Development of machine learning models for the surveillance of colon surgical site infections.

BACKGROUND: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency. METHODS: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method. RESULTS: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method. CONCLUSION: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV.

"Primer shot" fractionation with an early treatment break is theoretically superior to consecutive weekday fractionation schemes for early-stage non-small cell lung cancer.

PURPOSE: Radiotherapy is traditionally given in equally spaced weekday fractions. We hypothesize that heterogeneous interfraction intervals can increase radiosensitivity via reoxygenation. Through modeling, we investigate whether this minimizes local failures and toxicity for early-stage non-small cell lung cancer (NSCLC). METHODS: Previously, a tumor dose-response model based on resource competition and cell-cycle-dependent radiosensitivity accurately predicted local failure rates for early-stage NSCLC cohorts. Here, the model mathematically determined non-uniform inter-fraction intervals minimizing local failures at similar normal tissue toxicity risk, i.e., iso-BED3 (iso-NTCP) for fractionation schemes 18Gyx3, 12Gyx4, 10Gyx5, 7.5Gyx8, 5Gyx12, 4Gyx15. Next, we used these optimized schedules to reduce toxicity risk (BED3) while maintaining stable local failures (TCP). RESULTS: Optimal schedules consistently favored a "primer shot" fraction followed by a 2-week break, allowing tumor reoxygenation. Increasing or decreasing the assumed baseline hypoxia extended or shortened this optimal break by up to one week. Fraction sizes of 7.5 Gy and up required a single primer shot, while smaller fractions needed one or two extra fractions for full reoxygenation. The optimized schedules, versus consecutive weekday fractionation, predicted absolute LF reductions of 4.6%-7.4%, except for the already optimal LF rate seen for 18Gyx3. Primer shot schedules could also reduce BED3 at iso-TCP with the biggest improvements for the shortest schedules (94.6Gy reduction for 18Gyx3). CONCLUSION: A validated simulation model clearly supports non-standard "primer shot" fractionation, reducing the impact of hypoxia-induced radioresistance. A limitation of this study is that primer-shot fractionation is outside prior clinical experience and therefore will require clinical studies for definitive testing.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Tumor immune-gene expression profiles and peripheral immune phenotypes associated with clinical outcomes of locally advanced pancreatic cancer following FOLFIRINOX.

BACKGROUND: A comprehensive analysis of peripheral immune cell phenotypes and tumor immune-gene expression profiles in locally advanced pancreatic cancer patients treated with neoadjuvant chemotherapy in a phase II clinical trial was carried out. METHODS: Patients were treated with neoadjuvant modified folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX) followed by surgery and adjuvant gemcitabine at the Asan Medical Center. Correlations between survival outcomes and baseline peripheral immune cells and their changes during preoperative chemotherapy were analyzed. Patients who had surgery were divided into two groups according to achievement of disease-free survival >10 months (achieved versus failed). Differential expression and pathway analysis of immune-related genes were carried out using the Nanostring platform, and immune cells within the tumor microenvironment were compared by immunohistochemistry. RESULTS: Forty-four patients were treated in the phase II clinical trial. Higher baseline CD14+CD11c+HLA-DR+ monocytes (P = 0.044) and lower Foxp3+CD4+ T cells (P = 0.02) were associated with poor progression-free survival of neoadjuvant mFOLFIRINOX. During the preoperative chemotherapy, PD-1 T cells significantly decreased (P = 0.0110). Differential expression and pathway analysis of immune-genes from the resected tumor after neoadjuvant treatment revealed transforming growth factor-ß pathway enrichment and higher expression of MARCO (adjusted P < 0.05) associated with early recurrence. Enrichment of the Th1 pathway and higher peritumoral CD8+ T cells (P = 0.0103) were associated with durable disease-free survival from surgery (>10 months) following neoadjuvant mFOLFIRINOX. CONCLUSIONS: Our results identify potential immune biomarkers for locally advanced pancreatic cancer and provide insights into pancreatic cancer immunity.

Increased salivary syndecan-1 level is associated with salivary gland function and inflammation in patients with Sjögren's syndrome.

OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.

Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index <55%: single-arm phase II study.

BACKGROUND: Grade 3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) origin with Ki-67 indices <55% do not respond well to platinum-based chemotherapy. The combination of capecitabine and temozolomide (CAPTEM) has shown favorable responses in grade 1-2 NENs, but has rarely been studied in patients with grade 3 NENs. PATIENTS AND METHODS: This open-label, single-arm phase II trial included patients with unresectable or metastatic grade 3 NENs of GEP origin with Ki-67 indices <55% enrolled between June 2017 and July 2020. Patients received oral capecitabine 750 mg/m2 twice daily on days 1 to 14 and oral temozolomide 200 mg/m2 once daily on days 10 to 14 every 4 weeks. Histologic findings were centrally reviewed after the completion of enrollment. The primary endpoint was overall response rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Of the 30 patients included in the full analysis set, 1 (3.3%) achieved complete response, 8 (26.7%) had partial responses, and 14 (46.7%) had stable disease, making the overall response rate 30.0%. At a median follow-up of 19.2 months, the median PFS was 5.9 months and the median OS was not reached. Patients with well-differentiated NENs showed significantly better median PFS (9.3 months versus 3.5 months, P = 0.005) and median OS (not reached versus 6.2 months, P = 0.004) than patients with poorly differentiated tumors. Expression of O6-methyl-guanine methyltransferase protein did not correlate with clinical outcomes. The most common grade 3-4 adverse events were thrombocytopenia (10%), anemia (6.7%), and nausea (6.7%). CONCLUSIONS: CAPTEM was effective and well tolerated in patients with grade 3 GEP-NENs with Ki-67 indices <55%, with superior efficacy outcomes compared with the historical controls receiving platinum-based chemotherapy.

Intramedullary pneumorrhachis following a cervical epidural steroid injection.

Pneumorrhachis (PR) is a rare radiological condition characterized by the presence of intraspinal air. PR is commonly classified as spontaneous (nontraumatic), traumatic, or iatrogenic, and iatrogenic PR is the most common and often occurs secondary to invasive procedures such as epidural anesthesia, lumbar puncture, or spinal surgery. PR is usually asymptomatic, but it can produce symptoms associated with its underlying pathology. Here, we report a rare case of intramedullary cervical PR following a cervical epidural steroid injection (ESI) and include pertinent discussion.

Stacking Fault Energy Analyses of Additively Manufactured Stainless Steel 316L and CrCoNi Medium Entropy Alloy Using In Situ Neutron Diffraction.

Stacking fault energies (SFE) were determined in additively manufactured (AM) stainless steel (SS 316 L) and equiatomic CrCoNi medium-entropy alloys. AM specimens were fabricated via directed energy deposition and tensile loaded at room temperature. In situ neutron diffraction was performed to obtain a number of faulting-embedded diffraction peaks simultaneously from a set of (hkl) grains during deformation. The peak profiles diffracted from imperfect crystal structures were analyzed to correlate stacking fault probabilities and mean-square lattice strains to the SFE. The result shows that averaged SFEs are 32.8 mJ/m2 for the AM SS 316 L and 15.1 mJ/m2 for the AM CrCoNi alloys. Meanwhile, during deformation, the SFE varies from 46 to 21 mJ/m2 (AM SS 316 L) and 24 to 11 mJ/m2 (AM CrCoNi) from initial to stabilized stages, respectively. The transient SFEs are attributed to the deformation activity changes from dislocation slip to twinning as straining. The twinning deformation substructure and atomic stacking faults were confirmed by electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The significant variance of the SFE suggests the critical twinning stress as 830 ± 25 MPa for the AM SS 316 L and 790 ± 40 MPa for AM CrCoNi, respectively.

The impact of social media on citation rates in coloproctology.

AIM: This study aimed to investigate the association between Twitter exposure and the number of citations for coloproctology articles. METHOD: Original articles from journals using Twitter between June 2015 and May 2016 were evaluated for the following characteristics: publishing journal; article subject; study design; nationality, speciality and affiliation of the author(s); and reference on Twitter. Citation data for these articles were retrieved from Google Scholar (https://scholar.google.com) in January 2018. We performed a univariate analysis using these data followed by a multivariate, logistic regression analysis to search for factors associated with a high citation level, which was defined as accrual of more than five citations. RESULTS: Out of six coloproctology journals listed on the InCites JCR database, three (Diseases of the Colon & Rectum, Colorectal Disease and Techniques in Coloproctology) used Twitter, where 200 (49.5%) out of a total of 404 articles had been featured. Citation rates of articles that featured on Twitter were significantly higher than those that did not (11.4 ± 9.2 vs 4.1 ± 3.1, P < 0.001). In multivariate analysis, Twitter exposure (OR 8.6, P = 0.001), European Union nationality (OR 2.4, P = 0.004), Colorectal Disease journal (OR 3.3, P = 0.005) and systematic review articles (OR 3.4, P = 0.009) were associated with higher citation levels. CONCLUSION: Article exposure on Twitter was strongly associated with a high citation level. Medical communities should encourage journals as well as physicians to actively utilize social media to expedite the spread of new ideas and ultimately benefit medical society as a whole.

Ultrasound-guided lung sliding sign to confirm optimal depth of tracheal tube insertion in young children.

BACKGROUND: The tip of the tracheal tube should lie at the mid-tracheal level after tracheal intubation in paediatric patients. Auscultation does not guarantee optimal positioning of the tracheal tube. We compared auscultation and the ultrasound-guided lung sliding sign to confirm optimal positioning of the tracheal tube in paediatric patients. METHODS: We studied 74 paediatric patients aged 0-24 months of ASA physical status 1-3 who were scheduled for elective surgery under general anaesthesia. All were randomly assigned to one of two groups: depth of tracheal tube confirmed by auscultation (Group A) or using the ultrasound-guided lung sliding sign (Group S). RESULTS: Optimal positioning of the tracheal tube was observed in 32 of 37 (87%) subjects in Group S and 24 of 37 (65%) subjects in Group A (difference in proportion, 22%; 95% confidence interval, 2-39%; P=0.030). Optimal depth correlated with patient height (adjusted coefficient=0.888, P<0.001). CONCLUSIONS: In paediatric patients younger than 24 months, use of the ultrasound-guided lung sliding sign was more accurate than auscultation for optimal positioning of the tracheal tube. CLINICAL TRIAL REGISTRATION: KCT 0003015.

Ultrasound-guided vs. palpation-guided techniques for radial arterial catheterisation in infants: A randomised controlled trial.

BACKGROUND: The usefulness of ultrasound-guided techniques for radial arterial catheterisation has been well identified; however, its usefulness has not been completely evaluated in infants under 12 months of age, who are generally considered the most difficult group for arterial catheterisation. OBJECTIVE: We evaluated whether ultrasound guidance would improve success rates and reduce the number of attempts at radial arterial catheterisation in infants. DESIGN: A randomised, controlled and patient-blinded study. SETTING: Single-centre trial, study period from June 2016 to February 2017. PATIENTS: Seventy-four infants undergoing elective cardiac surgery. INTERVENTION: Patients were allocated randomly into either ultrasound-guided group (group US) or palpation-guided group (group P) (each n=37) according to the technique applied for radial arterial catheterisation. All arterial catheterisations were performed by one of two experienced anaesthesiologists based on group assignment and were recorded on video. MAIN OUTCOME MEASURES: The primary endpoint was the first-pass success. The number of attempts and total duration of the procedure until successful catheterisation were also analysed. RESULTS: The first-pass success rate was significantly higher in the group US than in the group P (68 vs. 38%, P = 0.019). In addition, fewer attempts were needed for successful catheterisation in the group US than in the group P (median 1 [IQR 1 to 2] vs. 2 [1 to 4], P = 0.023). However, the median [IQR] procedural time (s) until successful catheterisation in the two groups was not significantly different (102 [49 to 394] vs. 218 [73 to 600], P = 0.054). CONCLUSION: The current study demonstrated that the ultrasound-guided technique for radial arterial catheterisation in infants effectively improved first-pass success rate and also reduced the number of attempts required. TRIAL REGISTRATION: ClinicalTrials.gov NCT02795468.

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

OBJECTIVE: Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. MATERIAL AND METHODS: Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. RESULTS: Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. CONCLUSION: Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy.

Gastrointestinal inflammation by gut microbiota disturbance induces memory impairment in mice.

In this study, we tested our hypothesis regarding mechanistic cross-talk between gastrointestinal inflammation and memory loss in a mouse model. Intrarectal injection of the colitis inducer 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice caused colitis via activation of nuclear factor (NF)-κB and increase in membrane permeability. TNBS treatment increased fecal and blood levels of lipopolysaccharide (LPS) and the number of Enterobacteriaceae, particularly Escherichia coli (EC), in the gut microbiota composition, but significantly reduced the number of Lactobacillus johnsonii (LJ). Indeed, we observed that the mice treated with TNBS displayed impaired memory, as assessed using the Y-maze and passive avoidance tasks. Furthermore, treatment with EC, which was isolated from the feces of mice with TNBS-induced colitis, caused memory impairment and colitis, and increased the absorption of orally administered LPS into the blood. Treatment with TNBS or EC induced NF-κB activation and tumor necrosis factor-α expression in the hippocampus of mice, as well as suppressed brain-derived neurotrophic factor expression. However, treatment with LJ restored the disturbed gut microbiota composition, lowered gut microbiota, and blood LPS levels, and attenuated both TNBS- and EC-induced memory impairment and colitis. These results suggest that the gut microbiota disturbance by extrinsic stresses can cause gastrointestinal inflammation, resulting in memory impairment.

MIG-6 negatively regulates STAT3 phosphorylation in uterine epithelial cells.

Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4-resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of signal transducers and activators of transcription 3 (STAT3) and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr-positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4-responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells, and the antitumor effects of P4 are mediated by the endometrial stroma. These data help to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer.

Ischemic Preconditioning Produces Comparable Protection Against Hepatic Ischemia/Reperfusion Injury Under Isoflurane and Sevoflurane Anesthesia in Rats.

BACKGROUND: Various volatile anesthetics and ischemic preconditioning (IP) have been demonstrated to exert protective effect against ischemia/reperfusion (I/R) injury in liver. We aimed to determine whether application of IP under isoflurane and sevoflurane anesthesia would confer protection against hepatic I/R injury in rats. METHODS: Thirty-eight rats weighing 270 to 300 grams were randomly divided into 2 groups: isoflurane (1.5%) and sevoflurane (2.5%) anesthesia groups. Each group was subdivided into sham (n = 3), non-IP (n = 8; 45 minutes of hepatic ischemia), and IP (n = 8, IP consisting of 10-minute ischemia plus 15-minute reperfusion before prolonged ischemia) groups. The degree of hepatic injury and expressions of B-cell lymphoma 2 (Bcl-2) and caspase 3 were compared at 2 hours after reperfusion. RESULTS: Hepatic ischemia induced significant degree of I/R injuries in both isoflurane and sevoflurane non-IP groups. In both anesthetic groups, introduction of IP dramatically attenuated I/R injuries as marked by significantly lower aspartate aminotransferase and aminotransferase levels and better histologic grades compared with corresponding non-IP groups. There were 2.3- and 1.7-fold increases in Bcl-2 mRNA levels in isoflurane and sevoflurane IP groups, respectively, compared with corresponding non-IP groups (both P < .05). Caspase 3 level was significantly high in the isoflurane non-IP group compared with the sham group; however, there were no differences among the sevoflurane groups. CONCLUSIONS: The degree of hepatic I/R injury was significantly high in both isoflurane and sevoflurane groups in rats. However, application of IP significantly protected against I/R injury in both volatile anesthetic groups to similar degrees, and upregulation of Bcl-2 might be an important mechanism.

LAPAROSCOPIC OVARIECTOMY IN THE ASIATIC BLACK BEAR (URSUS THIBETANUS) WITH THE USE OF THE SONICISION™ DEVICE.

Laparoscopic ovariectomy was performed in two Asiatic black bears ( Ursus thibetanus ). Bears were placed in a 20° Trendelenburg position on a surgical table. A three-portal technique was used. A camera port was established 10 cm caudal to the umbilicus with a 5-mm cannula. Two instrument ports were made 1 cm caudal to the umbilicus with a 5-mm cannula and 8 cm caudal to the camera port with a 12-mm cannula, respectively. The suspensory ligament, ovarian vasculature, and uterine horn tip were progressively dissected following coagulation with the Sonicision™ cordless ultrasonic dissection device. The resected ovary was exteriorized through the 12-mm instrument portal site but enlarged to a 2-cm incision length. The abdominal musculature, subcutaneous tissue, and skin of the portal sites were closed separately. Total surgical time was 113 min (Bear A) and 49 min (Bear B), and no postoperative complications were encountered. This is the first report of laparoscopic ovariectomy in the Asiatic black bear.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy.

Retraction to: Cell Death Differ 2016;23(9):1471­1482. doi:10.1038/cdd.2016.32

Anti-inflammaging effects of Lactobacillus brevis OW38 in aged mice.

In the present study, lactic acid bacteria (LAB) strains were collected from kimchi and were screened to isolate strains that inhibit lipopolysaccharide (LPS) production by Escherichia coli and p16 expression and nuclear factor-kappa B (NF-κB) activation in LPS-stimulated macrophages. Oral administration of Lactobacillus brevis OW38 (1×109 cfu/mouse) to aged mice (male, 18 months old) for 8 weeks reduced the LPS level in colon fluid and blood. In addition, OW38 treatment also reduced the ratio of Firmicutes or Proteobacteria to Bacteroidetes, which was significantly higher in aged mice than in young mice. Treatment with OW38 in aged mice inhibited the expression of inflammatory markers, such as myeloperoxidase, tumour necrosis factor (TNF), and interleukin (IL)-1ß, and inhibited NF-κB activation. Furthermore, it induced the expression of colonic tight junction proteins zonula occludens-1, occludin, and claudin-1. OW38 treatment also suppressed the expression of senescence markers p16, p53, and SAMHD1 in the colon and the hippocampus of aged mice. In addition, it significantly restored spontaneous alternation as well as the expression of brain-derived neurotrophic factor and doublecortin in aged mice compared to that in young mice (P<0.05). Based on these findings, we conclude that OW38 treatment may ameliorate aging-associated colitis and memory impairment by inhibiting gut microbiota LPS production, NF-κB activation, and p16 expression.