[Follow-up study of coronary artery bypass grafting after Kawasaki disease--early and late postoperative evaluation].
In our hospital, 22 patients with severe coronary arterial lesion after Kawasaki disease underwent coronary artery bypass grafting (CABG) since 1982. The age of the cases at surgery ranged from 1 year to 19 years. Mean age was 8.3 years. Fifteen cases were bypassed using internal mammary artery (IMA) and 5 cases using IMA and autologous saphenous vein (SVG). Two cases were bypassed using only SVG. They have been examined until now by catheterization, by Treadmill test, and by Tl-201 myocardial imaging, around 1 month (Study 1) and around 1 year (Study 2) after surgery for the evaluation of results of CABG. One patient died from acute myocardial infarction 3 months after surgery and one patient shows return of anginal attack due to graft stenosis. Other patients are almost uneventful. In the study 1,20 (100%) IMA were patent, and 7 (88%) SVG were patent. In the study 2, 11 (92%) IMA and 6 (67%) SVG remained patent. Development of left anterior descending artery distal to IMA anastomosis was shown in 8 cases in the study 2. On the follow-up study with TI-201 myocardial imaging, disappearance or decrease of perfusion defect was seen in 7 cases (59%) in the study 1 and 9 cases (75%) in the study 2. On the Treadmill test, disappearance or improvement of ischemic change was seen in 15 cases (88%) in the study 1 and 10 cases (84%) in the study 2. These results suggest that IMA is more preferable for than SVG for young children who has an indication of CABG after Kawasaki disease.


Development and application of an enzyme immunoassay based on a monoclonal antibody against gonyautoxin components of paralytic shellfish poisoning toxins.
With a gonyautoxin 2/3 (GTX2/3)-specific monoclonal antibody (designated GT-13A) and a saxitoxin-horseradish peroxidase conjugate (STX-HRP), a direct competitive enzyme immunoassay (GTX-EIA) was established and its sensitivity to various toxin components was investigated. The concentrations resulting in 50% inhibition of the binding of STX-HRP to the solid-phase GT-13A antibody for GTX2/3, decarbamoyl-GTX2/3 (dc-GTX2/3), N-sulfocarbamoyl-GTX2/3 (C1/2), GTX1/4, STX, and neosaxitoxin (neoSTX) in GTX-EIA were found to be 0.28, 0.41, 0.52, 3.46, 4.06, and 89.37 ng/ml, respectively. When the minimum detection limit was assumed to be at a toxin concentration causing 30% inhibition of the binding of STX-HRP to the solid-phase GT-13A antibody, the detection limits for GTX2/3, dc-GTX2/3, C1/2, GTX1/4, STX, and neoSTX were found to be 0.15, 0.18, 0.19, 1.09, 1.50, and 22.93 ng/ml, respectively. These results indicate that all of the GTX components examined and STX are detectable at concentrations lower than the regulatory limit of 80 microg/100 g of shellfish tissue, even when a minimum dilution factor of 100 is applied to tissue extracts with the extraction procedure of the Association of Official Analytical Chemists. Therefore, GTX-EIA is thought to be a useful qualitative screening method for GTX components and STX in the mass monitoring of toxin-contaminated shellfish.


[Mini-laparoscopic cholecystectomy as an innovative method in minimally invasive abdominal surgery].
In our study, we applied a mini-laparosopic approach during laparoscopic cholecystectomy (LC) (using the minimum size of trocars with the simultaneous intention to reduce their number). The advantages and disadvantages of the mini-LC approach were compared with those of traditional LC. During mini-LC procedures, we used 3 ports (11 mm, 5 mm, 3.5 mm). Mini-LC was performed in 10 patients, and the results were compared with those of 10 cases of traditional LCs. The two groups were homogenous in terms of gender, age, BMI and ASA classification. Comparison criteria included operative time, the need to use an extra port, conversion rate, oral analgesic requirement, early/late complications and cosmetic results. There were no significant differences in terms of operative time, blood loss, hospital stay and complications. Cumulative size of incisions was 19.5 mm with mini-LC- and 41 mm in the LC group, respectively, and the tissue injury was 124.2 mm(2) and 448.2 mm(2). Cosmetic results of mini-LC were highly improved by these values. Increased oral analgetic requirements were detected in LC group. Mini-LC is a safe procedure with outstanding cosmetic results accompanied by less oral analgetic requirements. In selected patients, it can be recommended as an alternative method of traditional LC.


Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours.
Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, such as somatostatin receptors, which can be of great value in the localization and treatment of these tumours. Scintigraphy with (111)In-pentetreotide has become one of the most important imaging investigations in the initial identification and staging of gastro-enteropancreatic (GEP) tumours, whereas helical computed tomography (CT), magnetic resonance imaging (MRI), endoscopic and/or peri-operative ultrasonography are used for the precise localization of GEPs and in monitoring their response to treatment. Scintigraphy with (123)I-MIBG (meta-iodobenzylguanidine) is sensitive in the identification of chromaffin cell tumours, although scintigraphy with (111)In-pentetreotide may also have a role in the localization of malignant chromaffin cell tumours and medullary thyroid carcinoma; for further localization and monitoring of the response to treatment both CT and MRI are used with high diagnostic accuracy. More recently, positron emission tomography (PET) scanning is being increasingly used for the localization of NETs, particularly when other imaging modalities have failed, although its precise role and utility remain to be defined. Surgery is still the usual initial therapeutic, and only curative, modality of choice; however, the majority of NETs will require further treatment with somatostatin analogues and/or interferon; chemotherapy may be used for progressive and highly aggressive NETs, but its role has not been clearly defined. For those NETs that demonstrate uptake to a diagnostic scan with (123)I-MIBG or (111)In-octreotide, therapy with radionuclides such as (131)I-MIBG or (111)In/(90)Y-octreotide or other isotopes, presents a further evolving therapeutic modality.


Three-dimensional arterial spin labeling imaging and dynamic susceptibility contrast perfusion-weighted imaging value in diagnosing glioma grade prior to surgery.
The current study aimed to investigate whole-brain three-dimensional arterial spin labeling imaging (3D ASL) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI), in regards to their diagnostic value of preoperative glioma grade. The parameter values obtained after correction will be correlated with the diagnostic value of 3D ASL and DSC-PWI perfusion. In the current study, 50 patients with gliomas confirmed by pathology were used, including 27 low-grade gliomas (LGGs) and 23 high-grade gliomas (HGGs). Prior to surgery all patients underwent 3 Tesla magnetic resonance imaging (MRI), 3D ASL, DSC-PWI and conventional enhanced MRI scans to obtain original 3D ASL and DSC-PWI images, and the tumor regions with the most obvious parenchyma perfusion and contralateral normal white matter were selected. In these areas, the ASL-relative cerebral blood flow (ASL-rCBF), DSC-relative cerebral blood flow (DSC-rCBF) and DSC-relative cerebral blood volume (DSC-rCBV) parameter values were then obtained after correction for individual differences. The results of the present study show that ASL-CBF, DSC-CBF, DSC-CBV values and ASL-rCBF, DSC-rCBF, DSC-rCBV values increased as the grade of the glioma being imaged increased, and there was a marked difference between the HGGs and the LGGs. ASL-rCBF was significantly positively correlated with DSC-rCBF (r=0.580, P<0.01). In addition, ASL-rCBF was significantly positively correlated with DSC-rCBV (r=0.431, P<0.01). Receiver operating characteristic (ROC) curves were applied to compare the two perfusion parameters of DSC-PWI and 3D ASL in the diagnosis of glioma grade. ASL-rCBF had the highest area value under the ROC curve (0.836). The areas under the ROC curve of DSC-rCBF and DSC-rCBV were analyzed using the Z test, but the difference was not statistically significant. When ASL-rCBF, DSC-rCBF and DSC-rCBV were cutoff at 2.24, 1.85 and 1.68, the sensitivity of HGG diagnosis was 83.2, 91.3 and 91.3%, and the specificity was 77.7, 63.9 and 66.7%, respectively.


Comparison of water turnover rates in young swimmers in training and age-matched non-training individuals.
Total body water (TBW) and water turnover rates (WTR) of 8 competitive swimmers (SW) and 6 age-matched non-training individuals (CON) were determined using deuterium oxide dilution and elimination. During the 7-day study, individuals in the SW group trained 9 times, swimming on average 42.4 km, while the CON group did no regular exercise. Water temperature in the swimming pool was between 26 and 29 degrees C during training sessions. Body mass at the beginning and end of the study period remained essentially the same in the SW (67.8+/- 6.3 kg) and CON (61.1 +/- 8.5 kg) groups. Mean +/- SD TBW of the SW (38.7+/- 5.6 L) was similar to that of the CON (37.5 +/- 8.0 L). Mean WTR was faster in the SW (54 +/- 18 ml x kg x day(- 1) than the CON (28+/- 21 ml x kg x day(-1)). Mean daily urine output was similar in the SW (14 +/- 5 ml x kg x day(-1)) and CON (14+/- 3 ml x kg x day(-1)). Calculated non-renal daily water loss was faster in the SW (41 +/- 21 ml x kg x day(-1)) than the CON (13 +/- 20 ml x kg x day(-1)). This study demonstrates that WTR are faster in young swimmers who exercise strenuously in cool water than in non-training individuals and that the difference was due to the approximately 3-times greater non-renal water losses that the exercising group incurred. This suggests that exercise-induced increases in sweat rates are a major factor in water loss in swimmers training in cool water.


Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma.
The crucial role of competitive endogenous RNA (ceRNA) in the malignant biological behavior of tumors has been certificated. Nevertheless, the detailed function and molecular mechanism of ceRNA associated with cuproptosis in hepatocellular carcinoma (HCC) remains dismal. In this study, we first constructed a protein-protein interaction network and identified the module with the highest degree of aggregation degree. DLAT and PDHA1 were screened out of the module after differential expression and survival analysis. Next, we reverse-predicted the upstream miRNA and lncRNA from mRNA (DLAT, PDHA1) and successfully established the ceRNA network-SNHG3/miR-1306-5p/PDHA1. SNHG3 was identified to be an independent prognostic biomarker based on the outcome of univariate and multivariate Cox analyses. Subsequently, we implemented methylation, immune infiltration, and drug sensitivity analysis to investigate the potential biological functions of SNHG3 in HCC. In addition, SNHG3 expression was upregulated in liver cancer cell lines. In vitro functional assay revealed that SNHG3 knockdown significantly attenuated proliferation, migration, and invasion of liver cancer cells. In summary, SNHG3 exhibited oncogenic characterization via sponging miR-1306-5p to regulate PDHA1, which might function as a promising prognostic indicator and a potential therapeutic target for HCC and shed new light on the molecular mechanism of HCC progression.


1H NMR pattern recognition and 31P NMR studies with d-Serine in rat urine and kidney, time- and dose-related metabolic effects.
Proton NMR spectroscopy of urine has previously been used to gain insight into the site and mechanism of toxic injury to the kidney. d-Serine injures the rat kidney, causing selective necrosis of the proximal straight tubules. Damage is accompanied by proteinuria, glucosuria, and amino aciduria, the latter preceding the onset of necrosis. This study has employed (1)H NMR spectroscopy of urine and (1)H NMR and (31)P NMR spectroscopy of kidney extracts to examine the nephrotoxic action of d-serine. Urine was collected 0-8 h (all doses) and 8-24, 24-48, 48-72, 72-96, and 96-120 h (500 mg/kg only) postdosing from Alderley Park rats given d-serine (62.5, 125, 250, and 500 mg/kg ip). (1)H NMR spectra were monitored for markers of tubular damage. Additionally, ATP and ADP were quantitated in kidney perchloric acid extracts, prepared after 0.5, 1, 2, 4, and 8 h (500 mg/kg) to assess energy status; serine was also measured in these samples. At 500 mg/kg, glucosuria, amino aciduria, and reduced citrate, alpha-ketoglutarate, and succinate were observed in urine at 0-8 h. Furthermore, serine and pyruvate levels were elevated at this time. After 8-24 h, similar changes were observed; however, they were more severe reflecting the development of the lesion prior to recovery. These perturbations were dose-related, in particular, for serine and pyruvate, with no alterations seen at 62.5 mg/kg. Kidney serine concentration rapidly increased, where it was maximal after 30 min and cleared by 8 h. A decline in ATP, to approximately 60-70% of control, was observed within the kidney at 2-4 h postdosing, when necrosis first becomes evident suggesting that mitochondrial function might be impaired in the early stages of d-serine-induced nephrotoxicity. The use of NMR spectroscopy has given a comprehensive overview of the effects of d-serine in vivo. Information on the excretion of serine and its effect on renal energy metabolism provides insight into the possible mechanism of renal tubule injury.


miR-7 Increases Cisplatin Sensitivity of Gastric Cancer Cells Through Suppressing mTOR.
MicroRNAs have been reported to play an important role in diverse biological processes and cancer progression. MicroRNA-7 has been observed to be downregulated in human gastric cancer tissues, but the function of microRNA-7 in gastric cancer has not been well investigated. In this study, we demonstrate that the expression of microRNA-7 was significantly downregulated in 30 pairs of human gastric cancer tissues compared to adjacent normal tissues. Enforced expression of microRNA-7 inhibited cell proliferation and migration abilities of gastric cancer cells, BGC823 and SGC7901. Furthermore, microRNA-7 targeted mTOR in gastric cancer cells. In human clinical specimens, mTOR was higher expressed in gastric cancer tissues compared with adjacent normal tissues. More interestingly, microRNA-7 also sensitizes gastric cancer cells to cisplatin (CDDP) by targeting mTOR. Collectively, our results demonstrate that microRNA-7 is a tumor suppressor microRNA and indicate its potential application for the treatment of human gastric cancer in future.


Rare progression of cholangiocarcinoma: distal femoral metastasis.
Cholangiocarcinoma (CCA) is a rare cancer of the bile duct epithelial cells, with metastases to long bones rarely reported. We present the case of a woman aged 61 years, diagnosed with CCA 6 years previously. She presented with right thigh discomfort, rapidly progressing to immobility with severe pain. Radiological investigations revealed a lytic lesion in her right distal femur, most likely a metastatic deposit, at high risk of pathological fracture. This was managed with an en bloc resection and implantation of a distal femoral replacement. Pathology specimens from theatre confirmed metastatic CCA. Despite sustaining a subsequent fractured neck of femur on the operative side, she recovered well from surgery, with minimal pain and improved mobility on discharge. She restarted palliative chemotherapy. This case illustrates the option of definitive major surgery for the management of metastatic bone disease. As in this case, this can lead to improved symptom control and quality of remaining life.


microRNA-503 suppresses the migration, proliferation and colony formation of prostate cancer cells by targeting tumor protein D52 like 2.
The present study investigated the expression of microRNA-503 (miR-503) and its effect and mechanism of action on prostate cancer. Tumor tissues and tumor-adjacent tissues were collected from 20 patients with prostate cancer. TargetScan was used to predict the miRNA molecule that interacts with tumor protein D52 like 2 (TPD52L2). DU145 cells were transfected with a negative control, miR-503 mimic or miR-503 inhibitor. DU145 cells that had not undergone transfection were used as a control. Levels of miR-503 and TPD52L2 mRNA were determined using reverse transcription-quantitative polymerase chain reaction and the expression of TPD52L2 protein was measured using western blot analysis. The migration ability of DU145 cells was evaluated using a Transwell assay and cell proliferation was examined using an MTT assay. A flat plate colony formation test was conducted to examine the colony formation rate of DU145 cells. The current study demonstrated that TPD52L2 expression is increased while miR-503 expression is decreased in prostate cancer tissues. Overexpression of miR-503 inhibited the transcription and translation of TPD52L2 in DU145 cells and reduced cell migration, proliferation and colony formation. By contrast, inhibition of miR-503 expression increased the expression of TPD52L2 in DU145 cells and increased cell migration, proliferation and colony formation. The present study demonstrated that miR-503 is an oncogene that regulates the migration, proliferation and colony formation of prostate cancer cells by targeting the TPD52L2 gene. Thus, miR-503 has the potential to become a target for the molecular treatment and prognosis of prostate cancer in the future.


Evaluation of fluorescence in situ hybridization for the detection of bacteria in feline inflammatory liver disease.
The etiopathogenesis of feline inflammatory liver disease (ILD) is unclear. Therefore, we sought to determine the presence and distribution of bacteria within the livers of cats with ILD using eubacterial fluorescence in situ hybridization (FISH). Histopathology from 39 cats with ILD and 19 with histologically normal livers (C) were classified using World Small Animal Veterinary Association guidelines. Hepatic sections were examined by 16 and 23S ribosomal RNA FISH. Antibodies against cytokeratins and factor VIIIa were used to distinguish bile ducts and vascular structures. Histopathologic findings included non-specific reactive hepatitis (12), neutrophilic cholangitis (NC; 12), lymphocytic cholangitis (seven), cholestasis/obstruction (three), probable lymphoma (three) and acute hepatitis (two). Bacteria were observed in 21/39 ILD and 3/19 C (P = 0.0054). In 8/39 ILD and 2/19 C bacteria were restricted to the outer liver capsule (P = 0.29) and may represent contaminants. The prevalence of intrahepatic bacteria was higher (P = 0.008) in ILD (13/31) than C (1/17). Bacteria in ILD were more frequently (P <0.0001) localized to portal vessels, venous sinusoids and parenchyma (12/13) than bile duct (1/13). Bacterial colonization was highest in Escherichia coli-positive NC cats. Concurrent non-hepatic disease, predominantly pancreatic and intestinal (8/10 cats biopsied), was present in all 13 cats with intrahepatic bacteria. Bacterial culture was positive (predominantly E coli and Enterococcus species) in 11/23 (48%) samples, and concurred with FISH in 15/23 cases. The presence of intrahepatic bacteria in 13/31 (41%) cats with ILD suggests a role in etiopathogenesis. The distribution of bacteria within the liver supports the possibility of colonization via either enteric translocation or hematogenous seeding.


Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury.
Diffuse axonal injury (DAI) is a common type of traumatic brain injury, mostly associated with mild changes on computed tomography (CT) scan. Serum biomarkers might be used in the diagnosis and prognosis of this injury type. Our purpose was to determine temporal profile and predictive values of serum concentrations of protein S100BB and neuron-specific enolase (NSE) after DAI. Twenty-eight isolated severe DAI patients (Glasgow Coma Scale score ≤ 8) with normal CT were enrolled in the study. Serum levels of S100BB and NSE were determined at 6 hours, 24 hours, 48 hours, and 72 hours after injury, using enzyme-linked immunosorbent assay. Clinical outcome variables of DAI comprised survival at discharge and Glasgow Outcome scale (GOS) after 3 months and also 2 years. S100BB concentration was maximum in 6 hours after injury (median = 280.75 ng/L) followed by a quick drop. Its value was significantly higher on third day in patients with unfavorable outcome (GOS score = 1-3) versus favorable outcome (GOS score = 4, 5) (p < 0.0001). The values of NSE had mild changes during 3 days; however, these measured values at 72 hours after trauma manifested higher in unfavorable outcome (p < 0.05). Increased serum concentrations of NSE and S100BB within first 3 days after DAI are associated with poor outcome despite mild CT findings. S100BB level at 72 hours after injury can predict late outcome in DAI patients. Prognostic study, level III.


Bacillus subtilis AprX involved in degradation of a heterologous protein during the late stationary growth phase.
In Bacillus subtilis, extracellular protease-deficient mutants have been used in attempts to increase the productivity of heterologous proteins. We detected protease activity of AprX using protease zymography in the culture medium at the late stationary growth phase. An alpha-amylase-A522-PreS2 hybrid protein, in which the PreS2 antigen of human hepatitis B virus (HBV) is fused with the N-terminal 522-amino-acid polypeptide of B. subtilis alpha-amylase, has been produced in multiple-protease-deficient mutants. The B. subtilis KA8AX strain, which is deficient in eight extracellular proteases and AprX, did not show the proteolysis of alpha-amylase-A522-PreS2 in the late stationary growth phase. Moreover, the production of alpha-amylase-A522-PreS2 was about 80 mg/l, which was eight times higher than that by the KA8AX strain previously reported. In addition, we showed the degradation of the heterologous protein by AprX that leaked to the culture medium (probably caused by cell lysis) during the late stationary growth phase.


Purification of lectins by biospecific affinity chromatography.
Biospecific adsorbents which can be used for the purification of lectins are easily prepared by a one-step reaction between Epoxy-activated Sepharose 6 B and lectin-specific sugars. This paper reports the immobilization of N-acetyl-D-galactosamine and N-acetyl-D-glucosamine and the use of the resulting Sepharose derivatives for the purification of soybean lectin and wheat germ lectin, respectively. The former adsorbent had a maximal capacity of 15 mg of lectin/ml sedimented gel and the yield corresponded to 145 mg of lectin/100 g of soybeans. Similarly, yields of wheat germ lectin corresponding to 65 mg/100 g of wheat germ were obtained on an adsorbent which bound 10 mg of lectin/ml. The purified lectins were homogeneous as judged by electrophoresis in polyacrylamide gels at pH 4.5.


Dynamics of an age-structured heroin transmission model with vaccination and treatment.
Based on the development of heroin vaccine, in this paper, we propose an age structured heroin transmission model with treatment and vaccination. The model allows the drug reuse rate of the individuals in treatment to depend on a treatment-age and the vaccine waning rate of the vaccinated to depend on a vaccination age. Meanwhile, the model allows that the heroin vaccine provides an imperfect protection (i.e., the vaccinated individuals can also become drug addicted). We derive the basic reproduction number which dependents on vaccination. The basic reproduction number completely determines the persistence and extinction of heroin spread, i.e., if the basic reproduction number is less than one the drug-free steady state is globally asymptotically stable (i.e., the heroin spread dies out), if the basic reproduction number is larger than one, there exists an unique positive steady state and it is locally and globally stable in some special cases. Finally, some numerical simulations are carried out to illustrate the stability of the positive steady state.


Transferrin-a modulates hepcidin expression in zebrafish embryos.
The iron regulatory hormone hepcidin is transcriptionally up-regulated in response to iron loading, but the mechanisms by which iron levels are sensed are not well understood. Large-scale genetic screens in the zebrafish have resulted in the identification of hypochromic anemia mutants with a range of mutations affecting conserved pathways in iron metabolism and heme synthesis. We hypothesized that transferrin plays a critical role both in iron transport and in regulating hepcidin expression in zebrafish embryos. Here we report the identification and characterization of the zebrafish hypochromic anemia mutant, gavi, which exhibits transferrin deficiency due to mutations in transferrin-a. Morpholino knockdown of transferrin-a in wild-type embryos reproduced the anemia phenotype and decreased somite and terminal gut iron staining, while coinjection of transferrin-a cRNA partially restored these defects. Embryos with transferrin-a or transferrin receptor 2 (TfR2) deficiency exhibited low levels of hepcidin expression, however anemia, in the absence of a defect in the transferrin pathway, failed to impair hepcidin expression. These data indicate that transferrin-a transports iron and that hepcidin expression is regulated by a transferrin-a-dependent pathway in the zebrafish embryo.


Synthesis and Characterization of Two Novel Oxazol-5-ones Derivatives and Their Multifunctional Properties; pH Sensitivity, Electropolymerizability and Antiproliferative Activity.
The aim of this study is to synthesize oxazol-5-one derivatives, which have multi-functional properties. Nomenclatures of newly synthesized molecules are 4-(4-N,N-diethylaminophenylmethylene)-2-(3-thienyl)oxazol-5-one (4a) and 4-(4-(1,4,7,10-tetraoxa-13-azacyclopentadecyl)phenylmethylene)-2-(3-thienyl)oxazol-5-one (4b). These two novel derivatives contain pH sensitive and polymerizable groups. 3-Thienyl group was attached to position-2 of the oxazol-5-one ring to provide electrochemical polymerization capability. pH sensing properties were provided by attaching p-N,N-diethylaminophenylmethylene and p-aza-15-crown-5-phenylmethylene groups to the arylmethylene moiety at position-4 of the ring. Target molecules were synthesized by classical process known as Erlenmeyer-Plöchl Azlactone Synthesis Erlenmeyer (Justus Liebigs Ann Chem 275:1-12, 1893), Rodrigues et al. (J Chem Educ 92:1543-1546, 2015) . After structural characterization of 4a and 4b, absorption and emission characteristics were determined in solvents that have different polarities. Difference in maximum absorption and emission wavelengths of the molecules related to solvent polarities were observed at around 6-7 nm and 35-36 nm respectively. In pH studies of the target derivatives in PVC polymer matrix, ratiometric changes were observed at isosbestic point around 398 nm. Polymeric depositions of the molecules (4a, 4b) were proved by using cyclic voltammetry, electrochemical impedance spectrometry studies and scanning electron microscope images. MTT assay studies showed significant results like, 4b derivative's strong cytotoxic activity on PC-3 (cancerous cell line) with IC50 value of 12.57 ± 0.41 µg/ml without exhibiting any cytotoxic effect on HEK293 (healthy cell line).


Reclassification of Streptomyces hygroscopicus subsp. glebosus and Streptomyces libani subsp. rufus as later heterotypic synonyms of Streptomyces platensis.
We investigated the taxonomic relationships among Streptomyces hygroscopicus subsp. glebosus, Streptomyces libani subsp. rufus and Streptomyces platensis. The three species formed a single clade in the phylogenetic trees based on 16S rRNA gene sequence and multilocus sequence analyses. Digital DNA-DNA hybridization using whole genome sequences suggested that S. hygroscopicus subsp. glebosus, S. libani subsp. rufus and S. platensis belong to the same genomospecies. Previously reported phenotypic data also supported this synonymy. Therefore, S. hygroscopicus subsp. glebosus and S. libani subsp. rufus should be reclassified as later heterotypic synonyms of S. platensis.


Somatostatin analogs inhibit somatostatin secretion from cultured hypothalamus cells.
The effect of somatostatin (SRIF) analogs on the secretion of radioimmunoassayable SRIF (SRIF-LI) was studied in the model system of fetal rat hypothalamus cells maintained in long-term, primary dispersed culture. These experiments exploited the biologic activity of certain synthetic SRIFs which cross-react poorly in our standard RIA for SRIF. Carbachol-stimulated SRIF-LI secretion was suppressed by [DTrp8]-SRIF-14, [DTrp22]-SRIF-28 and the octapeptide, des-AA1,2,4,5,12,13[DTrp8]-SRIF. Effective concentrations of synthetic analogs were at or below 1 nM. des-Trp8-SRIF-14, an analog inactive in all other SRIF biological assays, was similarly ineffective in this assay system at doses up to 10 nM. Following removal of peptide by washing, peptide-treated and control cells responded similarly to depolarization with high potassium buffer. The data demonstrate a direct action of SRIF analogs on the hypothalamus to suppress SRIF-LI release and are consistent with the possibility that an endogenous peptide participates in 'ultrashortloop' negative feedback control of its own secretion in the intact animal.


Two-aperture measurements for GEO-feeder adaptive optics pre-compensation optimization.
We present a method to estimate the pre-compensation phase of ground-to-geostationary orbit (GEO) optical links based on downlink phase and log-amplitude measurements from two ground apertures. This method allows us to reduce the point-ahead anisoplanatism that currently limits the telecom performance of GEO-feeder links. It is shown to reduce the anisoplanatic phase variance by 50%, hence improving the statistics of the coupled flux aboard the satellite. It also outperforms the one-aperture estimation method for very severe atmospheric conditions. Besides, only low-resolution amplitude measurements are required on the second aperture to reach the performance of the novel estimator.


Relationship between porotic changes in alveolar bone and spinal osteoporosis.
Epidemiological studies have shown that post-menopausal women who do not use an estrogen supplement have fewer teeth than those who do. We hypothesized that changes in the dentition of post-menopausal women might be due to alveolar bone alterations by estrogen deficiency. To clarify this, we analyzed the microstructural alveolar bone changes in ovariectomized monkeys and compared these with their lumbar bone mineral density. The % of baseline bone mineral density showed a significant decrease in the ovariectomized group as compared with the controls. The second-molar interradicular septa in ovariectomized monkeys showed a significantly decreased nodes number, cortices number, and an increased structural model index value. More pores were seen in the ovariectomized group at the top of the septa. This study demonstrated that, in such monkeys, estrogen deficiency led to fragility of the trabecular structure of the molar alveolar bone, and such fragility was inversely correlated with lumbar bone mineral density.


Improvement in efficacy of DNA vaccine encoding HIV-1 Vif by LIGHT gene adjuvant.
DNA vaccine can induce the prolonged immune responses against the encoded antigen with the appropriate adjuvant. To study the immunogenicity of the HIV-1 vif DNA vaccine in inducing the humoral and cellular immune responses and the immunoadjuvant effect of LIGHT, which is a member of TNF superfamily and can stimulate the proliferation of naïve T cells as a co-stimulatory molecule, DNA vaccine plasmid pcDNA-Vif was constructed by inserting HIV-1 vif gene into the downstream of CMV promoter in eukaryotic expression vector pcDNA3.1(+). In vitro expression of HIV-1 Vif in pcDNA-Vif-transfected HeLa cells was confirmed in transcriptional and protein level by RT-PCR and Western blot, respectively. After BALB/c mice were injected muscularly with DNA vaccines for three times, the specific immune responses were analyzed. The data showed that anti-Vif antibody response, Vif-specific T cell proliferation, and CTL activities were induced in the mice that were inoculated with HIV-1 vif DNA vaccine plasmid. Interestingly, stronger humoral and cellular immune responses were detected in mice that were immunized with plasmid pcDNA-Vif and pcDNA-LIGHT together compared to the single immunization with plasmid pcDNA-Vif alone. Together, the results of the study suggest that candidate HIV-1 DNA vaccine can elicit HIV-1 Vif-specific immune responses in mice and that LIGHT plays the role of immunoadjuvant in co-immunization with DNA vaccine.


Neuroprotective effects of terpenoids against streptozotocin-nicotinamide-induced diabetic rats: An in silico, in vitro and in vivo study.
The present study focused to determine the neuroprotective effects of terpenoids in streptozotocin & nicotinamide-induced type-2 diabetes in rats. The in silico studies were carried out for 68 terpenoids using AutoDock 4.2. The in vitro cholinestrerase, α-amylase enzyme inhibitory assays were perfomed using standard procedures. For in vivo neuroprotective studies, male wistar rats were separated into five groups and each group comprised of six animals. Treatment groups were received low dose and high dose α-Bisabolol 100 and 200 mg/kg respectively, and the standard groups received rivastigmine 2 mg/kg, p.o. and metformin group 100 mg/kg, p.o. for 30 consecutive days. Administration of streptozotocin (45 mg/kg, i.p.) and nicotinamide (110 mg/kg, i.p.)-induced the type 2 diabetes in all groups except the control. The behavioural assessments such as Morris water maze, and open field test were performed and biochemical parameters such as acetylcholinesterase levels and enzymatic antioxidants and reduced glutathione level were estimated from brain homogenates. Treatment of diabetic rats with α-Bisabolol was lowered blood glucose level, improved spatial recognition memory in behavioural assessments in a concentration dependent manner. It can be concluded that α-Bisabolol could act as a potential drug candidate in the management of diabetic Alzheimer's disease.


Metastability of amorphous silicon from silicon network rebonding.
We propose a network rebonding model for light-induced metastability in amorphous silicon, involving bonding rearrangements of silicon and hydrogen atoms. Nonradiative recombination breaks weak silicon bonds and generates dangling bond-floating bond pairs, with very low activation energies. The transient floating bonds annihilate, generating local hydrogen motion. Charged defects are also found. Support for these processes is found with tight-binding molecular dynamics simulations. The model accounts for major experimental features of the Staebler-Wronski effect including electron-spin resonance data, the t(1/3) kinetics of defect formation, two types of metastable dangling bonds, and hysteretic annealing.


Protective effects of oleanolic acid on oxidative stress and the expression of cytokines and collagen by the AKT/NF‑κB pathway in silicotic rats.
Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to have several benefits and medicinal properties. However, its protective effects against silica‑induced lung injury and fibrosis remain to be elucidated. The aim of the present study was to investigate the effects of OA on oxidative stress, and the expression of cytokines and collagen in silicotic rats. Male rats were induced by intratracheal instillation of silicosis (250 mg/kg), with the exception of the control group (NS). The rats in the OA group were intragastrically administered with OA (60 mg/kg/d). The rats in the solvent control group were gavaged daily with 0.6% sodium carboxymethyl cellulose (10 ml/kg) solution for 56 consecutive days. The data showed that OA significantly attenuated the extent of silicosis fibrosis by histopathologic analysis of the lung tissues. In addition, oxidative stress activated by silica exposure, as evidenced by increasing of malondialdehyde content, and activities of superoxide dismutase and glutathione peroxidase in the lung, was regulated by treatment with OA. Furthermore, enzyme‑linked immunosorbent assay analysis showed that OA significantly decreased the levels of tumor necrosis factor‑α and transforming growth factor‑β1. Immunohistochemistry analysis showed that OA significantly decreased collagen types I and III. In investigating the mechanisms underlying the action of OA, it was found that OA decreased the level of phosphorylated AKT1, which in turn inactivated the transcriptional of nuclear factor (NF)‑κB in the development and progress of silicosis. In conclusion, these results suggested that the protective effects of OA were due, at least in part, to its anti‑oxidant activity and its ability to decrease the expression of cytokines and collagen by modulating the AKT/NF‑κB pathway.


Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin.
Canine parvovirus isolated from a case of haemorrhagic enteritis in a breeding kennel in England was passaged and cloned in cultured feline and canine cells. No significant evidence of pathogenicity was found during six serial passages of the modified virus back through young dogs. The attenuated virus was excreted by inoculated animals and spread rapidly to uninoculated animals held in contact. When high titre attenuated virus was given to the six-week-old offspring of a seropositive dam a prompt seroconversion was observed. When the attenuated virus was used as an experimental vaccine in 108 pups in an infected breeding colony a highly significant improvement was obtained in the accumulated morbidity and mortality compared with a parallel group vaccinated with modified live feline panleucopenia virus.


Full-length sequences of six hepatitis E virus isolates of genotypes III and IV from patients with sporadic acute or fulminant hepatitis in Japan.
Ranges of variation and conservation in sequence need to be defined for detecting and genotyping hepatitis E virus (HEV). Six HEV isolates from Japanese patients were sequenced over the entire genome and compared phylogenetically along with 16 reported HEV isolates, including two from pigs. Three of the six HEV isolates were of genotype III, and the remaining three were of genotype IV. Local clusterings of Japanese HEV isolates were observed in the phylogenetic analyses, including a swine HEV isolate reported previously (swJ570). All six HEV isolates possessed three open reading frames (ORFs). The ORF3 in the three isolates of genotype III were in a different reading frame, while that in the three isolates of genotype IV were in the same reading frame as ORF1. A stretch of 46-96 nucleotides was identified, point mutations and deletions in which were specific for the four genotypes (I-IV). A polymerase chain reaction method was developed with 9 nested universal primers, deduced from conserved regions in the 5'-terminal sequences of the 22 HEV genomes. Conserved and genotype-specific variation in HEV sequences, identified in the comparison of 22 full-length genomes, would be useful in designing primers for sensitive detection and specific genotyping of HEV RNA.


Rofecoxib 50 mg and valdecoxib 20 or 40 mg in adults and adolescents with postoperative pain after third molar extraction: results of two randomized, double-blind, placebo-controlled, single-dose studies.
These studies assessed the comparative efficacy of rofecoxib and valdecoxib in the treatment of acute postoperative dental pain. Two randomized, double-blind, placebo-controlled, single-dose studies were conducted in patients undergoing extraction of > or =2 third molars, with > or =1 mandibular impaction, who experienced moderate or severe pain after extraction. In study 1, patients were randomized in a 4:4:1 ratio to receive rofecoxib 50 mg, valdecoxib 20 mg, or placebo. In study 2, which was an exploratory study, patients were randomized in a 2:2:1 ratio to receive reofecoxib 50 mg, valdecoxib 40 mg, or palcebo. The primary efficacy end point was total pain relief at 12 hours (TOPAR12) for rofecoxib compared with valdecoxib 20 mg (study 1) or valdecoxib 40 mg (study 2). Tolerability was assessed based on clinical adverse experiences (AEs) and vital signs. These studies were performed before both agents were withdrawn from the market. In study 1, 200 patients were randomized to receive rofecoxib 50 mg, 201 to valdecoxib 20 mg, and 49 to placebo. In study 2, 51 patients were randomized to receive rofecoxib 50 mg, 50 to valdecoxib 40 mg, and 24 to placebo. The majority of patients in both studies were female (approximately 54%) and white ( approximately 66%), with a mean age of approximately 22 years and a mean weight of approximately 75 kg. Most (approximately 58%) patients reported experiencing moderate postoperative pain. In study 1, mean TOPAR12 scores were 30.7 for rofecoxib 50 mg, 28.9 for valdecoxib 20 mg, and 5.5 for placebo; in study 2, TOPAR12 scores were 27.0 for rofecoxib 50 mg, 28.6 for valdecoxib 40 mg, and 6.9 for placebo. In both studies, the active treatments were comparable in terms of the primary end point and were statistically superior to placebo (P<0.001). In study 1, rofecoxib was associated with a longer median time to use of rescue medication compared with valdecoxib 20 mg (>24 hours vs 23 hours 58 minutes; P=0.010) and a significantly smaller proportion of patients using rescue medication over 24 hours (35.0% vs 50.2%; P<0.001). In study 2, there were no significant differences in the median time to use of rescue medication or the proportion of patients using rescue medication between active treatments. There were no significant differences in total pain relief at 4 or 8 hours, patients' global assessment, onset of analgesia, or AEs between active treatments in either study. The incidence of clinical AEs in study 1 was similar for rofecoxib 50 mg, valdecoxib 20 mg, and placebo (39.5%, 36.8%, and 49.0%, respectively). In study 2, AEs occurred significantly less frequently with rofecoxib 50 mg compared with placebo (35.3% vs 70.8%, respectively; P<0.01); there was no significant difference between the rate of AEs with valdecoxib 40 mg (50.0%) and placebo. Rofecoxib 50 mg had comparable analgesic efficacy to valdecoxib 20 and 40 mg in these patients with pain after dental surgery. All active treatments were well tolerated.


Affective temperament, depressive symptoms and interleukins in patients with psoriasis.
Psoriasis is a chronic inflammatory skin disease, in which psychological factors play an important role. In the studies of common markers of psoriasis and depression, the abnormal function of the stress axis in both diseases is highlighted, whereas interleukin-6 (IL-6) and interleukin-1 are indicated as particularly important. To evaluate the relationship between the affective temperament traits and the intensity of depressive symptoms in patients with psoriasis in the context of immunoenzymatic markers. The study included 208 subjects. Severity of psoriasis was assessed by PASI. TEMPS-A was applied for the evaluation of affective temperament and BDI was used for the assessment of the intensity of depressive symptoms. The level of cytokines was determined by means of the immunoenzymatic method. Patients presented a specific profile of affective temperament, with higher scores on depressive, anxious and irritable dimensions. The severity of depressive symptoms correlated positively with the severity of psoriasis. A significant correlation was found between IL-6 and the severity of psoriasis in patients with depressive disorders and psoriasis. No similar correlation was found in patients without depressive disorder. Results of the present study show common mechanisms for psoriasis and depression. Specific traits of affective temperament may play an important role in the clinical picture of both diseases. Higher levels of IL-6 in patients with psoriasis predispose to more frequent occurrence of depressive disorders and the depressive dimension of affective temperament.


Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group.
A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.


High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats.
High physiological prolactin induced positive calcium balance by stimulating intestinal calcium absorption, reducing renal calcium excretion, and increasing bone calcium deposition in female rats. Although prolactin-induced increase in trabecular bone calcium deposition was absent after ovariectomy, its effects on cortical bones were still controversial. The present investigation, therefore, aimed to study the effect of in vivo long-term high physiological prolactin induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin injection on cortical bones in ovariectomized rats. Since the presence of prolactin receptors (PRLR) in different bones of normal adult rats has not been reported, we first determined mRNA expression of both short- and long-form PRLRs at the cortical sites (tibia and femur) and trabecular sites (calvaria and vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both PRLR isoforms with predominant long form at all sites. However, high prolactin levels induced by AP transplantation in normal rats did not have any effect on the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium deposition, and total calcium content in tibia and femur of adult ovariectomized rats. AP transplantation also had no effect on the cortical total calcium content in adult ovariectomized rats. Because previous work showed that the effects of prolactin were age dependent and could be modulated by high-calcium diet, interactions between prolactin and these two parameters were investigated. The results demonstrated that 2.0% wt/wt high-calcium diet significantly increased the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats but decreased the tibial total calcium content in 22-wk-old adult rats. As for the vertebrae, the total calcium contents in both young and adult rats were not changed by high-calcium diet. The present results thus indicated that the adult cortical bones were potentially direct targets of prolactin. Moreover, the effects of high physiological prolactin on cortical bones were age dependent and were observed only under the modulation of high-calcium diet condition.


[Li Shizhen's cognition on human life].
Through the comparison between Taoists and physicians of ancient time in our country, we make inquiry into Li Shizhen's cognition on human life and consider that Li Shizhen explicitly put forward, prior to the contemporary physicians, the original creative ideas for the first time,on human being including "the brain is the residence of original spirit", "channel is the tunnel of inner image", "vital gate is located between the two kidneys", "vital gate is the substance, triple burner, the function". In addition to these ideas, Li Shizhen also raised an idea of "spleen is the mother of vital energy", which, even though it was not created for the first time, strengthened and developed the ideas of the predecessors.


L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia.
Treatment with L-carnitine greatly enhanced the formation and excretion of short-chain acylcarnitines in three patients with propionic acidemia and in three normal controls. The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia. The normal children excreted mostly acetylcarnitine. Propionic acidemia and other organic acidurias are characterized by the intramitochondrial accumulation of short-chain acyl-Coenzyme A (CoA) compounds. The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion. We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders.


Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.
Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. Thirty-three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual-probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre-isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2-h postdose plasma samples and in cumulative 0-4-h urine collections using liquid chromatography-mass spectrometry. In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre-isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3-hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX-O-glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre-isotretinoin. Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.


Awareness and perceptions of a communitywide mental health program in New York city after September 11.
The Project Liberty program was established after the terrorist attacks of September 11, 2001, to offer free mental health services to New York City residents. The authors used data from a random-digit-dial telephone survey to assess public awareness of and willingness to make use of Project Liberty's services. They found that 24 percent of the New York City residents surveyed (480 of 2001 respondents) had heard of Project Liberty four months after September 11. Persons with lower socioeconomic status and those who had psychological symptoms consistent with posttraumatic stress disorder were more likely to say that they would contact Project Liberty. The results of the study suggest that although awareness of this public mental health services was low, Project Liberty was well received among the people who may be most likely to need its services.


Transcrestal Sinus Lift Using Platelet Concentrates in Association to Short Implant Placement: A Retrospective Study of Augmented Bone Height Remodeling.
No evidence has been reported yet about dimensional changes in maxillary sinuses grafted with autologous platelet concentrate. This study aimed to analyze the augmented height alterations around short implants (length ≤ 8.5 mm) placed after transcrestal sinus lift surgery in association with plasma rich in growth factors. A retrospective design was used. Patients with atrophic posterior maxilla were treated by inserting short implants in combination with transalveolar maxillary sinus floor augmentation. Radiographic bone level alterations over time were assessed on panoramic radiographs. Transalveolar sinus augmentation was performed to place 41 implants in 26 patients with a residual bone height of 4.7 ± 1.3 mm. The alveolar bone height was increased by 3.7 ± 1.7 mm and 4.2 ± 2.0 mm after 12 ± 3 months and 35 ± 11 months of surgery, respectively, whereas the apical augmented height (beyond the implant) apex was stable around 34 implants during the follow-up. It was increasing around seven implants that were not covered by the endo-sinus augmented height at the 1-year follow-up. Transalveolar sinus floor augmentation in association with plasma rich in growth factors and short implants resulted in a stable augmented height gain after 3 years follow-up. Atrophic posterior maxilla could be treated by transalveolar sinus lift in association with plasma rich in growth factors and the placement of short implants.


Abundant expression of polyomavirus middle T antigen and dihydrofolate reductase in an adenovirus recombinant.
A modular gene with a cDNA encoding the polyomavirus middle T antigen positioned behind the adenovirus type 2 major late promoter and tripartite leader was substituted for the E1a region in an adenovirus vector. Permissive human cells infected with this recombinant produce middle T protein at levels as high as those of the most abundant late adenoviral proteins, e.g., hexon or fiber. This level represents at least a 40-fold increase over that observed in a polyomavirus lytic infection of murine cells. Partial proteolytic mapping showed that this protein has the same primary structure as middle T protein produced in polyomavirus-infected murine cells. The adenovirus recombinant-generated middle T protein exhibited in vitro kinase activity, although at an approximately 10-fold-lower specific activity than that of middle T protein from polyomavirus-infected murine cells. Comparison of the expression levels of this middle T antigen-containing adenovirus vector with a similar construction encoding dihydrofolate reductase suggested that the translation efficiency of the inserted gene was dependent upon the proximity of its initiation codon to the tripartite leader. We tested this possibility by comparing three dihydrofolate reductase recombinants among which the spacing between the initiation codon and tripartite leader varied from 188 to 36 nucleotides. The efficiency of expression of dihydrofolate reductase protein dramatically increased as this spacing was reduced.


Inhibition of platelet aggregation by acetylsalicylic acid and other inhibitors.
Effects on platelet aggregation were examined of acetylsalicylic acid (ASA), indomethacin and a number of other agents including dipyridamole, phenylbutazone and sulfinpyrazone under standardized conditions. The Born turbidometric method of measuring platelet aggregation was used with collagen as the stimulus for aggregation. ASA and indomethacin were shown to be among the most potent inhibitors of aggregation, being active at minimal effective concentrations of 1-3 mug/ml using a 10 min time of pre-incubation with the platelet-rich plasma (degree of aggregation inhibition was time dependent). Most of the other agents tested were also active in vitro and both prostaglandin E1 and adenosine were more potent than ASA or indomethacin. However, these agents were shown not to exert significant inhibitory effects when administered orally to rats (dose 10 and 30 mg/kg). ASA proved to be effective in doses as low as 3 mg/kg, and indomethacin in doses as low as 1 mg/kg orally. The inhibitory effects of ASA on aggregation remained for several days after a single oral dose, whereas the effects of indomethacin disappeared within 24 h.


A Pilot Study on the Efficacy of Volunteer Mentorship for Young Adults With Self-Harm Behaviors Using a Quasi-Experimental Design.
Studies have shown that postdischarge care for self-harm patients is effective in reducing repeated suicidal behaviors. Little is known about whether volunteer support can help reduce self-harm repetition and improve psychosocial well-being. This study investigated the efficacy of volunteer support in preventing repetition of self-harm. This study used a quasi-experimental design by assigning self-harm patients admitted to the emergency departments to an intervention group with volunteer support and treatment as usual (TAU) for 9 months and to a control group of TAU. Outcome measures include repetition of self-harm, suicidal ideation, hopelessness, and level of depressive and anxiety symptoms. A total of 74 cases were recruited (38 participants; 36 controls). There were no significant differences in age, gender, and clinical condition between the two groups at the baseline. The intervention group showed significant improvements in hopelessness and depressive symptoms. However, the number of cases of suicide ideation and of repetition of self-harm episodes was similar for both groups at the postintervention period. Postdischarge care provided by volunteers showed significant improvement in hopelessness and depression. Volunteers have been commonly involved in suicide prevention services. Further research using rigorous methods is recommended for improving service quality in the long term.


Blood flow in normal tissues and tumors during hyperthermia.
The effect of hyperthermia on the blood flow was studied in skin, muscle, and Walker 256 carcinoma implanted in the legs of SD rats. The radioactive microsphere method was used to measure the blood flow. Hyperthermia for 1 hour with water at 43 degrees C increased the blood flow in skin and muscle by about threefold to fourfold. On the contrary, hyperthermia had no appreciable effect on the blood flow in tumors. Consequently, during hyperthermia blood flow in the skin and muscle surrounding the tumors was greater than that in tumors larger than about 2 g. Despite the apparent increase in heat dissipation by the increased blood flow, the temperature of the skin was 42.6-42.8 degrees C, and the temperature at the core of tumors larger than 2 cm in diameter was 42.3-42.7 degrees C during the hyperthermia. The lower temperature in the muscle could be attributed to an increase in heat dissipation as a result of the increased blood flow. This differential rise in temperature by heating may account in part for the differential effect of hyperthermia on tumors and normal tissues in vivo.


Loss and gain of function of Grp75 or mitofusin 2 distinctly alter cholesterol metabolism, but all promote triglyceride accumulation in hepatocytes.
In the liver, contact sites between the endoplasmic reticulum (ER) and mitochondria (named MAMs) may be crucial hubs for the regulation of lipid metabolism, thus contributing to the exacerbation or prevention of fatty liver. We hypothesized that tether proteins located at MAMs could play a key role in preventing triglyceride accumulation in hepatocytes and nonalcoholic fatty liver disease (NAFLD) occurrence. To test this, we explored the role of two key partners in building MAM integrity and functionality, the glucose-regulated protein 75 (Grp75) and mitofusin 2 (Mfn2), which liver contents are altered in obesity and NAFLD. Grp75 or Mfn2 expression was either silenced using siRNA or overexpressed with adenoviruses in Huh7 cells. Silencing of Grp75 and Mfn2 resulted in decreased ER-mitochondria interactions, mitochondrial network fusion state and mitochondrial oxidative capacity, while overexpression of the two proteins induced mirror impacts on these parameters. Furthermore, Grp75 or Mfn2 silencing decreased cellular cholesterol content and enhanced triglyceride secretion in ApoB100 lipoproteins, while their overexpression led to reverse effects. Cellular phosphatidylcholine/phosphatidylethanolamine ratio was decreased only upon overexpression of the proteins, potentially contributing to altered ApoB100 assembly and secretion. Despite the opposite differences, both silencing and overexpression of Grp75 or Mfn2 induced triglyceride storage, although a fatty acid challenge was required to express the alteration upon protein silencing. Among the mechanisms potentially involved in this phenotype, ER stress was closely associated with altered triglyceride metabolism after Grp75 or Mfn2 overexpression, while blunted mitochondrial FA oxidation capacity may be the main defect causing triglyceride accumulation upon Grp75 or Mfn2 silencing. Further studies are required to decipher the link between modulation of Grp75 or Mfn2 expression, change in MAM integrity and alteration of cholesterol content of the cell. In conclusion, Grp75 or Mfn2 silencing and overexpression in Huh7 cells contribute to altering MAM integrity and cholesterol storage in opposite directions, but all promote triglyceride accumulation through distinct cellular pathways. This study also highlights that besides Mfn2, Grp75 could play a central role in hepatic lipid and cholesterol metabolism in obesity and NAFLD.


Alpha coma in an adolescent with diabetic ketoacidosis.
Ostojic S, Vukovic R, Milenkovic T, Mitrovic K, Djuric M, Nikolic L. Alpha coma in an adolescent with diabetic ketoacidosis. Turk J Pediatr 2017; 59: 318-321. This is the first report of alpha coma (AC) caused by brain edema in a patient with diabetic ketoacidosis (DKA). A previously healthy 15-year-old girl was admitted to the intensive care unit due to altered state of consciousness during the course of treatment for DKA. Patient was in a coma, intubated and had tachycardia with poor peripheral perfusion. Results of laboratory analyses indicated severe DKA and computed tomography scan indicated diffuse brain edema. The EEG pattern showed uniform alpha activity. Treatment with intravenous fluids, insulin and mannitol was started. Patient`s state of consciousness gradually improved and on the third day she was extubated. On the fifth day, her neurologic status and EEG findings were completely normal with no residual neurological deficits. In conclusion, although AC is associated with a high fatality rate, favorable outcome can be achieved with prompt recognition and treatment of cerebral edema in pediatric patients with DKA.


Parkinson disease: a role for autophagy?
Autophagy is a term used to describe the process by which lysosomes degrade intracellular components. Known originally as an adaptive response to nutrient deprivation, autophagy has now been recognized to play important roles in several human disorders including neurodegenerative diseases. Experimental results from genetic, cellular, and toxicological studies indicate that many of the etiological factors associated with Parkinson disease (PD) can perturb the autophagic process in various model systems. Thus, the emerging data support the view that dysregulation of autophagy may play a critical role in the pathogenic process of PD.


Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.
The intercellular interactions of the desmosomal cadherins, desmoglein and desmocollin, are required for epidermal cell adhesion. Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by autoantibodies against desmoglein (Dsg) 3. During calcium-induced desmosome assembly, treatment of primary human keratinocytes with pathogenic monovalent anti-Dsg3 mAbs produced from a PV patient causes a decrease of Dsg3 and desmoplakin but not desmocollin (Dsc) 3 in the Triton-insoluble fraction of cell lysates within 2 hours. Immunofluorescence and antibody ELISA studies suggest that pathogenic mAbs cause internalization of cell-surface Dsg3 but not Dsc3 through early endosomes. Electron microscopy demonstrated a lack of well-formed desmosomes in keratinocytes treated with pathogenic compared to nonpathogenic mAbs. In contrast, pathogenic mAbs caused late depletion of Dsg3 from preformed desmosomes at 24 hours, with effects on multiple desmosomal proteins including Dsc3 and plakoglobin. Together, these studies indicate that pathogenic PV mAbs specifically cause internalization of newly synthesized Dsg3 during desmosome assembly, correlating with their pathogenic activity. Monovalent human PV anti-Dsg mAbs reproduce the effects of polyclonal PV IgG on Dsg3 and will facilitate future studies to further dissect the cellular mechanisms for the loss of cell adhesion in pemphigus.


DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome.
The prevalence of type 2 diabetes (T2D) and the metabolic syndrome (MetS) is increasing and several studies suggested an involvement of DNA methylation in the development of these metabolic diseases. This study was designed to investigate if differential DNA methylation in blood can function as a biomarker for T2D and/or MetS. Pyrosequencing analyses were performed for the candidate genes KCNJ11, PPARγ, PDK4, KCNQ1, SCD1, PDX1, FTO and PEG3 in peripheral blood leukocytes (PBLs) from 25 patients diagnosed with only T2D, 9 patients diagnosed with T2D and MetS and 11 control subjects without any metabolic disorders. No significant differences in gene-specific methylation between patients and controls were observed, although a trend towards significance was observed for PEG3. Differential methylation was observed between the groups in 4 out of the 42 single CpG loci located in the promoters regions of the genes FTO, KCNJ11, PPARγ and PDK4. A trend towards a positive correlation was observed for PEG3 methylation with HDL cholesterol levels. Altered levels of DNA methylation in PBLs of specific loci might serve as a biomarker for T2D or MetS, although further investigation is required.


Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study.
Neurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.


Distribution of antigenicity in chicken erythrocyte histone H5.
We have compared the inhibitory strengths of eight peptides from chicken histone H5 to that of the parent protein (189 residues) in complement fixation by guinea pig anti-H5 serum complexed with the homologous histone. Two precisely delineated regions (residues 59 to 65 and 94 to 99) and two less-defined regions (between 66 and 93; 100 and 189) are depicted. The sequences of particular consequences are quite conserved in avian histone H5 while the most variable N-terminal portion of 31 residues has no inhibitory effect.


Acute myeloblastic leukemia achieving complete remission with amifostine alone.
Amifostine, a phosphorylated thiol-amine, is known as a cytoprotective agent especially for cisplatin containing chemotherapies. Apart from the cytoprotective role, Amifostine could also be used in the treatment of hematologic malignancies such as myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML), as a treatment option or for potentiating the effects of cytotoxic agents. We tried to use Amifostine in a patient with AML, which did not respond to conventional cytotoxic chemotherapy and aimed to publish the results. The patient was a 77-year-old male patient, he was diagnosed as AML by peripheral blood smear and bone marrow aspiration. Treatment commenced with low dose cytosine arabinoside (Ara-C) but the therapy should have ceased due to patient intolerance. The patient refused further therapy and he was offered to have Amifostine treatment. Amifostine was administered 200 mg/m2 three times a week, with ciprofloxacin, pentoxifyllin and dexamethasone. Dramatic response was obtained after 8 weeks of administration. Blast rate was reduced from 35 to 7% in bone marrow aspiration; pancytopenia was restored to normal levels. This remission was maintained through 8 more weeks. Amifostine treatment was restarted after he relapsed but this time he did not respond to the treatment and died of gastrointestinal bleeding on the 8th week of treatment.


Effect of Heartfulness Meditation Among Long-Term, Short-Term and Non-meditators on Prefrontal Cortex Activity of Brain Using Machine Learning Classification: A Cross-Sectional Study.
Background Meditation is a mental practice with health benefits and may increase activity in the prefrontal cortex of the brain. Heartfulness meditation (HM) is a modified form of rajyoga meditation supported by a unique feature called "yogic transmission." This feasibility study aimed to explore the effect of HM on electroencephalogram (EEG) connectivity parameters of long-term meditators (LTM), short-term meditators (STM), and non-meditators (NM) with an application of machine learning models and determining classifier methods that can effectively discriminate between the groups. Materials and methods EEG data were collected from 34 participants. The functional connectivity parameters, correlation coefficient, clustering coefficient, shortest path, and phase locking value were utilized as a feature vector for classification. To evaluate the various states of HM practice, the categorization was done between (LTM, NM) and (STM, NM) using a multitude of machine learning classifiers. Results The classifier's performances were evaluated based on accuracy using 10-fold cross-validation. The results showed that the accuracy of machine learning models ranges from 84% to 100% while classifying LTM and NM, and accuracy from 80% to 93% while classifying STM and NM. It was found that decision trees, support vector machines, k-nearest neighbors, and ensemble classifiers performed better than linear discriminant analysis and logistic regression. Conclusion This is the first study to our knowledge employing machine learning for the classification among HM meditators and NM The results indicated that machine learning classifiers with EEG functional connectivity as a feature vector could be a viable marker for accessing meditation ability.


Plasma lipoprotein profile in fasted and refed chickens of two strains selected for high or low adiposity.
The plasma lipoprotein profile has been determined in fasted and refed 5-week-old male broilers selected for low or high adiposity. Lipoprotein classes were subfractionated by density gradient ultracentrifugation, appearing as distinct bands with the following densities: very low density lipoprotein (VLDL), d less than 1.013 g/ml; low density lipoprotein (LDL), d 1.023-1.046 g/ml and high density lipoprotein (HDL), d 1.052-1.130 g/ml; the physiochemical characteristics (chemical composition, electrophoretic mobility and particle size) of these particles were then assessed. HDL, seen as a single band, represented 80% of total lipoproteins, with VLDL and LDL accounting for 1% and 16%, respectively, in fasted birds. Lipoprotein profiles were similar in fasted and refed animals of both lines, with the exception that VLDL levels were some 14-fold and 7-fold higher in the lean and fat lines, respectively, in the refed state. The VLDL of fasted birds of both lines were enriched in protein and relatively homogeneous in size; by contrast, VLDL in the refed state contained more triglyceride and less cholesteryl ester and protein and were larger and more heterogeneous, possibly representing a mixture of portomicrons and VLDL of hepatic origin. Birds of the fat line in both nutritional states differed from lean birds in exhibiting elevated plasma lipid and lipoprotein [VLDL, intermediate density lipoprotein (IDL) and HDL] levels, evidence that liver activity is directed toward increased lipoprotein production and secretion in that line.


Poisoning in childhood.
Several variables must be considered in the treatment of a poisoned child, including the particular substance, the individual child, and the child's home environment. General principles of treatment are described, and the management of particular substances, including household cleaning products, petroleum distillate hydrocarbons, and salicylates, is detailed. The family should not leave the emergency room without instruction on prevention of poisoning.


Atrial natriuretic factor receptor on cultured Leydig tumor cells: ligand binding and photoaffinity labeling.
Atrial natriuretic factor (ANF) is a peptide hormone discovered recently from the heart atrium that possesses potent natriuretic and vasorelaxant activities. Recently we found that ANF markedly stimulates intracellular cGMP and almost completely inhibits cAMP accumulation in testicular interstitial tumor cells [Pandey, K. N., Kovacs, W. J., & Inagami, T. (1985) Biochem. Biophys. Res. Commun. 133, 800-806]. These actions of ANF suggest the presence of ANF receptors in testicular interstitial cells. In this study, cultured murine Leydig tumor cells have been shown to contain specific binding sites for ANF. Saturation binding studies indicated a single class of binding sites with a Kd of 5 X 10(-9) M at a density of 2 X 10(6) sites/cell. The binding of mono[125I]iodo-ANF (125I-ANF) was competed by unlabeled ANF in a dose-dependent manner. Hormones unrelated to ANF such as angiotensin I, bovine luteinizing hormone, and human chorionic gonadotropin were not able to compete against 125I-ANF. The binding of 125I-ANF was rapid, reaching maximum levels in 15 min at 4 degrees C. At 37 degrees C, the cell-bound 125I label was quickly decreased. Pretreatment of cells with NH4Cl, chloroquine, or NaN3 resulted in significant increases in maximum levels of the cell-bound 125I radioactivity. A photoaffinity reagent for ANF receptor was prepared by reacting ANF with succinimido 4-azidobenzoate, and resultant 4-azidobenzoyl- (AZB-) ANF was purified by high-performance liquid chromatography (HPLC). AZB-ANF was radioiodinated by use of chloramine T and purified again by HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)


The bacterial transformation of abietic acid.
An Alcaligenes species, which was isolated from soil, can utilize abietic acid as its sole carbon source. During growth, the bacterium transforms abietic acid into 5alpha-hydroxyabietic acid (I, R=OH), a product considered to be 7beta-hydroxy-13-isopropyl-8xi-podocarp-13-en-15-oic acid (II, R=H) and a compound, C(20)H(28)O(3), which is believed to be an epoxy-gamma-lactone.


Unequal Distribution of Overweight Adolescents in Immigrant-Rich Areas: Analysis of Disparities among Public and Private School Students in Shanghai, China.
Accelerated urbanization and rising immigration to the big cities in China has resulted in education policies that produce disparate treatment of immigrant and non-immigrant students. The two types of students frequently wind up in different types of junior high schools. However, there is little research on whether disparities exist between students in public and private schools with regard to overweight. This study aims to address this gap through a comparison of the overweight status of junior high school students in public and private schools in Shanghai and explore the possible reasons for the observed differences. Students from two public and two private junior high schools were measured. In order to determine what factors might shape overweight among adolescents. Logistic regression analysis was used to assess associations between overweight and personal characteristics, birth-related factors, levels of physical activity, diet, family socioeconomic status and school environment. Students in private schools proved more likely to be overweight (15.20%, p < 0.05) than public school students (10.18%). Similarly, gender, breastfeeding, parental care and number of classes excluding physical education per day were found to be significant factors. However, private school students were also influenced by gestational age (yes/no: OR = 4.50, p < 0.001), frequency of snacks (sometimes/often: OR = 0.53, p < 0.01) and family income (¥6001-12,000/below ¥6000: OR = 3.27, p < 0.05). Time for lunch was the sole risk factor for public school students in the study (p < 0.05). To reduce the unequal distribution of overweight students between the two types of schools, interventions that consider different multiple risk factors should be implemented.


Panitumumab-IRDye800 Improves Laryngeal Tumor Mapping During Transoral Laser Microsurgery.
Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor-targeted fluorescence-guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence-guided surgical resection of a T2N0M0 transglottic tumor using panitumumab-IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near-infrared (NIR) dye. Laryngoscope, 2023.


Uptake, turnover and release of norepinephrine in pigmented and albino rat eye.
The uptake, turnover and release of norepinephrine were studied in the rat eye as a function of its pigmentation. The endogenous norepinephrine level was increased in eyes with melanic pigments and the exogenous amine uptake was decreased. In the coloured eye, two sites for norepinephrine uptake and release were present. Desipramine did not inhibit in the same manner the amine in the albino and pigmented eye. No variation was found in the norepinephrine biosynthesis for the two races of rats. The release rate of exogenous amine was higher in the pigmented rat eye.


Veiling glare reduction methods compared for ophthalmic applications.
Veiling glare in ocular viewing was simulated by viewing the retina of an eye model through a sheet of light-scattering material lit from the front. Four methods of glare reduction were compared, namely, optical scanning, polarized light, viewing and illumination paths either coaxial or intersecting at the object, and closed circuit TV. Photographs show the effect of these methods on visibility. Polarized light was required to eliminate light specularly reflected from the instrument optics. The greatest glare reduction was obtained when the first three methods were utilized together. Glare reduction using TV was limited by nonuniform distribution of scattered light over the image.


Jaundice due to iprindole.
Twenty-one patients treated for depression with iprindole developed evidence of liver damage: 15 were jaundiced, five had bilirubinuria, and one had pruritus. These complications occurred between four and 21 days after initial exposure to the drug. All patients recovered. Light and electron microscopic findings in liver biopsies of one of these patients were those of cholestasis without inflammation.


A technique elucidating the retrieval of an adhered cover screw in a dental implant - a case report.
Dental implants have become one of the most popular and rapidly growing techniques for replacing missing teeth. While their predictability, functionality, and durability make them an attractive option for patients and clinicians alike, complications can arise at any stage from patient assessment to maintenance of therapy. Failure of dental implants not only occurs due to biological factors, like unsuccessful osseointegration or peri-implantitis but may also occur due to technical complications like, failures of implant-supported restorations relating those from the implant components, and those relating to the prosthesis. Technical problems related to implant components include abutment screw fractures and cover screw fractures. In this case report we have elucidated an adhered cover screw in an implant.


Enhanced 2- O-α-d-Glucopyranosyl-l-ascorbic Acid Synthesis through Iterative Saturation Mutagenesis of Acceptor Subsite Residues in Bacillus stearothermophilus NO2 Cyclodextrin Glycosyltransferase.
Low synthesis yields of the l-ascorbic acid (l-AA) derivative 2- O-α-d-glucopyranosyl-l-ascorbic acid (AA-2G) limit its application in the food industry. In this work, the AA-2G synthesis yield of Bacillus stearothermophilus NO2 cyclodextrin glycosyltransferase (CGTase) was improved. Nine residues within 10 Å of the catalytic residue Glu253 displaying ≤30% conservation and located in the acceptor subsite were selected for iterative saturation mutagenesis. The best mutant, K228R/M230L, produced a higher AA-2G yield with maltodextrin as the glucosyl donor than that produced by its parent wild-type. The l-AA Km values of the mutant K228R/M230L decreased by 35%, whereas the kcat/ Km increased by 2.69-fold. Kinetic analysis indicated that K228R/M230L displayed enhanced l-AA specificity. These results demonstrate that acceptor subsite residues play an important role in acceptor substrate specificity. Mutant K228R/M230L afforded the highest AA-2G concentration (211 g L-1, 624 mM) reported to date after optimization of the reaction conditions.


Endometrial stromal sarcoma-A retropsective analysis of factors affecting recurrence.
To assess the factors associated with disease free survival and overall survival in endometrial stromal sarcoma (ESS). This was a single institution retrospective analysis done at Amrita Institute of Medical Sciences. Records from January 2005 to October 2016 were analysed and 42 patients with ESS were identified. Clinicopathological, surgical management, adjuvant treatment and outcome data were collected. Disease free and overall survivals were analysed using Kaplan-Meier method and compared using log rank test. Out of 38 patients included in analysis 28 (73.7%) had low grade ESS (LGESS) and 10 (26.3%) had high grade ESS (HGESS). The median follow up period was 28 months (range 1-110 months). The 5year disease free survival (DFS) and overall survival (OS) for the entire cohort were 62.9 and 89.1% respectively. High grade ESS was significantly associated with recurrence on univariate analysis (p=0.045). Complete staging surgery in both HGESS and LGESS and adjuvant treatment in HGESS and advanced stage LGESS (cohort 1) were associated with improved 5-year DFS of 90.9% (p<0.001). Completion staging surgery in patients with initial incomplete surgery (cohort 3) was associated with improved 5-year DFS of 100% (p<0.001). Complete Staging surgery but no adjuvant treatment in HGESS and advanced stage LGESS (cohort 2) was associated with significantly poor 2-year DFS of 20% (5-year DFS rate 0%; as all patients recurred within 27 months) (P<0.001). Significantly reduced 5-year DFS rate of 25% (p<0.001) was also seen in cases where initial incomplete surgery was not followed by complete staging and adjuvant treatment (cohort 4). Adjuvant treatment in HGESS was associated with improved 5-year DFS of 66.7% (p=0.043). Resection of recurrent lesions were associated with improved mean survival of 41.2 months. Incomplete surgery and no adjuvant treatment in ESS are associated with poor DFS. Complete staging surgery is associated with improved DFS. Resection of recurrent disease is associated with survival advantage.


Inhibition of retinal ischemia-reperfusion injury in rats by inhalation of low-concentration hydrogen gas.
To investigate the inhibitory effect of hydrogen gas inhalation on retinal ischemia reperfusion (I/R) injury using a rat model. Six-week-old male Sprague-Dawley rats were used. A 27G needle connected by a tube to a saline bottle placed 200 cm above the eye was inserted into the anterior eye chamber to create a rat retinal I/R model. In the ischemia-plus-hydrogen-gas group (H2( +) group), the ischemia time was set to 90 min, and 1.8% hydrogen was added to the air delivered by the anesthesia mask simultaneously with the start of ischemia. In the non-hydrogen-treatment ischemia group (H2( -) group), I/R injury was created similarly, but only air was inhaled. ERGs were measured; after removal of the eyes, the retina was examined for histological, immunostaining, and molecular biological analyses. The mean thickness of the inner retinal layer in the H2( +) group was 107.2 ± 16.0 μm (n = 5), significantly greater than that in the H2( -) group (60.8 ± 6.7 μm). Immunostaining for Iba1 in the H2( -) group showed increased numbers of microglia and microglial infiltration into the subretinal space, while there was no increase in microglia in the H2( +) group. B-wave amplitudes in the H2( +) group were significantly higher than in the H2( -) group. In the membrane antibody array, levels of interleukin-6, monocyte chemotactic protein 1, and tumor necrosis factor alpha were significantly lower in the H2( +) group than in the H2( -) group. Inhalation of 1.8% hydrogen gas inhibited the induction of inflammation, morphological/structural changes, and glial cell increase caused by retinal I/R injury.


AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation.
Using neonatal rat ventricular myocytes, we previously reported that the expression of a dominant negative form of the c-Fos proto-oncogene (AFos) inhibited activator protein 1 activity and blocked the induction of the pathological gene profile stimulated by phenylephrine (PE) while leaving growth unaffected. We now extend these observations to the adult rat ventricular myocyte (ARVM) to understand the relationship between gene expression, growth, and function. Ventricular myocytes were isolated from adult rats and infected with adenovirus expressing beta-galactosidase (control) or AFos. The cells were subsequently treated with PE, and protein synthesis, gene program, calcium transients, and contractility were evaluated. As seen with the neonatal rat ventricular myocytes, in control cells PE stimulated an increase in protein synthesis, induced the pathological gene profile, and exhibited both depressed contractility and calcium transients. Although ARVMs expressing AFos still had PE-induced growth, pathological gene expression as well as contractility and calcium handling abnormalities were inhibited. To determine a possible mechanism of the preserved myocyte function in AFos-expressing cells, we examined phospholamban (PLB) and sarco(endo)plasmic reticulum calcium-ATPase proteins. Although there was no change in total PLB or sarco(endo)plasmic reticulum calcium-ATPase expression in response to PE treatment, PE decreased the phosphorylation of PLB at serine-16, an observation that was prevented in AFos-expressing cells. In conclusion, although PE-induced growth was unaffected in AFos-expressing ARVMs, the expression of the pathological gene profile was inhibited and both contractile function and calcium cycling were preserved. The inhibition of functional deterioration was, in part, due to the preservation of PLB phosphorylation.


24S-hydroxycholesterol suppresses neuromuscular transmission in SOD1(G93A) mice: A possible role of NO and lipid rafts.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the initial denervation of skeletal muscle and subsequent death of motor neurons. A dying-back pattern of ALS suggests a crucial role for neuromuscular junction dysfunction. In the present study, microelectrode recording of postsynaptic currents and optical detection of synaptic vesicle traffic (FM1-43 dye) and intracellular NO levels (DAF-FM DA) were used to examine the effect of the major brain-derived cholesterol metabolite 24S-hydroxycholesterol (24S-HC, 0.4 μM) on neuromuscular transmission in the diaphragm of transgenic mice carrying a mutant superoxide dismutase 1 (SODG93A). We found that 24S-HC suppressed spontaneous neurotransmitter release and neurotransmitter exocytosis during high-frequency stimulation. The latter was accompanied by a decrease in both the rate of synaptic vesicle recycling and activity-dependent enhancement of NO production. Inhibition of NO synthase with L-NAME also attenuated synaptic vesicle exocytosis during high-frequency stimulation and completely abolished the effect of 24S-HC itself. Of note, 24S-HC enhanced the labeling of synaptic membranes with B-subunit of cholera toxin, suggesting an increase in lipid ordering. Lipid raft-disrupting agents (methyl-β-cyclodextrin, sphingomyelinase) prevented the action of 24S-HC on both lipid raft marker labeling and NO synthesis. Together, these experiments indicate that 24S-HC is able to suppress the exocytotic release of neurotransmitter in response to intense activity via a NO/lipid raft-dependent pathway in the neuromuscular junctions of SODG93A mice.


Direct and Indirect Influence of Altruistic Behavior in a Social Network.
Prior research has suggested that recipients of generosity behave more generously themselves (a direct social influence). In contrast, there is conflicting evidence about the existence of indirect influence (i.e., whether interacting with a recipient of generosity causes one to behave more generously), casting doubt on the possibility that altruistic behavior can cascade through social networks. The current study investigated how far selfish and generous behavior can be transmitted through social networks and the cognitive mechanisms that underlie such transmission. Participants played a sequence of public goods games comprising a chain network. This network is advantageous because it permits only a single, unambiguous path of influence. Furthermore, we experimentally manipulated the behavior of the first link in the chain to be either generous or selfish. Results revealed the presence of direct social influence, but no evidence for indirect influence. Results also showed that selfish behavior exerted a substantially greater influence than generous behavior. Finally, expectations about future partners' behavior strongly mediated the observed social influence, suggesting an adaptive basis for such influence.


Pre-B cell colony enhancing factor/NAMPT/visfatin in inflammation and obesity-related disorders.
Whereas prototypic adipocytokines such as adiponectin or leptin are mainly derived from adipocytes, others such as pre-B cell colony enhancing factor (PBEF)/nicotinamide phosphoribosyl transferase (NAMPT)/visfatin or resistin are produced by various cell types throughout the body. Although first discovery of this molecule as PBEF suggested primarily a cytokine function, its rediscovery as the key enzyme in nicotinamide adenine dinucleotide (NAD) generation has considerably widened its biological perspective. Finally, the same molecule was introduced as visfatin claiming an insulin-mimetic effect which has been questioned. Both extracellular (cytokinelike) and intracellular (enzymatic) functions are responsible for its relevance in immune, metabolic and stress responses. Its cytokine functions are mainly pro-inflammatory as it induces potently various other pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFa) or interleukin-6 (IL-6). Its intracellular functions concentrate on the regulation of the activity of NAD-consuming enzymes such as various sirtuins thereby also affecting (TNFa) biosynthesis, cell life-span and longevity. Biochemical neutralization of PBEF/NAMPT/visfatin has been proven effective in various models of inflammation including sepsis/arthritis and in various models of cancer. Patients with non-alcoholic fatty liver disease (NAFLD) exhibit increased serum concentrations of PBEF/Nampt/visfatin and weight loss is associated both with a decrease in serum levels and reduced liver expression. Many of the biological functions of this "cytokine-enzyme" have been characterized in the last years, however, its definite role in various metabolic, inflammatory and malignant diseases has yet to be defined.


Prevalence and Predictors of Postoperative Depression and Anxiety After Anterior Cruciate Ligament Reconstruction.
Preoperative mood disorders influence postoperative outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR), but the prevalence and risk factors associated with postoperative depression/anxiety development remain unknown. The purposes of this study were to quantify the prevalence of postoperative diagnoses of depression or anxiety following ACLR in patients under the age of 25 and assess the interplay between patient sex and ACL reoperation on the prevalence of a depression or anxiety diagnosis following ACLR. ACLR patients under the age of 25 years old were identified in the Truven Healthcare Marketscan database. Patients with incomplete coverage +/- one year of the index surgical procedure were excluded. Patients were categorized by the presence of preoperative, postoperative, or no depression/anxiety using the International Classification of Diseases, Ninth Revision (ICD-9) codes. We compared patient demographics and reoperation rates following the index ACLR between the depression and anxiety categories. Additionally, logistic regression was fit to assess the interaction between sex and either ipsilateral or contralateral ACL surgery on postoperative depression/anxiety diagnosis. Of the 42,174 patients, 10.7% had a new depression/anxiety diagnosis after ACLR. Postoperative depression/anxiety was nearly twice as prevalent for females (F: 14.4%, M: 7.6%) despite having similar rates of secondary ACLR (F: 15.5%, M: 13.0%). Those with postoperative depression/anxiety had a considerably greater prevalence of reoperation (18.8%) than those without depression/anxiety (13.7%) and those with pre-existing preoperative depression/anxiety (12.9%). Sex and reoperation were independently associated with postoperative depression/anxiety diagnosis. Female sex and secondary ACL surgery are independently associated with an increased prevalence of postoperative depression/anxiety. Nearly one in seven young females are diagnosed with depression/anxiety after ACLR. Similarly, a greater proportion of patients who suffer a secondary ACL surgery are subsequently diagnosed with depression/anxiety. The orthopedic community must be cognizant of the increased risk of postoperative depression/anxiety for females and those who suffer a secondary ACL surgery, and screening for depression/anxiety in these at-risk populations with referrals to mental health professionals may be warranted.


Dosimetric Deviations of Bragg-Peak Position Shifts in Uniform Magnetic Fields for Magnetic Resonance Imaging-Guiding Proton Radiotherapy: A Monte Carlo Study.
Objective: To investigate dosimetric deviations in scanning protons for Bragg-peak position shifts, which were caused by proton spiral tracks in an ideal uniform field of magnetic resonance (MRI) imaging-guided proton radiotherapy (MRI-IGPRT). Methods: The FLUKA Monte-Carlo (MC) code was used to simulate the spiral tracks of protons penetrating water with initial energies of 70-270 MeV under the influence of field strength of 0.0-3.0 Tesla in commercial MRI systems. Two indexes, lateral shift (marked as WD) perpendicular to the field and a penetration-depth shift (marked as ΔDD) along the beam path, were employed for the Bragg-peak position of spiral proton track analysis. A comparison was performed between MC and classical analytical model to check the simulation results. The shape of the 2D/3D dose distribution of proton spots at the depth of Bragg-Peak was also investigated. The ratio of Gaussian-fit value between longitudinal and transverse major axes was used to indicate the asymmetric index. The skewness of asymmetry was evaluated at various dose levels by the radius ratio of circumscribed and inscribed circles by fitting a semi-ellipse circle of 2D distribution. Results: The maximum of WD deflection is 2.82 cm while the maximum of shortening ΔDD is 0.44 cm for proton at 270 MeV/u under a magnetic field of 3.0 Tesla. The trend of WD and ΔDD from MC simulation was consistent with the analytical model, which means the reverse equation of the analytical model can be applied to determine the proper field strength of the magnet and the initial energy of the proton for the planned dose. The asymmetry of 2D/3D dose distribution under the influence of a magnetic field was increased with higher energy, and the skewness of asymmetry for one proton energy at various dose levels was also increased with a larger radius, i.e., a lower dose level. Conclusions: The trend of the spiral proton track under a uniform magnetic field was obtained in this study using either MC simulation or the analytical model, which can provide an optimized and planned dose of the proton beam in the clinical application of MRI-IGPRT.


Dependency of blood pressure upon cardiac filling in patients with severe postural hypotension.
Autonomic denervation of the vascular bed results theoretically in a stronger dependency of blood pressure upon intravascular volume, and the study described aimed at an investigation of the relation between cardiac filling and arterial blood pressure in patients with severe postural hypotension. Seven patients were studied during head-up tilt at three different tilt angles using intra-arterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Blood pressure fell dramatically during head-up tilt due to reductions in cardiac output unopposed by vasoconstriction. The reduction in cardiac output resulted from reductions in left ventricular end-diastolic volumes with unchanged left ventricular ejection fractions and only moderate increments in heart rate. The study was demonstrated that blood pressure is strongly dependent upon cardiac filling in severe autonomic dysfunction, and that volume expansion is an important measure against postural hypotension.