Chylous drainage through percutaneous cholecystostomy: an extremely rare complication.

Chyle leak is a rare but potentially morbid complication of abdominal surgery. There have been seven reported cases of chylous ascites following cholecystectomy, but no such occurrences are reported with percutaneous cholecystostomy tube (PCT) insertion. We report the case of a 67-year-old female with stage IVb recurrent uterine papillary serous carcinoma and extensive abdominal surgical history including a paraesophageal hernia repair, and a robotic hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, gastrocolic omentectomy, and hepatoduodenal lymphadenectomy. The patient presented with clinical findings suggestive of acute cholecystitis and decision was made to proceed with PCT placement. The PCT was dislodged and replaced during her course and several days after chylous output was noted from the PCT. The remainder of her hospital course was complicated by persistent distributive shock, adrenal insufficiency, and continued chyle leak. She ultimately was transitioned to inpatient hospice and died shortly after.

Polygenic control of the wavy coat of the NCT mouse: involvement of an intracisternal A particle insertional mutation of the protease, serine 53 (Prss53) gene, and a modifier gene.

The Nakano cataract mouse (NCT) manifests a wavy coat for their first hair as a genetic trait. In this study, we explored the molecular genetic basis of the wavy coat. We revealed by crossing experiments that the wavy coat is controlled by a major gene on chromosome 7 of NCT, homozygosity of which is a prerequisite for developing the wavy coat, and by a gene on chromosome 9 with a minor effect to reinforce the manifestation of the trait. In humans, a polymorphism of the protease, serine 53 (PRSS53) gene on the homologous chromosome is known to be associated with curly scalp hair. We then investigated the Prss53 gene and discovered that NCT has an insertion of an intracisternal A particle element in the first intron of the gene. Nevertheless, the expression of the Prss53 is not altered in the NCT skin both in transcript and protein levels. Subsequently, we created C57BL/6J-Prss53em1 knockout mice and found that these mice manifest vague wavy coats. A portion of backcross and intercross mice between the C57BL/6J-Prss53em1 and NCT manifested intense or vague wavy coats. These findings demonstrate the polygenic nature of the wavy coat of NCT and Prss53 knockout mice and highlight the similarity of the trait to the curly hair of humans associated with the PRSS53 alteration.

Exercise suppresses mouse systemic AApoAII amyloidosis through enhancement of the p38 MAPK signaling pathway.

Exercise interventions are beneficial for reducing the risk of age-related diseases, including amyloidosis, but the underlying molecular links remain unclear. Here, we investigated the protective role of interval exercise training in a mouse model of age-related systemic apolipoprotein A-II amyloidosis (AApoAII) and identified potential mechanisms. Mice subjected to 16 weeks of exercise showed improved whole-body physiologic functions and exhibited substantial inhibition of amyloidosis, particularly in the liver and spleen. Exercise activated the hepatic p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and the downstream transcription factor tumor suppressor p53. This activation resulted in elevated expression and phosphorylation of heat shock protein beta-1 (HSPB1), a chaperone that defends against protein aggregation. In amyloidosis-induced mice, the hepatic p38 MAPK-related adaptive responses were additively enhanced by exercise. We observed that with exercise, greater amounts of phosphorylated HSPB1 accumulated at amyloid deposition areas, which we suspect inhibits amyloid fibril formation. Collectively, our findings demonstrate the exercise-activated specific chaperone prevention of amyloidosis, and suggest that exercise may amplify intracellular stress-related protective adaptation pathways against age-associated disorders, such as amyloidosis.

The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.

Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene PDCD1 was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, CDKN2A expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments. IMPLICATIONS: Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice.

AIMS: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism. MAIN METHODS: Female obese, type 2 diabetic KK-Ay mice were fed diets supplemented with 0.3% or 0.8% GRO (w/w) for 4-12 weeks. Mice were euthanized and autopsied at 20 weeks old. The effects of GRO on lipid and glucose metabolism were evaluated by measuring physiological and biochemical markers using mRNA sequencing, quantitative reverse-transcription PCR, and western blot analyses. KEY FINDINGS: Compared to mice fed the control diet, GRO-supplemented mice had reduced body and white adipose tissue weights, serum levels of triglycerides and cholesterol, and improved glucose tolerance, while food intake was not affected. We found remarkable reductions in the gene expression levels of stearoyl-coenzyme A desaturase 1 (Scd1) and pyruvate dehydrogenase kinase isoenzyme 4 (Pdk4) in the liver, in addition to decreased expression of fatty acid synthase (Fasn) in inguinal white adipose tissue (iWAT). These results suggest that GRO supplementation improves lipid profiles via reduced de novo lipogenesis in the liver and white adipose tissue. Glucose metabolism may also be improved by increased glycolysis in the liver. SIGNIFICANCE: Our analysis of long-term supplementation of GRO in obese and diabetic mice should provide novel insight into preventing insulin resistance and metabolic syndromes.

Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway.

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. Liver weights and plasma ApoA-II and high-density lipoprotein concentrations were significantly elevated in curcumin-supplemented groups. RNA-sequence analysis revealed that curcumin intake affected hepatic lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) pathway, especially PPARα activation, resulting in increased Apoa2 mRNA expression. The increase in liver weights was due to activation of PPARα and peroxisome proliferation. Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner.

[A Case of Advanced Rectal Cancer with Left Hydronephrosis Treated with Left Ureter-Sparing Laparoscopic High Anterior Resection after Chemotherapy].

A 47-year-old woman with a complaint of weight loss for the past 5 months was referred to our hospital. Colonoscopy revealed advanced rectal cancer 20 cm from the anal verge. The patient had left hydronephrosis caused by ureteral invasion. Firstly, we performed transverse colostomy and left nephrostomy. After 8 courses of capecitabine, oxaliplatin plus bevacizumab( CAPOX plus Bmab)therapy, colonoscopy and computed tomography revealed shrinkage of both the primary and metastatic lesions. Laparoscopic high anterior resection was performed, and the left ureter was successfully preserved. The patient received chemotherapy after surgery. Neither local recurrence nor enlargement of metastases has been observed 8 months after surgery.

[A Case of Synchronous Multiple Colorectal Cancer with Rectal Neuroendocrine Tumor and Ascending Colon Cancer].

A 43-year-old man who had no previous medical history or family history had positive fecal occult blood test in a local physician. Colonoscopy revealed a type 2 tumor of the ascending colon and a 10 mm submucosal tumor(SMT)of the lower rectum. Biopsy indicated moderately-differentiated adenocarcinoma of the ascending colon and neuroendocrine tumor (NET)of the lower rectum. No metastasis was detected by computed tomography. Therefore, the rectal SMT was resected first by endoscopic submucosal resection. Histopathologically, the lesion was localized in the submucosa and no lymphovascular invasion was found. Vertical margin was also negative. We decided not to perform additional intestinal resection for rectal NET. Thereafter, the patient underwent laparoscopic right hemicolectomy for ascending colon cancer. The histopathological findings were pT3, pN1, pM0, pStage Ⅲb. The patient received adjuvant chemotherapy. No relapse was found 18 months after surgery. We reported a rare case of a lower rectal NET with concomitant ascending colon cancer.

Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.

Plasma exosome-encapsulated microRNA-21 and microRNA-92a are promising biomarkers for the prediction of peritoneal recurrence in patients with gastric cancer.

In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC.

Suppression of Mouse AApoAII Amyloidosis Progression by Daily Supplementation with Oxidative Stress Inhibitors.

Amyloidosis is a group of diseases characterized by protein misfolding and aggregation to form amyloid fibrils and subsequent deposition within various tissues. Previous studies have indicated that amyloidosis is often associated with oxidative stress. However, it is not clear whether oxidative stress is involved in the progression of amyloidosis. We administered the oxidative stress inhibitors tempol and apocynin via drinking water to the R1.P1-Apoa2c mouse strain induced to develop mouse apolipoprotein A-II (AApoAII) amyloidosis and found that treatment with oxidative stress inhibitors led to reduction in AApoAII amyloidosis progression compared to an untreated group after 12 weeks, especially in the skin, stomach, and liver. There was no effect on ApoA-II plasma levels or expression of Apoa2 mRNA. Detection of the lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) revealed that the antioxidative effects of the treatments were most obvious in the skin, stomach, and liver, which contained higher levels of basal oxidative stress. Moreover, the unfolded protein response was reduced in the liver and was associated with a decrease in oxidative stress and amyloid deposition. These results suggest that antioxidants can suppress the progression of AApoAII amyloid deposition in the improved microenvironment of tissues and that the effect may be related to the levels of oxidative stress in local tissues. This finding provides insights for antioxidative stress treatment strategies for amyloidosis.

A Polling-Based Transmission Scheme Using a Network Traffic Uniformity Metric for Industrial IoT Applications.

The Industrial Internet of Things (IIoT) applications are required to provide precise measurement functions as feedback for controlling devices. The applications traditionally use polling-based communication protocols. However, in polling-based communication over current industrial wireless network protocols such as ISA100.11a, WirelessHART have difficulty in realizing both scheduled periodic data collection at high success ratio and unpredictable on-demand communications with short latency. In this paper, a polling-based transmission scheme using a network traffic uniformity metric is proposed for IIoT applications. In the proposed scheme, a center node controls the transmission timing of all polling-based communication in accordance with a schedule that is determined by a Genetic Algorithm. Communication of both periodic and unpredictable on-demand data collection are uniformly assigned to solve the above difficulties in the schedule. Simulation results show that network traffic is generated uniformly and a center node can collect periodic data from nodes at high success ratio. The average success probability of periodical data collection is 97.4 % and the lowest probability is 95.2 % .

Exosome­encapsulated microRNA­23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage.

Recently, exosome­encapsulated microRNAs (miRNAs) have been attracting attention as stable and minimally invasive biomarkers in cancer patients. The aim of the present study was to clarify the value of plasma exosomal microRNA­23b (miR­23b) as a diagnostic and prognostic biomarker in gastric cancer (GC) patients at each tumor stage. We first selected recurrence specific exosomal miRNA by miRNA microarray from 6 GC patients (stage I) with or without recurrence, and 3 healthy volunteers. In this analysis, miR­23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR­23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR­23b levels were evaluated by Taqman microRNA assays. Exosomal miR­23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR­23b levels and the expression of miR­23b in primary tumor tissues. Concerning the pathological condition, miR­23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low­miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II, III and IV. The disease­free survival (DFS) rates of low exosomal miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR­23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR­23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.

A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

Direct imaging of isofrequency contours in photonic structures.

The isofrequency contours of a photonic crystal are important for predicting and understanding exotic optical phenomena that are not apparent from high-symmetry band structure visualizations. We demonstrate a method to directly visualize the isofrequency contours of high-quality photonic crystal slabs that show quantitatively good agreement with numerical results throughout the visible spectrum. Our technique relies on resonance-enhanced photon scattering from generic fabrication disorder and surface roughness, so it can be applied to general photonic and plasmonic crystals or even quasi-crystals. We also present an analytical model of the scattering process, which explains the observation of isofrequency contours in our technique. Furthermore, the isofrequency contours provide information about the characteristics of the disorder and therefore serve as a feedback tool to improve fabrication processes.

Spawning rings of exceptional points out of Dirac cones.

The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformation of the Dirac cone often reveals intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. Dirac cones and exceptional points are connected: it was theoretically suggested that certain non-Hermitian perturbations can deform a Dirac cone and spawn a ring of exceptional points. Here we experimentally demonstrate such an 'exceptional ring' in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone resulting from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain.

Experimental Observation of Large Chern Numbers in Photonic Crystals.

Despite great interest in the quantum anomalous Hall phase and its analogs, all experimental studies in electronic and bosonic systems have been limited to a Chern number of one. Here, we perform microwave transmission measurements in the bulk and at the edge of ferrimagnetic photonic crystals. Band gaps with large Chern numbers of 2, 3, and 4 are present in the experimental results, which show excellent agreement with theory. We measure the mode profiles and Fourier transform them to produce dispersion relations of the edge modes, whose number and direction match our Chern number calculations.