Different Effects of Palmitoyl-L-carnitine and Palmitoyl-CoA on Mitochondrial Function in Rat Ventricular Myocytes

Although mitochondrial oxidative catabolism of fatty acid (FA) is a major energy source for the adult mammalian heart, cardiac lipotoxity resulting from elevated serum FA and enhanced FA use has been implicated in the pathogenesis of heart failure. To investigate the effects of the intermediates of FA metabolism, palmitoyl-L-carnitine (Pal-car) and palmitoyl-CoA (Pal-CoA), on mitochondrial function, we measured membrane potential(Δψm), opening of the mitochondrial permeability transition pore (mPTP) and the production of reactive oxygen species (ROS) in saponin-treated rat ventricular myocytes with a laser scanning confocal microscope. Our results revealed that: 1) lower concentrations of Pal-car (1 and 5μM) caused a slight hyperpolarization of Δψm (TMRE intensity increased to 115.5 ± 5.4 % and 110.7±1.6 % of the baseline, respectively. p<0.05) but did not open mPTP, 2) a higher concentration of Pal-car (10μM) depolarized Δψm (TMRE intensity decreased to 61.9 ± 12.2 % of the baseline, p<0.01) and opened mPTP (calcein intensity decreased to 70.7 ± 2.8% of the baseline, p<0.01), 3) Pal-CoA depolarized Δψm without opening mPTP, and 4) only the higher concentration of Pal-car (10μM) increased ROS generation (DCF intensity increased to 3.4 ± 0.3 fold of the baseline). We concluded that excessive exogenous intermediates of long chain saturated FA may disturb mitochondrial function in different ways between Pal-car and Pal-CoA. The distinct mechanisms of the deteriorating effects of long chain FA on mitochondrial function are important for our understanding of the development of cardiac diseases in systemic metabolic disorders.浜松医科大学学位論文　医博第517号(平成２０年１０月１７日

Deep Neural Network-Based Method for Detecting Central Retinal Vein Occlusion Using Ultrawide-Field Fundus Ophthalmoscopy

The aim of this study is to assess the performance of two machine-learning technologies, namely, deep learning (DL) and support vector machine (SVM) algorithms, for detecting central retinal vein occlusion (CRVO) in ultrawide-field fundus images. Images from 125 CRVO patients (n = 125 images) and 202 non-CRVO normal subjects (n = 238 images) were included in this study. Training to construct the DL model using deep convolutional neural network algorithms was provided using ultrawide-field fundus images. The SVM uses scikit-learn library with a radial basis function kernel. The diagnostic abilities of DL and the SVM were compared by assessing their sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve for CRVO. For diagnosing CRVO, the DL model had a sensitivity of 98.4% (95% confidence interval (CI), 94.3–99.8%) and a specificity of 97.9% (95% CI, 94.6–99.1%) with an AUC of 0.989 (95% CI, 0.980–0.999). In contrast, the SVM model had a sensitivity of 84.0% (95% CI, 76.3–89.3%) and a specificity of 87.5% (95% CI, 82.7–91.1%) with an AUC of 0.895 (95% CI, 0.859–0.931). Thus, the DL model outperformed the SVM model in all indices assessed (P < 0.001 for all). Our data suggest that a DL model derived using ultrawide-field fundus images could distinguish between normal and CRVO images with a high level of accuracy and that automatic CRVO detection in ultrawide-field fundus ophthalmoscopy is possible. This proposed DL-based model can also be used in ultrawide-field fundus ophthalmoscopy to accurately diagnose CRVO and improve medical care in remote locations where it is difficult for patients to attend an ophthalmic medical center

Local Resection by Combined Laparoendoscopic Surgery for Duodenal Gastrointestinal Stromal Tumor

Combined laparoendoscopic surgery is a novel surgical method which consists of both endoscopic surgery from inside the gastrointestinal tract and laparoscopic surgery from the outside. We report a case of duodenal GIST, in which combined laparoendoscopic local resection was attempted. The lesion was resected endoscopically using endoscopic submucosal dissection technique under laparoscopic assistance. Laparoscope was used for originating the orientation of the tumor, intra-operative EUS, and monitoring serosal injury from the peritoneal cavity. Postoperative hemorrhage occurred; however, precise orientation of the lesion helped us to manage the patient with minimal invasive reoperation. And thus, the bowel integrity was completely preserved, by avoiding segmental duodenal resection and pancreaticoduodenectomy. This novel, less invasive surgical procedure may become an attractive option for the lesions originating in the anatomically challenging portion of the GI tract for endoscopic or laparoscopic surgery alone

Urinary Exosomal WT1 in Diabetic Nephropathy

Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte-derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN

Validation of ozone data from the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES)

The Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) onboard the International Space Station provided global measurements of ozone profiles in the middle atmosphere from 12 October 2009 to 21 April 2010. We present validation studies of the SMILES version 2.1 ozone product based on coincidence statistics with satellite observations and outputs of chemistry and transport models (CTMs). Comparisons of the stratospheric ozone with correlative data show agreements that are generally within 10%. In the mesosphere, the agreement is also good and better than 30% even at a high altitude of 73km, and the SMILES measurements with their local time coverage also capture the diurnal variability very well. The recommended altitude range for scientific use is from 16 to 73km. We note that the SMILES ozone values for altitude above 26km are smaller than some of the correlative satellite datasets; conversely the SMILES values in the lower stratosphere tend to be larger than correlative data, particularly in the tropics, with less than 8% difference below similar to 24km. The larger values in the lower stratosphere are probably due to departure of retrieval results between two detection bands at altitudes below 28km; it is similar to 3% at 24km and is increasing rapidly down below

Coincident Port-site and Functional End-to-end Anastomotic Recurrences after Laparoscopic Surgery for Colon Cancer : A case report and literature review

Herein, we report coincident recurrences at the port site and functional end-to-end anastomosis after laparoscopic right hemicolectomy for cancer of the ascending colon. The patient was an 83-year-old man who had undergone the aforementioned procedure (Stage IIA) in the referral hospital. At the 10-month follow-up, computed tomography showed two tumours around 3 cm in diameter : one on the right-flank abdominal wall-the surgical port-site-and the other at the functional end-to-end anastomosis. Likewise, a positron emission tomography scan was positive for two tumours. Endoscopic examination showed an ulcerated tumour with a clear margin, and a biopsy confirmed moderately differentiated tubular adenocarcinoma. The patient was diagnosed with coincident recurrences at the port site and functional end-to-end anastomosis after laparoscopic right hemicolectomy for cancer of the ascending colon. We re-operated inMarch 2016. The tumours at the functional end-to-end anastomosisand functional end-to-end anastomosiswere resected. After 7 months, no recurrence was detected

Peritoneal cecal cancer metastasis to a mesh-plug prosthesis : A case report

We report the case of a 77-year-old man who presented to our hospital with cecal cancer, lung metastasis, and liver metastasis in January 2013. After four courses of modified infusional intravenous fluorouracil and levofolinate with oxaliplatin (mFOLFOX 6) + bevacizumab, there was no new metastatic lesion and lung metastasis reduction was observed. Ileocecal resection was performed in May, left lower lung lobectomy in August, and extended right posterior segmentectomy + S8 partial liver resection was performed in December. The tumor marker declined initially ; thereafter, it gradually increased. Computed tomography (CT) performed in April 2014 revealed right inguinal mass around the mesh-plug prosthesis. A positron emission tomography-CT (PET-CT) also revealed a high 2-fluoro-2-deoxy-D-glucose (FDG) uptake at the same site. Right inguinal tumor resection was performed in July. Cancer tissues were confirmed by performing intraoperative rapid pathological diagnosis, and R0 resection could be achieved. Previous studies have reported malignant tumor metastases to the mesh-plug prosthesis, and this was believed to one of the sites that cancer cells can easily engraft. In particular, in patients with a history of advanced malignant tumors, if mass formation around the artifact insertion site is observed, the possibility of peritoneal metastasis should be considered

Combined resection of re-recurrent lateral lymph nodes and external iliac vein : Case Report and Literature

Herein, we describe the operative procedure for combined resection of re-recurrent lateral lymph nodes and the external iliac vein. There is no consensus on the clinical implications of resection of locally re-recurrent colorectal tumors, as the operative procedure is extremely difficult. We present the case of a 52- year-old woman who underwent abdominoperineal resection. About one year later, we excised a recurrent lymph node in the left lateral obturator area through an extraperitoneal approach. About 18 months later, lymph node re-recurrence in the left external iliac area was observed. Re-recurrent lymph nodes directly invade the left external iliac vein.We removed the re-recurrent lymph node with combined, radical segmental resection of the left external iliac vein, left obturator artery and vein, and left obturator nerve