07, respectively. Vildagliptin exposure over 24 hours was similar between the SR and IR tablets. In addition, the PK profiles of the SR tablets were not altered by food. The SR tablets can be administered without a food effect and be an alternative option to IR tablets.