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Abstract Background Jejunogastric intussusception (JGI) is a rare, but potentially fatal complication that can occur following gastric surgery, and the reported incidence of JGI is as low as 0.1%. Early diagnosis and treatment are critical for JGI to prevent major complications such as bowel necrosis and death. Although emergency surgery is the standard treatment, endoscopic reduction has also been reported to be effective in JGI patients without bowel necrosis. Several early recurrent cases treated with surgical or endoscopic reduction have been reported. We report an extremely rare case of JGI after pancreaticoduodenectomy (PD) using Child’s procedure that was successfully treated with surgical reduction and fixation. Case presentation An 81-year-old man who had undergone PD using Child’s procedure 3 years ago presented to our hospital with epigastric pain and nausea. His vital signs were stable, and abdominal examination revealed mild tenderness with a palpable mass in the mid-epigastrium. Abdominal computed tomography (CT) and gastroscopy revealed a JGI of the efferent loop, and exploratory laparotomy was immediately performed. During the operation, the efferent loop showed no adhesions and was intussuscepted through the gastrojejunostomy into the gastric lumen. An incision in the anterior wall of the stomach revealed no evidence of ischemia of the intussusceptum. The efferent loop was reduced using Hutchinson’s maneuver and fixed to the afferent loop to prevent a recurrence. The postoperative course was uneventful, and there was no sign of recurrence 12 months postoperatively. Conclusions JGI after PD is an extremely rare, but has severe complications. Surgery might be the optimal treatment for JGI in terms of preventing recurrence, even in cases without bowel necrosis.

Abstract Background Subtotal cholecystectomy is an effective surgical method to decrease the risk of complications for gallbladders that are difficult to remove. However, there is a risk for postoperative refractory bile leakage through the gallbladder stump. Here, we report a new management technique involving the use of argon plasma coagulation (APC) to stop bile leakage after a subtotal cholecystectomy. Case presentation A 74-year-old man was referred to our hospital for abdominal pain and fever. Contrast-enhanced computed tomography of the abdomen showed fluid collection, such as an abscess, surrounding the gallbladder and hepatic flexure colon. The patient was diagnosed with colonic perforative peritonitis, and he underwent emergency surgery. On laparotomy, the abscess was observed outside of the hepatic flexure colon and gallbladder necrosis was detected. The neck of the gallbladder and the area close to the hepatoduodenal ligament was severely inflamed prohibiting dissection. The hepatic flexure colon was part of the abscess wall, and resection was needed. A subtotal cholecystectomy and right hemicolectomy confirmed peritonitis caused by cholecystic perforation. The mucous membrane of the gallbladder neck that remained was necrotic or detached. Therefore, the stump of the gallbladder was closed by primary sutures without cauterization of the mucosa. On postoperative day 6, bile leakage from the gallbladder stump was revealed. Percutaneous and endoscopic retrograde cholangiography drainage were performed. However, the liquid, which seemed to be secreted from the mucosa of the remnant gallbladder, was continuously obtained. We used APC to cauterize the gallbladder mucosa through the fistula of the abdominal drainage tube. Bile leakage and mucus discharge were improved after three rounds of APC cauterization. Conclusions APC effectively treated refractory bile leakage from a gallbladder stump after subtotal cholecystectomy for severe cholecystitis.

Abstract Background The safety and feasibility of laparoscopic colectomy for T4 colorectal cancer remain controversial. We believe that setting a “Goal” that will guide the surgeons in returning from the deep layer could be the key to safe en bloc resection of neighboring organs. For descending colon cancer, the cranial-first approach makes it possible to clearly visualize the pancreas and origin of the transverse mesocolon, leading to safe splenic flexure mobilization and complete mesocolic excision, which is the strongest advantage of this approach. Case presentation A 75-year-old woman was diagnosed with T4 descending colon cancer invading the Gerota’s fascia. We performed laparoscopic left colectomy using the cranial-first approach to set a “Goal” at the inferior border of the pancreas for safe resection of the Gerota’s fascia. The total operative time was 233 min, and the estimated blood loss was 98 ml. She was discharged after surgery without postoperative complications. Pathological findings revealed the invasion into the Gerota’s fascia, and the resection margin was negative for cancer. Conclusions The cranial-first approach of laparoscopic left colectomy appears to be safe and feasible and could be a promising method for selected patients with T4 descending colon cancer invading the Gerota’s fascia.

Abstract Background Segmental arterial mediolysis is a rare nonarteriosclerotic and noninflammatory vascular disease that may cause intraperitoneal bleeding. Scleroderma renal crisis is a rare complication of systemic sclerosis, leading to severe hypertension and renal dysfunction. To the best of our knowledge, this is the first reported case of a patient with concurrent systemic sclerosis with scleroderma renal crisis and pathologically confirmed segmental arterial mediolysis. Case presentation We report a case of a 68-year-old Chinese woman diagnosed with systemic sclerosis who was found to have coexisting segmental arterial mediolysis. She presented with back pain, and massive intraperitoneal bleeding was detected by computed tomography. She underwent laparotomy, and the bleeding was found to originate from the gastroepiploic artery. The pathological examination demonstrated gastroepiploic arterial dissection caused by segmental arterial mediolysis. After surgery, she developed severe hypertension with hyperreninemia and progressive renal dysfunction. Given the risk factors of corticosteroid administration and the presence of anti-ribonucleic acid polymerase III antibody, she was diagnosed with scleroderma renal crisis. The patient was proved to have a very rare case of coexisting scleroderma renal crisis and segmental arterial mediolysis. Conclusions There is no known etiological connection between segmental arterial mediolysis and systemic sclerosis or scleroderma renal crisis, but it is possible that coexisting segmental arterial mediolysis and scleroderma renal crisis may have interacted to trigger the development of the other in our patient.

Summary: The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics. : Fujita et al. report a crystal structure of the trimeric LUBAC core and show that motifs in HOIL-1L and SHARPIN fold into a single domain critical for LUBAC stabilization. The authors also develop an inhibitor of this interaction that destabilizes LUBAC and kills cancer cells. Keywords: linear ubiquitin chains, LUBAC, LUBAC-tethering motif, HOIP, HOIL-1L, SHARPIN, ubiquitin-like domain, ubiquitin-associated domain, cancer

Abstract Two kinds of wearable cooling devices were evaluated for their cooling effect by a thermal manikin. All measurements were conducted in a climatic chamber. The cooling fans worked almost 3 h. Their cooling effect was large at the head and had little effects on other parts of the manikin. They decreased the insulation of a typical clothing ensemble of outdoor workers in construction industries from 0.75 clo to 0.48 clo. The cooling vest for heat protective clothing mainly worked on the trunk. It did not have enough effect nor had steady cooling effect. But the vest worked as direct cooling device for the trunk. The effect of the fans to Standard Effective Temperature (SET) is evaluated by simulation. The difference of SETs between the case of the typical ensemble and the case with the cooling fans at 35 °C of the surrounding environment is 2.6 °C. The lower the surrounding temperature is, the larger the difference between SETs of different clothing insulation value is.

Ventral midbrain cavernous malformations are rare, and annual bleeding rate is higher than supratentorial lesions. Rebleeding rate is also high if surgical resection is incomplete. The ventral midbrain is deeply located and surrounded by many perforators, which make the approach to this region difficult. We experienced two cases of ventral midbrain cavernous malformations successfully removed via orbitozygomatic interpeduncular approach. In these cases, most parts of the lesions exist behind the cerebral peduncle extending interpeduncular fossa. In the first case involving a 15-year-old girl, we removed the lesion completely through an ipsilateral orbitozygomatic interpeduncular approach with minimum sacrifice of the right cerebral peduncle. However, in the second case involving a 43-year-old man, the same approach did not reach the lesion behind the ipsilateral cerebral peduncle. At the second operation, a contralateral orbitozygomatic interpeduncular approach was used to remove the residual lesion completely. Ipsilateral and contralateral orbitozygomatic interpeduncular approaches with minimum destruction of the cerebral peduncle are options for the lesions which exist in the interpeduncular fossa and behind the cerebral peduncle.

Dysregulation of p62 has been implicated in tumorigenesis. Here, the authors show that p62 promotes hepatocellular carcinoma by reprogramming glucose and glutamine metabolism through Nrf2 and present a novel compound that can inhibit p62 action thus sensitizing cancer cells to chemotherapy.

The feasibility and safety of laparoscopic surgery for locally advanced colorectal cancer remain controversial due to the high rate of incomplete resection and conversion to open surgery. Especially for T4 colorectal cancer, laparoscopic techniques are still demanding mainly because of the difficulty in distinguishing between inflammation and tumor involvement, which often lead surgeons to do overtreatment in surgery. We believe laparoscopic magnified and multidirectional approach might be useful for pathologically complete resection and minimizing an unnecessary extended surgery for these cases. A 49-year-old man was diagnosed with locally advanced T4 sigmoid colon cancer invading the urinary bladder and ureter. We performed laparoscopic anterior resection with en bloc resection of the urinary bladder and the left ureter. Total operative time was 462 min, and the estimated blood loss was 50 ml. This patient was discharged on the 28th day after surgery without any ostomies and urinary functional disorders. The magnified view by laparoscopic techniques from multiple directions would enable surgeons to set surgical landmarks for another approach, which is the key for safe and feasible laparoscopic surgery in patients with locally advanced T4 colorectal cancer.

During the treatment of viral or bacterial infections, it is important to evaluate any resistance to the therapeutic agents used. An amino acid substitution arising from a single base mutation in a particular gene often causes drug resistance in pathogens. Therefore, molecular tools that discriminate a single base mismatch in the target sequence are required for achieving therapeutic success. Here, we synthesized peptide nucleic acids (PNAs) derivatized with tolane via an amide linkage at the N-terminus and succeeded in improving the sequence specificity, even with a mismatched base pair located near the terminal region of the duplex. We assessed the sequence specificities of the tolane-PNAs for single-strand DNA and RNA by UV-melting temperature analysis, thermodynamic analysis, an in silico conformational search, and a gel mobility shift assay. As a result, all of the PNA-tolane derivatives stabilized duplex formation to the matched target sequence without inducing mismatch target binding. Among the different PNA-tolane derivatives, PNA that was modified with a naphthyl-type tolane could efficiently discriminate a mismatched base pair and be utilized for the detection of resistance to neuraminidase inhibitors of the influenza A/H1N1 virus. Therefore, our molecular tool can be used to discriminate single nucleotide polymorphisms that are related to drug resistance in pathogens.

Protein ubiquitination plays indispensable roles in the regulation of cell homeostasis and pathogenesis of neoplastic, infectious, and neurodegenerative diseases. Given the importance of this modification, it is to be expected that several pathogenic bacteria have developed the ability to utilize the host ubiquitin system for their own benefit. Modulation of the host ubiquitin system by bacterial effector proteins inhibits innate immune responses and hijacks central signaling pathways. Bacterial effectors mimic enzymes of the host ubiquitin system, but may or may not be structurally similar to the mammalian enzymes. Other effectors bind and modify components of the host ubiquitin system, and some are themselves subject to ubiquitination. This review will describe recent findings, based on structural analyses, regarding how pathogens use post-translational modifications of proteins to establish an infection.

For the purpose of developing a vibration-isolation table with flexibility and/or scalability (which means “with adaptability to desired load specification”), this study investigates a self-identification method with regard to positions or arrangement and effective pressure areas of pneumatic actuators which support a vibration-isolation table. The proposed identification method is a fundamental technique necessary to construct a scalable vibration-isolation table in which the actuators supporting the table can be added or removed flexibly according to the load demand, easily, and in a short period of time. First, this study constructs a mathematical model for a vibration-isolation table supported by a redundant number of actuators and a type 1 digital servo controller to control the position and inclination angles of the table. Next, we derive the identification method for obtaining the position of the added pneumatic actuator and the effective pressure areas of the pneumatic actuators. We then demonstrate the proposed identification method by numerical simulations using our detailed mathematical model. Finally, this study shows an example of the application of the proposed identification method coupled with a force redistribution technique by addition of an actuator into the vibration-isolation table system during continuous operation. The validation and success of our method was confirmed by the displacement and pressure responses of the vibration-isolation table.

It is well accepted that bacterial and virus infections elevate the levels of cytokines in serum and cerebrospinal fluids. Such high levels of cytokines might alter the integrity of the blood-brain barrier (BBB) and/or blood-cerebrospinal fluid barrier (BCSFB), subsequently affecting brain penetration of drugs. However, few reports have addressed this issue. Thus, we investigated brain penetration of cyclooxygenase (COX) inhibitors, commonly used as antipyretics, in mice treated with Shiga-like toxin II (SLT-II) derived from E. coli O157:H7, which significantly elevates cytokine levels. As antipyretics, we used diclofenac, mefenamic acid, and acetaminophen. We found that SLT-II significantly increased the brain-to-plasma concentration ratio (Kp) of diclofenac and mefenamic acid, but not of acetaminophen. Moreover, the Kp of diclofenac and mefenamic acid was increased by probenecid, an anionic compound. These results suggest that efflux anion transporters might be involved in the transport of diclofenac and mefenamic acid. Western blot analysis revealed that SLT-II decreased the expression of organic anion transporter-3, an efflux transporter located on the BBB and/or BCSFB. Taken together, these results suggest that SLT-II and/or SLT-II-stimulated cytokines might change brain penetration of drugs and could possibly increase the risk of their side-effects by altering the expression of transporters. Keywords:: blood-brain barrier, Shiga-like toxin II, organic anion transporter, cyclooxygenase inhibitor

The Skp1-Cul1-F-box protein (SCF) complex catalyzes protein ubiquitination in diverse cellular processes and is one of the best-characterized ubiquitin ligases. F-box proteins determine the substrate specificities of SCF ubiquitin ligases. Among these, Fbs1/FBG1/FBXO2, Fbs2/FBG2/FBXO6, and Fbs3/FBG5/FBXO27 recognize the N-glycans of glycoproteins, whereas FBG3/FBXO44 has no sugar-binding activity, despite the high sequence homology and conservation of the residues necessary for oligosaccharide binding between Fbs1-3 and FBG3. Here we determined the crystal structure of the Skp1-FBG3 complex at a resolution of 2.6 Å. The substrate-binding domain of FBG3 is composed of a 10-stranded antiparallel β-sandwich with three helices. Although the overall structure of FBG3 is similar to that of Fbs1, the residues that form the Fbs1 carbohydrate-binding pocket failed to be superposed with the corresponding residues of FBG3. Structure-based mutational analysis shows that distinct hydrogen bond networks of four FBG3 loops, i.e., β2-β3, β5-β6, β7-β8, and β9-β10, prevent the formation of the carbohydrate-binding pocket shown in Fbs1.

Takotsubo cardiomyopathy, also called stress-induced cardiomyopathy or transient apical ballooning, has been described as a novel cardiac syndrome of left ventricular apical ballooning, electrocardiographic changes, and minimal elevation of cardiac enzymes resembling acute myocardial infarction, but without evidence of coronary artery disease [1,2]. Characteristic left ventricular apical ballooning in end-systole resembles a pot with round bottom and narrow neck used as an octopus trap called "Takotsubo" in Japanese. Takotsubo cardiomyopathy predominantly occurs in postmenopausal women, and a period of acute emotional or physiologic stress precedes the onset of symptoms in most cases. The prognosis is usually favorable, and the left ventricular wall motion dyskinesis normalizes within days to weeks. Here we report a case of Takotsubo cardiomyopathy associated with snake bite.

Some evidence indicates that nitric oxide (NO) contributes to inflammation, while other evidence supports the opposite conclusion. To clarify the role of NO in inflammation, we studied carrageenin-induced pleurisy in rats treated with an NO donor (NOC-18), a substrate for NO formation (L-arginine), and/or an NO synthase inhibitor (S-(2-aminoethyl) isothiourea or NG-nitro-L-arginine). We assessed inflammatory cell migration, nitrite/nitrate values, lipid peroxidation and pro-inflammatory mediators. NOC-18 and L-arginine reduced the migration of inflammatory cells and edema, lowered oxidative stress, and normalized antioxidant enzyme activities. NO synthase inhibitors increased the exudate formation and inflammatory cell number, contributed to oxidative stress, induced an oxidant/antioxidant imbalance by maintaining high O−2, and enhanced the production of pro-inflammatory mediators. L-arginine and NOC-18 reversed the proinflammatory effects of NO synthase inhibitors, perhaps by reducing the expression of adhesion molecules on endothelial cells. Thus, our results indicate that NO is involved in blunting—not enhancing—the inflammatory response.

Background Complete mesocolic excision (CME) and central vascular detachment are very important procedures in surgery for colorectal cancer. Preoperative and intraoperative assessments of the anatomy of major colorectal vessels are necessary to avoid massive bleeding, especially in endoscopic surgery. A case with a rare anomaly in which the middle colic artery (MCA) and ileocolic artery (ICA) had a common trunk is reported. Case presentation The patient was a 73-year-old woman diagnosed with ascending colon cancer on colonoscopy. Preoperative abdominal contrast-enhanced computed tomography confrmed that the MCA and ICA had a common trunk. She underwent laparoscopic ileocecal resection for the ascending colon cancer with D3 lymph node dissection. Intraoperative indocyanine green fuorescence imaging was conducted. After confrming vessel bifurcation, the ICA was dissected at the distal end of the MCA bifurcation. The patient has been followed as an outpatient, with no signs of recurrence as of 2 years postoperatively. Conclusion A case of an ascending colon cancer with a unique vascular bifurcation pattern was presented. Preoperative and intraoperative evaluations of the major colorectal vessels are very important for preventing perioperative and postoperative complications. [ABSTRACT FROM AUTHOR]