Impact of near-infrared fluorescence imaging with indocyanine green on structural sequelae of anastomotic leakage after laparoscopic intersphincteric resection of malignant rectal tumors.

BACKGROUND: Recent studies have indicated the potential benefit of intraoperative near-infrared fluorescence imaging (NIR-FI) with indocyanine green in reducing early anastomotic leakage in colorectal surgery. Nonetheless, whether NIR-FI is effective in reducing structural sequelae of anastomotic leakage (SSAL) remains unclear. The aim of the present study was to investigate the impact of NIR-FI on SSAL after laparoscopic intersphincteric resection (ISR) of malignant rectal tumors. METHODS: This study was a retrospective single-center cohort study. A total of 293 consecutive patients who underwent elective laparoscopic ISR from May 2010 to August 2017 were included. Patients were divided into 2 groups; those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors using NIR-F (NIR-FI group) and those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors without using NIR-FI (control group). Thirty were excluded from the analyses (13 died, 7 had pelvic recurrence, and 10 were lost to follow-up). The primary endpoint was the rate of SSAL within 2 years after the primary resection, whereas the secondary endpoint was the rate of natural defecation via the anus at 2 years after the primary resection. Using various statistical analyses, such as propensity score matching, the rate of SSAL was compared between groups. RESULTS: A total of 263 patients were analyzed [177 males and 86 females, median age 61 (27-84) years]. Prior to propensity score matching (n = 263), NIR-FI was performed in 70 patients (26.6%) The rates of SSAL were 1.4% (1/70) in the NIR-FI group and 10.4% (20/193) in the control group (p = 0.02). After propensity score matching (n = 163), the rates of SSAL were 1.5% (1/66) in the NIR-FI group and 11.7% (12/103) in the control group (p = 0.02). Propensity score analyses, as well as simple regression analyses, revealed that NIR-FI was associated with a significantly lower risk of SSAL (OR 0.10-0.13; p = 0.03-0.05). CONCLUSIONS: NIR-FI is useful in reducing the rate of SSAL after laparoscopic ISR.

Impact of prompt intervention in response to positive blood culture results during weekends by collaboration between infectious disease specialists and microbiology laboratory staff.

The purpose of this investigation was to elucidate the impact of prompt intervention for patients whose blood culture results became positive during weekends, as this is not standard care in some countries. A retrospective cohort study was conducted in a tertiary referral hospital. From June 2015, results of positive blood cultures became available during weekends. If infectious disease specialists identified cases of bacteremia on suboptimal antimicrobial coverage, they contacted the primary team for modification of antibiotic treatment. We reviewed patients whose blood culture results became positive during weekends, comparing the pre-intervention (September 2014 to May 2015) and post-intervention (June 2015 to February 2016) periods. In total, 1081 (post-intervention 568 [52.5%]) bacteremia episodes were included (median patient age [interquartile range, IQR]: 72 [60-82] years; men: 625 [57.8%]). During the post-intervention period, 187 (32.9%) bacteremia episodes were detected during weekends. Infectious disease specialists evaluated the positive blood culture results 1, 2, and ≥3 days prior in 77 (13.6%), 88 (15.5%), and 22 (3.9%) cases, respectively. Although the 7- and 30-day mortality did not significantly improve after the intervention, the length of hospital stay (LOS) in the hospital-acquired bacteremia group was significantly reduced during the post-intervention period after controlling for confounders (post- vs. pre-intervention: median days [IQR]: 37 [19-63] vs. 46.5 [24.8-86.3], p = 0.030). Blood culture results became positive during weekends in one-third of bacteremia cases. The LOS was shortened after the intervention in the hospital-acquired bacteremia group. This could be an important antimicrobial stewardship target.

Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in blood and can serve as useful biomarkers for cancer. METHODS: We performed an miRNA array using serum samples obtained from oesophageal squamous cell carcinoma (ESCC) patients or healthy controls. MiR-1246 was the most markedly elevated in ESCC patients. Therefore, miR-1246 was selected as a candidate for further analysis. The serum miR-1246 level in 46 healthy controls and 101 ESCC patients was evaluated and compared among various clinicopathological characteristics. MiR-1246 expressions in tissue, exosomal, and cellular samples were also examined. RESULTS: Serum miR-1246 alone yielded an receiver-operating characteristic curve area of 0.754, with 71.3% sensitivity and 73.9% specificity for distinguishing ESCC patients from healthy controls. Serum miR-1246 was significantly correlated with the TNM stage and showed to be the strongest independent risk factor for poor survival (HR, 4.032; P=0.017). Unlike the tendency shown in previous reports, miR-1246 was not upregulated in ESCC tissue samples. Furthermore, exosomal miR-1246 did not reflect the abundance in the cell of origin. CONCLUSION: These data support our contention that serum miR-1246 has strong potential as a novel diagnostic and prognostic biomarker in ESCC, and its releasing mechanism is selective and independent of tissue miRNA abundance.

Salmonella enterica serotype Paratyphi A carrying CTX-M-15 type extended-spectrum beta-lactamase isolated from a Japanese traveller returning from India, Japan, July 2013.

Emerging drug resistance in Salmonella Typhi and S. Paratyphi is a substantial public health concern. We report what appears to be the first case and isolation of multidrug resistant S. Paratyphi A carrying CTXM-15-type extended-spectrum beta-lactamase from a Japanese traveller returning from India.

HIF-2α Inhibits Ameloblast Differentiation via Hey2 in Tooth Development.

Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α-Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.

Anomalous metallic state in the vicinity of metal to valence-bond solid insulator transition in LiVS2.

We investigate LiVS2 and LiVSe2 with a triangular lattice as itinerant analogues of LiVO2 known for the formation of a valence-bond solid (VBS) state out of an S=1 frustrated magnet. LiVS2, which is located at the border between a metal and a correlated insulator, shows a first order transition from a paramagnetic metal to a VBS insulator at Tc approximately 305 K upon cooling. The presence of a VBS state in the close vicinity of insulator-metal transition may suggest the importance of itinerancy in the formation of a VBS state. We argue that the high temperature metallic phase of LiVS2 has a pseudogap, likely originating from the VBS fluctuation. LiVSe2 was found to be a paramagnetic metal down to 2 K.

Manometer extension for high pressure measurement: nuclear quadrupole resonance study of Cu2O with a modified Bridgman anvil cell up to 10 GPa.

We report (63)Cu nuclear quadrupole resonance (NQR) measurement of Cu(2)O under pressure up to about 10 GPa at low temperatures. Because the lattice parameter of Cu(2)O changes with increasing pressure, the electric field gradient at the Cu site also changes correspondingly with pressure. This enables us to use the Cu(2)O as an in situ manometer for high pressure nuclear magnetic resonance/NQR up to about 9 GPa.

Unique characteristics of community-onset healthcare- associated bloodstream infections: a multi-centre prospective surveillance study of bloodstream infections in Japan.

BACKGROUND: Analysis of bloodstream infections (BSIs) is valuable for their diagnosis, treatment and prevention. However, limited data are available in Japan. AIM: To investigate the characteristics of patients with bacteraemia in Japan. METHODS: This study was conducted in five hospitals from October 2012 to September 2013. Clinical, demographic, microbiological and outcome data for all blood-culture-positive cases were analysed. FINDINGS: In total, 3206 cases of BSI were analysed: 551 community-onset healthcare-associated (CHA)-BSIs, 1891 hospital-acquired (HA)-BSIs and 764 community-acquired (CA)-BSIs. The seven- and 30-day mortality rates were higher in patients with CHA- and HA-BSIs than in patients with CA-BSIs. The odds ratios (ORs) for seven-day mortality were 2.56 [95% confidence interval (CI) 1.48-4.41] and 2.63 (95% CI 1.64-4.19) for CHA- and HA-BSIs, respectively. The ORs for 30-day mortality were 2.41 (95% CI 1.63-3.57) and 3.31 (95% CI 2.39-4.59) for CHA- and HA-BSIs, respectively. There were 499 cases (15.2%) of central-line-associated BSI and 163 cases (5.0%) of peripheral-line-associated BSI. Major pathogens included coagulase-negative staphylococci (N = 736, 23.0%), Escherichia coli (N = 581, 18.1%), Staphylococcus aureus (N = 294, 9.2%) and Klebsiella pneumoniae (N = 263, 8.2%). E. coli exhibited a higher 30-day mortality rate among patients with HA-BSIs (22.3%) compared with patients with CHA-BSIs (12.3%) and CA-BSIs (3.4%). K. pneumoniae exhibited higher 30-day mortality rates in patients with HA-BSIs (22.0%) and CHA-BSIs (22.7%) compared with patients with CA-BSIs (7.8%). CONCLUSION: CHA- and HA-BSIs had higher mortality rates than CA-BSIs. The prognoses of E. coli- and K. pneumonia-related BSIs differed according to the category of bacteraemia.

Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein are decreased in streptozocin-induced diabetes. Possible marker for diabetic osteopenia.

To investigate the pathophysiology of diabetic osteopenia, circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein (BGP) were measured in streptozocin-induced diabetic rats . Plasma calcium and total protein were significantly decreased (P less than .01) in the diabetic group, and the plasma level of BGP in diabetic rats was 19.6 +/- 2.8 (mean +/- SE) ng/ml, which is significantly lower than the value of 89.2 +/- 14.0 ng/ml in control rats (P less than .01). Bone contents of calcium and hydroxyproline per femur were significantly decreased in the diabetic group (P less than .01), and the ratios of bone calcium to hydroxyproline were not different. Bone BGP content per femur in the diabetic group was 669 +/- 58 micrograms, which was also significantly lower compared with 1241 +/- 126 micrograms in control rats (P less than .01). The decreased bone content of BGP is consistent with the hypothesis that BGP synthesis is impaired in insulin-deficient diabetes. Because a relationship between plasma levels of BGP and bone turnover has been established, the low plasma BGP value suggests there is a decrease in bone turnover in diabetic rats. Therefore, we postulate that the low bone turnover is one of the pathological features of diabetic osteopenia and is at least partly responsible for the occurrence of this complication in diabetes mellitus.

Characterization of heparin-induced osteopenia in rats.

Heparin has been known to induce osteopenia, but its precise mechanism of action is unknown. In the present study, we examined the effect of heparin on the rat femur using single photon absorptiometry and characterized the osteopenia biochemically and pharmacologically. Daily heparin injection dose dependently induced osteopenia in rats. Significant bone loss was observed from 2 weeks after starting heparin treatment (2000 U/kg.day) and peaked at 4 weeks. Serum PTH levels were significantly elevated from 1 week onward after starting heparin treatment, whereas no significant changes were seen in serum total calcium or ionized calcium levels. A bone resorption inhibitor, FR78844 (a bisphosphonate compound), significantly attenuated the heparin-induced osteopenia, as did 1 alpha-hydroxyvitamin D3; with the latter, the effective dose was 10 times lower than that needed for a similar effect against immobilization and ovariectomy-induced osteopenia, suggesting an up-regulation of 1 alpha, 25-dihydroxyvitamin D3 receptors in the heparin-treated rats. This speculation was supported by the finding that serum 1 alpha, 25-dihydroxyvitamin D levels were significantly decreased by 54% in the heparin-treated rats compared to those in normal rats. These results suggest that the enhanced bone resorption by high PTH blood levels and the reduction of 1 alpha, 25-dihydroxyvitamin D are involved in the pathogenesis of heparin-induced osteopenia.

Non-peptide inhibitors of HCV serine proteinase.

We screened a chemical library of 2000 compounds for inhibitors of hepatitis C virus (HCV) serine proteinase using an in vitro screening method measuring the hydrolysis of the peptide substrate. Three compounds were found to be the most potent inhibitors (IC50 < 10(-5) M). Two of them had a similar structure, that of halogenated benzanilide, and were not inhibitory for common serine proteinases. They inhibited the enzyme non-competitively with the substrate. Together with the result of the analogous compounds in the chemical library, the presumed structural requirements of the inhibition are pointed out.

Meta-chlorophenylpiperazine attenuates formalin-induced nociceptive responses through 5-HT1/2 receptors in both normal and diabetic mice.

1. This study was designed to investigate the effect of meta-chlorophenylpiperazine (m-CPP; a 5-hydroxytryptamine (5-HT) receptor agonist) on the formalin-induced nociceptive responses in normal, insulin-dependent streptozotocin (STZ) diabetic and non-insulin dependent genetically diabetic (db/db) mice. 2. A subcutaneous injection of diluted formalin (1% formaldehyde in 0.9% saline, 10 microliters) under the plantar surface of the left hindpaw induced biphasic nociceptive responses, the first and second phases considered to represent acute and chronic pain, respectively. The former response in db/db mice was significantly lower than those in normal mice, and the latter responses in STZ and db/db mice were significantly lower than those in normal mice. 3. In normal mice, m-CPP (0.32-3.2 mg ml-1, p.o.) exhibited potent antinociceptive activity, dose-dependently attenuating the first and second phase; the ID50 value of the second phase was 0.4 mg kg-1. m-CPP (0.32-3.2 mg kg-1, p.o.) also dose-dependently attenuated the formalin-induced nociceptive responses in STZ-induced diabetic mice and genetically diabetic db/db mice, and the activities were comparable to those in normal mice. 4. The antinociceptive activities of m-CPP (1 mg kg-1, p.o.) were significantly inhibited by pretreatment with pindolol (a 5-HT1-receptor antagonist, 1 mg kg-1, i.p.) or ketanserin (a 5-HT2 receptor antagonist, 1 mg kg-1, i.p.) but were hardly affected by ICS205-930 (a 5-HT3 receptor antagonist, 1 mg kg-1, i.p.). 5. These results suggest that m-CPP inhibits not only acute but also chronic pain transmission through 5-HT1 and 5-HT2 receptors, and that the 5-hydroxytryptaminergic antinociceptive pathways are little affected by diabetes.

Expression of the mC26 gene encoding GlyCAM-1 in the lactating mouse mammary gland.

We previously reported the partial sequence of a cloned genomic DNA, mC26, which codes for a protein highly expressed in the lactating mouse mammary gland [mC26: Satow et al. (1986) J. Biochem. 99, 1639-1643; partial sequence: Kawamura et al. (1987) J. Biochem. 101, 103-110]. In this study, we sequenced the EcoRI-HindIII fragment (5,394 bp) of this gene and found that this gene contains a sequence completely (100%) homologous to the cDNA sequence currently reported to code for GlyCAM-1, a putative ligand for L-selectin. We show by means of an RNA protection assay that the mRNA of this gene is expressed in the mammary glands of lactating mice as well as in the lymph nodes. Semi-quantitative analysis of expression of the mC26 gene in the mammary glands revealed that the amount of mRNA was not detectable in the early stage of pregnancy, increased in the late stage, and remained quite abundant during lactation. The potential role of this gene highly expressed in the mammary gland in a stage-specific and tissue-specific manner is discussed.

Partial left ventriculectomy to treat end-stage heart disease.

BACKGROUND: It is reasoned that reducing left ventricular diameter (Laplace's law) in patients with dilated cardiomyopathy, will improve ventricular function. METHODS: Partial left ventriculectomy was performed in 120 patients with end-stage dilated cardiomyopathies of varying causes. Most patients were in New York Heart Association functional class IV. The procedure consisted of removal of a wedge of left ventricular muscle from the apex to the base of the heart. Depending on the distance between the two papillary muscles, the mitral valve apparatus was either preserved, repaired, or replaced with a tissue prosthesis. RESULTS: The 30-day mortality was 22% and the 2-year survival was 55%. Although 10% of surviving patients showed no improvement in New York Heart Association functional class, most of the surviving patients were in either class I (57%) or II (33.3%), and the others were in class III and IV. CONCLUSIONS: Partial left ventriculectomy can be used to treat end-stage dilated cardiomyopathy. Further studies and a longer follow-up period are needed to fully assess the effects of this procedure.

Effects of porcine galanin on the mesenteric microcirculation and arteriolar smooth muscle in the rat.

The actions of porcine galanin on the mesenteric circulation at the arteriolar level and on the isolated mesenteric small artery were studied in the rat. Male Wistar rats were anesthetized then laparotomized. Microscopic observation of the mesenteric microvascular area was made with a video camera and changes in arteriolar diameter were measured continuously with a width analyzer. Galanin (0.03-300 pmol), given intra-arterially into the mesenteric arteriole, caused an intermittent interruption of blood flow within 40 s and finally stopped the blood flow within a few minutes. The diameter of arterioles was not changed or was slightly widened. Galanin also relaxed the preconstricted small mesenteric artery in an endothelium-independent manner. Furthermore, the relaxing action of galanin was not antagonized by glibenclamide, indicating that activation of ATP-sensitive K+ channels was not involved. The present results suggest that galanin plays a modulatory role in the mesenteric circulation.

Congenital changes of platelet functions in stroke-prone SHR: aggregability of gel-filtered platelets, PRP and whole blood, and effects of hypotensive treatment.

Platelet aggregation in whole blood, platelet rich plasma, and gel-filtered platelets were markedly attenuated in SHRSP compared with those in age-matched normotensive WKY. The result was consistent with the previous report of washed platelets. Despite prevention of high blood pressure, a long duration of hypotensive treatment only slightly improved aggregability of washed platelets but did not restore it to the range of age-matched WKY platelets. Blood pressure, heart ratios and thrombin-induced washed platelet aggregation were examined in SHRSP, WKY, and the cross (F1: WKY x SHRSP). The higher blood pressure and heart ratios the lower platelet aggregability was observed in the three strains, and there was no overlapping distribution of these values. F1 progeny exhibited intermediate values in blood pressure, heart ratio and platelet aggregability between the parental values. These results suggested that hypofunctions of SHRSP platelet were not secondary changes due to high blood pressure, but primary changes which are genetically linked to high blood pressure.

Galanin-immunoreactive nerve fibers in the periodontal ligament during experimental tooth movement.

Neuropeptides have been suggested to play a role in pain transmission during orthodontic tooth movement. We examined this hypothesis by examining the effect of orthodontic tooth movement on the expression of galanin (GAL)-immunoreactive (ir) nerve fibers in the periodontal ligament (PDL) of one mesial root (MR) and two distal roots (DRs) of the rat maxillary first molar. In control rats, GAL-ir fibers were very rare in the PDL. One day after the insertion of the elastic band, the number of GAL-ir fibers increased, becoming most numerous at 3 days. From 5 to 28 days, GAL-ir fibers tended to decrease. Electron microscopic observation showed that all of the GAL-ir fibers were unmyelinated. These findings suggest that GAL-containing nerve fibers in the PDL may play an important role in the response of the tissue to experimental tooth movement.

Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group.

To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated osteopenia, we examined age-related changes of the femur metaphyseal bone mineral density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the same strain using single photon absorptiometry and characterized the osteopenia pharmacologically and biochemically. Bone mineral density increased with age in the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice at 8 weeks of age, and significant differences between the two groups were observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur and A/D ratio were significant lower in the db/db mice than in the +/+ mice after 8 weeks of age. Significant elevations of serum calcium and parathyroid hormone (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum 1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice. These results suggest that an impaired bone mineralization probably by insufficient vitamin D activity and high PTH levels are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted beneficial effects on the bone loss.