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Time course of radiation-induced apoptosis in the adult rat spinal cord. Radiation-induced apoptosis has been reported in thymic, lymphoid, haematopoietic cells and intestinal epithelium but is infrequently documented in other adult mammalian cell types. In this study, we examined the time course of radiation-induced apoptosis in the adult cervical rat spinal cord following a single dose of 8 or 22 Gy. Apoptosis was assessed by morphological criteria under light and electron microscopy, and immunohistochemically in-situ using Apoptag to detect 3' -OH ends of DNA fragments. Little evidence of apoptosis (0.3 +/- 0.1 apoptotic nuclei per spinal cord section) was observed in control un-irradiated spinal cord. A significant increase in the number of apoptotic cells per spinal cord section was seen at 4 h after 8 (13.6 +/- 1.3) or 22 Gy (22.0 +/- 2.7). The number of apoptotic nuclei reached a peak at 8 h (44.7 +/- 3.7 after 8 Gy, 49.5 +/- 4.3 after 22 Gy), and returned to the baseline level by 24 h (2.4 +/- 0.7 after 8 Gy, 3.3 +/- 0.7 after 22 Gy). A dose of 22 Gy induced significantly more apoptoses than 8 Gy at 4, 6, 10 and 12 h (P < or = 0.033), but not at 8 h. More apoptotic nuclei were observed in white matter (64-92%) than gray matter (8-36%). All the apoptotic cells were observed in glial cells, and there was no evidence of radiation-induced apoptosis in the vascular endothelial cells or neurons. The morphological features of the apoptotic cells under electron microscopy and the absence of GFAP staining suggested that they were oligodendrocytes. We conclude that radiation induces apoptosis in the adult rat spinal cord, and that the development of apoptosis follows a specific time course.

The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs. The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.

Sudden cardiac death. Sudden cardiac death can occur after exposure to extreme stress and sometimes as a complication of acute neurologic disease. Excessive adrenergic stimulation of the heart is most likely the responsible mechanism for the majority of cases of sudden cardiac death. The neurocardiogenic injury induced by sympathetic overstimulation can affect the myocardium and the electrical conduction system, leading to heart failure and arrhythmias. The characteristic features of stress cardiomyopathy (also known as takotsubo cardiomyopathy or apical ballooning syndrome) can be diagnosed by echocardiography and cardiovascular magnetic resonance imaging. This chapter reviews the history, definition, pathophysiology, triggers, and clinical manifestations of neurocardiogenic injury. It also discusses specific neurologic conditions associated with sudden death: epilepsy (sudden unexplained death in epilepsy, SUDEP) and stroke.

Oral supplementation with Lactobacillus rhamnosus CGMCC 1.3724 prevents development of atopic dermatitis in NC/NgaTnd mice possibly by modulating local production of IFN-gamma. Prevalence of allergies has increased during the last two decades. Alteration of the gut microbiota composition is thought to play a crucial role in development of atopic diseases. Oral administration of probiotics has been reported to treat and/or prevent symptoms of atopic diseases in infants, but the results are still controversial. We investigated the potential efficacy of dietary interventions by a probiotic strain on prevention and treatment of atopic dermatitis (AD) in a human-like AD model, NC/NgaTnd mice by perinatal administration. Pregnant NC/NgaTnd mice were orally treated with the probiotic strain Lactobacillus rhamnosus CGMCC 1.3724 (LPR), which was followed by treatment of pups until 12 weeks of age. LPR-treated mice exhibited significant lower clinical symptoms of dermatitis, reduced scratching frequency, lower levels of plasma total Immunoglobulin E and higher levels of interferon-gamma in skin biopsies, compared with untreated mice. The protective effect was also observed when mice started to be treated at weaning time (5 weeks of age) even with limited supplementation period of 2 weeks. However, treatment of mice with the probiotic starting 1 week after the onset of the disease (8 weeks of age) had limited effects. The usefulness of LPR for primary prevention of AD was supported.

[Spectral analysis of different boundary discharge domain in dielectric barrier discharge]. Different discharge modes in different boundary discharge domains at the same experimental condition are observed in argon/air mixture in a dielectric barrier discharge system with two large diameter water electrodes. Regular patterns and random filaments are formed in the closed square boundary and the semiopen domain respectively. It is found that the relatively intensity of the several higher excitation energy spectral lines such as 696.5, 727.3, 750.4 and 772.4 nm increases with the applied voltage in the closed boundary domain while decreases in the semiopen domain. Results show that the electron average energy in the closed boundary is higher than that in the semiopen domain and the difference of the electron average energy increases with the applied voltage. The results of molecular vibration temperature estimated by the second positive spectrum of N2 molecular indicate that the vibration temperature increases with the applied voltage in the closed boundary and decreases with the applied voltage in the semiopen boundary domain.

Abstracting meaning from complex information (gist reasoning) in adult traumatic brain injury. Gist reasoning (abstracting meaning from complex information) was compared between adults with moderate-to-severe traumatic brain injury (TBI, n = 30) at least one year post injury and healthy adults (n = 40). The study also examined the contribution of executive functions (working memory, inhibition, and switching) and memory (immediate recall and memory for facts) to gist reasoning. The correspondence between gist reasoning and daily function was also examined in the TBI group. Results indicated that the TBI group performed significantly lower than the control group on gist reasoning, even after adjusting for executive functions and memory. Executive function composite was positively associated with gist reasoning (p < .001). Additionally, performance on gist reasoning significantly predicted daily function in the TBI group beyond the predictive ability of executive function alone (p = .011). Synthesizing and abstracting meaning(s) from information (i.e., gist reasoning) could provide an informative index into higher order cognition and daily functionality.

Acrylamide polymerization: new method for determining the oxygen content in blood. A new principle for determining the oxygen content of 0.1-milliliter blood samples has been developed, based on measurement of the delay in gelation during copolymerization of acrylamide and bisacrylamide initiated by free radicals. The logarithm of this time interval is linearly proportional to the oxygen content of the blood sample over the range 0 to 22 milliliters of oxygen per 100 milliliters of whole blood. Physiological variations of pH and pCO(2) do not affect the sensitivity of the assay.

Misdiagnosis of atrial fibrillation and its clinical consequences. Computer algorithms are often used for cardiac rhythm interpretation and are subsequently corrected by an overreading physician. The purpose of this study was to assess the incidence and clinical consequences of misdiagnosis of atrial fibrillation based on a 12-lead electrocardiogram (ECG). We retrieved 2298 ECGs with the computerized interpretation of atrial fibrillation from 1085 patients. The ECGs were reinterpreted to determine the accuracy of the interpretation. In patients in whom the interpretation was incorrect, we reviewed the medical records to assess the clinical consequences resulting from misdiagnosis. We found that 442 ECGs (19%) from 382 (35%) of the 1085 patients had been incorrectly interpreted as atrial fibrillation by the computer algorithm. In 92 patients (24%), the physician ordering the ECG had failed to correct the inaccurate interpretation, resulting in change in management and initiation of inappropriate treatment, including antiarrhythmic medications and anticoagulation in 39 patients (10%), as well as unnecessary additional diagnostic testing in 90 patients (24%). A final diagnosis of paroxysmal atrial fibrillation based on the initial incorrect interpretation of the ECGs was generated in 43 patients (11%). Incorrect computerized interpretation of atrial fibrillation, combined with the failure of the ordering physician to correct the erroneous interpretation, can result in the initiation of unnecessary, potentially harmful medical treatment as well as inappropriate use of medical resources. Greater efforts should be directed toward educating physicians about the electrocardiographic appearance of atrial dysrhythmias and in the recognition of confounding artifacts.

The oligodendrocyte-specific antibody 'CC1' binds Quaking 7. The mouse monoclonal antibody marketed as anti-adenomatous polyposis coli clone CC1, often referred to as CC1, is the antibody most commonly used to specifically label mature oligodendrocytes without labeling myelin. Previous studies have shown that despite being raised against adenomatous polyposis coli, this antibody binds another unknown antigen. We show that the CC1 antibody binds Quaking 7, an RNA-binding protein that is highly up-regulated in myelinating oligodendrocytes in the central nervous system. The monoclonal antibody anti-adenomatous polyposis coli (APC) clone CC1, is the antibody most commonly used to specifically label the cell bodies of mature oligodendrocytes. Despite being raised against APC, previous studies showed this antibody binds another unknown antigen. We show that the CC1 antibody binds Quaking (QKI) 7, an RNA-binding protein which is highly up-regulated in myelinating oligodendrocytes.

Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer. Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epithelial to mesenchymal transition have been associated with increased chemoresistance and metastatic spread in SCLC. The biopsy specimens of 38 SCLC patients were used for marker evaluation by immunohistochemistry. The markers for CSCs were CD44 and SOX2. The markers for epithelial to mesenchymal transition were E-cadherin, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, vimentin, and c-MET. Staining was scored as low (weak) or high (strong) intensity for SOX2, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, and c-MET and using the immunoreactive score for CD44, E-cadherin, and vimentin, expressed as low or high expression. High expression of c-MET (c-METH) and low expression of E-cadherin (E-cadL) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E-cadL resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-METHE-cadL (P = .09) with low CTCs. The CSC markers SOX2 and CD44 were not associated with overall survival in this patient cohort. SCLC with a mesenchymal-like phenotype (c-METHE-cadL) is associated with longer survival and showed a trend toward lower CTCs.

Factor VIII procoagulant protein interacts with phospholipid vesicles via its 80 kDa light chain. In a previous report, we detailed fractionation of polyclonal human anti-Factor VIII:C into a component directed exclusively against the phospholipid-binding site on Factor VIII (PL-site antibody) and another directed at other sites (non-PL-site antibody). The location on the F.VIII molecule of its PL-binding site has now been studied by two different methods using this fractionated 125I-labelled anti-F.VIII:C Fab'. The first method was modified from that of Weinstein et al. (Proc Natl Acad Sci USA 1981; 78: 5137-41), involving electrophoresis of F.VIII peptide-125I-Fab' A/F.VIII immunocomplexes in SDS-polyacrylamide gels. PL-site antibody reacted with F.VIII peptides of apparent Mr approximately 80 kDa and sometimes 160 kDa in plasma and concentrate, but not with larger peptides. Non-PL-site antibody, however, reacted with a range of peptides of apparent Mr 90 kDa to 280 kDa. In addition, when purified F.VIII containing heavy and light chains (HC + LC), and isolated LC peptides were analysed, PL-site antibody bound to LC peptides whereas non-PL-site antibody did not. The second method used the antibody pools in immunoradiometric assays (IRMA's) of purified F.VIII peptides. Both labels measured similar amounts of F.VIII:Ag in a sample of purified F.VIII containing both HC and LC; on assaying an HC preparation, however, PL-site label measured only 2% of F.VIII:Ag found by non-PL-site label, indicating that PL-binding sites are absent in HC preparations. These results indicate that F.VIII binds to PL via its 80 kDa light chain.

Cost-effectiveness analysis of treatments involving radioembolization in intermediate-stage hepatocellular carcinoma. We evaluated two treatment sequences, transarterial radioembolization followed by transarterial chemoembolization and possibly sorafenib (=TTS) versus transarterial radioembolization followed by sorafenib alone (=TS), to identify the most cost-effective pathway to treat intermediate-stage hepatocellular carcinoma from the Italian healthcare system perspective. A Markov model was developed to project costs and health outcomes for TTS and TS over a lifetime horizon. Data available at three hospitals in Italy were collected. Healthcare resource utilization was derived from standard clinical protocols. Costs were obtained from official regional tariffs. Taking into consideration 16 patients for TTS and 22 patients for TS pathways, the TTS sequence provided a dominant strategy in comparison to TS. Further evidence is desirable to confirm these results.

[Laparoscopic adrenalectomy]. The authors performed three left and one right sided laparoscopic adrenalectomies between 3rd April and 8th August 1997. The indication of surgery was hormonally active cortical adenoma of about 2 cm size in three cases, a 6 cm large hormonally inactive tumour in one case respectively. For the operation on the left side three, on the right side four trocars with 11 mm diameter was used. The duration of the operations was between 115 and 220 min. The patients left one the second or third postoperative day, no complication was observed. The authors' opinion based on both literature data and their own experience is that laparoscopic approach to adrenalectomies is the method of choice today.

Insights into the function of FhaA, a cell division-associated protein in mycobacteria. FhaA is a forkhead-associated domain-containing protein, the depletion of which leads to accumulation of peptidoglycan (PG) precursors at the septum and poles in Mycobacterium smegmatis (M. smegmatis), by a mechanism undefined thus far. To elucidate its function, we constructed an fhaA (MSMEG_0035) knockout (ΔfhaA) strain in M. smegmatis and demonstrated that this gene is dispensable for in vitro growth. The mutant showed a short cell length phenotype due to a probable defect in cell elongation/cell wall synthesis, which was reversed by complementation with both M. smegmatis and Mycobacterium tuberculosis (M. tb) fhaA (Rv0020c), confirming their association with the observed phenotype. The identification of penicillin binding protein A (PbpA), a PG biosynthesis enzyme as an interacting partner for mycobacterial FhaA, provided a hint into the functioning of FhaA. A drastic reduction in the levels of ectopically expressed PbpA in the ΔfhaA mutant vs wild-type M. smegmatis suggested that FhaA interacts with and stabilises PbpA. In addition, the fhaA deletion mutant was sensitive to multiple classes of antibiotics pointing to a general permeability defect. Our findings uncover a role for FhaA in PG biosynthesis and suggest its involvement in the maintenance of mycobacterial cell envelope integrity.

p38 MAPK-mediated activation of NF-kappaB by the RhoGEF domain of Bcr. The oncogenic fusion protein p210 Bcr-Abl is causally associated with virtually all cases of chronic myelogenous leukemia. The wild-type Bcr product has several recognizable structural and functional motifs including a domain that contains guanine nucleotide exchange activity for Rho family GTPases (DH/PH domain). Although this domain is retained within p210 Bcr-Abl, it has no known signaling activities in vivo. Here we report that a fragment of Bcr that encodes the isolated DH/PH domain is a potent activator of the NF-kappaB transcription factor. Within the context of full length Bcr, this activity is regulated by proximal flanking sequences that suppress the DH/PH domain encoded guanine nucleotide exchange activity. NF-kappaB activation by Bcr is not mediated by nuclear translocation, but rather by p38 mitogen-activated protein kinase (MAPK)-dependent modification of the RelA/p65 transactivation domain. Although we were able to demonstrate that Bcr can function as an exchange factor for Cdc42 in vivo, NF-kappaB activation appears to occur via a Cdc42-independent mechanism. These studies constitute direct evidence that the Bcr RhoGEF domain can function in vivo, and identify a new signaling activity that may contribute to the transforming potential of p210 Bcr-Abl.

10-Gingerol, a Phytochemical Derivative from "Tongling White Ginger", Inhibits Cervical Cancer: Insights into the Molecular Mechanism and Inhibitory Targets. With the aim of evaluating anticancerous activities of 10-gingerol (10-G) against HeLa cells, it was purified and identified from "Tongling white ginger" by HSCCC, UPLC-TOF-MS/MS, and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity, and arrested cell cycle in the G0/G1 phase. Most cell cycle related genes and protein expression significantly decreased, followed by a slight decrease in a few without affecting cyclin B1 and cyclin E1 (protein). Both death receptors significantly up-regulated and activated apoptosis indicators (caspase family). Furthermore, significant changes in mitochondria-dependent pathway markers were observed and led to cell death. 10-G led to PI3K/AKT inhibition and AMPK activation to induce mTOR-mediated cell apoptosis in HeLa cells. These results can be an asset to exploit 10-G with other medicinal plant derivatives for future applications.

An evaluation of non-invasive blood pressure (NIBP) monitoring on the wrist: comparison with upper arm NIBP measurement. The arm is the traditional site for application of an oscillometric non-invasive blood pressure (NIBP) cuff This study, which compares upper arm NIBP to wrist NIBP, involved 510 same arm sequential paired blood pressure (BP) measurements in 85 volunteers. Wrist NIBP consistently overestimated mean arterial, systolic and diastolic pressure by approximately 10 mmHg. Ninety per cent of the mean arterial pressure differences at the wrist were within a range of +/- 9 mmHg around a mean difference of 10.6 mmHg. The systolic pressure difference was 11.2 mmHg with 90% of differences between +/- 12 mmHg. The diastolic pressure difference was 10.2 mmHg with 90% of differences between +/- 9 mmHg. With the device used and within the normal blood pressure range, compensation can be performed by subtracting 10 mmHg from the measured values or simply by elevating the wrist about 15 cm and taking the BP at face value. Wrist NIBP may be a viable clinical alternative in situations where difficulty occurs with upper arm NIBP measurement.

The balance simplex in non-competitive 2-species scaled Lotka-Volterra systems. Explicit expressions in terms of Gaussian Hypergeometric functions are found for a 'balance' manifold that connects the non-zero steady states of a 2-species, non-competitive, scaled Lotka-Volterra system by the unique heteroclinic orbits. In this model, the parameters are the interspecific interaction coefficients which affects the form of the solution used. Similar to the carrying simplex of the competitive model, this balance simplex is the common boundary of the basin of repulsion of the origin and infinity, and is smooth except possibly at steady states.

Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin inhibitor of the intrinsic coagulation pathway. Nitrophorin 2 (NP2) is a salivary lipocalin from Rhodnius prolixus that binds with coagulation factors IX (fIX) and IXa (fIXa). Binding of NP2 with fIXa results in potent inhibition of the intrinsic factor Xase complex. A panel of site-directed surface mutants of NP2 was generated to locate determinants of high affinity fIX(a) binding. The locations of the mutations were based on comparisons with the related, but less potent, inhibitor nitrophorin 3 (NP3). Three point mutants (K21A, K92A, and V94A) were found that clearly reduced the inhibitory potency as measured by the activity of a reconstituted factor Xase system. Binding of NP2 with fIXa and fIX as measured by surface plasmon resonance and isothermal titration calorimetry was reduced in a similar manner. Of the three mutants, two (K92A and V94A) were located on the loop connecting beta-strands E and F of the lipocalin beta-barrel. The largest changes were seen with the K92A mutation, which lies at the apex of the loop, with a smaller effect being seen with mutation of Val(94). Combination of four E-F loop mutations (K92A, A93K, V94A, E97A) in a single mutant reduced the inhibitory potency and binding to levels similar to those seen with NP3 without affecting heme or histamine binding.

Gait Patterns in Children With Cancer and Vincristine Neuropathy. Children treated with vincristine often develop chemotherapy-induced peripheral neuropathy (CIPN), but effects of CIPN on gait have not been reported. Gait variables of 52 children/adolescents treated for non-central nervous system cancers with CIPN were compared with an age- and sex-matched control group. Gait data were collected via GaitRite walkway before and after completing a 6-minute walk test (6MWT). Ankle range-of-motion (ROM) measures, balance, and strength tests were also completed. Participants with CIPN had decreased velocity and step length. Ankle ROM and balance explained variability in step length. Both groups increased self-selected velocity after the 6MWT, but participants with cancer walked with slower velocity, shorter step length, and decreased cadence. Strength, neuropathy, and self-selected velocity measured before the 6MWT explained variability in 6MWT scores. Ankle ROM and balance are important factors when treating step length deficits, whereas strength is also an important consideration for walking capacity.

Soft tissue reaction to de novo plaque formation on implants and teeth. An experimental study in the dog. The aim of the present investigation was to assess the effect of de novo plaque formation on the gingiva and masticatory mucosa around teeth and implants. The study was performed in 5 beagle dogs which at the initiation of the experiment were 15 months old. During a preparatory period, the mandibular right premolars were extracted, 3 fixtures installed, abutment connection performed and a 4-month period of plaque control completed. A clinical examination was performed and biopsies of the second mandibular premolar (P2) and the contralateral implant site (2P) were sampled. The dogs were allowed to form plaque during a period of 3 weeks. The clinical examination was repeated and biopsies harvested from the 2 remaining implants and the contralateral tooth sites. The tissue samples were prepared for histometric and morphometric analysis. Both the masticatory mucosa at implants and the gingiva responded to de novo plaque formation with the development of an inflammatory lesion. The size as well as the composition of the lesions in the 2 tissues had many features in common. It was concluded that the mucosa around implants and the gingiva around teeth had a similar potential to respond to early plaque formation.

Prediction of CYP-mediated drug interactions in vivo using in vitro data. Over the past 15 years, a concerted effort has been undertaken by the pharmaceutical industry to reduce the attrition of clinical candidates resulting from undesirable ADME characteristics. Increasing regulatory and competitive pressures demand that pharmaceutical products brought to the market possess pristine safety and drug co-administration profiles for most therapeutic areas. The high-profile withdrawal of drugs such as mibefradil from the market because of unfavorable drug-drug interaction profiles has focused efforts on screening for cytochrome P450 (CYP)-mediated drug interactions early in the discovery paradigm and on predicting the impact of inhibition on the in vivo situation. This paper discusses current practices used to screen for CYP-mediated drug-drug interactions in vitro (inhibition and induction) and how these data are being used to predict whether a clinically relevant drug-drug interaction is likely to occur in vivo.

A dual-sensitive mesoporous silica nanoparticle based drug carrier for cancer synergetic therapy. A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.

Maintaining standards of aesthetic practice in trainees subject to NHS restrictions. The Specialist Advisory Committee (SAC) in plastic surgery within the United Kingdom (UK) recommends a modular training programme to include aesthetic surgery. The intercollegiate board examinations test candidates on all aspects of aesthetic practice yet there is no formal, national aesthetic training in the UK. Closure of National Health Service (NHS) private patient facilities has reduced training opportunity [Nicolle FV. Sir Harold Gillies Memorial Lecture; Aesthetic plastic surgery and the future plastic surgeon. Br J Plast Surg 1998;51:419-24.] Calmanisation [Hospital doctors: training for the future. The Report of the Working Group on Specialist Medical Training (The Calman Report). London: HMSO; 1993.], the European Working Time Directive (EWTD) [; Phillips H, Fleet Z, Bowman K. The European Working time Directive-interim report and guidance from The Royal College of Surgeons of England working party chaired by Mr Hugh Phillips; 2003 []; Chesser S, Bowman K, Phillips H. The European Working Time Directive and the training of surgeons. BMJ Careers Focus 2002;s69-7.], and more importantly the implementation of "local" aesthetic guidelines have placed further pressures on training. Reductions of NHS case mix will ultimately lead to a reduction in trainee experience. With increasing regulatory pressure from the Commission for Healthcare Improvement, standards of aesthetic practice can only be maintained by increasing private/independent sector involvement. At present a disparity exists between the demand and provision of aesthetic surgery training in the UK. Aesthetic surgery forms part of the training curriculum for plastic surgery and as such remains a training issue. A review of aesthetic surgery training is needed in the UK through consultation with trainers and trainee representatives.

Terminal ligature of inferior thyroid artery branches during total thyroidectomy for multinodular goiter is associated with higher postoperative calcium and PTH levels. To evaluate the impact of truncal versus terminal branch ligature of the inferior thyroid artery (ITA) on postoperative calcium and PTH plasma levels in patients undergoing total thyroidectomy for multinodular goiter. A prospective randomized study was performed comparing a group of patients that underwent either truncal ligature of the ITA (group 1) or terminal ligature of ITA branches (group 2). A series of 126 consecutive patients with non-toxic euthyroid multinodular goiter underwent total thyroidectomy. Truncal ligature of the ITA was performed in 63 patients (group 1) and terminal branch ITA ligature in 63 patients (group 2). Postoperative ionized serum calcium (mmol/L) at 24 hours was significantly lower in group 1 than in group 2 patients (1.22 ± 0.06 vs. 1.25 ± 0.05, P<0.05) and at 48 hours (1.20 ± 0.05 vs. 1.23 ± 0.05, P<0.05). Mean postoperative PTH levels (pg/mL) at 4 hours after thyroidectomy were significantly lower in group 1 than in group 2 patients (22.32 ± 11.64 vs. 25.82 ± 12.87, P=0.044). Mean hospital stay (hours) was higher in group 1 than in group 2 patients (87.47 ± 41.04 vs. 70.34 ± 24.82, P<0.05). This study shows that terminal ligature of ITA branches during total thyroidectomy for multinodular goiter is associated with higher mean postoperative calcium and PTH levels, and shorter hospital stay. However, no significant difference in terms of permanent hypoparathyroidism was observed between the two groups.

The role of dietary fat in adipose tissue metabolism. Energy intake and expenditure tend on average to remain adjusted to each other in order to maintain a stable body weight, which is only likely to be sustained if the fuel mix oxidised is equivalent to the nutrient content of the diet. Whereas protein and carbohydrate degradation and oxidation are closely adjusted to their intakes, fat balance regulation is less precise and that fat is more likely to be stored than oxidised. It has been demonstrated that dietary fatty acids have an influence not only on the fatty acid composition of membrane phospholipids, thus modulating several metabolic processes that take place in the adipocyte, but also on the composition and the quantity of different fatty acids in adipose tissue. Moreover, dietary fatty acids also modulate eicosanoid presence, which have hormone-like activities in lipid metabolism regulation in adipose tissue. Until recently, the adipocyte has been considered to be no more than a passive tissue for storage of excess energy. However, there is now compelling evidence that adipocytes have a role as endocrine secretory cells. Some of the adipokines produced by adipose tissue, such as leptin and adiponectin, act on adipose tissue in an autocrine/paracrine manner to regulate adipocyte metabolism. Furthermore, dietary fatty acids may influence the expression of adipokines. The nutrients are among the most influential of the environmental factors that determine the way adipose tissue genes are expressed by functioning as regulators of gene transcription. Therefore, not only dietary fat amount but also dietary fat composition influence adipose tissue metabolism.

Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults - a functional magnetic resonance imaging (fMRI) study. Attention deficit hyperactivity disorder (ADHD) is a common, genetically transmitted common childhood-onset disorder with a high rate of persistence in adulthood. Although many studies have shown anatomical and functional abnormalities in children and adolescents, studies with adult patients are rare. Nineteen adults with ADHD (11 ADHD, combined type; 8 ADHD, partially remitted) and 17 controls were included in this functional magnetic resonance imaging (fMRI) study. Brain activation was investigated with a continuous performance test (CPT). Impaired activation of a fronto-striatal and a parietal attentional network was observed during the NoGo condition in ADHD subjects. Correlations of reduced activity of the caudate nuclei, the anterior cingulate cortex, and parietal cortical structures, as well as increased activity in the insular cortex, with inattention and impulsivity symptom scores were found. The activation patterns were similar to those known from children and adolescents with ADHD. In conclusion we found not only a widespread dysfunction of brain regions that are involved in cognitive processing in adults with ADHD compared with controls, but also correlations between symptom severity and dysfunction of neuronal systems across adult subjects with a history of ADHD in childhood but whose symptoms did (persistent ADHD) and did not (not persistent ADHD) qualify for a full diagnosis of ADHD in adulthood.

[Identification of the mode of stab-and-hack wound infliction to the chest based on wound features]. The objective of this study was to obtain morphological characteristics of stab-and-hack wounds inflicted by falling down on the knife blade. A formula is derived based on the results of discrimination analysis that can be used in combination with wound morphological features to differentiate between chest stabbing modes.

Health care auxiliaries in the detection and prevention of oral cancer. Oral cancer is one among the few human cancers with a vast potential for prevention. One of the operational strategies considered to translate preventive measures into practice in developing countries has been the use of community health workers and other health auxiliaries of the primary health care system to disseminate anti-tobacco health education messages and to provide mouth examinations in high-risk individuals during their routine home visits and community meetings. Studies conducted in India and Sri Lanka to address the role of the above approach indicate that it is feasible to train community health workers and other health auxiliaries in primary prevention and early detection of oral cancer and precancerous lesions. However, no evidence of the efficacy of such an approach in reducing the incidence and mortality from oral cancer is yet available. Sufficient evidence in terms of efficacy and cost effectiveness is needed to justifiably convince health administrators for the inclusion of non-communicable disease control in general and oral cancer screening in particular as part of the primary health care delivery by community health workers and other health auxiliaries especially when considering the burden of already existing work responsibilities. The need for studies in this direction is very obvious. However, the opportunities for 'case-finding' and health education should be utilised when encountering high-risk subjects both in primary medical and health care.

[Results of volar transposition of the ulnar nerve in cubital tunnel syndrome]. 66 volar transpositions of the ulnar nerve were performed in 63 patients with cubital tunnel syndrome. 53 patients were male, 10 female. The average age was 49.2 years ranging from 21-74 years. 64 patients had a neurological deficit, 2 merely suffered from pain. The nerve conduction velocity was delayed in all patients. 14 patients had had a cubital fracture in their history, 6 patients showed an arthrosis of the cubital joint. 5 patients suffered from a habitual luxation of the ulnar nerve. In 14 cases there had been recurrent distorsions of the cubital joint. 4 patients were diabetics, 2 alcoholics. In 31 cases no pathogenetic factor could be found. A deep intramuscular transposition with insertion of the intramuscular septa was performed. There were excellent and good results in 82% of all cases. 15% remained unchanged. In 3% a deterioration was observed. The shorter the preoperative history the better the prognosis. Complete recovery was less frequent in patient with severe neurological deficit than with slight. The results were better in younger patients than in elder. But long lasting severe atrophies in elder patients recovered completely in some cases. Diabetes mellitus and alcoholism could not be proved as contributing factors but seemed to cause poorer results.

[Extraction and analysis of profenofos residue in tomato and cabbage by gas chromatography-flame photometric detector]. A quick and effective extraction and clean-up method of profenofos residue in tomato and cabbage is presented. Tomato and cabbage samples were homogenized with a mixture of acetone-hexane (1:1, V/V) using a mechanical homogenizer. The resultant homogenate was cleaned-up by adding active carbon and then filtered under reduced pressure. The filter cake was extracted twice with the same solvent mixture. The filtrates were combined and transferred into a separatory funnel. The organic layer was separated and evaporated to dryness using a rotary evaporator. The residue was dissolved in 2 mL of acetone and transferred into a small glass vial and then determined by GC on a 5% OV-101 Chromosorb W-HP column with flame photometric detector. The results showed that this analytical method can be used for an accurate determination of profenofos residues in tomato and cabbage. The minimum detectable concentration of profenofos in samples was 0.06 mg/kg. The recoveries of profenofos in tomato and cabbage were in the range of 96.2%-105.9% and 94.7%-102.3%, respectively. The relative standard deviations were in the range of 3.7%-4.9% and 3.7%-5.0%, respectively. The tomato and cabbage samples were collected 3 weeks after applying profenofos in the field, and the contents of profenofos were determined. The average contents of profenofos in tomato and cabbage were (13.8 +/- 0.8) mg/kg and (14.4 +/- 0.7) mg/kg, respectively.

A reverse transcription loop-mediated isothermal amplification method for rapid detection of bovine viral diarrhea virus. A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized to detect bovine viral diarrhea viral (BVDV) RNA. The RT-LAMP assay is highly sensitive and able to detect 4.67×10(0)copies of BVDV RNA. Additionally, the RT-LAMP method is capable of detecting both genotypes of BVDV. No cross-reaction with other bovine viruses was observed. The ability of RT-LAMP to detect BVDV RNA from bovine fecal swabs was also evaluated. Of the 88 fecal swabs, 38 were found to be positive by RT-LAMP assay, whereas 39 were positive by real-time RT-PCR. Taken together, the BVDV specific RT-LAMP method is highly specific and sensitive and can be used as a rapid and direct diagnostic assay for testing clinical samples.

Successful third renal transplantation in a child with an occluded inferior vena cava: A novel technique to use the venous interposition between the transplant renal vein and the infrahepatic inferior vena cava. A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

Epidermal Basement Membrane in Health and Disease. Skin, as the organ protecting the individual from environmental aggressions, constantly meets external insults and is dependent on mechanical toughness for its preserved function. Accordingly, the epidermal basement membrane (BM) zone has adapted to enforce tissue integrity. It harbors anchoring structures created through unique organization of common BM components and expression of proteins exclusive to the epidermal BM zone. Evidence for the importance of its correct assembly and the nonredundancy of its components for skin integrity is apparent from the multiple skin blistering disorders caused by mutations in genes coding for proteins associated with the epidermal BM and from autoimmune disorders in which autoantibodies target these molecules. However, it has become clear that these proteins not only provide mechanical support but are also critically involved in tissue homeostasis, repair, and regeneration. In this chapter, we provide an overview of the unique organization and components of the epidermal BM. A special focus will be given to its function during regeneration, and in inherited and acquired diseases.

IgA-mediated elimination of antigens by the hepatobiliary route. Polymeric IgA antibody mediates the transport of corresponding antigens, in the form of IgA immune complexes (IC), from the circulation into the bile, whereas monomeric IgA, IgG, and IgM are ineffective. Transport has been shown with dinitrophenyl albumin and bacterial polysaccharides such as pneumococcal SIII and C-substance. The process does not result in breakdown of the antigen, which can be detected in the bile in intact free and IgA-bound forms. Although IgG promotes clearance of antigen from the circulation mainly to the liver, only low levels of breakdown fragments are detectable in bile. In mice, the mechanism of IgA IC transport does not appear to involve Kupffer cells, the complement system, or the glycoprotein receptors on liver cells because attempts to block these systems failed to affect transport. The mechanism appears to be analogous to that for free IgA. Transport could be inhibited by antigen-nonspecific IgA, but not IgG or IgM. IgA IC were found in the bile but not in the saliva, milk, urine, or bronchial or intestinal washings. A similar pattern of appearance was seen when IgA alone was injected. Thus hepatobiliary transport appears to be the major pathway for the clearance of both IgA IC and free IgA from the circulation.

Uncultured adipose-derived regenerative cells (ADRCs) seeded in collagen scaffold improves dermal regeneration, enhancing early vascularization and structural organization following thermal burns. Advances in tissue engineering have yielded a range of both natural and synthetic skin substitutes for burn wound healing application. Long-term viability of tissue-engineered skin substitutes requires the formation and maturation of neo-vessels to optimize survival and biointegration after implantation. A number of studies have demonstrated the capacity of Adipose Derived Regenerative Cells (ADRCs) to promote angiogenesis and modulate inflammation. On this basis, it was hypothesized that adding ADRCs to a collagen-based matrix (CBM) (i.e. Integra) would enhance formation and maturation of well-organized wound tissue in the setting of acute thermal burns. The purpose of this study was to evaluate whether seeding uncultured ADRCs onto CBM would improve matrix properties and enhance healing of the grafted wound. Full thickness thermal burns were created on the backs of 8 Gottingen mini-swine. Two days post-injury wounds underwent fascial excision and animals were randomized to receive either Integra seeded with either uncultured ADRCs or control vehicle. Wound healing assessment was performed by digital wound imaging, histopathological and immunohistochemical analyses. In vitro analysis demonstrated that freshly isolated ADRCs adhered and propagated on the CBM. Histological scoring revealed accelerated maturation of wound bed tissue in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM. This was associated with a significant increase in depth of the wound bed tissue and collagen deposition (p<0.05). Blood vessel density in the wound bed was 50% to 69.6% greater in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM (p=0.05) at day 14 and 21. In addition, ADRCs delivered with CBM showed increased blood vessel lumen area and blood vessel maturation at day 21(p=0.05). Interestingly, vascularity and overall cellularity within the CBM were 50% and 45% greater in animals receiving ADRC loaded scaffolds compared to CBM alone (p<0.05). These data demonstrate that seeding uncultured ADRCs onto CBM dermal substitute enhances wound angiogenesis, blood vessel maturation and matrix remodeling.

The adoption of fertility control on Mykonos, 1879-1959: stopping, spacing or both? This abstract examines the timing and means of the fertility transition on the Greek island of Mykonos in the period 1879 to 1959. By combining the results of family reconstitution with oral evidence, an unusual insight into the pathways of the fertility transition of this island population is offered. The paper concludes by outlining a model of the adoption of fertility control, a model which sees the transition from high to low fertility as a transition from spacing to stopping, and from innovation of methods to innovation of ideas.

Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic. We compared clinical presentation, complications and outcome in patients with influenza A (H1N1) and seasonal influenza pneumonia. The group of patients with influenza A (H1N1) pneumonia consisted of 75 patients. 52 patients with pneumonia associated with seasonal influenza were included for comparison. Patients with pneumonia associated with novel H1N1 influenza were younger (mean age 39.7 yrs versus 69.6 yrs) and had fewer chronic comorbidities and less alcoholism. Infiltrates were more extensive and frequently interstitial. Respiratory failure was more frequent (those with an arterial oxygen tension/inspiratory oxygen fraction ratio <200 28% versus 12%, p = 0.042), leading to a higher rate of intensive care unit (ICU) admission and mechanical ventilation (29.3% versus 7.7% (p<0.0030) and 18.7% versus 2% (p<0.0045)). Mortality was twice as high in patients with novel H1N1 (12% versus 5.8%; p = 0.238), although this was not significant, and was attributable to pneumonia in most instances (77.8% versus 0%; p = 0.046). Younger age, fewer comorbidities, more extensive radiographic extension and more severe respiratory compromise, and ICU admissions are key features of the clinical presentation of patients with novel H1N1-associated pneumonia compared with seasonal influenza pneumonia.

[The use of verapamil in tests for determining the drug resistance of leukemic blasts]. To determine prognostically unfavourable groups of acute leukemia patients, the authors studied the in vitro accumulation of 3H-vincristine (Vcr) and adriamycin (ADR) as well as inclusion of 3H-cytosar (Ara-C) into marrow blast DNA from patients showing different effects of treatment. It was found resistant to induction chemotherapy increases with verapamil addition to culture medium (Vrp+ cells). ADR inclusion into Vrp+ cells was the same as that into Vrp- cells. The inclusion of 3H-Ara-C into S-phase cell DNA in the cells Vrp+ was 3 time that in the cells Vrp-. All the responders to cytosar treatment had Vrp- blasts. It is evident that evaluation of Vrp effect on 3H-Vcr accumulation under short-term culturing is able to indicate groups of patients with low probability of achieving complete remissions in response to standard regimens of Vcr, Ara-C and anthracyclines treatment.

Metastasis in vertebra mimicking acute compression fractures in a patient with osteoporosis: MRI findings. Elderly patients who have osteoporosis and a cancer history with backache and vertebral fractures are diagnostic challenges. We present a case of an 87-year-old man who complained of severe low-back pain with radiation to the lower limbs and weakness of the lower limbs. The patient had had a fall on a bus 1 month before admission. The patient also had a history of colon cancer and had received a colostomy 9 years before. In this admission, lumbar spine radiographs showed compressive fractures of vertebral bodies at L1 and L3. Magnetic resonance imaging (MRI) showed hyperemic change of the L3 marrow with osteonecrosis (fluid sign). The ventral thecal sac was slightly compressed due to retropulsion of L3. The L1 marrow was normal. Bone densitometry of the calcaneous revealed osteoporosis. The patient was then treated by vertebroplasty and bilateral foraminotomy of L3 after a diagnosis of acute compressive fracture. On histology, there was a metastatic adenocarcinoma arranged in glands and nests in the bone and paraspinal soft tissue. On retrospective viewing, an axial gadolinium-enhanced MRI revealed paraspinal extension of soft tissue at L3, which is highly suggestive of metastasis in a vertebra.

Spectroscopic study of cis-to-trans tunneling reaction of HCOOD in rare gas matrices. The higher energy conformer (cis) of HCOOD is prepared by vibrational excitation of the trans form. The cis conformer decays back to the conformational ground state (trans) via tunneling of deuterium. The tunneling process in HCOOD in rare gas matrices is extremely slow (in scale of weeks). We present new measurements of the tunneling rate constants, which characterize the efficiency of the cis-to-trans conversion process in Ne, Ar, Kr, and Xe matrices. The tunneling rates of HCOOD follow the trend k(Xe) approximately = k(Kr)>k(Ar) approximately = k(Ne), which is anomalous with respect to the reaction barrier of the solvated molecule. We propose a semiempirical energetic scheme of solid state solvation, which is consistent with all experimental observation. The temperature dependence of the tunneling constants rates of HCOOD is very weak compared to HCOOH in all matrices. The fundamental vibrational frequencies of the cis and trans conformers of HCOOD in various matrices are reported.

[Thymidine phosphorylase and angiogenesis]. Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). TP has an angiogenic activity and confers resistance to hypoxia-induced apoptosis on cells. TP expression is correlated with microvessel count, invasion and poor prognosis in many solid tumors. TPI, an inhibitor of TP, suppresses growth and metastasis of tumors by inhibiting the effect of TP.

The binding of a neutral aromatic molecule to a negatively-charged lipid membrane. I. Thermodynamics and mode of binding. This paper presents a detailed study of the binding of the fluorescent dye N-phenyl naphthylamine (NPN) to bilayers composed of the negatively-charged phospholipid methylphosphatidic acid. Binding to the liquid-crystalline membrane is enthalpy-driven. It is shown by determination of the binding constant and confirmed by n.m.r. that most of the dye ("guest") molecules reside between the lipid hydrocarbon chains at a fixed distance from the head-group, and are not distributed uniformly throughout the hydrocarbon phase. Each guest molecule is surrounded by about four lipid molecules. Transition of the membrane from the liquid-crystalline to the crystalline state results in almost total expulsion of the bound NPN into the water phase. Electrostatic theory is developed to find the effect of electrostatics upon the binding of a neutral molecule to charged membranes. Although the charge product is zero, electrostatic interactions play a part in determining the strength of binding, if each guest molecule incorporated increases the area of the membrane. For NPN this increase was found to be ca. 41 A(2).

Evidence for recombination between vaccine and wild-type mumps virus strains. Recombination of mumps virus (MuV) has rarely been reported. In this study, phylogenetic and recombination analyses were performed on 30 complete MuV genomes, including 17 vaccine and 13 wild-type strains. One potentially significant recombination event was found to have occurred between the lineage represented by the vaccine strain L3/Russia/Vector (AY508995) as the minor parent and wild MuV strain Drag94 (AY669145) as the major parent, and this led to a recombinant, 9218/Zg98 (EU370206), a wild-type MuV strain isolated from a 3-year-old boy with parotitis. In summary, we found a recombinant of MuV derived from vaccine and wild-type MuV strains.

Calcium, vitamin D supplements with or without alendronate and supragingival calculus formation in osteoporotic women: a preliminary study. Long-term calcium intake is related to the formation of urinary stones. Structure and composition of kidney and gallstones are similar to dental calculus. Saliva is the source of calcium for supragingival dental calculus formation. The aim of this preliminary study was to evaluate the possible effects of long-term calcium and vitamin D supplementation with or without alendronate administration on salivary electrolyte concentrations and supragingival calculus formation in osteoporotic women. Thirty-one female patients with osteoporosis for at least 3 years participated in this study. Eighteen women were taking calcium plus vitamin D plus alendronate, while 13 women were taking only calcium plus vitamin D supplements. Eleven systemically healthy women volunteered for the control group. Whole saliva samples were collected from all women before initiation of any periodontal intervention. Plaque index, probing depth, clinical attachment level, bleeding on probing, and calculus index were recorded at six sites/tooth. Salivary concentrations of ionic calcium, potassium, magnesium and sodium were determined by atomic absorption spectrophotometer. Results were evaluated statistically by non-parametric tests. No significant differences were found in clinical parameters or results of saliva analysis between the study groups (p > 0.05). Within the limits of this preliminary study, it is suggested that long-term calcium and vitamin D supplementation with or without alendronate does not appear to have a significant effect on supragingival calculus formation or saliva total calcium, potassium, magnesium and sodium concentrations. Larger-scale studies investigating the possible effects of various treatment modalities of osteoporosis on supragingival calculus formation are required to better clarify this issue.

Effects upon Radiant Intensity Measurements Due to Scattering by Optical Elements. Measurements to determine the radiance of one portion of a nonuniform source can be strongly influenced by radiation from other portions of the source scattered by the optical system used to transmit the radiation to the detector. Conditions under which such scattering is important and procedures to correct for it are discussed. An illustration is provided from measurements made on a nitrogen arc source.

Independent actions on cyclin-dependent kinases and aryl hydrocarbon receptor mediate the antiproliferative effects of indirubins. Indirubin, a bis-indole obtained from various natural sources, is responsible for the reported antileukemia activity of a Chinese Medicinal recipe, Danggui Longhui Wan. However, its molecular mechanism of action is still not well understood. In addition to inhibition of cyclin-dependent kinases and glycogen synthase kinase-3, indirubins have been reported to activate the aryl hydrocarbon receptor (AhR), a cotranscriptional factor. Here, we confirm the interaction of AhR and indirubin using a series of indirubin derivatives and show that their binding modes to AhR and to protein kinases are unrelated. As reported for other AhR ligands, binding of indirubins to AhR leads to its nuclear translocation. Furthermore, the apparent survival of AhR-/- and +/+ cells, as measured by the MTT assay, is equally sensitive to the kinase-inhibiting indirubins. Thus, the cytotoxic effects of indirubins are AhR-independent and more likely to be linked to protein kinase inhibition. In contrast, a dramatic cytostatic effect, as measured by actual cell counts and associated with a sharp G1 phase arrest, is induced by 1-methyl-indirubins, a subfamily of AhR-active but kinase-inactive indirubins. As shown for TCDD (dioxin), this effect appears to be mediated through the AhR-dependent expression of p27(KIP1). Altogether these results suggest that AhR activation, rather than kinase inhibition, is responsible for the cytostatic effects of some indirubins. In contrast, kinase inhibition, rather than AhR activation, represents the main mechanism underlying the cytotoxic properties of this class of promising antitumor molecules.

[Surgical treatment of major obesity by biliopancreatic bypass: our experience]. The Authors report their experience in the surgical management of morbid obesity. The efficacy of the bilio-pancreatic by-pass, method created by Nicola Scopinaro in the 1976, is underlined. From November 1988, 41 patients affected by morbid obesity were treated with this method. Results obtained are comparable to those reported in literature, with important weight loss and decrease of the cardiovascular risk-factors.

The effects of feedback on focal epileptic discharges in man. A preliminary report. The history of the control of epileptic disturbances by conditioning techniques is reviewed. The preliminary results of a three year trial of feedback techniques in 13 epileptic patients are presented. Thirteen epileptic patients (age 2.5 leads to 39 mean, 15.1 years) with lateralized focal discharges in the EEG were given repeated trials of feedback, the focal discharges being used to trigger auditory and somatosensory stimuli. Dosages and serum levels of medication were unchanged throughout the experimental period. The number of epileptic spikes per 15 seconds was assessed by automatic trend analysis during 20 to 30 minute control, biofeedback and post-feedback epochs. On-going EEG activity was quantified by 8 channel frequency analysis over 10 second epochs. The patients made efforts to increase and decrease the number of spike discharges with and without feedback and the results of both triggered and random auditory, somatosensory, photic and combined stimulation were compared at various intervals over a period of up to three years. A marked reduction in the number of focal discharges was noted in eight (61.5%) patients during and immediately following the sessions. Intermittent biofeedback sessions were not associated with a serial reduction in the number of focal EEG discharges. There was a reduction in the number of clinical epileptic disturbances in six patients (46%) and possible reasons for this improvement are discussed. One patient suffered an increase in focal temporal lobe discharges during triggered and random auditory stimulation whereas there was a marked reduction in the number of discharges during minimal electrical stimulation of the contralateral arm. The need for careful assessment of each patient to determine appropriate feedback stimulation is stressed. One aim of this research has been to assess the feasibility of using miniature units for continuous feedback of focal discharges in epileptic patients.

[The surface ECG in the diagnosis of cardiac arrhythmias: the value of the right precordial leads]. The surface electrocardiogram (ECG) is a simple noninvasive method to assess the electrical activity of the heart and provides important information to identify patients with cardiac arrhythmias and increased arrhythmic risk. This brief review highlights cardiac conditions in which the right precordial leads recorded on the surface ECG during sinus rhythm or tachycardia are of important diagnostic and prognostic value. Epsilon waves seen in the right precordial ST segments are the electrocardiographic hallmark of arrhythmogenic right ventricular cardiomyopathy. The diagnosis of Brugada syndrome and risk stratification of affected patients are based on a coved-type >or=2 mm ST-segment elevation in the right precordial leads. This typical ECG pattern may be present persistently, intermittently or only after administration of sodium-channel blockers. The early repolarization syndrome, most commonly seen in healthy young individuals, is characterized by a ST-segment elevation of 1 to 4 mm in the mid-precordial leads with a notched and elevated J point in lead V4. The precordial ECG T-wave repolarization pattern may be helpful in identifying the genotype in patients with suspected long QT syndrome. In patients with overt preexcitation, the surface leads V1 and V2 play a key role in localizing the site of bypass-tract insertion. Finally, the right precordial lead V1 is often crucial in the diagnosis of narrow and broad QRS-complex tachycardias.

Characteristic features of the heterologous functional synthesis in Escherichia coli of a 2[4Fe-4S] ferredoxin. Different strategies have been used to express synthetic genes all encoding Clostridium pasteurianum 2[4Fe-4S] ferredoxin (Fd) in Escherichia coli. The polypeptide can be produced as the C-terminal addition to a hybrid Cro::Protein A fusion protein lacking the metallic centers. The incorporation of the [4Fe-4S] clusters into the cleaved apoFd cannot be carried out in the same conditions as those affording holoFd from purified C. pasteurianum apoFd. In contrast, fully functional Fds can be produced from non-fused synthetic genes under the dependence of strong promoters. The yields of recombinant Fd, although sufficient to purify significant quantities of protein, are limited by the very short half-life of the 2[4Fe-4S] Fd in E. coli, irrespective of the expression system used. These features are characteristic of 2[4Fe-4S] Fds when compared with the far more stable recombinant rubredoxin, and probably other small iron-sulfur proteins which have already been produced in high yields. The reasons for the high turnover of 2[4Fe-4S] Fds are discussed.

Oxidative burden in prediabetic and diabetic individuals: evidence from plasma coenzyme Q(10). Individuals with diabetes and prediabetes are at risk of vascular injury. However, the exact mechanisms are unclear. The mitochondria mobile electron carrier coenzyme Q(10) (CoQ(10)) is a potent lipophilic antioxidant. We hypothesize that oxidative stress, detectable as changes in plasma CoQ(10) concentrations and composition, plays an important role in vascular disease in diabetes. We measured plasma CoQ(10) concentrations (including reduced ubiquinol and oxidized ubiquinone subfractions) in 60 subjects with normal glucose tolerance [NGT; fasting plasma glucose (FPG) < 5.5 mmol/l], 63 with impaired fasting glucose (IFG; FPG 5.6-6.9 mmol/l) and 69 with Type 2 diabetes (DM; FPG > 6.9 mmol/l). In men and women, the total CoQ(10)/total cholesterol ratio was reduced in DM (mean +/-sd) [male (M) 0.09 +/- 0.04; female (F) 0.07 +/- 0.04] compared with NGT (0.29 +/- 0.08; 0.21 +/- 0.07) and IFG (0.27 +/- 0.07; 0.23 +/- 0.07) (DM vs. NGT and IFG P = 0.001). A stepwise reduction in the plasma ubiquinol fraction (ubiquinol/total CoQ10) was observed from NGT (M 0.93 +/- 0.06; F 0.95 +/- 0.06) compared with IFG (0.43 +/- 0.25; 0.41 +/- 0.15) and DM (0.24 +/- 0.11; F 0.29 +/- 0.16) (DM vs. IFG vs. NGT P = 0.001). In contrast, the plasma ubiquinone/ubiquinol ratio increased from NGT (M 0.08 +/- 0.07, F 0.06 +/- 0.08) to IFG (2.14 +/- 1.84, 1.75 +/- 1.04) to DM (4.77 +/- 4.88, 3.81 +/- 3.71) (DM vs. IFG vs. NGT P = 0.001). These differences remained after adjusting for age, body mass index and FPG. The change in CoQ(10) with increasing FPG concentration suggests an increase in oxidative burden, already evident in the prediabetic IFG individuals. This increase in oxidative stress might contribute to the increased risk of vascular disease.

Factors affecting the effectiveness of biomedical document indexing and retrieval based on terminologies. The aim of this work is to evaluate a set of indexing and retrieval strategies based on the integration of several biomedical terminologies on the available TREC Genomics collections for an ad hoc information retrieval (IR) task. We propose a multi-terminology based concept extraction approach to selecting best concepts from free text by means of voting techniques. We instantiate this general approach on four terminologies (MeSH, SNOMED, ICD-10 and GO). We particularly focus on the effect of integrating terminologies into a biomedical IR process, and the utility of using voting techniques for combining the extracted concepts from each document in order to provide a list of unique concepts. Experimental studies conducted on the TREC Genomics collections show that our multi-terminology IR approach based on voting techniques are statistically significant compared to the baseline. For example, tested on the 2005 TREC Genomics collection, our multi-terminology based IR approach provides an improvement rate of +6.98% in terms of MAP (mean average precision) (p<0.05) compared to the baseline. In addition, our experimental results show that document expansion using preferred terms in combination with query expansion using terms from top ranked expanded documents improve the biomedical IR effectiveness. We have evaluated several voting models for combining concepts issued from multiple terminologies. Through this study, we presented many factors affecting the effectiveness of biomedical IR system including term weighting, query expansion, and document expansion models. The appropriate combination of those factors could be useful to improve the IR performance.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory. Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM.

Haematologists' approaches to the management of adolescents and young adults with acute leukaemia. Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.

Recognition sequence for the restriction endonuclease BglI from Bacillus globigii. Restriction endonuclease BglI recognizes the DNA sequence (Formula: see text) and cleaves each strand at the site indicated, thus generating 3' protruding ends. The recognition sequence was deduced by correlating mapping data with nucleotide sequence information and the position of cleavage was unambiguously determined by 32P labeling of 5' termini produced by BglI digestion.

Pediatric fluid resuscitation after thermal injury. Fluid resuscitation after thermal injury in a child or infant can pose a set of unique and significant challenges. Many approaches to fluid resuscitation of children after burns exist, and most are nonevidence based. This review will highlight the important concepts involved in pediatric fluid resuscitation from thermal injury.

Confidence in delegation and leadership of registered nurses in long-term-care hospitals. Effective delegation improves job satisfaction, responsibility, productivity and development. The ageing population demands more nurses in long-term-care hospitals. Delegation and leadership promote cooperation among nursing staff. However, little research describes nursing delegation and leadership style. We investigated the relationship between registered nurses' delegation confidence and leadership in Korean long-term-care hospitals. Our descriptive correlational design sampled 199 registered nurses from 13 long-term-care hospitals in Korea. Instruments were the Confidence and Intent to Delegate Scale and Multifactor Leadership Questionnaire. Confidence in delegation significantly aligned with current-unit clinical experience, length of total clinical-nursing experience, delegation-training experience and leadership. Transformational leadership was the most statistically significant factor influencing delegation confidence. When effective delegation integrates with efficient leadership, staff can deliver optimal care to long-term-care patients.

Studies on platinum-promoted sulfated zirconia alumina: effects of pretreatment environment and carrier gas on n-butane isomerization and benzene alkylation activities. A series of platinum-promoted sulfated zirconia alumina catalysts (SZA) with different amounts of platinum (0.5, 1, and 2 wt%) were synthesized. Two other catalysts were prepared by mechanically mixing different proportions of the Al-promoted sulfated zirconia with Pt/Al(2)O(3). The 650 degrees C calcined catalysts were characterized by N(2) adsorption/desorption (BET), TPR, and TPD analysis. Butane isomerization activity of the catalysts was studied at 270 degrees C, varying the pretreatment environment and carrier gases. Though the textural properties of the catalysts did not change significantly with platinum loading, the maximum surface area of 116 m(2)/g was exhibited by the catalyst with 1 wt% Pt loading. Under the studied reaction conditions, the air-pretreated catalysts (sulfated zirconia alumina (SZA) and platinated SZA) showed higher n-butane conversion than the N(2)-pretreated catalyst. However, nitrogen was a better carrier gas than H(2), CO(2) or air, and CO(2) and air deactivated the catalyst very fast. Unlike the platinated SZA catalysts, the mechanically mixed catalysts showed an induction phenomenon. A redox mechanism is suggested for butane isomerization over these catalysts. The catalyst SZA was also found to be active for alkylation of benzene with isopropanol, which gave 93% selectivity toward cumene.

Ent-Kaurane diterpenes from Annona glabra and their cytotoxic activities. A new ent-kaurane glycoside, annoglabasin H (1), and three known ent-kauranes, annoglabasin E (2), annoglabasin B (3), and 19-nor-ent-kaurent-4-ol-17-oic acid (4) were isolated from the fruits of Annona glabra. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D- and 2D-NMR spectroscopy, as well as by comparison with the NMR data reported in the literature. The cytotoxic activities of these compounds were evaluated on four human cancer cell lines, LU-1, MCF-7, SK-Mel2, and KB. Compound 1 exhibited significant cytotoxic activity on all tested human cancer cell lines with IC50 values ranging from 3.7 to 4.6 μM.

Polyclonal IgM anti-GM1 ganglioside antibody in patients with motor neuron disease and variants. Recent studies reported the presence of anti-ganglioside antibodies in occasional patients with motor neuron disease. We found polyclonal serum IgM anti-GM1 antibodies by an anti-GM1 enzyme-linked immunosorbent assay (ELISA) in 9 (19%) of 48 patients with motor neuron disease. A comparable frequency of IgM anti-GM1 antibodies was found in 4 (10%) of 40 sera from patients with other neurological disease. Three (17%) of 18 sera from the patients with motor neuron disease and 2 (17%) of 12 sera from patients with other neurological diseases had anti-GM1 immunostaining as shown by thin layer chromatography immunoblot. One patient with a lower motor neuron variant of motor neuron disease or motor axonopathy without multifocal conduction block had a markedly elevated polyclonal IgM anti-GM1 ELISA titer (greater than 1:64,000) with prominent immunostaining of GM1, moderate immunostaining of GM2, and weak and inconsistent immunostaining of GD1b by thin layer chromatography immunoblot. Treatment with prednisone resulted in clinical improvement despite increasing anti-GM1 antibody titers. These data indicate that patients with motor neuron disease have measurable levels of anti-ganglioside antibodies as frequently as patients with other neurological diseases. This contrasts with a small subgroup of patients with a lower motor neuron variant of motor neuron disease or motor axonopathy who have markedly elevated levels of serum anti-ganglioside antibodies and a clinical syndrome that is treatable with immunosuppression.

[A quantitative approach to sports training-adapted social determinants concerning sport]. Identifying and quantitatively analysing social determinants affecting disabled teenagers' inclusion/exclusion in high-performance sports. This was a descriptive cross-sectional study involving 19 12- to 19-year-old athletes suffering physical and sensory disability and 17 staff from the District Institute of Recreation and Sport. Likert-type rating scales were used, based on four analysis categories, i.e. social structure, socio-economic, educational and living condition determinants. Social inequity pervades the national paralympic sports' system. This is because 74 % of individuals only become recognised as sportspeople when they have obtained meritorious results in set competition without appropriate conditions having been previously provided by such paralympic sports institution to enable them to overcome structural and intermediate barriers. The social structure imposed on district-based paralympic sport stigmatises individuals regarding their individual abilities, affects their empowerment and freedom due to the discrimination experienced by disabled teenagers regarding their competitive achievements.

Acute infection with Sin Nombre hantavirus without pulmonary edema. Acute infection with Sin Nombre virus has been associated with development of hantavirus cardiopulmonary syndrome (HCPS), a severe cardiopulmonary illness with respiratory failure and shock. We present two cases of Sin Nombre hantavirus infections that did not lead to marked pulmonary complications in two otherwise healthy young adults from Utah and California. Sin Nombre virus causes a wider spectrum of disease severity than has been previously reported.

Neurocognitive biases and the patterns of spontaneous correlations in the human cortex. When the brain is 'at rest', spatiotemporal activity patterns emerge spontaneously, that is, in the absence of an overt task. However, what these patterns reveal about cortical function remains elusive. In this article, we put forward the hypothesis that the correlation patterns among these spontaneous fluctuations (SPs) reflect the profile of individual a priori cognitive biases, coded as synaptic efficacies in cortical networks. Thus, SPs offer a new means for mapping personal traits in both neurotypical and atypical cases. Three sets of observations and related empirical evidence provide support for this hypothesis. First, SPs correspond to activation patterns that occur during typical task performance. Second, individual differences in SPs reflect individual biases and abnormalities. Finally, SPs can be actively remodeled in a long-term manner by focused and intense cortical training.

Ab initio calculations and reduced density gradient analyses of the structure and energetics of hydrated calcium fluoride and calcium carbonate. We studied microhydrated calcium fluoride, calcium carbonate and their ions at the MP2/6-311++G** level of theory due to the lack of basic thermodynamic information about solvation of these salts and of systematic analyses of hydrogen bonding in their solvated species. Low-lying configurations were obtained through a molecular dynamics search involving stepwise hydration of the species of interest. The molecular dynamics employed a semiempirical Hamiltonian. The resulting configurations were then geometry-optimized at the MP2/6-311++G** level of theory and characterized as energy minima through vibrational analysis. We report a first estimate of the enthalpies of hydration at infinite dilution for calcium fluoride, calcium carbonate and their constituent anions. We also find that the dissociation processes of both hydrated calcium fluoride and calcium carbonate are endothermic processes. We analyze the interrelation of hydrogen bonding and van der Waals interactions in defining the structure of the first solvation shells of calcium fluoride, fluoride ion, calcium carbonate and carbonate ion by invoking geometric criteria, by calculations yielding critical points obtained from quantum theory of atoms in molecules (QTAIM) and by examination of reduced density gradient (RDG) surfaces. RDG surfaces reveal that water-water non-covalent interactions tend to destabilize the solvation shell, and are compensated for by cooperative hydrogen bonds.

Satellite and defective RNAs of Cryphonectria hypovirus 3-grand haven 2, a virus species in the family Hypoviridae with a single open reading frame. Cryphonectria parasitica hypovirus 3-Grand Haven 2 (CHV3-GH2) is the most recently characterized member of the Hypoviridae family of viruses associated with hypovirulence of the chestnut blight fungus. Isolates of CHV3-GH2 contain either three or four double-stranded (ds) RNAs that are visible on ethidium bromide-stained agarose or polyacrylamide gels. Only the largest dsRNA appears to be required for virus infectivity, and was characterized previously (C. D. Smart et al., 1999, Virology 265, 66-73). In this study, we report the cloning, sequencing, and analysis of the other three dsRNAs. Sizes of the accessory dsRNAs are 3.6 kb (dsRNA 2), 1.9 kb (dsRNA 3), and 0.9 kb (dsRNA 4), compared to 9.8 kb for the genomic dsRNA segment (dsRNA 1). All three accessory dsRNA species are polyadenylated on the 3'-end of one strand, as is genomic dsRNA. DsRNA 2 represents a defective form of dsRNA 1, with the 5'-terminal 1.4 kb derived from the 5'-end of dsRNA 1 and the 3'-terminal 2.2 kb from the 3'-end of dsRNA 1. A single major open reading frame (ORF) is evident from deduced translations of dsRNA 2. The deduced translation product is a 91-kDa protein that represents a fusion consisting of the entire N-terminal protease and the entire putative helicase domain. DsRNAs 3 and 4 represent satellite RNAs that share very little sequence with dsRNA 1 and 2. DsRNA 4 is 937 nucleotides, excluding the poly(A)(+). The first AUG of the polyadenylated strand of dsRNA 4 occurs eight residues in from the 5'-terminus and would initiate the largest ORF on dsRNA 4, with the coding capacity for a 9.4-kDa protein. Within the deduced ORF and approximately 100 nucleotides from the 5'-end of dsRNA 4 is a 22-base sequence that is identical to sequences found in the nontranslated leaders of dsRNAs 1 and 2. DsRNA 3 accumulation in infected cultures varied, but it was less abundant than dsRNA 4. DsRNA 3 was found to represent a head-to-tail dimer of dsRNA 4 linked by a poly(A)/(U) stretch of 40-70 residues.

Sleep habits in native Brazilian Terena children in the state of Mato Grosso do Sul, Brazil. Sleep habits in childhood vary in function of physiological factors. Cultural traits also influence sleep habits. This research evaluates sleep habits of Native Brazilian Terena children. The Terena group here studied live in the central region of Mato Grosso do Sul, Brazil, on the plains; they are peaceful and dedicated mainly to agriculture. Two villages were studied, Tereré and Córrego do Meio, both in Reservations. Sleep characteristics of 67 children (40M;27F), 2 to 10 year olds, were evaluated in interviews with their mothers. The results evidenced that cosleeping, in the same bed with family members is the standard Terena pattern present in every evaluated child. The presence of two or more beds and a mean of five or more people in each bedroom was the typical finding. The authors propose that cosleeping and the presence of numerous family members reflect the high values attributed to family links in the Terena culture.

Pharmacologic management of cancer pain. More than three quarters of cancer patients experience chronic pain during the course of their disease. With optimal pharmacotherapy alone, 70% to 90% could achieve adequate relief. Optimal pharmacotherapy begins with a comprehensive pain assessment, which defines the nature of the pain complaint and clarifies the degree to which pain and other factors contribute to impaired quality of life. Although the potential analgesic consequences of primary therapy are always considered, only radiotherapy is used commonly. Patients with persistent moderate to severe pain should be treated with an appropriate opioid regimen, which is based on careful selection of an opioid drug and route of administration, individualization of the dose through titration based on repeated assessment of the patient, and ongoing efforts to manage side effects. The use of adjuvant analgesics and the use of sequential opioid trials may improve the outcome of therapy for patients who fail to promptly attain a favorable balance between analgesia and side effects during an opioid trial.

Geographical variation in admissions due to poisoning in Sri Lanka: a time series analysis. To carry out time series analyses of hospital admissions for poisoning between 1995-2008 in all districts in Sri Lanka to identify trends and geographical variations in the substances used in poisoning. Data of hospital admissions from 1995-2008 due to poisoning were obtained from the Annual Health Bulletins published by the Ministry of Health. Data were converted to annual rates per 100,000 population. Time trends in the rates of suicide and self-poisoning were calculated using univariate time series analysis. All districts except Kilinochchi and Mullaitivu showed an increase in the rates of admissions due to poisoning with drugs, medicaments and biological substances. Colombo, Hambantota, Kalutara and Anuradhapura showed an exponential increase. Hambantota, Monaragala, Nuwara Eliya and Colombo show an increase in the rate of admissions after pesticide poisoning. All other districts showed a linear decrease. Admissions due to all types of poisoning showed a negative trend in Anuradhapura, Polonnaruwa, Ampara, Matale and Batticoloa districts. Other districts show a positive trend in the rate of admissions for all types of poisoning. Results should be viewed with caution because they are based on analysis of secondary data. Although the rate of suicides has reduced since 1995, admissions due to self poisoning have increased in almost all districts. While pesticide poisoning is becoming less, there is a gradual shift to the use of drugs and medicaments in self poisoning. Poisoning with drugs, medicaments and biological substances are increasing both in urban and rural areas.

Volatile anesthetics decrease calcium content of isolated myocytes. The calcium transient of myocytes was measured using a fluorescent dye, Fura-2. Caffeine, halothane, enflurane, and isoflurane increased the resting calcium level and decreased the calcium transient. The amount of caffeine-induced calcium release was suppressed if myocytes were pretreated with halothane. The amount of halothane-induced calcium release was suppressed if myocytes were pretreated with caffeine. Both halothane and caffeine were found to have similar effects on the sarcoplasmic reticulum (SR). The effect of 4 mM halothane (equivalent to 13.6% v/v) was approximately equivalent to that of 10 mM caffeine. Caffeine, halothane, enflurane, and isoflurane all decreased the total calcium content of myocytes by 10-70%. These data suggest that volatile anesthetics decrease the calcium content of the cardiac SR by increasing the calcium permeability of the SR, and that the mechanism of action of volatile anesthetics may be similar to certain actions of caffeine.

A versatile label-free electrochemical biosensor for circulating tumor DNA based on dual enzyme assisted multiple amplification strategy. A versatile label-free electrochemical biosensor based on dual enzyme assisted multiple amplification strategy was developed for ultrasensitive detection of circulating tumor DNA (ctDNA). The biosensor consists of a triple-helix molecular switch (THMS) as molecular recognition and signal transduction probe, ribonuclease HII (RNase HII) and terminal deoxynucleotidyl transferase (TdT) as dual enzyme assisted multiple amplification accelerator. The presence of target ctDNA could open THMS and trigger RNase HII-assisted homogenous target recycling amplification to produce substantial signal transduction probe (STP). The released STP hybridized with the capture probe immobilized on a gold electrode, then TdT and assistant probe were further employed to fulfill TdT-mediated cascade extension and generate stable DNA dendritic nanostructures. The electroactive methyl blue (MB) was finally used as the signal reporter to realize the multiple electrochemical amplification ctDNA detection as the amount of MB is positively correlated with the target ctDNA. Combined with the efficient recognition capacity of the designed THMS and the excellent multiple amplification ability of RNase HII and TdT, the constructed sensing platform could detect KRAS G12DM with a wide detection range from 0.01 fM to 1 pM, and the limit of detection as low as 2.4 aM. Besides, the platform is capable of detecting ctDNA in biological fluid such as plasma. More importantly, by substituting the loop of THMS with different sequences, this strategy could be conveniently expanded into the detection of other ctDNA, showing promising potential applications in clinical cancer screening and prognosis.

Palliative care research: methodological and ethical challenges. Nursing research in palliative care has, to date, been limited. As palliative care is increasingly recognized as a nursing specialty area, it requires the scientific foundation that research provides. Palliative care clients are particularly vulnerable because of the intensity of their illnesses and the emotional impact of impending death. This article identifies and discusses ethical and methodological challenges faced by those conducting research with this population. Suggestions for strategies that may help researchers meet these challenges are included.

HPLC quantification of kaempferol-3-O-gentiobioside in Cassia alata. Kaempferol-3-O-gentiobioside, the major flavonoid glycoside in Indonesian Cassia alata was quantified in various parts of the plant. The mature leaf was found to contain the highest content of this metabolite. A decrease of the flavonoid content in the juvenile leaf during the period of October through December was also observed. The contents ranged from 2.0 to 5.0% and 1.0 to 4.0% in mature and juvenile leaves, respectively. The other parts studied were flower (sepal and petal), rachis, stem and seed. Kaempferol-3-O-gentiobioside was not detected in the seed.

Stability of citrate, PVP, and PEG coated silver nanoparticles in ecotoxicology media. Silver nanoparticles (AgNPs) are present in the environment and a number of ecotoxicology studies have shown that AgNPs might be highly toxic. Nevertheless, there are little data on their stability in toxicology media. This is an important issue as such dynamic changes affect exposure dose and the nature of the toxicant studied and have a direct impact on all (eco)toxicology data. In this study, monodisperse citrate, PVP, and PEG coated AgNPs with a core size of approximately 10 nm were synthesized and characterized; their behavior was examined in standard OECD media used for Daphnia sp. acute and chronic tests (in the absence of Daphnia). Surface plasmon resonance, size, aggregation, and shape were monitored over 21 days, comparable to a chronic exposure period. Charge stabilized particles (citrate) were more unstable than sterically stabilized particles. Replacement of chloride in the media (due to concerns over chloride-silver interactions) with either nitrate or sulfate resulted in increased shape and dissolution changes. PVP-stabilized NPs in a 10-fold diluted OECD media (chloride present) were found to be the most stable, with only small losses in total concentration over 21 days, and no shape, aggregation, or dissolution changes observed and are recommended for exposure studies.

Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.

[The significance of erythrocyte fragment count to predicting hemolysis in roller pumps]. Hemolysis in blood pumps has been measured by various in vitro tests, in which normalized index of hemolysis (NIH) was established. As NIH is complicated and difficult to calculate, erythrocyte fragment count (EFC) is proposed in the present study to predict hemolysis in roller pumps. Five paired in vitro tests were conducted using the POLYSTAN pediatric pump (group A) and COBE pump (group B). Ten whole blood samples (400ml) were circled in the roller pump for 16 hours. Erythrocyte fragments count and plasma-free hemoglobin (FHb) were measured before pumping and every 2 hours through circulation after 4 hours pumping. The morphological changes of erythrocyte were observed by scanning electron microscope. Simple linear regression analysis showed the two groups' EFC and FHb levels increased linearly during a long period of pumping, and the coefficient of determination (R2) was 0.64. These data suggested that Erythrocyte fragments count could be used as an index in evaluating the in vitro hemolytic properties of blood pumps.

[Alcohol dependence syndrome and BDIM (before-discharge intervention method)--Report 3. The patients' self-reports about BDIM]. The purpose of this study is to identify how the effects of BDIM are evaluated by patients who were practiced BDIM. 153 patients were treated by the structured BDIM (Before-Discharge Intervention Method) program. Among them, 82 patients (53.6%) have attended self-help group meetings or maintained the therapeutic relationship (as outpatients or inpatients) in the 4 months' study period. To identify the maintenance of the effects of BDIM, we made our questionaire that consist of the patients' choice of answer and the patients' self-reporting. 76 of 82 patients answered our questionaire. After 76 patients discharged from hospital, 4 1/3 years have passed on the average. Their positive answers are as follows. (1) I became aware that my drinking had bad effect on my beloved family. (2) I became aware that my family have kept compassion, expectation and appreciation for me. Their message treated me and strengthened my self-esteem. In addition, I accepted the reality of my drinking problems. (3) I recognized all my family members want my abstinence and functional communication. (4) I was extremely impressed by my family members' tears. Their tears made me decide strong abstinence. (5) I was empowered by my family members. Through BDIM, I felt a sense of security, self-esteem and freedom. (6) I thought that BDIM was a good treatment program. And I thought that the application of letters is useful to recover the patients from alcohol dependence syndrome. Their negative answers are as follows. (1) I thought it was impossible for me to be abstinent. (2) I couldn't keep the motivation of abstinence. (3) I thought BDIM was a negative treatment method. Some findings of this study are as follows: First, the letters which was handed from family members to the patient were read again and again, also preserved with much care. Therefore we get know that BDIM is useful for the patient to get and remember some good memories of the family members for a long time. Second, BDIM is helpful for the patients to become aware of their own drinking problems and realize the necessity of recovery.

Quantum-optical coherence tomography with collinear entangled photons. Quantum-optical coherence tomography (QOCT) combines the principles of classical OCT with the correlation properties of entangled photon pairs [Phys. Rev. A 65, 053817 (2002)]. The standard QOCT configuration is based on the Hong-Ou-Mandel interferometer, which uses entangled photons propagating in separate interferometer arms. This noncollinear configuration imposes practical limitations, e.g., misalignment due to drift and low signal-to-noise. Here, we introduce and implement QOCT based on collinear entangled photons. It makes use of a two-photon Michelson interferometer and offers several advantages, such as simplicity, robustness, and adaptability.

Recommendations concerning the costing and management for patients requiring domiciliary ventilation. Reinstallation back in their own homes of severely disabled people who are ventilator dependent is increasingly becoming a viable trend. Such a development calls for detailed and imaginative planning and negotiations with several agencies. More than a decade of experience in Southport has highlighted the need for early and comprehensive negotiations to ensure that these profoundly disabled people are not denied a quality of life to which they are entitled and which advances in technology has made possible.

[Rheumatoid purpura and Berger's disease in the same patient. 2 cases]. The two patients reported experienced initially typical Henoch Schönlein purpura, and Berger disease some years later. Same cases are described in the literature pleading for the relationship between the two entities; Berger disease may be considered as a symptomatic form of anaphylactoïd purpura.

Epicardial adipose tissue as new cardio-metabolic risk marker and potential therapeutic target in the metabolic syndrome. Increased visceral adiposity, is an emerging cardiovascular risk factor. There is now a compelling need to quantify visceral adipose tissue not only for diagnostic purposes, but also for therapeutic interventions with weight reduction drugs or pharmaceuticals targeted to adipose tissue, as well as anti-obesity medications, thiazolidinediones, fibrates, angiotensin receptor blockers, highly active antiretroviral therapy and hormone replacement therapy. Among visceral adipose tissues, growing evidences suggest that cardiac adiposity may play an important role in the development of an unfavorable cardiovascular risk profile. Recent papers suggest that epicardial fat, index of cardiac and visceral adiposity, could locally modulate the morphology and function of the heart. The close anatomical relationship between epicardial adipose tissue and the adjacent myocardium should readily allow local paracrine interactions between these tissues. Echocardiography has been recently proposed for the direct assessment of epicardial adipose tissue. Echocardiographic assessment of epicardial fat may be a helpful tool not only for diagnostic purposes, as marker of visceral adiposity and inflammation, but also for therapeutic interventions with drugs that can modulate the adipose tissue. In this article, epicardial adipose tissue's structure, function, method of assessment and reliability as a diagnostic tool and potential therapeutic target is reviewed.

Pyrroloquinoline quinone attenuates iNOS gene expression in the injured spinal cord. Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. PQQ has been demonstrated to oxidize the redox modulatory site of N-methyl-d-aspartic acid (NMDA) receptors. Such agents are known to be neuroprotective in experimental stroke models. Therefore, we examined the possible ameliorating effect of PQQ on spinal cord injury (SCI) in adult rats. Intraperitoneal administration of PQQ effectively promoted the functional recovery of SCI rats after hemi-transection, which was preceded by the attenuation of the expression of inducible nitric oxide (NO) synthase (iNOS) mRNA in the injury site. NO is involved in the secondary detrimental mechanisms and has been implicated in NMDA receptor-mediated neurotoxicity. In fact, administration of PQQ induced significantly decreased lesion size and increased axon density adjoining the lesion area. These observations suggest that PQQ protects against the secondary damage by reducing iNOS expression following primary physical injury to the spinal cord.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study. The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 μg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 μg/mL (25·8-56·3) in the low-dose group, and 5·2 μg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 μg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 μg/mL (19·3-28·6) in the low-dose group, and 3·2 μg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.

Expression of mRNAs encoding oestrogen receptor (ER) alpha and ERbeta, androgen receptor and progesterone receptor during gonadal and follicular development in the marsupial brushtail possum (Trichosurus vulpecula). The objective of the present study was to determine which ovarian cells express mRNAs for oestrogen (ERalpha and ERbeta), androgen (AR) and progesterone (PR) receptors during ovarian and follicular development in the brushtail possum. Expression of ERalpha and/or ERbeta mRNA was observed from birth, initially in cells of the blastema, then in the medullary cords from Day 20. ERalpha was expressed in the oocytes and granulosa cells of secondary and antral follicles. Preovulatory follicles did not express ERalpha mRNA, although their oocytes were not examined for any gene. ERbeta mRNA was observed in oocytes at all follicular stages examined, but was not consistently observed in granulosa or theca cells. Expression of AR mRNA before Day 40 was very faint; thereafter, expression was observed in the medullary cords, peaking between Days 60 and 120. Oocytes, granulosa cells and theca of secondary and antral, but not preovulatory, follicles expressed AR mRNA. PR mRNA was expressed throughout the gonad by Day 20. Granulosa cells of some secondary and antral follicles and theca of antral follicles expressed PR mRNA. Thus, the expression of mRNAs encoding steroidogenic receptors in a time- and cell-specific manner supports a role for steroids in the process of ovarian follicular formation and growth.

New insights into the role of centrosomes in mammalian fertilization and implications for ART. In non-rodent mammalian species, including humans, the oocyte and sperm both contribute centrosomal components that are most important for successful fertilization. Centrosome pathologies in sperm and the oocyte can be causes for infertility which may be overcome by assisted reproductive technologies based on proper diagnosis of specific centrosomal pathologies. However, we do not yet fully understand the cell and molecular mechanisms underlying centrosome functions in germ cells and in the developing embryo, which calls for directed specific investigations to identify centrosome-related pathologies that include components in sperm, egg, or centrosome regulation within the fertilized oocyte. The present review highlights cellular and molecular aspects of centrosomes and centrosome-nuclear interactions focused on nuclear mitotic apparatus protein during fertilization and proposes future directions in expanding therapeutic approaches related to centrosome pathologies that may play a role in still unexplained causes of infertility.

Normal and neoplastic stem cells. Stem cells are cells that at the single cell level both self-renew and give rise to differentiated progeny. Self renewal is the property that distinguishes stem cells and progenitors, and in the blood-forming system explains why haematopoietic stem cells (HSCs), not progenitors, are the only cells capable of providing rapid and sustained regeneration of the blood-forming system after ablation by cancer chemo- and radiotherapies. Cancer-free prospectively purified HSCs regenerate the haematopoietic system of patients as rapidly as a marrow or mobilized blood transplant, but without the risk of re-seeding the body with cancer cells. Further, purified allogeneic HSCs can establish donor-specific tolerance to subsequent tissue grafts. However, in contrast to widely-publicized reports of HSC plasticity, we have not been able to show transdifferentiation of HSC to muscle, heart, brain or gut, and conclude that rare cell fusions and incomplete purifications are likely explanations for the other published results. The ability to self-renew is also potentially dangerous, as poorly regulated self renewal is, we believe, a central lesion in all cancers. We have recently shown that myeloid leukaemias in mouse and human are often driven by rare leukaemia (cancer) stem cells which are at the progenitor stage of differentiation, but have activated the self-renewing cell division pathway normally used only by HSCs. Similar cancer stem cells have been isolated in other tumours.

[Free amino acids in plasma and milk of mexican rural lactating women]. To determine the free amino acid pool in plasma and milk in Mexican rural lactating women. Twenty-eight women with an age 24 +/- 5.0 (+/- SD) years, weight 50 +/- 4.9 kg and height 148 +/- 4.8 cm were studied under metabolic balance conditions. Subjects were divided into five groups (three groups of lactation at 1st, 3rd and 6th month, one post-weaning group and a control group of non pregnant, non lactating women). Amino acid analyses of the diet and of plasma and milk samples were performed using an automated amino acid analyzer. Differences were observed between the lactation groups and the other groups: aspartate increased at the 6th month (p < 0.05) while leucine, valine and isoleucine declined in the 3rd month (p < 0.05). In milk, valine, proline and taurine decreased at 6 months (p < 0.05), while serine and threonine raised at 3 months. Plasma levels were > 4 fold greater than milk levels for branched chain amino acids and for the basic, aromatic and neutral amino acids. In contrast, glutamate was 40 fold higher in milk than plasma and it was the predominant amino acid in the free pool of milk. Our results suggest that the metabolic use of amino acids and the presence of specific amino acid transport systems during lactation, contribute to specific concentrations of free amino acids in milk that were not associated with the pool of free amino acids in plasma.

Solid-state anomalies in IR spectra of compounds of pharmaceutical interest. Solid-state anomalies in the IR spectra of lysine monohydrochloride, etoxadrol hydrochloride, thiamine hydrochloride, and L-histidine in a potassium bromide matrix were noted. With the first three compounds, the anomalies were due to metathetical exchange of the halide anion between the compound and the matrix. The anomaly seen with L-histidine was related to the crystal structure.

Can connectionist models of phonology assembly account for phonology? Connectionist models have gained considerable success as accounts of how printed words are named. Their success challenges the view of grapheme-to-phoneme correspondences (GPCs) as rules. By extension, however, this challenge is sometimes interpreted also as evidence against linguistic rules and variables. This inference tacitly assumes that the generalizations inherent in reading (specifically, GPCs) are similar in their scope to linguistic generalizations and that they are each reducible to token associations. I examine this assumption by comparing the scope of generalizations required for mapping graphemes to phonemes and several linguistic phonological generalizations. Marcus (1998b) distinguishes between two types of generalizations: those that fall within a model's training space and those that exceed it. The scope of generalizations is determined by the model's representational choices--specifically, the implementation of operations over mental variables. An analysis of GPCs suggests that such generalizations do not appeal to variables; hence, they may not exceed the training space. Likewise, certain phonological regularities, such as syllable phonotactic constraints and place assimilation, may be captured by an associative process. In contrast, other phonological processes appeal to variables; hence, such generalizations potentially exceed the training space. I discuss one such case, the obligatory contour principle. I demonstrate that speakers conform to this constraint and that their behavior is inexplicable by the statistical structure of the language. This analysis suggests that, unlike GPCs, phonological generalizations may exceed the training space. Thus, despite their success in modeling GPCs, eliminative connectionist models of phonology assembly may be unable to provide a complete account for phonology. To the extent that reading is subject to phonological constraints, its modeling may require implementing operations over variables.

Placement of metallic stents for treatment of postoperative biliary strictures: long-term outcome in 25 patients. This study was undertaken to evaluate the results of our 7-year experience with Gianturco-Rosch metallic stents, used for the management of postoperative biliary strictures. From January 1989 to April 1995, self-expanding Gianturco-Rosch metallic stents were placed in 25 patients with postoperative bile duct stenosis. All patients had a history of bile duct injury during cholecystectomy. Twenty-four patients had a conventional open cholecystectomy and one patient had a laparoscopic cholecystectomy. Eight patients had stenosis at the level of the common bile duct. The other 17 patients, who had undergone surgical repair of the bile duct, had a stricture at the level of the hepaticojejunostomy. These anastomotic strictures recurred after simple cholangioplasty. Patients were monitored for 9-84 months (mean, 55 months). Treatment was considered successful if the initial stenosis did not recur. Treatment was considered a failure if the initial stenosis recurred within the stent. Two patients had early complications: one had bile pleural effusion, treated with percutaneous drainage, and the other had arterial hemobilia, treated with embolization. Eighteen (72%) of 25 patients had no recurrence of the initial strictures. Among these patients, 11 had no further symptoms of biliary obstruction and seven, all with strictured hepaticojejunostomies, had recurrent episodes of cholangitis caused by secondary sclerosing cholangitis or intrahepatic stone formation. Seven (28%) of 25 patients had recurrence of the initial stenoses, causing repeated episodes of cholangitis. Among these seven patients, six had common bile duct stenoses and one had an anastomotic stricture. Recurrent biliary obstruction was treated surgically or with percutaneous methods, despite the presence of the metallic stent. Gianturco-Rosch stent placement should be considered in patients with postoperative bile duct stenoses in whom another operation is not indicated and cholangioplasty has failed. The results are better in patients who have hepaticojejunostomy strictures rather than common bile duct strictures. Overall, a long-term recurrence rate of cholangitis of more than 50% of patients was seen because of recurrence of the original stenosis or intrahepatic bile duct obstruction.

Endovascular management of pararenal aortic aneurysms with multiple overlapping uncovered stents. This study aims at evaluating the safety and efficacy of a porous stent system consisting of multiple overlapping uncovered stents in the treatment of complex aortic aneurysms with vital branches. Data of all patients with aortic aneurysms treated in our center with multiple overlapping uncovered stents between February 2010 and December 2011 were retrospectively reviewed. Preoperative characteristics, intraoperative details, and follow-up outcomes were documented. Technical success was defined as successful deployment of the stents to target locations without procedure-related complications. Clinical success was characterized by complete shrinkage or stabilization of the aneurysm, preservation of vital branches, and absence of major complications. Patients were grouped, according to rapidity of aneurysm thrombosis, into fast-thrombosis group (complete thrombosis of aneurysmal sac was achieved in ≤6 months) and a delayed-thrombosis group (>6 months required for complete thrombosis). Possible factors affecting the speed of thrombosis were analyzed statistically with the Fisher exact test and the t-test. This porous stent system was used to treat 34 patients (23 men, 11 women; mean age, 65.7 years). Technical success was achieved in all patients (100%). Regular follow-up over 6 months was achieved in 29 patients (mean length of follow-up, 11.4 months). Complete thrombosis of the aneurysm sac within 12 months was observed in 24 patients (83%). Aneurysm shrinkage was documented in seven patients (24%) and stabilization in 21 (72%). All branch arteries covered by bare stents stayed patent during follow-up. The overall clinical success rate reached 97% in the follow-up group. Risk factors for delayed thrombosis included fewer stents implanted (P = .013), longer sac entrance (P = .043), and use of antiplatelet medication (P = .040). An alternative method of management of complicated aortic aneurysm appears to be feasible using overlapping bare stents, which may prevent aneurysm growth while preserving vital branches. The short-term outcome of our study seems encouraging but is not sufficient to draw a robust conclusion. Further hemodynamic and clinical studies are warranted to evaluate long-term efficacy.

Intercalation of alcohols in Ag sulfonates: topotactic behavior despite flexible layers. This article presents the inaugural intercalation study of a layered metal sulfonate network. Silver triflate forms intercalation complexes with straight chain primary alcohols from ethanol (C(2)H(5)OH) to eicosanol (C(20)H(41)OH). Single-crystal data for the EtOH adduct, 1, are presented which show that the intercalation is coordinative to Ag. In contrast to many other layered hosts, no preheating of Ag triflate is required to liberate a coordination site for intercalation to take place, owing to the ability of the triflate ion to reorient. Crystal structure parameters for 1: C(4)H(6)F(6)S(2)O(7)Ag(2), a = 5.345(7) A, b = 11.310(2) A, c = 12.004(2) A, alpha = 116.87(1) degrees, beta = 90.46(1) degrees, gamma = 99.59(1) degrees, triclinic, space group P, Z = 2. Intercalate 1 presents the triflate ion in an unprecedented mu(5)-coordination mode. PXRD data on the family of complexes show that the intercalation is topotactic, as verified by the linear increase in d-spacing and calculated c-axis lengths for the intercalates, with increasing chain length. The data also show that the alcohol intercalates adopt an interdigitated rather than bilayer arrangement.

Calibration of piezoelectric positioning actuators using a reference voltage-to-displacement transducer based on quartz tuning forks. We use a piezoelectric quartz tuning fork to calibrate the displacement of ceramic piezoelectric scanners that are widely employed in scanning probe microscopy. We measure the static piezoelectric response of a quartz tuning fork and find it to be highly linear, nonhysteretic and with negligible creep. These performance characteristics, close to those of an ideal transducer, make quartz transducers superior to ceramic piezoelectric actuators. Furthermore, quartz actuators in the form of a tuning fork have the advantage of yielding static displacements comparable to those of local probe microscope scanners. We use the static displacement of a quartz tuning fork as a reference to calibrate the three axis displacement of a ceramic piezoelectric scanner. Although this calibration technique is a nontraceable method, it can be more versatile than using calibration grids because it enables characterization of the linear and nonlinear response of a piezoelectric scanner in a broad range of displacements, spanning from a fraction of a nanometer to hundreds of nanometers. In addition, the creep and the speed dependent piezoelectric response of ceramic scanners can be studied in detail.

Identification of Endocrine Disrupting Chemicals using a Virus-Based Colorimetric Sensor. A simple and portable colorimetric sensor based on M13 bacteriophage (phage) was devised to identify a class of endocrine disrupting chemicals, including benzene, phthalate, and chlorobenzene derivatives. Arrays of structurally and genetically modified M13 bacteriophage were fabricated so as to produce a biomimetic colorimetric sensor, and color changes in the phage arrays in response to several benzene derivatives were characterized. The sensor was also used to classify phthalate and chlorobenzene derivatives as representatives of endocrine disrupting chemicals. The characteristic color patterns obtained on exposure to various benzene derivatives enabled similar chemical structures in the vapor phase to be classified. Our sensing approach based on the use of a genetically surface modified M13 bacteriophage offers a promising platform for portable, simple environmental monitors that could be extended for use in numerous application areas, including food monitoring, security monitoring, explosive risk assessment, and point of care testing.

[Analgesic activity of derivatives of 7-amino-2,3-polymethylenindoles and their congeners]. Some N-trifluoromethylsulphonyl and N-trifluoroacetylderivatives of 7-amino-2,3-polymethyleneindoles and of 7-amino-3-propylindole [(I) - (XIII)] were prepared and tested, together with corresponding aniline derivates [(XIV) - (XIX)] and with N-trifluoromethylsulphonylcyclopentylamine (XX), against formic acid induced writhings in mice. With very few exceptions, at the oral dose of 0.167 mmole/kg, they proved from 2 to 3.4 times more active than acetanilide.

Alpha-skeletal actin is associated with increased contractility in the mouse heart. BALB/c mice express abnormally high levels of alpha-skeletal actin in the heart, which may be related to a duplication in the promoter of the alpha-cardiac actin gene. To evaluate the effects of overexpression of the alpha-skeletal actin isoform on cardiac contractile function, we studied these mice using the isolated perfused work-performing murine heart model and measured actin isoform expression in the same hearts. We quantified myocardial contractility from the maximum rate of contraction (+dP/dt) and time to peak pressure and relaxation from -dP/dt and time to half relaxation of left intraventricular pressure. Dot blots of total RNA hybridized against oligonucleotide sequences specific for either alpha-skeletal or alpha-cardiac actin mRNA showed that increased levels of alpha-skeletal actin RNA correlated significantly with increased contractility of hearts from the BALB/c mice (r = .80, n = 15, P < .001). The present study demonstrates a significant functional correlation between alpha-actin isoform content and cardiac contractile function and also that alpha-skeletal actin may promote an increased contractile function in the heart compared with alpha-cardiac actin.

Embryo cell wall properties in relation to development and desiccation in the recalcitrant-seeded Encephalartos natalensis (Zamiaceae) Dyer and Verdoorn. Plant cell walls are dynamic entities that may change with development, differ between plant species and tissue type and play an important role in responses to various stresses. In this regard, the present investigation employed immunocytochemistry to determine wall composition and possible changes during development of immature and mature embryos of the recalcitrant-seeded cycad Encephalartos natalensis. Fluorescent and gold markers, together with cryo-scanning and transmission electron microscopy (TEM) were also used to analyse potential changes in the cell walls of mature embryos upon desiccation. Immature cell walls were characterised by low- and high methyl-esterified epitopes of pectin, rhamnogalacturonan-associated arabinan, and the hemicellulose xyloglucan. Arabinogalactan protein recognised by the LM2 antibody, along with rhamnogalacturonan-associated galactan and the hemicellulose xylan, were not positively localised using immunological probes, suggesting that the cell walls of the embryo of E. natalensis do not possess these epitopes. Interestingly, mature embryos appeared to be identical to immature ones with respect to the cell wall components investigated, implying that these may not change during the protracted post-shedding embryogenesis of this species. Drying appeared to induce some degree of cell wall folding in mature embryos, although this was limited by the abundant amyloplasts, which filled the cytomatrical space. Folding, however, was correlated with relatively high levels of wall plasticisers typified by arabinose polymers. From the results of this study, it is proposed that the embryo cell walls of E. natalensis are constitutively prepared for the flexibility required during cell growth and expansion, which may also facilitate the moderate cell wall folding observed in mature embryos upon drying. This, together with the abundant occurrence of amyloplasts in the cytomatrix, may provide sufficient mechanical stabilisation if water is lost, even though the seeds of this species are highly desiccation-sensitive.

Integrating social science and design inquiry through interdisciplinary design charrettes: an approach to participatory community problem solving. Interdisciplinary collaborations that aim to facilitate meaningful community outcomes require both the right mix of disciplinary knowledge and effective community participation, which together can deepen collective knowledge and the capacity to take action. This article explores three interdisciplinary design charrettes, intensive participatory workshops that addressed specific community problems and provided a context for integrating design and social science inquiry with local community knowledge. Evaluation data from the charrettes shed light on how students from the design and social science disciplines experienced the charrettes, and on their interactions with community members. Key advantages to this interdisciplinary, community-based collaboration included expanded knowledge derived from the use of multiple modes of inquiry, particularly the resulting visualization tools that helped community members understand local issues and envision novel solutions. Key drawbacks included difficulties in balancing the two disciplines, the tendency for social scientists to feel out of place on designers' turf, and the increased disciplinary and interpersonal conflicts arising from a more diverse pool of participants.

Clustering of metabolic comorbidity in schizophrenia: a genetic contribution? People with schizophrenia are more likely to develop type 2 diabetes than the general population. Although an increased risk of diabetes has been attributed to environmental determinants such as diet, lifestyle and antipsychotic drugs, the association between these two disorders was noticed well before the advent of current lifestyles and pharmacological interventions, raising the possibility of a shared genetic basis. Schizophrenia and type 2 diabetes are common diseases with a complex mode of inheritance which includes both genetic factors and environmental determinants. As susceptibility genes for both type 2 diabetes and schizophrenia are beginning to be identified there is increasing interest in the possibility of shared susceptibility loci between the two conditions. This article reviews the genetic basis to schizophrenia and type 2 diabetes and discusses the potential for shared loci between both conditions.

Physico-chemical properties and biological effects of diesel and biomass particles. Diesel combustion and solid biomass burning are the major sources of ultrafine particles (UFP) in urbanized areas. Cardiovascular and pulmonary diseases, including lung cancer, are possible outcomes of combustion particles exposure, but differences in particles properties seem to influence their biological effects. Here the physico-chemical properties and biological effects of diesel and biomass particles, produced under controlled laboratory conditions, have been characterized. Diesel UFP were sampled from a Euro 4 light duty vehicle without DPF fuelled by commercial diesel and run over a chassis dyno. Biomass UFP were collected from a modern automatic 25 kW boiler propelled by prime quality spruce pellet. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of both diesel and biomass samples showed aggregates of soot particles, but in biomass samples ash particles were also present. Chemical characterization showed that metals and PAHs total content was higher in diesel samples compared to biomass ones. Human bronchial epithelial (HBEC3) cells were exposed to particles for up to 2 weeks. Changes in the expression of genes involved in xenobiotic metabolism were observed after exposure to both UFP already after 24 h. However, only diesel particles modulated the expression of genes involved in inflammation, oxidative stress and epithelial-to-mesenchymal transition (EMT), increased the release of inflammatory mediators and caused phenotypical alterations, mostly after two weeks of exposure. These results show that diesel UFP affected cellular processes involved in lung and cardiovascular diseases and cancer. Biomass particles exerted low biological activity compared to diesel UFP. This evidence emphasizes that the study of different emission sources contribution to ambient PM toxicity may have a fundamental role in the development of more effective strategies for air quality improvement.