CD8+ T-cell expansion and maintenance after recombinant adenovirus immunization rely upon cooperation between hematopoietic and nonhematopoietic antigen-presenting cells.
We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.


Continuous growth of mean tumor diameter in a subset of grade II gliomas.
Serial magnetic resonance images of 27 patients with untreated World Health Organization grade II oligodendrogliomas or mixed gliomas were reviewed retrospectively to study the kinetics of tumor growth before anaplastic transformation. Analysis of the mean tumor diameters over time showed constant growth. Linear regression, using a mixed model, found an average slope of 4.1mm per year (95% confidence interval, 3.8-4.4mm/year). Untreated low-grade oligodendrogliomas or mixed gliomas grow continuously during their premalignant phase, and their pattern of growth can be predicted within a relatively narrow range. These findings could be of interest to optimize patients management and follow-up.


Characterization of Nonmicrobiological Paper Mill Deposits by Simultaneous TG-IR-MS.
The problem of deposits and their identification is one of the most persistent ones facing paper mills. Materials other than fibers accumulate in closed water circulation systems and may appear as impurities in pulp and paper or can contaminate wires and felts or build up deposits at various points in the mills. Traditionally, chromatographic and spectroscopic methods have been employed in the analysis of deposits and other pulp and paper process impurities. Simultaneous thermogravimetry-infrared-mass spectrometric (TG-IR-MS) analysis is a relatively new technique which, when applied to the analysis of mill deposits, provides a rapid means of identifying the source of these contaminants.


Association of serum concentration of organochlorine pesticides with dietary intake and other lifestyle factors among urban Chinese women.
Concerns about the carcinogenic and endocrine-disrupting characteristics of organochlorine pesticides (OCPs) have led to a global ban on OCP use. However, OCPs persist in the environment for decades because of their long half-life. We evaluated serum levels of OCPs and their correlations with usual dietary intake and other lifestyle factors among 250 healthy women who participated as controls in the Shanghai Breast Cancer Study. Serum levels of hexachlorocyclohexane isomers (alpha-HCH, beta-HCH, gamma-HCH), dichloro-di-phenyl-trichloroethane (DDT) isomers (p,p'-DDE and p,p'-DDT), hexachlorobenzene (HCB), trans-nonachlor (TNC), and eight polychlorinated biphenyls (PCB) congeners (IUPAC no. 74, 118, 138, 153, 170, 180, 183, and 187) were measured. Lifestyle factors and usual dietary habits over the past 5 years were assessed through an in-person interview. With the exception of PCB, total OCP levels in our study population were significantly higher than those observed in other countries. Age, income, body mass index, waist-to-hip ratio, number of pregnancies, and/or total duration of breastfeeding were all significantly correlated with all types of OCPs. Of the 20 food groups evaluated, correlations with serum total OCPs were observed for eggs (r=0.13), fresh beans (r=-0.17), tea (r=0.14), and animal fat (r=0.18). Multiple regression analyses showed that age and animal fat intake were positively associated with serum total level OCPs, while leafy vegetable and fresh bean consumption was negatively associated with OCPs level. Our study suggests that dietary intake may be an important contributor of serum levels of OCPs in Chinese women.


Surgical management for persistent pupillary membrane with vitreous scissors.
Persistent pupillary membranes are common congenital disorders. To reduce the surgical complications, we used vitreous scissors instead of conventionally used Vannas scissors to remove the membrane and reviewed the surgical results. Five eyes of 4 children with persistent pupillary membrane were treated by surgery. Through the 1.5 mm limbal incision, the membrane was removed by using vitreous scissors after intracameral sodium hyaluronate. After 22.6 months follow-up, all pupils of operated eyes were round and no complications associated with the surgery were found. Three eyes showed improved visual acuities after the operation. We suggest that the surgery with vitreous scissors is better than with Vannas scissors.


Optimal expiratory volume profile in tidal liquid ventilation under steady state conditions, based on a symmetrical lung model.
Liquid-assisted ventilation (LAV) using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation. During tidal liquid ventilation (TLV) the residual capacity of the lungs is filled with PFC and a liquid ventilator is necessary to inhale and exhale the tidal volume of PFC. However, during the expiration phase, a flow limitation (choked flow) can be observed, which compromises minute ventilation and consequently the gas exchange. The hypothesis of the presented works is that the choked flow can be avoided by profiling the expiratory volume. To validate this concept, an elastic symmetrical lung numerical model, used to characterize forced expiration in gas ventilation, was transposed to TLV. The parameters of the developed numerical model were fitted from experimental data obtained on a newborn lamb. The results obtained demonstrate that general observations made with gas ventilation still hold, however, in TLV: flow limitation in the central airways is the result of a coupling between viscous pressure losses and airway compliance, and the flow limiting segment is located in the central airways. Using the model results, an optimal theoretical expiratory profile seems to be exponential as first approximation, and its time constant is dependent on the chocked flow mechanism and not on the product of resistance by compliance. This optimal profile is used to compute the maximal minute ventilation allowable with an acceptable risk of collapse. Also, the sensitivity of minute ventilation to different parameter variations were analyzed and practical recommendations are proposed.


Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572.
Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS(R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well. We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult out-patients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS(R) 5570, WS(R) 5572, WS(R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained > or = 50 % decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of > or =20 % HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement'). For Hypericum extract, early improvement had a sensitivity of 87 % (95 % confidence interval [CI], 82-93 %) and a specificity of 54 % (95 % CI, 45-62 %) at day 14, and a sensitivity of 43 % (95 % CI, 35-51 %) and a specificity of 86 % (95 % CI, 80-92 %) at day 7 for predicting sustained response. After 2 weeks of treatment, 78 % (95 % CI, 69-87 %) of the patients who failed to improve did not show sustained response later during treatment. A substantial fraction of the patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.


Chinese herbal medicines for benign thyroid nodules in adults.
A thyroid nodule is a discrete lesion within the thyroid gland that might be palpable and is ultrasonographically distinct from the surrounding thyroid parenchyma. Thyroid nodules are more common as age increases and occur more frequently in women. Benign thyroid nodules often cause pressure symptoms and cosmetic complaints. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat thyroid nodules. To assess the effects of Chinese herbal medicines in the treatment of benign thyroid nodules in adults. Review authors searched the following electronic databases: The Cochrane Library, MEDLINE, EMBASE, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), VIP information (a Chinese database), WANFANG Data (a Chinese database), the Chinese Conference Papers Database and the Chinese Dissertation Database (all searched up to April 2013). Randomised controlled trials comparing CHM or CHM plus levothyroxine versus levothyroxine, placebo or no treatment in adults with benign thyroid nodules. Two review authors independently extracted data, assessed studies for risk of bias and evaluated overall study quality according to GRADE (Grading of Recommendations Assessment, Development and Evaluation), with differences resolved by consensus. We included one randomised trial involving 152 participants with a randomisation ratio of 2:1 (CHM vs no treatment). The trial applied adequate sequence generation; however, allocation concealment was unclear. Duration of treatment was three months, and follow-up six months. Our a priori defined outcomes of interest (i.e. nodule volume reduction ≥ 50%; pressure symptoms, cosmetic complaints or both; health-related quality of life; all-cause mortality; cancer occurrence; changes in number and size of thyroid nodules; changes in thyroid volume; and socioeconomic effects) were not investigated in the included study. Thyrotropin (TSH), thyroxine (T4) and tri-iodothyronine (T3) serum levels were normal in both groups before and after the trial was conducted. No adverse events were reported (low quality evidence). Firm evidence cannot be found to support or refute the use of Chinese herbal medicines for benign thyroid nodules in adults.


[Differences in susceptibility of Helicobacter pylori to macrolide and other antibiotics in tests using blood agar and albumin agar].
Minimum inhibitory concentrations (MICs) of penicillin G, cefazolin, tetracycline, chloramphenicol, four aminoglycosides, and seven macrolides against Helicobacter pylori strains were determined on Brucella agar supplemented with bovine serum albumin fraction V (albumin agar) and compared with those on blood agar. MICs of the macrolides against H. pylori determined on albumin agar were markedly lower than those found with blood agar. The susceptibilities of 26 H. pylori strains to the macrolides were estimated from the MIC50 values determined on blood agar and albumin agar, which were 0.39 and < or = 0.05 micrograms/ml for erythromycin, midecamycin and rokitamycin, 3.13 and 0.10 micrograms/ml for clindamycin, 1.56 and < or = 0.05 micrograms/ml for josamycin, 1.56 and 0.10 micrograms/ml for kitasamycin, and 0.10 and < or = 0.05 micrograms/ml for roxithromycin, respectively. However, the MICs of other antibiotics against H. pylori and of all antibiotics against two reference Campylobacter strains differed minimally between values obtained on blood agar and albumin agar.


Selection of surfactant in remediation of DDT-contaminated soil by comparison of surfactant effectiveness.
With an aim to select the most appropriate surfactant for remediation of DDT-contaminated soil, the performance of nonionic surfactants Tween80, TX-100, and Brij35 and one anionic surfactant sodium dodecyl benzene sulfonate (SDBS) in enhancement of DDT water solubility and desorption of DDT from contaminated soil and their adsorption onto soil and ecotoxicities were investigated in this study. Tween80 had the highest solubilizing and soil-washing ability for DDT among the four experimental surfactants. The adsorption loss of surfactants onto soil followed the order of TX-100 > Tween80 > Brij35 > SDBS. The ecotoxicity of Tween80 to ryegrass (Lolium perenne L.) was lowest. The overall performance considering about the above four aspects suggested that Tween80 should be selected for the remediation of DDT-contaminated soil, because Tween80 had the greatest solubilizing and soil-washing ability for DDT, less adsorption loss onto soil, and the lowest ecotoxicity in this experiment.


[Study on influence of floods on bacillary dysentery incidence in Liaoning province, 2004 -2010].
To understand the influence of floods on bacillary dysentery in Liaoning province. The monthly surveillance data of bacillary dysentery, floods, meteorological and demographic data in Liaoning from 2004 to 2010 were collected. Panel Poisson regression analysis was conducted to evaluate the influence of floods on the incidence of bacillary dysentery in Liaoning. The mean monthly morbidity of bacillary dysentery was 2.17 per 100 000 during the study period, the bacillary dysentery cases mainly occurred in during July-September. Spearman correlation analysis showed that no lagged effect was detected in the influence of floods on the incidence of bacillary dysentery. After adjusting the influence of meteorological factors, panel data analysis showed that the influence of floods on the incidence of bacillary dysentery existed and the incidence rate ratio was 1.439 4(95%CI: 1.408 1-1.471 4). Floods could significantly increase the risk of bacillary dysentery for population in Liaoning.


A fatal case of buflomedil self-poisoning: toxicological data and literature review.
A fatal case of buflomedil (Fonzylane) self-poisoning is presented. Drug identification and quantification in postmortem blood, urine and gastric contents was achieved by means of high pressure liquid chromatography with diode-array detection (HPLC/DAD). Blood concentration was 275 micrograms/ml, > 70 times the usual therapeutic values. Toxicological results are discussed in the light of the existing literature.


Baseline cortisol levels, cortisol response to corticotropin, and prognosis in late septic shock.
The prognostic value of basal and corticotropin-stimulated cortisol concentration in patients with sepsis remains a controversial issue. In a retrospective cohort study, 82 consecutive patients with septic shock underwent a short corticotropin test performed more than 24 h after the onset of vasopressor therapy. Forty-one (50%) patients died within 28 days after the onset of septic shock. The mean (SD) basal cortisol level was 22.7 (10.6) microg/dL. With threshold values of 7 and 9 microg/dL maximal increases in cortisol level, 28 (34%) and 31 (38%) patients were, respectively, classified as nonresponders to the short corticotropin test. On multivariate analysis, a cortisol level >20 microg/dL (P = 0.0002), a maximal response to corticotropin <9 microg/dL (P = 0.044), abnormal lactate values (P = 0.0098), and positive blood cultures (P = 0.004) were independent predictors of 28-day mortality. In conclusion, high basal cortisol and low increase on corticotropin stimulation are predictors of a poor outcome in late septic shock. The underlying mechanisms of these prognostic patterns remain to be elucidated.


Spatial attention related SEP amplitude modulations covary with BOLD signal in S1--a simultaneous EEG--fMRI study.
Recent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1.


Postnatal changes in adrenergic and neuropeptide Y-containing nerve fibres in pineal gland of the pig. An immunohistochemical study.
Postnatal development of the innervation of the porcine pineal gland by tyrosine hydroxylase-(TH-), dopamine-beta-hydroxylase-(D beta H), phenylethanolamine-N-methyltransferase-(PNMT-) and neuropeptide Y- (NPY-) immunoreactive (IR) nerve fibres was examined using the double-labelling immunohistochemical technique. TH-IR nerve fibres appeared in the pineal gland of new-born piglets and formed plexus in the capsula and connective tissue septa of the gland. In 20-day-old pigs and older ones, the nerve terminals branched off from the plexus and penetrated into adjacent parenchyma. The nerve fibres formed network; its density increased with age and depended on the region of the gland. In mature pigs, some differences in the innervation pattern between cortex and medulla were also observed. Most of TH-IR fibres were also D beta H- and NPY-positive. Some PNMT-positive fibres were noted in new-born piglets, but not in older animals. NPY-IR fibres were distributed in pattern overlapping that observed in the case of TH- and D beta H-IR fibres. Most of NPY-IR fibres were also positive for TH.


The effect of REM sleep deprivation on motivation for food reward.
Prolonged sleep deprivation in rats produces a characteristic syndrome consisting of an increase in food intake yet a decrease in weight. Moreover, the increase in food intake generally precedes the weight loss, suggesting that sleep deprivation may affect appetitive behaviors. Using the multiple platform method to produce rapid eye movement (REM) sleep deprivation, we investigated the effect of REM sleep deprivation (REMSD) on motivation for food reward utilizing food-reinforced operant tasks. In acquisition or maintenance of an operant task, REM sleep-deprived rats, with or without simultaneous food restriction, decreased responding for sucrose pellet reward in comparison to controls, despite the fact that all REM sleep-deprived rats lost weight. Furthermore, the overall response deficit of the REM sleep-deprived rats was due to a within-session decline in responding. REM sleep-deprived rats showed evidence of understanding the contingency of the task comparable to controls throughout deprivation period, suggesting that the decrements in responding were not primarily related to deficits in learning or memory. Rather, REM sleep deprivation appears to alter systems involved in motivational processes, reward, and/or attention.


1.5 V battery driven reduced graphene oxide-silver nanostructure coated carbon foam (rGO-Ag-CF) for the purification of drinking water.
A porous carbon foam (CF) electrode modified with a reduced graphene oxide-Ag (rGO-Ag) nanocomposite has been fabricated to purify water. It can perform as an antibacterial device by killing pathogenic microbes with the aid of a 1.5 V battery, with very little power consumption. The device is recycled ten times with good performance for long term usage. It is shown that the device may be implemented as a fast water purifier to deactivate the pathogens in drinking water.


Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis.
The renal effects of low-dose cyclosporin A (CsA) treatment in severe psoriasis was investigated in 10 patients treated with a mean CsA dose of 3.23 (range 1.94-4.10) mg/kg/day for 12 months. The psoriasis area and severity index was reduced by 63-76%. Ambulatory GFR (iothalamate-125I), ERPF (hippuran-131I), RVR and MAP were examined at 3-months intervals. A control renal biopsy was performed shortly before treatment start and a second biopsy was taken after 12 months of therapy. GFR was slightly but significantly reduced after 6 and 9 months; after 12 months the decrease was not significant (121.0 +/- 7.6 versus 115.2 +/- 7.8 ml/min/1.73M2, P > 0.10). After 12 months serum creatinine increased from 82 +/- 4 to 94 +/- 7 mumol/litre (P < 0.05), while an insignificant increase of ERPF was seen and FF decreased from 0.29 +/- 0.01 to 0.26 +/- 0.01 (P < 0.05). MAP remained unchanged. GFR and serum creatinine correlated significantly within each 3-month interval. A slight de novo interstitial fibrosis was seen in the second biopsy in 4 of 10 patients receiving a mean CsA dose of 3.2-4.1 mg/kg/day. In three of these patients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fall in GFR and potentially progressive structural changes not always accompanied by corresponding functional alterations. One should consider reducing the daily dose of CsA to 3.0 mg/kg bodyweight or less in CsA therapy up to 1 year.


Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma.
Tumor cell biological factors, such as urokinase plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), cathepsin D, and c-myc play a role in tumor invasion, metastasis, and proliferation. In this study, the prognostic importance of these factors in patients with primary head and neck squamous cell carcinoma (HNSCC) was evaluated and correlated with clinicopathologic variables. In 46 paired primary tumors and normal tissues, levels of uPA, PAI-1, cathepsin D, and c-myc amplification were determined. The clinical follow-up was over 10 years. Relationships between cell biological factors and patient and tumor characteristics were studied by the Mann-Whitney test. The Cox proportional hazard model was used for univariate and multivariate analysis. In this study, only a high level of PAI-1 was associated with a significantly shorter disease-free survival (p < .01). PAI-1 levels were higher in tumors with perineural invasion (p < .01). Both PAI-1 and uPA levels were higher in patients who smoked (p < .01 and p = .02). In univariate analysis, smoking (p= .04), excessive alcohol intake (p = .02), perineural invasion (p = .001), and vaso-invasion (p = .009) were associated with a shorter disease-free survival. The only factor related to overall survival was perineural invasion (p = .045). The combination of a high PAI-1 level and perineural invasion appeared to be a significant predictor of a shorter disease-free interval (p = .01). PAI-1 may present a novel prognostic factor for patients with HNSCC. Perineural invasion and PAI-1 level combined seemed to be prognostic for disease-free survival.


Pyruvic-acid-containing polysaccharide in the cell wall of Bacillus polymyxa AHU 1385.
Three acidic polymer fractions with molecular masses of about 16 kDa, 35 kDa and 70 kDa were isolated from lysozyme digests of N-acetylated cell walls of Bacillus polymyxa AHU 1385 by ion-exchange chromatography and gel chromatography. These fractions, containing mannosamine, glucosamine and pyruvic acid in a molar ratio of about 1:1:1 together with glycopeptide components, were characterized as polysaccharide-linked glycopeptides with one, two and more polysaccharide chains. On the other hand, treatment of the cell walls with glycine/HC1 buffer, pH 2.5, at 100 degrees C for 10 min followed by separation of water-soluble products on ion-exchange chromatography gave three polysaccharide fractions, PS-I-III, which contained different amounts of pyruvic acid (0,0.6 and 0.9 residue/mannosamine residue) along with equimolar amounts of mannosamine and glucosamine. Pyruvate-free polysaccharides similar to PS-I were also obtained from PS-II, PS-III and polysaccharide-linked glycopeptides by treatment with 10 mM HC1 at 100 degrees C for 1 h. Results of analyses of these polysaccharide preparations by 1H-NMR and 13C-NMR measurement and methylation, together with data from characterization of fragments obtained by hydrogen fluoride hydrolysis, lead to the most likely structure, ----3)[4,6-O-(1-carboxyethylidene)]ManNAc(beta 1----4)GlcNac(beta 1----, for the acidic polysaccharide of this strain.


Intensity dependence of auditory evoked cortical potentials in migraine families.
Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. Apart from migraine, the age of the participants was an important predictive variable of intensity dependence. Analysis of individual differences revealed low sensitivity and moderate specificity of intensity dependence for migraine. Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache.


Acute quadriparesis caused by calcification of the entire cervical ligamentum flavum in a white female--report of an unusual case and a brief review of the literature: case report.
Case report. To describe an extremely unusual case of acute quadriparesis in a white female caused by calcification of the ligamentum flavum (LF) from C1 to T2, and to review briefly the pertinent literature. Diseases characterized by abnormal calcium deposition on the spinal ligaments have an unclear etiology. The overwhelming majority of these cases has been reported in people of Asian descent and has a predilection for the thoracic spine. Multilevel involvement of the cervical LF in white patients is exceptionally rare. To our knowledge, complete calcification of the entire cervical LF has not been previously reported in the literature. The history, physical examination, and radiographic studies of a 64-year-old white female with a history of scleroderma are described. The patient presented with neck pain and acute quadriparesis caused by spinal cord impingement by calcified cervical LF from C1 to T2. The patient underwent emergent C3-C7 laminectomy and C2-C7 posterior spinal fusion. Operative intervention resulted in marked neurologic improvement and relief from neck pain. Histopathologic examination of the calcified LF showed that the deposits consisted of hydroxyapatite crystals exclusively with no heterotopic bone. However, kyphosis did develop in the patient after laminectomy. To our knowledge, this unusual case of complete calcification of the entire cervical LF has not previously been described. Multilevel laminectomy and fusion can improve neurologic function but may result in kyphosis.


Effect of genotype on mutagenicity of niridazole in nitroreductase-deficient bacteria.
The mutagenicity of niridazole for Salmonella typhimurium depends upon the enzymic reduction of the nitro function. The response of niridazole nitroreductase-deficient bacteria to niridazole is reduced to 4.4 and 0.19% that exhibited by the enzyme-proficient parent strain when the deficiency is the result of a base substitution and frame-shift mutation, respectively. The results are taken to indicate that the residual activity (4.4%) seen in the strain with a base substitution mutation reflects the activity of an enzyme with an amino acid substitution, while the basal level (0.19%) of activity indicates the action of a different nitroreductase with a low specificity for niridazole.


[Change in circulating blood volume during prolonged pentamine-induced ganglionic blockade without hypotonia in surgery of gastrointestinal hemorrhage].
The investigation of the volume of the circulating blood in 129 patients operated for gastro-intestinal hemorrhage has shown that by the end of the operation there was an increasing deficiency of the circulating blood volume and HO in spite of hemotransfusion therapy. The use of prolonged ganglionic blockade resulted in the increased circulating blood volume and HO in patients by the end of operation at the expense of redeposition of blood.


Fibroblast growth factor induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation.
Neural stem (NS) cell lines may be derived via differentiation of pluripotent embryonic stem (ES) cells or from foetal forebrain. However, because NS cells arise in vitro from heterogeneous populations their immediate cellular origin remains unclear. We used microarray-based expression profiling to identify a set of markers expressed by mouse NS cells but not ES cells. One differentially expressed gene encodes the cell surface protein, CD44. CD44 expression is activated by FGF-2 in a subset of cells in both differentiating ES cells and foetal forebrain cultures. Following isolation by flow cytometry the CD44+ population was found to be highly enriched for NS cell founders. We found that other NS cell marker genes are also induced by FGF in culture, including: Adam12, Cadherin20, Cx3cl1, EGFR, Frizzled9, Kitl, Olig1, Olig2 and Vav3. We speculate that the self-renewing NS cell state may be generated in vitro following transcriptional resetting induced by FGF.


The influence of a bupivacaine and fentanyl epidural infusion after epidural fentanyl in patients allowed to ambulate in early labor.
Epidural fentanyl after a lidocaine and epinephrine test dose provides adequate analgesia and allows for ambulation during early labor. This study was designed to determine the influence of an epidural infusion of bupivacaine plus fentanyl administered after initiation of epidural labor analgesia with fentanyl. Specifically, we evaluated whether there is an increase in motor block or an increased time to request for further analgesic medication. Fifty-one laboring primigravid women at <5 cm cervical dilation who requested epidural analgesia were enrolled. After a 3-mL epidural test dose of 1.5% lidocaine with epinephrine (5 microg/mL), patients received fentanyl 100 microg via the epidural catheter. They then randomly received either an infusion (10 mL/h) of 0.0625% bupivacaine with fentanyl (3 microg/mL) or an infusion of preservative-free saline. After the administration of the initial analgesic, pain scores and side effects were recorded for each patient at 10, 20, and 30 min, every 30 min thereafter, and at the time of request for additional analgesic medication, by an observer blinded to the technique used. There were no demographic differences between the two groups. The mean duration of analgesia (time from initial dose to request for additional analgesia) was increased in the group that received a continuous infusion of bupivacaine and fentanyl compared with the Saline group (198 +/- 86 vs 145 +/- 50 min; P < 0.009). Side effects were similar between the two groups. No patient in either group experienced any detectable motor block. Fourteen patients chose to ambulate in the Saline group, and 12 patients chose to ambulate in the Infusion group. In early laboring patients, a continuous infusion of 0.0625% bupivacaine infusion with fentanyl (3 microg/mL) prolonged the duration until top-up was required, after epidural fentanyl 100 microg after a lidocaine and epinephrine test dose, and did not cause any clinically detectable motor block. A 0.0625% bupivacaine and fentanyl (3 microg/mL) infusion, when added to epidural fentanyl (100 microg), prolongs the analgesic duration without increasing motor block in women in early labor.


Hepatitis C virus subtype 3a was introduced in the USSR in the early 1980s.
A total of 2120 nucleotide sequences of the NS5b region of HCV subtype 3a were analysed, including 310 strains derived from former republics of the USSR (Azerbaijan, Estonia, Lithuania, Russia, Tajikistan and Uzbekistan). Among the viral isolates collected from former regions of the Soviet Union, 294 strains formed 3 sustained phylogenetic clusters, with each having a common origin. Phylodynamic analysis demonstrated that the most recent common ancestors of the current strains inside the three clusters were introduced into the USSR population in 1981±1, 1984±2 and 1985±2, respectively (the confidence intervals were calculated using Student's t-distribution, P<0.05). The time estimation obtained for HCV subtype 3a correlated well with the historical and epidemiological context of this period, and in particular with the start of widespread injection drug use in the USSR in the first half of the 1980s.


Curing atrial fibrillation: Two decades of progress.
Since the original description of the Cox-Maze procedure two decades ago, there has been considerable refinement and expansion of surgical techniques for atrial fibrillation (AF). During this same time, there has been a parallel evolution of catheter-based ablation techniques designed to cure AF. Recent guidelines have been developed to guide patient selection for pharmacologic and nonpharmacologic options for therapy of AF. Understanding the mechanisms of AF will lead to better management strategies and improved patient outcomes.


Contemporaneous and longitudinal associations of sibling conflict with family relationship assessments and family discussions about sibling problems.
The first purpose of this study was to examine contemporaneous and longitudinal associations of maternal and paternal measures of family functioning with observational and self-report assessments of sibling conflict. The second purpose was to determine whether the ways in which families attempt to solve siblings' problems are associated with contemporaneous and longitudinal assessment of sibling conflict. The results indicate that paternal equality of treatment and family harmony during family discussions about sibling problems, as well as parents' perceptions of family cohesiveness, are associated with lower sibling conflict levels.


Hydroxyurea: use in determining the duration of G2 in Tetrahymena.
Observation of division of individual cells in microdrops, plus autoradiographic studies using tritiated thymidine and standard cell cycle analysis techniques, reveal that hydroxyurea (10 mM) reversibly arrests the normal progression of exponentially growing Tetrahymena pyriformis through the initial 92% of S-phase while not affecting cells in the terminal 8% and in G2 and division. Thus the fraction of the population of cells that is in G2 can be approximately determined by the fraction of the population able to divide in the presence of hydroxyurea. This fraction can be related to the approximate duration of G2 by calculations which compensate for the age gradient.


Expression of Defense Genes in Strawberry Fruits Treated with Different Resistance Inducers.
The expression of 18 defense genes in strawberry fruit treated with elicitors: chitosan, BTH, and COA, at 0.5, 6, 24, and 48 h post-treatment was analyzed. The genes were up-regulated differentially, according to the elicitor. Chitosan and COA treatments promoted the expression of key phenylpropanoid pathway genes, for synthesis of lignin and flavonoids; only those associated with flavonoid metabolism were up-regulated by BTH. The calcium-dependent protein kinase, endo-β 1,4-glucanase, ascorbate peroxidase, and glutathione-S-transferase genes were up-regulated by BTH. The K+ channel, polygalacturonase, polygalacturonase-inhibiting protein, and β-1,3-glucanase, increased in response to all tested elicitors. The enzyme activities of phenylalanine ammonia lyase, β-1,3-glucanase, Chitinase, and guaiacol peroxidase supported the gene expression results. Similarity of gene expression was >72% between chitosan and COA treatments, while BTH showed lower similarity (38%) with the other elicitors. This study suggests the relationship between the composition of the elicitors and a specific pattern of induced defense genes.


A multiple shutdown method for managing evacuation in case of major fire accidents in chemical clusters.
This paper may be regarded as the second part of a larger article. The basic decision model developed in the first part of the article by Reniers et al. [G.L.L. Reniers, N. Pauwels, A. Audenaert, B.J.M. Ale, K. Soudan, Management of evacuation in case of fire accidents in chemical industrial areas, J. Hazard. Mater., 147 (2007) 478-487] is extended to determine both the optimal time and the optimal mode to stop the ongoing activities in case of a major fire possibly giving rise to an escalating event. Chemical plants have multiple modes to stop their production processes, differing with respect to the resulting costs, and with respect to the required time and personnel to complete the shutdown operations. The existence of an additional and more economic (but slower) shutdown mode might encourage the decision maker to stop the production processes earlier, in a less intervening manner, whereas the availability of an additional faster (but less economic) shutdown procedure might stimulate the decision maker to stop the production processes later, in a more intervening manner.


A virally inactivated platelet-derived growth factor/vascular endothelial growth factor concentrate fractionated from human platelets.
Human platelet concentrates (PCs) may be a source material to produce purified growth factors (GFs) for clinical use or cell therapy. However, no fractionation process of therapeutic-grade GF from PCs has ever been developed. PCs were virally inactivated by solvent/detergent (S/D) treatment, subjected to oil extraction to remove part of the S/D agents, and fractionated on a SP-Sepharose (SP) chromatographic column equilibrated in a phosphate-buffered saline (PBS) buffer, pH 7.5. The breakthrough was recovered, and the column was washed with the PBS buffer and then eluted by a 0.7 mol/L NaCl-PBS buffer pH 7.5 (SP-eluate). The SP-breakthrough and SP-eluate were characterized for their content in GF, proteins, lipids, and S/D agents. The MTS value of three cell lines cultivated in a medium containing 10% fetal bovine serum supplemented with 1% to 3% of SP-eluate or recombinant human (rHu) platelet-derived growth factor (PDGF)-BB was compared. The SP-eluate contained a mean of 47, 17, and 6 ng/mL PDGF-AB, -BB, and -AA, respectively, and 0.26 ng/mL vascular endothelial growth factor (VEGF). It was largely depleted of transforming growth factor-β1 (2.33 ng/mL), epidermal growth factor (0.09 ng/mL), insulin-like growth factor (3.40 ng/mL), albumin, immunoglobulin (Ig)G, IgM, IgA, and fibrinogen, which were mostly in the breakthrough. tri-n-butyl phosphate and Triton X-45 were less than 2 ppm. Cell growth-promoting activity of the SP-eluate was at least as good as that of rHu-PDGF-BB. Human PC can be fractionated into a purified, virally inactivated PDGF and VEGF concentrate, opening perspectives for the development of a new range of blood products for clinical use and cell therapy procedures.


Mid-Term Outcomes of Minimally Invasive Direct Coronary Artery Bypass Grafting.
Minimally invasive direct coronary artery bypass grafting (MIDCAB) has gained wide acceptance for the treatment of single vessel disease of the left anterior descending artery (LAD). Here, we present our single center experience of 152 consecutive patients. All patients underwent MIDCAB through a left anterior minithoracotomy between January 1, 2009, and December 31, 2012. Preoperative, intraoperative, postoperative, and follow-up data including major adverse cardiac and cerebrovascular events (MACCE) and need for re-intervention were collected. Mean age was 64.4 ± 11 years, median additive EuroSCORE 3 (0-11), 84% were male. All except one patient were successfully operated without cardiopulmonary bypass. Seven patients with unexpected severely calcified LADs were converted to sternotomy (4.6%); 91.3% were extubated in the operating room or on the day of surgery. Median stay at the intensive care unit and in hospital were 1 (0-97) and 7 (1-49) days, respectively. Thirty-day mortality was 1.9%. There was no stroke. Five patients (3.2%) had to be re-explored for bleeding and 95% received no transfusion. Median follow-up was 24 months (0-97) and complete in 93.3% with overall survival of 92.4 ± 0.2% and MACCE-free survival of 96.1 ± 1.7%. Two patients had a re-intervention of the LAD. MIDCAB is a safe procedure with low postoperative morbidity, mortality, and favorable mid-term MACCE-free survival in selected patients that should be discussed in a heart team setting to evaluate the "ideal" individual treatment option.


Novel fusion transcripts in bladder cancer identified by RNA-seq.
Urothelial carcinoma (UC) is the most common type of bladder cancer and is the second most frequently diagnosed genitourinary tumor. The identification of fusion genes in bladder cancer might provide new perspectives for its classification and significance. In this study, we present a thorough search on three UC samples for novel fusion transcripts in bladder cancer using high-throughput RNA sequencing. We used stringent requirements for 819 fusion candidates and nominated 10 candidate fusion transcripts. Among them four novel fusion genes SEPT9/CYHR, IGF1R/TTC23, SYT8/TNNI2 and CASZ1/DFFA were validated and characterized in 48 formalin-fixed paraffin-embedded (FFPE) specimens of bladder cancer. Chromosomal rearrangements of regions 17q25, 15q26.3 and 1p36.22 resulting in the fusion transcripts SEPT9/CYHR, IGF1R/TTC23 and CASZ1/DFFA, appeared to be rare or unique events because they were not detected in the 48 UC samples. In contrast, the SYT8/TNNI2 fusion transcript resulting from transcription-induced chimerism by read-through mechanisms was a rather common and tumor-specific event occurring in 37.5% (18/48) of the UC specimens. Further investigation of functional and clinical relevance of novel fusion genes remains to be elucidated to reveal their role in bladder carcinogenesis.


[Clinical study of anticoagulation with warfarin and heparin in patients after mechanical valve replacement].
To investigate the effect of different methods of anticoagulation after mechanical valve replacement. Totally 172 cases of mechanical valve replacement performed from October 2005 to June 2008 were divided into two groups and then analyzed retrospectively. Patients on warfarin and heparin were classified as the heparin group while those on warfarin alone were classified as the warfarin group. The operation, anticoagulation, anticoagulation index and associated complications were recorded to compare the effect of anticoagulation between two groups. warfarin group: the overall anticoagulation effect was satisfactory except for cerebral embolism (n=1, 1.1%) and lower gastrointestinal hemorrhage (n=1, 1.1%) during hospitalization. Heparin group: no anticoagulation-related complication was found. The time to reach stable warfarin anticoagulation was shorter than the warfarin group and difference was of significance (8 d±3 d vs 11 d±4 d, P<0.01). After adjustment of potential confounding factors such as age, gender, weight by linear regression analysis, the result showed that, the time to reach stable warfarin anticoagulation was shortened than the warfarin group by 2.11 days. Statistical significance of difference was observed between two groups (P<0.01). It is both safe and effective to anticoagulated the patients after mechanical valve replacement with warfarin and heparin.


Effect of arginine methylation on the RNA recognition and cellular uptake of Tat-derived peptides.
Arginine (Arg) methylation is a common post-translational modification that regulates gene expression and viral infection. The HIV-1 Tat protein is an essential regulatory protein for HIV proliferation, and is methylated in the cell. The basic region (residues 47-57) of the Tat protein contains six Arg residues, and is responsible for two biological functions: RNA recognition and cellular uptake. In this study, we explore the effect of three different methylation states at each Arg residue in Tat-derived peptides on the two biological functions. The Tat-derived peptides were synthesized by solid phase peptide synthesis. TAR RNA binding of the peptides was assessed by electrophoresis mobility shift assays. The cellular uptake of the peptides into Jurkat cells was determined by flow cytometry. Our results showed that RNA recognition was affected by both methylation state and position. In particular, asymmetric dimethylation at position 53 decreased TAR RNA binding affinity significantly, but unexpectedly less so upon asymmetric dimethylation at position 52. The RNA binding affinity even slightly increased upon methylation at some of the flanking Arg residues. Upon Arg methylation, the cellular uptake of Tat-derived peptides mostly decreased. Interestingly, cellular uptake of Tat-derived peptides with a single asymmetrically dimethylated Arg residue was similar to the native all Arg peptide (at 120 μM). Based on our results, TAR RNA binding apparently required both guanidinium terminal NH groups on Arg53, whereas cellular uptake apparently required guanidinium terminal NH₂ groups instead. These results should provide insight into how nature uses arginine methylation to regulate different biological functions, and should be useful for the development of functional molecules with methylated arginines.


Potential hippocampal region atrophy in diabetes mellitus type 2: a voxel-based morphometry VSRAD study.
Among diabetes mellitus type 2 (DM2) patients, the frequency of cognitive dysfunction is higher and the relative risk of Alzheimer's disease (AD) is approximately twice that of nondiabetics. Cognitive impairment symptoms of AD are induced by limbic system dysfunction, and an early-stage AD brain without dementia has the potential for atrophy in the hippocampal region. In this study, we estimated potential hippocampal region atrophy in DM2 and pursued the association between DM2 and cognitive impairment/AD. Voxel-based morphometry analysis was performed in 28 diabetics (14 men, 14 women; ages 59-79 years, mean 70.7 years) and 28 sex- and agematched (+/-1 year) nondiabetics. Severity of gray matter loss in the hippocampal region and whole brain were investigated. Group analysis was performed using twotailed unpaired t-test; significance was assumed with less than 1% (P < 0.01) of the critical rate. There was a significant difference between diabetics and nondiabetics regarding the severity of hippocampal region atrophy and whole-brain atrophy. Only diabetics showed a positive correlation for severity of hippocampal region atrophy and whole-brain atrophy (rs = 0.69, P < 0.0001). Aged DM2 patients have the potential for hippocampal region atrophy, and its dysfunction can be related to the expression of a cognitive impairment that resembles AD.


[Comparative characteristics of several properties of the estradiol-binding system of the human uterus and fallopian tubes].
Kinetic and thermodynamic parameters of estradiol-receptor interactions were studied in cytosol of human uterus endometrium and of uterus tubes. Specificity of these reactions was investigated. The receptor systems studied were distinctly dissimilar in the values of Ka equilibria, rate constants of association and dissociation with estradiol as well as in the affinity to a series of natural and synthetic estrogens.


Molecular characterization and expression analysis of interferon-gamma in black seabream Acanthopagrus schlegelii.
Interferon gamma (IFN-γ) is a major component in immunological signaling and plays a key role in resisting viral infection. In this study, we identified and characterized an IFN-γ gene (AsIFN-γ) in the marine fish black seabream (Acanthopagrus schlegelii). We cloned AsIFN-γ genomic sequence, which comprises four exons, three introns and an upstream promoter including several conserved regulatory elements. The complete cDNA of AsIFN-γ was 816 bp in length and encoded a putative 194 amino acids (aa) protein with a 22 aa signal peptide, six α-helices and one nuclear localization signal (NLS). Multiple alignment showed that AsIFN-γ protein shared 31-60% identity with IFN-γ of other fish but low identity with fish IFN-γrel and IFN-γ of other vertebrates. AsIFN-γ was constitutively expressed in all examined tissues with the highest expression level in immune organs, such as spleen, gill and kidney. In black seabream infected by red spotted nervous necrosis virus (RGNNV), the expression of AsIFN-γ was significantly up-regulated in most tissues, and RGNNV infection in vitro also induced significant up-regulation of AsIFN-γ, indicating that AsIFN-γ was involved in immune response to RGNNV infection. Overexpression of AsIFN-γ in cultured Acanthopagrus schlegelii brain (AsB) cells rapidly and transiently stimulated the expression of JAK-STAT signaling pathway related genes including STAT1, STAT2 and IRF9, as well as the downstream antiviral genes MX1 and ISG15. Furthermore, overexpression of AsIFN-γ was able to significantly inhibit RGNNV replication and virus production in AsB cells. In summary, we identified a conserved IFN-γ gene of black seabream, and demonstrated the rapid and strong antiviral activities of AsIFN-γ against RGNNV in black seabream.


Assessment of genetic diversity of Tunisian orange, Citrus sinensis (L.) Osbeck using microsatellite (SSR) markers.
Citrus are one of the most cultivated crops in the world. Economically, they are very important fruit trees in Tunisia. Little is known about the genetic diversity of the Tunisian Citrus germplasm. Exploring this diversity is a prerequisite for the identification and characterization of the local germplasm to circumvent and controlling genetic erosion caused by biotic and abiotic stress to aid its conservation and use. In the present study, we explored the genetic diversity of 20 Tunisian orange cultivars [Citrus sinensis (L.) Osbeck] and established their relationships by using seven simple sequence repeat (SSR) loci. In total, 37 alleles and 44 genotypes were scored. The sizes of alleles ranged from 90 to 280 bp. The number of alleles per locus was from 4 to 7, with an average of 5.28. Polymorphic information content value changed from 0.599 to 0.769 with an average of 0.675. Analysis of the genotypes revealed a heterozygote deficiency across all the genotypes. The observed heterozygosity varied from 0 to 1 (average of 0.671). Cluster analysis showed that three groups could be distinguished and the polymorphism occurred independently of the geographical origin of the studied orange cultivars. The detected SSR genotypes allowed the establishment of an identification key with a discriminating power of 100%. Multivariate analysis and the neighbor-joining phylogenetic tree indicated a narrow genetic base for the orange cultivars. The usefulness of SSR markers for orange fingerprinting and evaluation of the genetic diversity in the Tunisian germplasm are discussed in this paper.


Analysis of the soluble human tooth proteome and its ability to induce dentin/tooth regeneration.
While the soluble proteins of human teeth consist of various extracellular matrix and bioactive proteins, they have not yet been characterized fully. Moreover, the role they play in tooth regeneration is not clear. Analysis of the soluble proteins in human teeth by liquid chromatography-mass spectrometry revealed 147 different ethylenediaminetetraacetic acid-soluble tooth proteins (ESTPs). Of these, 29 had not been shown previously to be present in human teeth. To determine their effect on the in vitro responses of dental pulp stem cells (DPSCs), DPSCs were cultured in ESTP-coated culture plates and three-dimensional scaffolds. The ESTPs significantly enhanced DPSC odontoblast differentiation and mineralization in vitro, but had only partial effect on bone marrow stem cells or adipose tissue stem cells. To test the effect of ESTPs on in vivo dentin and tooth formation, mouse embryonic tooth-forming primordia and xenogenic murine apical bud epithelium/human DPSC composites were treated with ESTPs before implantation under the renal capsule of ICR mice. ESTP treatment promoted the formation of morphologically normal teeth by the tooth-forming primordium regions and enhanced the development of a regular and large dentin structure by the composites. These observations suggest that human ESTPs contain dentinogenic proteins and can promote dentin and tooth formation.


An Evaluation of Patient Comfort During Acute Psychiatric Hospitalization.
To assess the difference in the level of comfort between psychiatric inpatients who received a warmed blanket and psychiatric inpatients who did not receive a warmed blanket. A descriptive pilot study from a convenience sample of 37 psychiatric patients aged 18-59. Subject's level of comfort was measured with Kolcaba's verbal rating scale (VRS). Independent t-tests showed that the VRS mean score was lower in the control group (6.81) than the experimental group (7.29). Comfort is central to nursing and there has been little research regarding the effects of warm topical applications in the psychiatric hospital setting. Warmed blankets are not routinely offered to patients in the psychiatric setting. The use of warmed blankets may increase patient comfort.


[Effect of the type of dental burs, their rotation rate and load on the quality of the cavity wall preparation].
In 540 extracted teeth the cavities were drilled using different burs at various rotation speeds. Microphotometry of the quality of walls preparation showed that steel drills had an optimum of under 10,000 rev/min while for hard-alloy and diamond drills the quality increased parallel with the drilling speed.


Cancer-specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells.
The metabolic phenotype of cancer is considered an ideal target for anticancer therapy. In ovarian cancer, glucose transporter 1 (GLUT1) is overexpressed and positron emission tomography (PET) using [18(F)] fluorodeoxyglucose (FDG), as a metabolic tumor parameter, has been found to be an effective diagnostic tool. In this study, we have characterized the selective cytotoxicity of resveratrol (RSV) in ovarian cancer cells through glucose metabolism regulation via GLUT1 modulation. We have demonstrated that, in contrast to primary normal ovarian epithelial cells, RSV selectively inhibited glucose uptake and induced apoptosis irrespective of p53 status in vitro. RSV had no affect on GLUT1 mRNA and protein expressions but interrupted intracellular GLUT1 trafficking to the plasma membrane. Suppressed plasma membrane GLUT1 localization in ovarian cancer was found to be associated with the inhibition of Akt activity by RSV, as confirmed by the action of the Akt inhibitors (LY294002 and Akt inhibitor IV), as well as overexpression of a constitutive active form of Akt. Taken together, these findings suggested that RSV induced apoptosis in ovarian cancer cells by impairing glucose uptake, a process involving Akt-regulated plasma membrane GLUT1 trafficking.


Palladium-catalyzed addition of alkynes to cyclopropenes.
The palladium catalyzed coupling of alkynes and cyclopropenes provides a powerful method for the synthesis of alkynylcyclopropanes, proceeding under mild conditions in the presence of many functional groups (such as esters, carboxylic acids, aldehydes, and alcohols).


Association study between the TNXB locus and schizophrenia in a Japanese population.
The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.


Resolution-recovery for EPR imaging of free radical molecules in mice.
A method of post-processing to enhance the image resolution of the distribution of free radical molecules obtained with continuous-wave electron paramagnetic resonance (CW-EPR) imaging is reported. The low spatial resolution of EPR imaging, which has created difficulties in biomedical applications, was overcome by the method of resolution-recovery for EPR imaging. High spatial resolution images for the distribution of free radical molecules with a very short relaxation time were obtained with this method. The method's two-step postprocessing consists of conventional deconvolution and filtered back-projection and a process of iterative deconvolution. The resolution-recovery method was demonstrated with three-dimensional (3D) imaging of stable nitroxyl radicals in mouse head. In phantom experiments with a solution of triarylmethyl (TAM) radicals, the spatial resolution was improved by a factor of 7 with the resolution-recovery method.


Morphological study of the lingual papillae in the fruit bat (Rousettus amplexicaudatus) by scanning electron microscopy and light microscopy.
This study was carried on the tongues of ten normal, healthy and adult fruit bats (Rousettus amplexicaudatus, also known as the nyap biasa bat) in Yogyakarta, Java Island, Indonesia. The tongue was protrusible, elongated and flat with a rounded apex, and its width and thickness increased gradually towards to lingual root. There were two main types of lingual papillae, mechanical (filiform) and gustatory (fungiform and circumvallate). The tongue was divided into three parts (apex, corpus and radix), and then, each part was subdivided into three regions (two lateral regions and a median region). There were six subtypes of the filiform papillae-three types on the anterior part (small, scale-like and giant), one type on the middle part (leaf-like papillae) and two types on the posterior part (rosette-shaped filiform and conical filiform papillae)-in addition to transitional papillae presented on the corpus and radix. Two types of gustatory papillae were represented by a small number of fungiform papillae that are scattered among the filiform papillae on the lingual apex and corpus, while three circumvallate papillae on the posterior part are arranged in a "V" shape pointing directly at the larynx.


Isotopic characterisation of lead in contaminated soils from the vicinity of a non-ferrous metal smelter near Plovdiv, Bulgaria.
Soil samples from the vicinity of a non-ferrous metal smelter near Plovdiv, Bulgaria contained very high concentrations of cadmium, lead and zinc (up to 140, 4900 and 5900 mg kg(-1), respectively). A roadside soil in a relatively uncontaminated area also contained high concentrations of the same metals (24, 1550 and 1870 mg kg(-1), respectively) indicating that the transport of ores could be a source of contamination. Even though the lead isotope ratios in all the samples fell within a very narrow range (for example, 1.186-1.195 for (206)Pb/(207)Pb), the samples could be differentiated into three distinct groups: ores ((206)Pb/(207)Pb and (208)Pb/(207)Pb ratios of 1.1874-1.1884 and 2.4755-2.4807, respectively), current deposition (1.1864 and 2.4704-2.4711, respectively) and local background (1.1927-1.1951 and 2.4772-2.4809, respectively). Although most of the current deposition has its origin in the ores used at the smelter, up to 12% could be from other sources such as petrol lead.


An economic evaluation of salt reduction policies to reduce coronary heart disease in England: a policy modeling study.
Dietary salt intake has been causally linked to high blood pressure and increased risk of cardiovascular events. Cardiovascular disease causes approximately 35% of total UK deaths, at an estimated annual cost of £30 billion. The World Health Organization and the National Institute for Health and Care Excellence have recommended a reduction in the intake of salt in people's diets. This study evaluated the cost-effectiveness of four population health policies to reduce dietary salt intake on an English population to prevent coronary heart disease (CHD). The validated IMPACT CHD model was used to quantify and compare four policies: 1) Change4Life health promotion campaign, 2) front-of-pack traffic light labeling to display salt content, 3) Food Standards Agency working with the food industry to reduce salt (voluntary), and 4) mandatory reformulation to reduce salt in processed foods. The effectiveness of these policies in reducing salt intake, and hence blood pressure, was determined by systematic literature review. The model calculated the reduction in mortality associated with each policy, quantified as life-years gained over 10 years. Policy costs were calculated using evidence from published sources. Health care costs for specific CHD patient groups were estimated. Costs were compared against a "do nothing" baseline. All policies resulted in a life-year gain over the baseline. Change4life and labeling each gained approximately 1960 life-years, voluntary reformulation 14,560 life-years, and mandatory reformulation 19,320 life-years. Each policy appeared cost saving, with mandatory reformulation offering the largest cost saving, more than £660 million. All policies to reduce dietary salt intake could gain life-years and reduce health care expenditure on coronary heart disease.


The effects of physical activity as maintenance for smoking cessation.
The effects of physical activity as a maintenance strategy for smoking cessation were evaluated. After a standard smoking cessation program, forty-two women were randomly assigned to one of three groups that received equal number of maintenance meetings: a physical activity program, smoking habit change information and contact control. Abstinence decreased from 83% at the end of treatment to 73% at 3 months, 49% at six months and 34% at 18 months. No differences were shown in cessation across groups. Group differences were shown for subjective levels of tension-anxiety, those who exercised showed increased tension anxiety levels compared to subjects in the no activity groups.


[Tiotropium. A new anti-cholinergic agent for treatment of chronic obstructive pulmonary disease].
Tiotropium is a new anti-cholinergic drug with a long duration of action designed for maintenance treatment of chronic obstructive pulmonary disease (COPD). Tiotropium is the first drug specifically developed for the treatment of COPD, but it is also amongst the most expensive drugs used for this condition. The clinical pharmacology of tiotropium and results from published controlled clinical trials are reviewed. It is concluded that tiotropium seems suitable as a symptomatic treatment for patients with moderate to severe COPD (typically a forced expiratorical volume FEV1 < 50% of the predicted volume), who despite optimal use of short acting bronchodilators still suffer from severe symptoms.


Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta.
Studies were performed in the rabbit aortic rings, precontracted with norepinephrine, to determine the subtype(s) of muscarinic receptors involved in endothelium-dependent relaxation and contraction in the absence of endothelium elicited by cholinergic stimuli. Acetylcholine (ACh) and arecaidine propargyl ester (APE), a M2 and M3 agonist, produced a dose-dependent relaxation and contraction in endothelium-intact and endothelium-denuded rabbit aortic rings, respectively. Both of these responses were blocked by the muscarinic receptor antagonist atropine. M1 selective agonist McN-A-343 [4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium+ ++ chloride] did not produce any effect on the tone of precontracted aortic rings. ACh- and APE-induced relaxation in aortic rings with intact endothelium was selectively blocked by M3 receptor antagonists hexahydrosila-difenidol and p-fluoro-hexahydro-sila-difenidol (pA2 of 7.84 and 7.18) but not by M1 antagonist pirenzepine or M2 receptor antagonists AF-DX 116 [11-(2-[(diethylamino)methyl]- 1-piperidinyl]acetyl)-5, 11-dihydro-6H-pyrido-[2,3-b][1,4]-benzo-diazepin-6-one] and methoctramine. ACh- and APE-induced contraction was inhibited by M2 receptor antagonists AF-DX 116 and methoctramine (pA2 of 7.11 and 6.71) but not by pirenzepine, hexahydro-sila-difenidol or p-fluoro-hexahydro-sila-difenidol. ACh- and APE-induced relaxation or contraction were not altered by nicotinic receptor antagonist hexamethonium or cyclooxygenase inhibitor indomethacin. These data suggest that relaxation elicited by cholinergic stimulin in endothelium-intact aortic rings is mediated via release of endothelium-derived relaxing factor consequent to activation of M3 receptors located on endothelial cells, whereas the contraction in aortic rings denuded of their endothelium is mediated via stimulation of M2 receptors located on smooth muscle cells.


Discovery of novel antitubercular 1,5-dimethyl-2-phenyl-4-([5-(arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol-3-one analogues.
In search of potential therapeutics for tuberculosis, we describe herewith the synthesis, characterization and antimycobacterial activity of 1,5-dimethyl-2-phenyl-4-([5-(arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol-3-one analogues. Among the synthesized compounds, 4-[(5-[(4-fluorophenylamino]-1,3,4-oxadiazol-2-yl)methylamino]-1,2-dihydro-1,5-dimethyl-2-phenylpyrazol-3-one (4a) was found to be the most promising compound active against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentrations, 0.78 and 3.12μg/mL, respectively, free from any cytotoxicity (>62.5μg/mL).


Comparison of reactivity to allergens using the TRUE Test and IQ chamber system.
The reproducibility of the patch test is of great importance to its diagnostic utility. The objective of this study was to quantitatively and qualitatively compare the reproducibility of patch test reactions between the manufacturer-loaded TRUE Test (TT) panel and the investigator-loaded IQ Chamber (IQC) system using the European Standard Series (ESS) (Chemotechnique Diagnostics, Malmö, Sweden). Consecutive patients were simultaneously patch tested with 21 allergens using the TT and IQC system. The concordance and discordance of the 2 methods were analysed. Testing was performed in 207 patients (85 men and 122 women) who yielded 317 positive reactions, 188 with the IQ system and 129 with the TT. A total of 204 tests were positive with both methods, showing a positive concordance rate of 64.4%, with IQC producing more positive results. A high concordance rate of positive results was achieved for Cl+ Me- isothiazolinone (81.5%), nickel sulfate (79%), formaldehyde (76.9%), and paraphenylenediamine (PPD) (72.7%); a moderate concordance was noted for quaternium 15 (66.7%), potassium dichromate (64.3%), and fragrance mix (58.1%); and a low concordance was noted for cobalt chloride (27.6%) and Balsam of Peru (18.2%). The IQC and the TT are similar in finding allergy to allergens with high concordance. The IQC system has an advantage in detecting clinically relevant reactions to allergens that have a moderate and a low concordance.


Africanity theory and the new student in nursing.
Recognition and acceptance of Africanity theory in schools of nursing curricular has been presented as one strategy to address the needs of the new student in general and the ethnic minority student in particular. It was postulated that acceptance of the legitimacy of African-American culture would facilitate the recognition of the unique attributes of other "sub" cultures. Factors such as the (a) prevailing nursing shortage and (b) the changing applicant pool demand that nursing develop and incorporate innovative approaches to attract and retain the new student in nursing. Are we as a profession ready for the "new" students? It's either now or ...


Genetic variants of methionine metabolism and X-ALD phenotype generation: results of a new study sample.
X-linked adrenoleukodystrophy (X-ALD) is the most common inherited leukodystrophy. Nevertheless, no genotype-phenotype correlation has been established so far. Unidentified modifier genes or other cofactors are suspected to modulate phenotype and prognosis. We recently described polymorphisms of methionine metabolism as possible disease modifiers in X-ALD. To retest these findings, we analyzed 172 new DNA samples of X-ALD patients from different populations (France, Germany, USA, China) by genotyping eight genetic variants of methionine metabolism, including DHFR c.594+59del19bp, CBS c.844_855ins68, MTR c.2756A>G, MTHFR c.677C>T and c.1298A>C, MTRR c.60A>G, RFC1 c.80G>A, and Tc2 c.776C>G. We compared three X-ALD phenotypes: childhood-onset cerebral demyelinating inflammatory type (CCALD; n = 82), adulthood onset with focal cerebral demyelination (ACALD; n = 38), and adulthood onset without cerebral demyelination (AMN; n = 52). The association of genotypes and phenotypes was analyzed with univariate two-sided Pearson's chi(2). In the comparison between AMN and CCALD, the G allele of Tc2 c.776C>G was associated with X-ALD phenotypes (chi(2) = 6.1; P = 0.048). The prevalence of the GG genotype of Tc2 c.776C>G was higher in patients with CNS demyelination compared to those without CNS demyelination (chi(2) = 4.42; P = 0.036). The GG genotype was also more frequent in CCALD compared to AMN (chi(2) = 4.7; P = 0.031). The other polymorphisms did not show any significant associations in this study sample. Whereas the influence of other polymorphisms of methionine metabolism was not confirmed, the present study supports the previously made observation that the Tc2 genotype contributes to X-ALD phenotype generation.


Electrically controlled release of ibuprofen from conductive poly(3-methoxydiphenylamine)/crosslinked pectin hydrogel.
The pristine pectin hydrogels and conductive polymer/hydrogel blends were prepared by the solution casting using ferrous chloride (FeCl2) and citric acid as the crosslinking agents, and ibuprofen as the model drug and the doping agent. A conductive polymer, poly(3-methoxydiphenylamine), was successfully synthesized and embedded into the pristine pectin hydrogels as the drug encapsulation host. The in-vitro release of ibuprofen from the hydrogels was investigated by a modified Franz diffusion cell filled with a MES buffer solution, with pH of 5.5, at 37°C, for a period of 48h to investigate the effects of the crosslinking agent type, crosslinking mole ratio, mesh size, electric potential, and conductive polymer. The release behavior of ibuprofen from the pectin hydrogels was found to involve 4 modes of release: Fickian diffusion; Anomalous transport; Case-II transport; and Super case II transport. The diffusion coefficient was shown to be significantly improved by two factors: using a FeCl2 as the crosslinking agent and applied electric potential. For both crosslinking agents, the drug diffusion coefficient increased with decreasing crosslinking ratio. Under electric field of 5V, the drug diffusion coefficients of the FeCl2 and citric acid hydrogels were enhanced by more than a factor of two due to the electro-repulsive interaction between ibuprofen and the negatively charged electrode. Moreover, the synthesized poly(3-methoxydiphenylamine) embedded in the pectin hydrogels as the drug encapsulation host was shown to enhance the diffusion coefficients and to reduce the overall release times.


Effects of glucocorticoids on serum amino acid levels during cardiac surgery in children.
Children undergoing cardiac surgery with cardio pulmonary bypass often receive glucocorticoids to reduce the systemic inflammatory response. Glucocorticoids stimulate protein breakdown and increase amino acid availability. We studied whether glucocorticoid treatment influences the availability of amino acids, specifically those involved in the nitric oxide pathway. We prospectively studied 49 children with congenital heart disease undergoing cardiac surgery. Serum cortisol and amino acid levels were measured in arterial blood sampled before surgery (t = -5 min), directly after surgery (t = 0 h) and at t = 12 h and t = 24 h after surgery. Serum cortisol and amino acid levels were compared between children who had received glucocorticoids (G+) and children who had not (G-). Of 49 patients included ((49% male, age 1.7 (0.5-8.7) y)), 33 (67%) received glucocorticoids. Baseline characteristics were not different between groups, except a higher weighted inotropic score in the G+ group. At t = 0 h, serum cortisol levels in the G+ group were significantly higher than in the G- group (7218 vs. 660 nmol/L; (p < 0.05)), but not different at the other time points. The levels of plasma amino acids had dropped after surgery. Compared to the G- group, in the G+ group the total amount of amino acids was significantly higher at t = 12 and t = 24; citrulline levels were higher at t = 12 and t = 24; and glutamine and arginine levels were higher at t = 12. Glucocorticoid treatment during cardiac surgery in children preserves serum amino acid levels post-surgery. The preservation of glutamine, citrulline and arginine levels might have a beneficial effect on the related NO metabolism.


Induction of apoptosis in Neuro-2A cells by Zn2+ chelating.
Metal ions such as Ca2+, Mg2+, or Zn2+, are important for many cell functions, for example, signal transduction and the modulation of enzyme activity. The relationship between apoptosis and metal cations, especially Ca2+, has been described in many reports. We have investigated the role of metal cations in the regulation of apoptosis in the mouse neuroblastoma cell line, Neuro-2A. When Neuro-2A cells were treated with ethylene diaminetetraacetic acid (EDTA), apoptosis was detected as growth inhibition, DNA fragmentation with a ladder pattern in agarose gel electrophoresis, and nuclear decomposition. However, in case of the treatment with ethylene glycol bis- (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), which has a higher chelating specificity for Ca2+ than EDTA, DNA fragmentation was not detected. Moreover, the apoptosis induced by EDTA was inhibited by exogenous Zn2+. The membrane permeable Zn2+ chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) also induced apoptosis of the Neuro-2A cells, and addition of equimolar exogenous Zn2+ or Cu2+, but not Mn2+ or Fe2+, prevented TPEN-induced apoptosis. The results suggest that Zn2+ may be a key regulator of apoptosis in Neuro-2A cells.


Is occupation missing from occupational therapy in palliative care?
The role of occupational therapists in palliative care is largely undocumented in Western Australia (WA). Little is known about the services occupational therapists provide or the needs of people who are dying and their carers in relation to these services. The aims of this study were as follows. First, to determine the number of occupational therapists employed and the range of services they provide in palliative care in WA. Second, with particular reference to self care, leisure, productive roles and occupations, to explore the daily experiences of people who were dying as well as their primary carers to determine the services that might be offered by occupational therapy to this population. Semi-structured interviews were used to gather information from carers (n=10 metro, n=4 rural) and occupational therapists (n = 13 metro, n = 5 rural). Data were analysed qualitatively using grounded theory to develop categories. Themes were defined using the constant comparison method. Four themes emerged that impacted people who were dying and their carers. These were; ongoing disengagement from usual activities with resultant occupational deprivation; disempowerment of both people who are dying and their carers within palliative care services; 'occupation' not being addressed adequately in palliative care, and occupational therapists experience frustration with limited opportunities to contribute to the care of people who are dying. This paper highlights gaps in service provision in WA to people who are dying and their carers. It provides direction for occupational therapists to offer an occupation-focussed approach to the care of this vulnerable group.


State screening for metabolic disorders in newborns.
Most states have mandatory screening programs for congenital and inherited disorders of metabolism. Physicians may be unaware of their state's requirements, and compiled lists of testing requirements are generally unavailable or incomplete. All states test for congenital hypothyroidism and phenylketonuria. Some states require that newborns be tested for up to six other specific congenital and inherited disorders of metabolism. Some states base their decision to test on demographic data, but there is no uniformity in the tests.


Influence and critique of the JUPITER Trial (Statins v no statins for primary prevention of cardiovascular events in patients with normal lipids and elevated C-reactive protein).
Perhaps no recent trial in primary prevention of cardiovascular disease has resulted in more controversy than the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, which was first published in 2008. The study evaluated a patient cohort previously considered to be "healthy," ie, men 50 years of age or older and women 60 years of age or older, who did not have a history of cardiovascular disease and, at the initial screening visit, had a low-density lipoprotein cholesterol level of <130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level ≥2.0 mg/L. The trial showed that rosuvastatin is a powerful statin that, at lower doses, can reduce low-density lipoprotein cholesterol to levels previously not seen with other agents. Concurrently, it can also reduce high-sensitivity C-reactive protein to levels below what are considered normal, but that might be more physiologic. In the trial participants who achieved such lowering, major cardiovascular events, including venous thromboembolic events, were reduced even in the short term. Despite these results, many still question whether the trial results should influence high-sensitivity C-reactive protein testing or the prescription of statins for individuals at low risk for cardiovascular disease.


Single-crystal, Si nanotubes, and their mechanical resonant properties.
Single-crystalline Si nanotubes (NTs) were fabricated using vapor-liquid-solid grown, Ge nanowires (NWs) as a template upon which a Si shell was deposited to first grow Ge-core, Si-shell NWs. The tips of these NWs were removed, enabling exposure of the Ge core to H(2)SO(4) and H(2)O(2). After removing the Ge core, single-crystalline Si NTs remained. In addition to growing these Ge-core, Si-shell NWs from a Si (111) substrate, these NWs were also grown horizontally from a vertical Si surface to enable the fabrication of horizontal NTs after focused ion-beam cutting and etching steps. The resonant properties of the Ge-core, Si-shell NW, and the Si NT after the cutting and etching steps were measured and found to have a quality factor, Q, of approximately 1800.


[Redo operation for recurrent, disseminated and metastaic thymoma].
In this article, redo operation for recurrent thymoma was reviewed. Several cohort studies according the issues of the role of surgery for recurrent thymoma have been reported. Although these studies are of relatively small of seize and have selection biases, most of authors recommend surgical treatment for recurrent thymoma. Best results are expected in case of complete resection of the recurrence. Usually local recurrences are approached by a resternotomy, a clamshell incision or a hemi clamshell incision. Resternotomy associates with the risks of injury of brachiocepharic vein, heart and lungs and catastrophic hemorrhage. The degree of retrosternal adhesions and tumor invasion caused by recurrence are diverse. An oscillating saw is recommended for dividing the sternum. Video-assisted thoracic surgery(VATS)may help to dissect retrosternal adhesions. The most frequent pattern of recurrence is pleural implants after the initial operation with complete resection. In those cases, thoracotomy or VATS are often used. Redo operations for distant metastasis of thymoma are rare. Pleuropneumonectomy for pleural implantation is associated high morbidity and mortality rates, therefore this option is suitable for highly selected patients. Preoperative radiological evaluation of recurrent thymoma is important on planning of approach procedures.


[Ultrastructure of Sertoli cells of the human testis in agenesis of the vas deferens].
Ten testicular biopsies from adult males with agenesis of the vas deferens have been investigated with light and electron microscopy. The ultrastructural study of SERTOLI cells has demonstrated that: (a) the junctions between SERTOLI cells and between SERTOLI and germinal cells retain their normal ultrastructural features. (b) Lanthanum permeates SERTOLI cells tight junctions, but its diffusion towards the adluminal compartment is prevented. (c) SERTOLI cells present unusual amounts of cytoplasmic inclusions, especially lipofuscin granules. A relationship between these inclusions and phagocytosis has not been demonstrated. (d) "Dark" SERTOLI cells which show alterations of their typical junctional complex have been frequently observed, although their frequency varies among the different patients. The results are discussed in relation to diagnostic significance of the ultrastructural study of testicular biopsies.


Effects of prostaglandin E2 on salicylate-induced damage to the rat gastric mucosa: cytoprotection is not associated with preservation of the gastric mucosal barrier.
The effects of pretreatment with prostaglandin E2 (PGE2) on salicylate-induced gastric damage in the rat were studied with a gastric chamber model. Transmural potential difference (PD) and net potassium ion (K+) efflux were monitored as indices of gastric mucosal barrier integrity. Topical application of 20 mM salicylate for 10 min produced an abrupt drop in PD, an increase in net K+ flux, and the formation of hemorrhagic erosions covering approximately 24% of the glandular mucosa. Prior topical application of PGE2 at doses of 25, 75, and 300 micrograms/kg significantly reduced the extent of hemorrhagic erosions. However, PG pretreatment did not produce a reduction in the effects of topical salicylate on either PD or net K+ efflux. Rather, the drop in PD was initially accelerated and the net K+ efflux was increased by PGE2 pretreatment. Subsequently, in PGE2-pretreated mucosae, both parameters showed more rapid recovery toward control values. These results suggest that the mechanism of "cytoprotection" by PGE2 against salicylate-induced gastric damage is not a consequence of preservation of the gastric mucosal barrier.


Albendazole induces apoptosis in adults and microfilariae of Setaria cervi.
Setaria cervi, a filarial nematode of cattle, inhabits in the peritoneal cavity and has been used as a suitable model for screening antifilarial agents. Albendazole (ABZ), a tubulin-disrupting benzimidazole (BZ) and a potent microfilaricide binds to β-tubulin, is causing structural impairment of cytoskeleton and worm death. Our present study has revealed that exposure of microfilaria (Mf) and adult to gradually increasing concentration of ABZ leads to a dose-dependent gradual impairment of their motility followed by early death in vitro. We found extreme cellular disturbances in ABZ-treated worms characterized by nucleosomal DNA laddering and chromatin condensation. However, in the treated Mf no nucleosomal DNA laddering was found although presence of TUNEL reactive DNA was evident, thus indicating an apoptotic pathway independent of DNA fragmentation. We present data from molecular studies to provide evidence for ABZ-induced apoptosis in Mf and adult worms of S. cervi.


Follicular Lymphoma: Past, Present, and Future.
Even in the modern era, follicular lymphoma (FL) remains largely an incurable but treatable disease with both standard and novel treatment modalities. Despite the abundance of efficacious treatment modalities currently available, there is no universally agreed upon standard approach to treatment for patients with FL, particularly in the relapsed/refractory (R/R) setting. There is an increasing need for better tools to risk-stratify patients and to identify those likely to experience relapse early. Additionally, the use of gene expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis; however, much of this knowledge is not currently applicable on a day to day basis in the clinic setting. Further studies are needed to determine a validated, clinically relevant predictive model that incorporates patient factors and molecular factors that will guide clinicians on the most effective treatment strategy. With many questions left unanswered, it is our opinion that the treatment of FL and sequencing of therapy in the R/R setting should be a personalized approach that balances patient-specific factors such as preferences and comorbidities with treatment-related factors such as known response rates and toxicity profiles.


In vitro studies of chemical mutagens and carcinogens. I. Stability studies in cell culture medium.
A quantitative microbial assay was used to study the stability of known mutagenic and carcinogenic compounds in cell culture medium. Ten direct-acting carcinogens, when incubated in culture medium with 15% fetal bovine serum at pH 7.2-7.4 and 37 degrees C, became inactive at varying rates. Biologic half-lives of the test compounds ranged from 8 minutes to 67 hours. In contrast, six procarcinogens showed no significant inactivation after 3 weeks' incubation. The biologic half-lives of each compound were presented, and the significance of these findings as they relate to cell culture carcinogenesis and mutagenesis assays was discussed.


Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies.
The PVSG study is unique in that it is prospective and composed of 432 patients randomized to three treatment arms. This study also provides the opportunity for serial studies of numerous sequential biopsies. Large numbers of cases with sequential biopsies covering the entire long course are essential to appreciate the full spectrum of tissue changes in this disease. The PVSG was initiated in 1967 and in mid-1985 approximately one third of the patients are alive and on protocol. For these reasons, the results must still be considered preliminary. Pretreatment biopsies from patients randomized in the PVSG have been analyzed for total cellularity, megakaryocyte concentration, and reticulin content. Considerable variation in these elements was found in these biopsies. Sequential posttreatment biopsies from these patients have also been studied and correlated with the clinical course of the disease. None of the morphologic parameters analyzed was shown to be of prognostic significance. Early in the course of PV the marrow reticulin content is almost always normal. The length of the developmental stage is unknown and the precise timing of the clinical onset may be difficult. Therefore, the 11% of patients that showed a significant increase in reticulin on initial evaluation may have had PV longer than was indicated clinically. If large numbers of sequential biopsies are studied, an increase in reticulin content can frequently be demonstrated during the active phase of the disease and before the onset of the spent phase. Currently 39 patients (9%) have developed the spent phase, or PPMM. PPMM occurred in about the same incidence in the patients treated with myelosuppressive therapy as by phlebotomy alone, the spent phase occurring in 16 patients treated by phlebotomy alone, 11 with chlorambucil, and 12 with 32P. The course of the reticulin fibrosis is slowly progressive. There is some evidence for regression in a few patients in the erythrocytotic phase, but sampling variation cannot be completely ruled out. At this time in the study, AL has developed in 37 patients (8.6%). The incidence of AL is quite low in the phlebotomy group (three cases). Presumably this represents the natural incidence in PV unmodified by therapeutic agents. The frequency is approximately equal and quite high in the chlorambucil and 32P groups. There are 19 cases in the chlorambucil-treated group and 15 in the 32P-treated group. The leukemias that developed in the PV patients occurred either de novo or following PPMM.(ABSTRACT TRUNCATED AT 400 WORDS)


Neuregulin 1-β regulates cell adhesion molecule L1 expression in the cortex and hippocampus of mice.
Neuregulin 1 (Nrg1) functions in neuronal migration, survival and differentiation as well as synaptogenesis during ontogenetic development and maintenance of synaptic functions in the adult mammalian brain. The neural adhesion molecule L1 (L1CAM) functions in similar overlapping, but also non-overlapping roles in the nervous system. In the present study, we therefore investigated some aspects of the functional relationship between Nrg1 and L1 in mammalian neural cells. Nrg1 regulates the expression of L1 in cultures of both human neuroblastoma SK-N-SH cells and mouse cortical and hippocampal neurons. To analyze the role of Nrg1 on L1 expression in vivo, young adult male mice received intraperitoneal injections of Nrg1 or PBS (vehicle control). The correlation between Nrg1 and L1 expression was tested by qPCR, Western blot analysis, and immunocytology. Our data indicate that neuregulin 1-β (Nrg1β) increases L1 expression in neurons of the cerebral cortex, and decreases expression in neurons of the hippocampus in vitro and in vivo. In addition, Nrg1 induces phosphorylation of its receptors, ErbB2 and ErbB4, the predominant ErbB receptors in the nervous system. These results show that Nrg1β affects expression of L1 in the central nervous system and in parallel activates the ErbB receptors for Nrg1, suggesting a crosstalk between molecules that are of prime importance for nervous system functions.


Assessment of groundwater quality in Virudhunagar district (India): a statistical approach.
The present work was undertaken to analyze the various water quality parameters, viz. pH, electrical conductivity, total dissolved solids, total alkalinity, total hardness, Cl-, SO4(2-), Ca2+, Mg2+, Na+ and K+ and study the WQI in bore well and dug well water samples. 30 water samples were collected from different localities of Virudhunagar district, Tamil Nadu (India). The results were compared with the values stipulated by World Health Organization (WHO), Indian Council of Medical Research (ICMR) and European Economic Community (EEC) for drinking water quality. The present study showed the overall water quality of Virudhunagar district is poor and unsuitable for drinking purpose which recommends the use of indigenous technologies, to make water fit for drinking purpose.


A retrospective analysis of ezetimibe treatment in renal transplant recipients.
A retrospective review was conducted to determine the safety and efficacy of ezetimibe as a treatment option for renal transplant recipients. We evaluated the medical records of 34 adult renal transplant recipients receiving ezetimibe as monotherapy or combination therapy. Fasting lipid profiles were obtained at baseline and at 1-6 months post-ezetimibe initiation. Twenty patients received cyclosporine, 12 patients received tacrolimus, 1 patient received either sirolimus or no calcineurin therapy at the time of ezetimibe initiation. Monotherapy was started in 8 patients, who had all previously failed statins, and combination therapy was utilized in 26 patients. Monotherapy or combination therapy resulted in a mean reduction in total cholesterol of 23.3%, triglycerides 40.2%, low-density lipoproteins 16.8% and high-density lipoproteins 4.8% after 3.1 months of therapy. Ezetimibe as combination or monotherapy is a safe and effective treatment option for dyslipidemia in renal transplant recipients without changes in calcineurin inhibitor levels or renal function.


Estrogenic activity removal of 17beta-estradiol by ozonation and identification of by-products.
This work investigated the degradation of a natural estrogen (17beta-estradiol) and the removal of estrogenic activity by the ozonation process in three different pHs (3, 7 and 11). A recombinant yeast assay (YES assay) was employed to determine estrogenic activity of the ozonized samples and of the by-products formed during the ozonation. Ozonation was very efficient for the removal of 17beta-estradiol in aqueous solutions. High removals (>99%) were achieved with low ozone dosages in the three different pHs. Several by-products were formed during the ozonation of 17beta-estradiol. However, only a few compounds could be identified and confirmed. Different by-products are formed at different pHs, which is probably due to different chemical pathways and different oxidants (O(3) and OH radical). The by-products formed at pH 11 were 10epsilon-17beta-dihydroxy-1, 4-estradieno-3-one (DEO) and 2-hydroxyestradiol, which were not formed in pH 3. Only testosterone could be observed in pH 3, whereas at pH 7 all three by-products were found. At pH 7 and 11 the applied ozone dosages were not enough to remove all the estrogenicity from samples, even though the 17beta-estradiol residual concentration for these two pHs was lower than at pH 3. Higher estrogenicity was detected at pH 11. An explanation to this fact may be that oxidation via OH radical forms more by-products with estrogenic activity. Probably, the formation of 2-hydroxyestradiol at pHs 7 and 11 is contributing to the residual estrogenicity of samples ozonized at these pHs. In this work, complete removal of estrogenic activity was only obtained at pH 3.


Numerical evaluation of cytologic data. XIII. Curve fitting and curvilinear regression.
A method of curve fitting is described by which curves can be fitted to data for which the independent variables are not spaced equidistantly. The method uses the calculation of regression coefficients for an appropriate polynomial. Testing of the plotted curve by computation of the residual sum of squares is shown also, as is use of a "coefficient of partial determination" to test the statistical significance of the degree of polynomial chosen.