On-shelf circulation of warm water toward the Totten Ice Shelf in East Antarctica.

The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features. Access of warm water to the Totten Ice Shelf (TIS) cavity is facilitated by a deep shelf break, a broad and deep depression on the shelf, a cyclonic circulation that carries warm water to the inner shelf, and deep troughs that provide direct access to the TIS cavity. The temperature of the warmest water reaching the TIS cavity varies by ~0.8 °C on an interannual timescale. Numerical simulations constrained by the updated bathymetry demonstrate that the deep troughs play a critical role in regulating ocean heat transport to the TIS cavity and the subsequent basal melt of the ice shelf.

Bilateral video-assisted thoracic surgery for esophageal cancer with left inferior pulmonary vein invasion following chemoradiation therapy.

BACKGROUND: The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response. CASE PRESENTATION: A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up. CONCLUSIONS: Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response.

Novel endoscopic management of gastroenterological anastomosis leakage by injecting gel-forming solutions: an experimental animal study.

BACKGROUND: Anastomotic leakage (AL) after gastrointestinal surgery remains a challenging complication that requires surgical or non-surgical treatment. Although various therapeutic endoscopic techniques are available, no definitive interventions exist. We developed a therapeutic endoscopic submucosal injection method using novel gel-forming mixed solutions to close AL and evaluated the elasticity of the developed hydrogel. The safety and efficacy of the injection method were explored in porcine AL models. METHODS: We developed a novel gel-forming solution, and the formed gel lasted approximately one week within the gastrointestinal wall. An indentation test evaluated the elasticity of the novel hydrogel. After the confirmation of AL on porcine anterior gastric walls, sodium alginate was endoscopically injected into the submucosal layer around the leakage site circularly, followed by a calcium lactate/chitosan-based solution. After that, the outcomes data were collected, and histopathological effectiveness was evaluated. RESULTS: The increased sodium alginate elasticity with the addition of calcium lactate/chitosan-based solution facilitated long-lasting gel formation. Four pigs with AL underwent this intervention consecutively. Each endoscopic injection was completed in less than 5 min. No significant complications were observed for 3 weeks after the intervention. All AL sites were macroscopically healed. Histopathologic findings at 3 weeks showed that the wall defect was filled with collagen fibers that had grown around the site of the muscle layer tear. No tissue necrosis was observed. CONCLUSION: This preclinical study demonstrated that the therapeutic injection method for gastroenterological AL using gel-forming solutions could be an alternative endoscopic treatment, especially in patients with severe conditions or comorbidities. The optimal target of this treatment is small size and early AL without poor blood flow or intense hypertrophic scar lesions.

TFAM expression in brown adipocytes confers obesity resistance by secreting extracellular vesicles that promote self-activation.

The occurrence of diet-induced obesity has been increasing worldwide and has become a major health concern. Mitochondria are densely distributed in brown adipose tissue and are involved in lipid consumption. Therefore, increasing energy expenditure through the activation of brown adipocytes may be a potential therapy for obesity. Our findings showed that mitochondrial transcription factor A (TFAM) homozygous transgenic (TgTg) mice had highly activated brown adipocytes and increased expression of oxidative phosphorylation, leading to resistance to obesity. Transplantation models of TFAM-expressing brown adipocytes could mimic the phenotype of TFAM TgTg mice, and proving their anti-obesity effect. We found that brown adipocytes secrete exosomes which enable self-activation in an autocrine and paracrine manner. The secretion was enhanced in TFAM TgTg brown adipocytes, resulting in a higher activation. These findings may lead to a promising treatment strategy for obesity through selective stimulation of exosome secretion.

Carbon dioxide embolism during transanal total mesorectal excision: A hint of prevention from a case report.

Transanal total mesorectal excision is a relatively new approach for treating lower rectal cancer. Carbon dioxide embolism is a critical complication of this procedure. We report the case of a 69-year-old man with lower rectal cancer who underwent transanal total mesorectal excision followed by laparoscopic low anterior resection. He had a sudden intraoperative carbon dioxide embolism during the transanal mesorectal excision. During the ventral dissection of the rectum, end-tidal carbon dioxide and blood oxygen saturation suddenly decreased. We stopped the insufflation of carbon dioxide and suspended the procedure. There was no circulatory collapse, and the vital signs gradually recovered; therefore, we resumed the surgery approximately 30 minutes later and completed it without additional complications. Upon reviewing the video, we found a small injured vein that would aspirate carbon dioxide. These findings suggested that careful hemostasis is essential to prevent carbon dioxide embolus during transanal total mesorectal excision.

A case report of necrotizing soft tissue infection of the chest wall: Effective management with serial debridement.

INTRODUCTION: Necrotizing soft tissue infection (NSTI) of the chest wall is a rare, rapidly spreading, highly lethal surgical disease. Radical debridement interferes with the important anatomical function of the chest wall. We report a case of chest wall NSTI that was successfully managed with early diagnosis and serial debridement. PRESENTATION OF CASE: A 43-year-old, previously healthy woman presented with severe malaise and worsening right axillary pain. She was severely lethargic and had a painful, large, pale lesion with surrounding erythema of the right chest and trunk. Computed tomography revealed NSTI, with diffuse soft tissue inflammation extending from the axilla to the lower abdomen. There was no obvious entry portal. Prompt surgical drainage was established. Group A streptococcus infection was diagnosed. During her 3-month postoperative course, she underwent four more surgeries, including two debridements. This treatment proved successful and avoided the need for complicated muscle flap reconstruction. She was discharged on postoperative day 109. DISCUSSION: Group A streptococcus can cause NSTI even in immunocompetent patients without an entry portal. Radical debridement is recommended for infection control. Preserving anatomical chest wall function, however, is also important. Serial debridement with close follow-up solved the problem in this patient. CONCLUSIONS: Serial debridement with close follow-up enabled to avoid large tissue deficits and complicated reconstruction in the case of NSTI of the chest wall.

Gastric remnant reconstruction with left gastroepiploic artery supercharge after esophagectomy in a patient with an occluded right gastroepiploic artery: A technical and case report.

INTRODUCTION: Gastric remnant reconstruction is commonly used for esophagectomy reconstruction. However, standard reconstruction cannot be performed in some patients with a specific medical history. We report a case of esophagectomy and gastric remnant reconstruction with left gastroepiploic artery (LGEA) supercharge to treat esophageal cancer in a patient in whom the right gastroepiploic artery (RGEA) had previously been occluded. PRESENTATION OF CASE: A 65-year-old man underwent endoscopic submucosal dissection for thoracic esophageal squamous cell carcinoma. He was diagnosed with pathological T1b cancer with lymphatic invasion and a positive horizontal margin, and needed curative resection. He had previously undergone RGEA embolization to treat a pseudoaneurysm caused by chronic pancreatitis. We successfully performed esophagectomy and gastric remnant reconstruction with preoperative left gastric artery embolization and intraoperative LGEA supercharge. DISCUSSION: An absent RGEA blood supply is not always a contraindication for gastric remnant reconstruction when the collateral blood flows are well developed and supercharge can maintain the blood supply to the gastric remnant. CONCLUSIONS: Gastric remnant reconstruction with preoperative selective arterial embolization and intraoperative supercharge represents one of the options for high-risk patients with an altered gastric blood supply.

Strong ice-ocean interaction beneath Shirase Glacier Tongue in East Antarctica.

Mass loss from the Antarctic ice sheet, Earth's largest freshwater reservoir, results directly in global sea-level rise and Southern Ocean freshening. Observational and modeling studies have demonstrated that ice shelf basal melting, resulting from the inflow of warm water onto the Antarctic continental shelf, plays a key role in the ice sheet's mass balance. In recent decades, warm ocean-cryosphere interaction in the Amundsen and Bellingshausen seas has received a great deal of attention. However, except for Totten Ice Shelf, East Antarctic ice shelves typically have cold ice cavities with low basal melt rates. Here we present direct observational evidence of high basal melt rates (7-16 m yr-1) beneath an East Antarctic ice shelf, Shirase Glacier Tongue, driven by southward-flowing warm water guided by a deep continuous trough extending to the continental slope. The strength of the alongshore wind controls the thickness of the inflowing warm water layer and the rate of basal melting.

Redox regulation of the actin cytoskeleton and its role in the vascular system.

The actin cytoskeleton is critical for form and function of vascular cells, serving mechanical, organizational and signaling roles. Because many cytoskeletal proteins are sensitive to reactive oxygen species, redox regulation has emerged as a pivotal modulator of the actin cytoskeleton and its associated proteins. Here, we summarize work implicating oxidants in altering actin cytoskeletal proteins and focus on how these alterations affect cell migration, proliferation and contraction of vascular cells. Finally, we discuss the role of oxidative modification of the actin cytoskeleton in vivo and highlight its importance for vascular diseases.

Polymerase delta-interacting protein 2 regulates collagen accumulation via activation of the Akt/mTOR pathway in vascular smooth muscle cells.

OBJECTIVES: Polymerase delta interacting protein 2 (Poldip2) has previously been implicated in migration, proliferation and extracellular matrix (ECM) production in vascular smooth muscle cells. To better understand the role of Poldip2 in ECM regulation, we investigated the mechanism responsible for collagen I accumulation in Poldip2(+/-) mouse aortic smooth muscle cells (MASMs). APPROACH AND RESULTS: Protein degradation and protein synthesis pathways were investigated. Depletion of Poldip2 had no effect on proteasome activity, but caused a partial reduction in autophagic flux. However, the rate of collagen I degradation was increased in Poldip2(+/-) vs. Poldip2(+/+) MASMs. Conversely, activation of the PI3K/Akt/mTOR signaling pathway, involved in regulation of protein synthesis, was significantly elevated in Poldip2(+/-) MASMs as was ß1-integrin expression. Suppressing mTOR signaling using Akt inhibitor or rapamycin and reducing ß1-integrin expression using siRNA prevented the increase in collagen I production. While collagen I and fibronectin were increased in Poldip2(+/-) MASMs, overall protein synthesis was not different from that in Poldip2(+/)(+)MASMs, suggesting selectivity of Poldip2 for ECM proteins. CONCLUSIONS: Poldip2(+/-) MASMs exhibit higher ß1-integrin expression and activity of the PI3K/Akt/mTOR signaling pathway, leading to increased ECM protein synthesis. These findings have important implications for vascular diseases in which ECM accumulation plays a role.

Maternal high-fat diet induces insulin resistance and deterioration of pancreatic ß-cell function in adult offspring with sex differences in mice.

Intrauterine environment may influence the health of postnatal offspring. There have been many studies on the effects of maternal high-fat diet (HFD) on diabetes and glucose metabolism in offspring. Here, we investigated the effects in male and female offspring. C57/BL6J mice were bred and fed either control diet (CD) or HFD from conception to weaning, and offspring were fed CD or HFD from 6 to 20 wk. At 20 wk, maternal HFD induced glucose intolerance and insulin resistance in offspring. Additionally, liver triacylglycerol content, adipose tissue mass, and inflammation increased in maternal HFD. In contrast, extending previous observations, insulin secretion at glucose tolerance test, islet area, insulin content, and PDX-1 mRNA levels in isolated islets were lower in maternal HFD in males, whereas they were higher in females. Oxidative stress in islets increased in maternal HFD in males, whereas there were no differences in females. Plasma estradiol levels were lower in males than in females and decreased in offspring fed HFD and also decreased by maternal HFD, suggesting that females may be protected from insulin deficiency by inhibiting oxidative stress. In conclusion, maternal HFD induced insulin resistance and deterioration of pancreatic ß-cell function, with marked sex differences in adult offspring accompanied by adipose tissue inflammation and liver steatosis. Additionally, our results demonstrate that potential mechanisms underlying sex differences in pancreatic ß-cell function may be related partially to increases in oxidative stress in male islets and decreased plasma estradiol levels in males.

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.

It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress.

We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-ß and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.

In vivo kinematics of high-flex mobile-bearing total knee arthroplasty, with a new post-cam design, in deep knee bending motion.

PURPOSE: The objective of this study was to evaluate the in vivo knee kinematics to assess the available functional motion of the characteristic mobile-bearing prosthesis design and to examine whether the artificial joint would work in vivo according to its design concept. METHODS: We studied 14 knees (11 patients) implanted with the Vanguard RP Hi-Flex prosthesis. This prosthesis has a highly original form of post-cam called a PS saddle design with high compatibility, and with a rotating plate mobile-bearing mechanism. The cylinder-type post-cam is designed to enable contact in early flexion ranges, and to prevent paradoxical anterior femoral component movement. Each patient performed weight-bearing deep knee bending under fluoroscopic surveillance. Motion between each component including the polyethylene insert was analyzed using the 2D/3D registration technique. RESULTS: The mean range of motion was 122.0°. The mean femoral component rotation for the tibial tray was 5.0°. No paradoxical anterior movement of the nearest point was confirmed between the femoral component and the tibial tray in the early flexion ranges. Initial contact of the post-cam was confirmed at a knee flexion angle of 33.8°. Subsequently, the wide contact of the post-cam was maintained until flexion reached 120° in all knees, but disengagement of the post-cam was observed in two knees when flexion was ≥130°. CONCLUSIONS: The results of this study demonstrated that the prosthesis design generally works in vivo as intended by its design concept. The present kinematic data may provide useful information for improvement of high-flex type prostheses.

Reduced expression of adipose triglyceride lipase enhances tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB.

We examined the effects of adipose triglyceride lipase (ATGL) on the initiation of atherosclerosis. ATGL was recently identified as a rate-limiting triglyceride (TG) lipase. Mutations in the human ATGL gene are associated with neutral lipid storage disease with myopathy, a rare genetic disease characterized by excessive accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, shows massive TG accumulation in both coronary atherosclerotic lesions and the myocardium. Recent reports show that myocardial triglyceride content is significantly higher in patients with prediabetes or diabetes and that ATGL expression is decreased in the obese insulin-resistant state. Therefore, we investigated the effect of decreased ATGL activity on the development of atherosclerosis using human aortic endothelial cells. We found that ATGL knockdown enhanced monocyte adhesion via increased expression of TNFα-induced intercellular adhesion molecule-1 (ICAM-1). Next, we determined the pathways (MAPK, PKC, or NFκB) involved in ICAM-1 up-regulation induced by ATGL knockdown. Both phosphorylation of PKC and degradation of IκBα were increased in ATGL knockdown human aortic endothelial cells. In addition, intracellular diacylglycerol levels and free fatty acid uptake via CD36 were significantly increased in these cells. Inhibition of the PKC pathway using calphostin C and GF109203X suppressed TNFα-induced ICAM-1 expression. In conclusion, we showed that ATGL knockdown increased monocyte adhesion to the endothelium through enhanced TNFα-induced ICAM-1 expression via activation of NFκB and PKC. These results suggest that reduced ATGL expression may influence the atherogenic process in neutral lipid storage diseases and in the insulin-resistant state.

Recurrent allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis treated with etanercept and tocilizumab.

We report the case of a 68-year-old woman with Stage III and Class II rheumatoid arthritis (RA) that was resistant to prednisolone, methotrexate, and infliximab. After treatment with etanercept or tocilizumab, suspicious allergic bronchopulmonary aspergillosis (ABPA) repeatedly occurred and then rapidly improved after the withdrawal of each drug. We suspect that administration of etanercept and tocilizumab caused suspicious ABPA in this patient. The relevance to the pathogenesis of ABPA under these biological drugs is also discussed.

Effect of posterior design changes on postoperative flexion angle in cruciate retaining mobile-bearing total knee arthroplasty.

The Dual Bearing Knee (DBK) prosthesis is a new concept which has a mobile-bearing insert. In May 2001, the posterior femoral condyle design of the DBK was changed to become smaller and there was a posterior shift in the base of the insert dish (Hi-Flex). Between 1998 and 2004, 371 DBKs (112 Hi-Flex and 220 Standard) were performed by one surgical team. There was a significant difference in postoperative flexion angle between the Hi-Flex and Standard DBKs (117.0° and 111.3°; p = 0.001). The delta flexion angle in the Hi-Flex (-2.4°) was significantly increased compared with that in the Standard DBK (-9.6°) (p = 0.001). In the Hi-Flex DBK, the postoperative flexion angle (5.7°) and the delta flexion angle (7.2°) were significantly larger than for the Standard DBK (p < 0.001). These results suggest that the flexion is greater for a design with smaller posterior condyle prosthesis and with a posterior shift in the base of the insert dish in CR mobile-bearing TKA.

Inhibition of chymase protects against diabetes-induced oxidative stress and renal dysfunction in hamsters.

Accumulating evidence suggests that the intrarenal renin-angiotensin system may be involved in the progression of diabetic nephropathy. Chymase is a potent local angiotensin II-forming enzyme in several species, including humans and hamsters. However, the pathophysiological role of chymase is not fully understood. Here, we report a causal role of chymase in diabetic nephropathy and the therapeutic effectiveness of chymase inhibition. In the present study, renal chymase expression was markedly upregulated in streptozotocin-induced diabetic hamsters. Oral administration of a specific chymase inhibitor, TEI-F00806, completely ameliorated proteinuria, the overexpression of transforming growth factor-ß and fibronectin in glomeruli, and renal mesangial expansion, by normalizing the increase in intrarenal angiotensin II levels in diabetic hamsters independently of blood pressure levels. In contrast, ramipril did not show such sufficient effects. These effects occurred in parallel with improvements in superoxide production and expression of NAD(P)H oxidase components [NAD(P)H oxidase 4 and p22(phox)] in glomeruli. This study showed for the first time that chymase inhibition may protect against elevated intrarenal angiotensin II levels, oxidative stress, and renal dysfunction in diabetes. These findings suggest that chymase offers a new therapeutic target for diabetic nephropathy.