Changes in alanine aminotransferase and body composition and metabolic factors among individuals receiving medical health checkups.

AIM: To examine the relationship between changes in alanine aminotransferase (ALT) and those in body composition and metabolic factors in participants receiving medical health checkups (4350 men [mean age 52.5 years] and 5398 women [mean age 50.5 years]) METHODS: We divided the participants into four types based on their ALT value at baseline and 1 year: A, ALT ≤30 (baseline) and ≤30 (1 year); B, ALT ≥31 (baseline) and ≤30 (1 year); C, ALT ≤30 (baseline) and ≥31 (1 year); and D, ALT ≥31 (baseline) and ≥31 (1 year). The change in each body composition-related parameter (waist circumference, fat mass, fat-free mass, fat mass to fat-free mass ratio, etc.) after 1-year was defined as Δ. RESULTS: The mean changes in waist circumference (cm) in the four types (A, B, C, and D) were -0.33, -1.54, 0.66, and -0.29 (overall p < 0.0001) in men, and -0.19, -0.90, 0.30, and 0.090 (overall p < 0.0001) in women. The mean changes in fat mass (kg) in the four types were -0.027, -0.86, 0.62, and 0.092 (overall p < 0.0001) in men, and 0.0067, -0.48, 0.39, and 0.063 (overall p < 0.0001) in women. The mean changes in fat-free mass (kg) in the four types were -0.028, -0.55, 0.42, and -0.034 (overall p < 0.0001) in men, and -0.0091, -0.34, 0.12, and -0.045 (overall p = 0.0012) in women. The mean changes in fat mass to fat-free mass ratio in the four types were -0.00042, -0.0120, 0.00837, and 0.00171 (overall p < 0.0001) in men, and -0.00013, -0.00817, 0.00730, and 0.00628 (overall p < 0.0001) in women. CONCLUSION: A decrease in ALT to ≤30 IU/L may be associated with improved body composition balance, but caution should be exercised for the decrease in muscle mass.

Genetic characterization of coliform bacterial isolates from environmental water in Thailand.

INTRODUCTION: In contrast to the study in other part of the world, information about characteristics of plasmids carrying antimicrobial resistance genes (ARGs) in Enterobacteriaceae derived from environmental water in tropical Asian countries including Thailand is limited. This study, therefore, aimed to gain insight into genetic information of antimicrobial resistance in environmental water in Thailand. METHODS: Coliform bacteria were isolated from environmental water collected at 20 locations in Thailand and identified. Then, susceptibility profiles to ampicillin, cefazoline, cefotaxime, kanamycin, ciprofloxacin, sulfamethoxazole, tetracycline, and nalidixic acid were assessed. In addition, antimicrobial resistant genes integrons, and replicon types were analyzed. And furthermore, plasmids carrying blaTEM and tetM were identified by S1-PFGE analysis and confirmed transmissibility by transconjugation experiments. RESULTS: In 130 coliform bacteria isolated, 89 were resistant to cefazoline while 41 isolates were susceptible. Cefazoline-resistant coliform bacteria were found to be significantly resistant to cefotaxime and tetracycline as compared to susceptible isolates. Hence, blaTEM and tetM correlating with ß-lactam antibiotics and tetracycline, respectively, were analyzed found to co-localize on the IncFrepB plasmids in isolates from pig farms' wastewater by S1-PFGE analysis. And furthermore, transmissibility of the plasmids was confirmed. CONCLUSIONS: Results obtained in this study suggested that ARGs in coliform bacteria may have been spreading on the farm via IncFrepB plasmids. Hence, appropriate use of antimicrobials and good hygiene management on the farm are required to prevent the emergence and spread of resistant bacteria.

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

[A Case of HER2 Positive Unresectable Gastric Cancer Leading to Conversion Therapy with Chemotherapy].

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.

[A Case Report of Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastases and Multiple Liver Metastases Resected after FOLFOX Therapy].

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

[Two Cases of Advanced Gastric Cancer Diagnosed as Pathological Complete Response after Preoperative Chemotherapy with S-1 and Oxaliplatin].

We herein report 2 cases of gastric cancer treated by S-1 and oxaliplatin combination therapy before later undergoing gastrectomy. The pathological results of both cases demonstrated complete response. Case 1 had a giant tumor which was suspected to have invaded the pancreas. Case 2 was associated with extensive lymph node metastasis. Based on the findings of these 2 cases, preoperative chemotherapy with S-1 and oxaliplatin for advanced gastric cancer shows sufficient efficacy.

[Case of Peritoneal Dissemination from Gastrointestinal Stromal Tumor of Jejunum Treated with Repeated Non-Curative Surgery].

A 71-year-old male presented with abdominal distension and fever to our hospital. Abdominal CT revealed a huge tumor in abdomen, and non-curative surgery was performed. Peritoneal dissemination was widespread and the tumor invaded the bladder and sigmoid-colon mesenterium. Two months after the initial surgery, CT showed liver metastasis, and oral administration of imatinib mesylate was started. The peritoneal dissemination and liver metastasis showed a decrease, and this was well controlled for 45 months without severe side effects. Abdominal CT revealed peritoneal dissemination in the ileocecum after 43 months since the administration of imatinib. Therefore, sunitinib treatment was initiated. After 3 months of sunitinib administration, the tumor perforated. Emergency operation was performed to resect the ileocecum, and sunitinib was continued for 1 year. In GIST with liver metastasis and peritoneal dissemination, repeated surgical resection combined with chemotherapy is important to improve the patient's survival.

YHp as a highly stable, hyper-copy, hyper-expression plasmid constructed using a full 2-µm circle sequence in cir0 strains of Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the yeast episomal plasmid (YEp), containing a partial sequence from a natural 2-µm plasmid, has been frequently used to induce high levels of gene expression. In this study, we used Japanese sake yeast natural cir0 strain as a host for constructing an entire 2-µm plasmid with an expression construct using the three-fragment gap-repair method without Escherichia coli manipulation. The 2-µm plasmid contains two long inverted repeats, which is problematic for the amplification by polymerase chain reaction. Therefore, we amplified it by dividing into two fragments, each containing a single repeat together with an overlapping sequence for homologous recombination. TDH3 promoter-driven yEmRFP (TDH3p-yEmRFP) and the URA3 were used as a reporter gene and a selection marker, respectively, and inserted at the 3' end of the RAF1 gene on the 2-µm plasmid. The three fragments were combined and used for the transformation of sake yeast cir0 ura3- strain. The resulting transformant colonies showed a red or purple coloration, which was significantly stronger than that of the cells transformed with YEp-TDH3p-yEmRFP. The 2-µm transformants were cultured in YPD medium and observed by fluorescence microscopy. Almost all cells showed strong fluorescence, suggesting that the plasmid was preserved during nonselective culture conditions. The constructed plasmid maintained a high copy state similar to that of the natural 2-µm plasmid, and the red fluorescent protein expression was 54 fold compared with the chromosomal integrant. This vector is named YHp, the Yeast Hyper expression plasmid.

MuCHLoc: Indoor ZigBee Localization System Utilizing Inter-Channel Characteristics.

The deployment of a large-scale indoor sensor network faces a sensor localization problem because we need to manually locate significantly large numbers of sensors when Global Positioning System (GPS) is unavailable in an indoor environment. Fingerprinting localization is a popular indoor localization method relying on the received signal strength (RSS) of radio signals, which helps to solve the sensor localization problem. However, fingerprinting suffers from low accuracy because of an RSS instability, particularly in sensor localization, owing to low-power ZigBee modules used on sensor nodes. In this paper, we present MuCHLoc, a fingerprinting sensor localization system that improves the localization accuracy by utilizing channel diversity. The key idea of MuCHLoc is the extraction of channel diversity from the RSS of Wi-Fi access points (APs) measured on multiple ZigBee channels through fingerprinting localization. MuCHLoc overcomes the RSS instability by increasing the dimensions of the fingerprints using channel diversity. We conducted experiments collecting the RSS of Wi-Fi APs in a practical environment while switching the ZigBee channels, and evaluated the localization accuracy. The evaluations revealed that MuCHLoc improves the localization accuracy by approximately 15% compared to localization using a single channel. We also showed that MuCHLoc is effective in a dynamic radio environment where the radio propagation channel is unstable from the movement of objects including humans.

Danger-Pose Detection System Using Commodity Wi-Fi for Bathroom Monitoring.

A bathroom has higher probability of accidents than other rooms due to a slippery floor and temperature change. Because of high privacy and humidity, we face difficulties in monitoring inside a bathroom using traditional healthcare methods based on cameras and wearable sensors. In this paper, we present a danger-pose detection system using commodity Wi-Fi devices, which can be applied to bathroom monitoring, preserving privacy. A machine learning-based detection method usually requires data collected in target situations, which is difficult in detection-of-danger situations. We therefore employ a machine learning-based anomaly-detection method that requires a small amount of data in anomaly conditions, minimizing the required training data collected in dangerous conditions. We first derive the amplitude and phase shift from Wi-Fi channel state information (CSI) to extract low-frequency components that are related to human activities. We then separately extract static and dynamic features from the CSI changes in time. Finally, the static and dynamic features are fed into a one-class support vector machine (SVM), which is used as an anomaly-detection method, to classify whether a user is not in bathtub, bathing safely, or in dangerous conditions. We conducted experimental evaluations and demonstrated that our danger-pose detection system achieved a high detection performance in a non-line-of-sight (NLOS) scenario.

Factors Affecting Rural Patients' Primary Compliance with e-Prescription: A Developing Country Perspective.

Background:The electronic prescription system has emerged to reduce the ambiguity and misunderstanding associated with handwritten prescriptions. The opportunities and challenges of e-prescription system, its impact on reducing medication error, and improving patient's safety have been widely studied. However, not enough studies were conducted to explore and quantify the factors that affect rural patients' compliance with e-prescription, especially from the perspective of Asian developing countries where most of the world's population resides.Objective:The objective of this study is to explore and assess the factors that affect rural patients' primary compliance with e-prescription in Bangladesh.Methods:Data were collected from 95 randomly selected rural patients who received e-prescription through a field survey with a structured questionnaire from Bheramara subdistrict, Bangladesh, during June and July 2016. Logistic regression analysis was performed to test the research hypotheses.Results:The study found patients' gender as the most significantly influential factor (regression coefficient [Coef.] = 2.02, odds ratio [OR] = 7.51, p < 0.05) followed by visiting frequency (Coef. = 0.99, OR = 2.70, p < 0.05); education (Coef. = 0.92, OR = 2.51, p < 0.05); and distance to healthcare facility (Coef. = 0.82, OR = 2.26, p < 0.01). However, patients' age, monthly family expenditure, and use of cell phone were found insignificant. The model explains 59.40% deviance (R2 = 0.5940) in the response variable with its constructs. And the "Hosmer-Lemeshow" goodness-of-fit score (0.99) is also above the standard threshold (0.05), which indicates the data fit well with the model.Conclusions:The findings of this study are expected to be helpful for e-health service providers to gain a better understanding of the factors that influence their patients to comply with e-prescriptions.

[Long-Term Survival of Gastric Cancer with Multiple Liver and Lymph Node Metastases-A Case Report].

Currently, chemotherapy against unresectable advanced gastric cancer is progressing with the development new drugs and due to results of several clinical trials. Here, we reported a case of long-term survival of gastric cancer with multiple liver and lymph node metastases. A 68-year-old man was diagnosed with gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple liver metastases at another hospital. He was referred to our hospital from Yamashita Naika Syokakika. We administrated 4 courses of S-1 plus CDDP. The main tumor and all metastatic lesions were significantly reduced. Subsequently, total gastrectomy, partial liver resection, and left neck and para-aortic lymph node resection(conversion surgery)were performed. The cancer cell was remnant at the main tumor and para-gastric lymph node. No cancer cells were detected in another lesion(R0 resection). Postoperatively, only S-1 was administered. However, 28 months after undergoing gastrectomy, liver metastasis occurred. Therefore, S-1 plus oxaliplatin, paclitaxel plus ramucirumab, and CPT-11 plus CDDP were administered. Liver metastases again increased and decreased, respectively. However, 46 months after gastrectomy, liver metastasis recurred and nivolumab was administered. Subsequently, liver metastases disappeared. At 55 months after gastrectomy, rectal resection was performed against rectal cancer and partial liver resection against liver metastases. Cancer cells were not detected in the resected specimens.

[A Super-Elderly Patient with Recurrent Colon Cancer with Metastasis Effectively Treated with Capecitabine plus Bevacizumab Chemotherapy-A Case Report].

The safety and feasibility of chemotherapy for elderly patients is unclear. We report a super-elderly patient with liver metastases from colorectal cancer successfully treated with capecitabine plus bevacizumab chemotherapy. An 87-year-old woman underwent a colectomy for transverse colon. At 4 months postoperatively, she underwent hepatectomy for liver metastases. At 9 months after the first surgery, a new liver metastases(S4)was found. At this time, she rejected another hepatectomy. Therefore, we selected capecitabine plus bevacizumab chemotherapy, considering her age. After 18 courses of administration, the liver metastasis did not progress, and no new metastatic lesions were found on CT examination. Although as adverse events Grade 2 hand-foot syndrome developed, no other adverse event occurred. The patient's PS score was maintained at 0. We suggest capecitabine plus bevacizumab chemotherapy is an effective regimen for super-elderly patients with colorectal cancer.

[A Case of Unresectable Pancreas Cancer with 32 Months Survival after Chemotherapy].

We report a case of unresectable pancreas cancer. A 70-year-old woman presented with worsening diabetes and serum CA19-9 elevation. A tumor with portal vein and supra-mesenteric vein invasion was observed by computed tomography. She was diagnosed with unresectable pancreas head cancer that was locally advanced. Chemotherapy was administered with gemcitabine and nab-paclitaxel for 19 courses, followed by gemcitabine alone for 4 courses. After the addition of 6 courses of chemotherapy, a 60%dose of chemotherapy was administered for 13 courses due to severe neutropenia. The patient died 32 months after the first visit. The 60% dose of gemcitabine and nab-paclitaxel also inhibited tumor growth. These findings suggest the effective and safe long-term use of gemcitabine and nab-paclitaxel.

[A Study of Therapy for Locally Advanced Breast Cancer with Metastasis].

We reviewed 21 patients with locally advanced breast cancer with distant metastasis.The median age was 61 years.The median time to presentation at hospital was 13 months, and the median neoplasm diameter on the first visit was 10 cm.The main histological type was scirrhous carcinoma.Sixteen cases tested positive for hormone receptor(76%), 4 tested positive for HER2(19%), and 3 were triple negative(14%).Four patients underwent surgery.The techniques performed included mastectomy and axillary lymph node dissection.Three patients experienced local recurrence.The first-line treatment was surgery for 1 patient, chemotherapy for 12 patients, hormonal therapy for 7 patients, and trastuzumab for the HER2 positive patients.The median follow-up period was 49 months.The patients for where an operation was performed were 49 months and the operation not- enforcement patients were 54 months.If treatment is possible for patients with locally advanced breast cancer with distant metastasis, multidisciplinary treatment according to individual patient characteristics is recommended. In the case of surgical treatment, careful consideration must also be given to these characteristics.

[Resection of Paraaortic Lymph Node Recurrence Wherein Complete Response to Bevacizumab Was Observed after Surgery for Sigmoid Colon Cancer].

We report a case of resection of a paraaortic lymph node recurrence, wherein complete response to bevacizumab was observed. Our patient was a 50-year-old woman who had a paraaortic lymph node recurrence during adjuvant chemotherapy with FOLFOX 6 months after surgery for sigmoid colon cancer. She was treated with chemotherapy consisting of FOLFOX plus bevacizumab/FOLFIRI plus bevacizumab, which suppressed progression of the periaortic lymph node recurrence. She underwent surgery for the paraaortic lymph node recurrence, and the pathologic result was complete response. We report that bevacizumab was effective for her paraaortic lymph node recurrence.

Sigmoid volvulus is associated with a decrease in enteric plexuses and ganglion cells: a case-control study.

PURPOSE: Although sigmoid volvulus (SV) causes acute obstruction, its pathogenesis and mechanism of torsion are unknown, and few reports have described its pathological findings. Here, we evaluated the clinicopathological characteristics of volvulus and factors contributing to volvulus of the sigmoid colon. METHODS: We compared 14 patients with SV (10 men and 4 women; median age, 78.5 years) with 14 age- and sex-matched control patients for differences in clinical characteristics, focusing on dysmotility (enteric visceral myopathy, neuropathy, and mesenchymopathy). RESULTS: Of the 14 SV patients, 7 had recurrent volvulus, 11 had an associated condition, and 5 required emergency surgery. Atrophy and fibrosis of the inner muscle were more prevalent in the SV than control patients (p = 0.041). Median extent (per centimeter of muscularis propria) of the myenteric plexus (12.5 versus 17.5, p < 0.001) and submucous plexus (15.0 versus 25.5, p < 0.001) was lower in the SV patients, as were the median numbers of myenteric (9.7 versus 30.4, p < 0.001) and submucous ganglion cells (10.0 versus 23.2, p < 0.001). Inflammatory neuropathy was more prevalent in the SV than control patients (p = 0.046); whereas, the prevalence of mesenchymopathy did not differ (p = 0.481). CONCLUSIONS: A decrease in the extent of enteric plexus and ganglion cells precedes the clinical manifestation of SV. Although further elucidation is needed, this decrease may play an important role in the diagnosis of SV and in identifying the mechanism leading to torsion in SV.

Xylose fermentation by Saccharomyces cerevisiae using endogenous xylose-assimilating genes.

OBJECTIVES: To genetically engineer Saccharomyces cerevisiae for improved ethanol productivity from glucose/xylose mixtures. RESULTS: An endogenous gene cassette composed of aldose reductase (GRE3), sorbitol dehydrogenase (SOR1) and xylulose kinase (XKS1) with a PGK1 promoter and a terminator was introduced into two S. cerevisiae strains, a laboratory strain (CEN.PK2-1C) and an industrial strain (Kyokai No. 7). The engineered Kyokai No. 7 strain (K7-XYL) exhibited a higher sugar consumption rate (1.03 g l(-1) h(-1)) and ethanol yield (63.8 %) from a glucose and xylose mixture compared to the engineered CEN.PK2-1C strain. Furthermore, K7-XYL produced a larger amount of ethanol (39.6 g l(-1)) compared to K7-SsXYL (32 g l(-1)) with integrated xylose reductase and xylitol dehydrogenase from a xylose-assimilating yeast Scheffersomyces stipitis instead of GRE3 and SOR1. CONCLUSION: The created S. cerevisiae strain showed sufficient xylose-fermenting ability to be used for efficient ethanol production from glucose/xylose.

[A case of multiple liver metastases from colon cancer treated with complete resection via two-stage hepatectomy after regeneration of the liver].

A 55-year-old woman underwent low anterior resection for sigmoid colon cancer with multiple bilobar metastases. She then received 23 courses of Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of hepatic failure due to radial resection of bilobar metastases. Therefore, a right lobectomy was performed, and curative resection was achieved 54 days after the first hepatectomy. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein embolization may have contributed to the improved prognosis of the initially unresectable multiple bilobar liver metastases.

An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis.

Osteoarthritis is the most common form of human arthritis. We investigated the potential role of asporin, an extracellular matrix component expressed abundantly in the articular cartilage of individuals with osteoarthritis, in the pathogenesis of osteoarthritis. Here we report a significant association between a polymorphism in the aspartic acid (D) repeat of the gene encoding asporin (ASPN) and osteoarthritis. In two independent populations of individuals with knee osteoarthritis, the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in individuals with hip osteoarthritis. Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. The effect on TGF-beta activity is allele-specific, with the D14 allele resulting in greater inhibition than other alleles. In vitro binding assays showed a direct interaction between asporin and TGF-beta. Taken together, these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis.