Modulation of energy metabolism in c6 glioma cells as possible mechanism contributing to zinc neurotoxicity.
Elevated tissue levels of zinc (Zn) have been associated with neurodegenerative diseases such as global ischemia, seizure, and Alzheimer's. The mechanism of action of Zn in causing neuronal injury is not clear. One of the possible mechanisms is the ability of Zn to alter cellular energy metabolism. Using the C6 glioma cell as a model, the present study aimed to determined the effects of increasing concentrations of Zn on cellular energy states, as defined by the levels of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP), the total adenosine nucleotides (TAN) (TAN = ATP + ADP + AMP), and the energy charge potential (ECP = [ATP + 0.5 ADP]/TAN). Uptake of Zn was visualized by the appearance of N-(6-methoxy-8-quinolyl)-p-toluene sulfonamide (TSQ)-stained fluorescent granules after a 3-h exposure to Zn in the medium. At [Zn] = 1 mM, cells appeared apoptotic. Levels of ATP and TAN decreased as the level of Zn increased. The change mirrors the increase in cell death as determined by the trypan blue exclusion test. However, when the ratio of ATP:ADP:AMP within the TAN was calculated, the percentage of ATP in the TAN increased significantly, while that of AMP decreased. The change in the relative AMP level mirrored the change in cell viability as measured by the MTT assay, which indicated a decreased in mitochondrial activity. Cellular ECP increased significantly from 0.85 +/- 0.007 to 0.92 +/- 0.04. The elevated ECP and relative ATP level, together with a significant decrease in the relative AMP level, are all indicators of inhibition of cellular metabolism. These results support the notion that acute exposure of C6 glioma cells to a high concentration of Zn might initially result in a decrease in relative AMP and an inhibition of mitochondrial activity. However, the ultimate toxic action of Zn on the C6 glioma cells appears to be due to a gradual inhibition of energy utilization, leading to cell shrinkage and apoptosis.


Acetaldehyde involvement in positive and negative alcohol expectancies in han Chinese persons with alcoholism.
The ALDH2*2 allele has been shown to be a protective factor against alcoholism in a normal population owing in part to the elevated blood level of acetaldehyde and its accompanying physiological discomforts after drinking alcohol. Despite the well-established link between the ALDH2*2 allele and the physiological discomforts after drinking, very little is known regarding the psychological expectancies of drinking among persons with alcoholism with different ALDH genotypes. To determine whether there are differences in craving, alcohol consumption, and alcohol outcome expectancies between persons with alcoholism who have the ALDH2*1/*2 genotype and persons with alcoholism who have the ALDH2*1/*1 genotype. Cross-sectional survey. Six outpatient alcohol treatment facilities in Taiwan. Ninety-eight persons with alcoholism who met the DSM-IV criteria for current alcohol dependence. Alcohol Craving Scale, Form 90, and Alcohol Expectancies Scale scores. Overall, the ALDH2*1/*2 group had lower negative alcohol outcome expectancies (F(4,93) = 2.43, P < or = .05, eta(p)2 = 0.10). Specifically, they had fewer expected negative outcomes in the social or interpersonal domain (P < .05) and the emotional and physical domain (P < or = .005) than did the ALDH2*1/*1 group. Moreover, the ALDH2*1/*2 group had higher positive alcohol outcome expectancies (F(7,90) = 2.36, P < .05, eta(p)2 = 0.16), and they had more expected positive outcomes in the relaxation and tension reduction domain (P < .05). The 2 groups did not differ in alcohol craving (P = .61) or consumption (P = .11). Although the ALDH2*2 allele has been associated with negative physiological responses in normal samples in past research, the psychological expectancies of drinking are more positive and less negative for persons with alcoholism who have the ALDH2*1/*2 genotype. A role of acetaldehyde is implied in these effects, which seem to override the usual discomfort effects associated with protection against alcohol drinking. Future studies are needed to assess alcohol outcome expectancies at different phases of alcohol dependence and to evaluate the concurrent relationships of blood levels of acetaldehyde with physiological and psychological outcomes among persons with alcoholism who have different ALDH genotypes.


Anterior Combined Endopelvic (ACE) approach for the treatment of acetabular and pelvic ring fractures: A new proposal.
We present our experience of using the Anterior Combined Endopelvic (ACE) approach, which consists of a combination of a newly modified Stoppa approach with the lateral approach to the iliac crest. This approach is discussed in terms of fracture reduction and fixation, technical aspects, and the incidence of complications, and as an alternative to the ilioinguinal approach for the treatment of acetabular fractures. A consecutive group of 34 adult patients with acetabular fractures treated surgically with the ACE approach was compared with a group of 42 adult patients treated with the ilioinguinal approach between 2010 and 2013. Both approaches were performed by a single surgeon to fix the acetabular fractures with main anterior displacement and the anterior and lateral parts of the pelvis. All the patients were analysed with typical X-ray projections for acetabular fractures and CT-scan. Charts and radiographs were reviewed for fracture pattern. Operative time, blood loss, quality of reduction, functional outcomes and perioperative complications were compared between the two groups of patients. The mean follow-up of patients was 26 months (range 6-49 months), with a median of 24.5 months. The types of acetabular fraction in the study were as follows: 32 anterior and posterior columns, 18 anterior columns, 10 anterior columns with posterior hemitransverse, 10 transverse associated with posterior walls, two transverse; two T-Type transverse and two anterior walls. Average blood loss was 1090 mL in the ACE group and 1200 mL in the ilioinguinal group. Anatomic or satisfactory reduction was achieved in 94% of the acetabular fractures. Two patients (one in each group) had mild symptoms of the lateral femoral cutaneous nerve and improved within 4-6 months; one patient in the ilioinguinal group developed ossification Brooks grade III. The ACE approach for the treatment of acetabular fractures is highly recommended when the fracture involves the quadrilateral surface and anterior column. This approach provides a direct good-to-excellent visualisation and access to the entire fracture, which makes reduction and fixation easier. The clinical outcomes were slightly better with ACE compared with the ilioinguinal approach. Complication rate was similar in the two groups. The ACE technique is a viable alternative to the ilioinguinal approach when exposure of the anterior acetabulum is required.


Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D(28k)-deficient mice.
The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to glutamatergic neurotransmission and synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice, with the use of extracellular recordings in the ex vivo slice preparation. The amplitude of non-N-methyl-D-aspartate receptor (non-NMDAr)-mediated extracellular field excitatory postsynaptic potentials (fEPSPs) recorded in control medium was significantly greater in CaBP-deficient mice, whereas the afferent fiber volley was not affected. In contrast, the amplitude of NMDAr-mediated fEPSPs isolated in a magnesium-free medium after blockade of non-NMDAr and GABAergic receptors was significantly depressed in these animals. No alteration in the magnitude of paired-pulse facilitation was found, indicating that the presynaptic calcium mechanisms controlling glutamate release were not altered in CaBP-deficient mice. The magnitude and time course of the short-term potentiation (STP) of fEPSPs induced by a 30 Hz conditioning stimulation, which was blocked by the NMDAr antagonist 2-amino-5-phosphonovalerate acid (2-APV), was not impaired in the transgenic mice, whereas long-term potentiation (LTP) induced by a 100 Hz tetanus was not maintained. The long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 15 min) in the presence of the GABA antagonist bicuculline was not altered. These results argue for a contribution of CaBP to the mechanisms responsible for the maintenance of long-term synaptic potentiation, at least in part by modulating the activation of NMDA receptors.


Flexural resistance of Cerec CAD/CAM system ceramic blocks. Part 2: Outsourcing materials.
To test different Cerec CAD/CAM system ceramic blocks, comparing mean flexural strength (sigma), Weibull modulus (m), and Weibull characteristic strength (sigma0) in an ISO standardized set-up. Following the recent ISO Standard (ISO 6872:2008), 11 types of ceramic blocks were tested: IPS e.max CAD MO, IPS e.max CAD LT and IPS e.max CAD HT (lithium disilicate glass-ceramic); In-Ceram SPINELL, In-Ceram Alumina and In-Ceram Zirconia (glass-infiltrated materials); inCoris AL and In-Ceram AL (densely sintered alumina); In-Ceram YZ, IPS e.max Zir-CAD and inCoris ZI (densely sintered zirconia). Specimens were cut out from ceramic blocks, finished, crystallized/infiltrated/sintered, polished, and tested in a three-point bending test apparatus. Flexural strength, Weibull characteristic strength, and Weibull modulus were obtained. A statistically significant difference was found (P < 0.001) among lithium disilicate glass-ceramic (sigma = 272.6 +/- 376.8 MPa, m = 6.2 +/- 11.3, sigma0 = 294.0 +/- 394.1 MPa) and densely sintered alumina (sigma = 441.8 +/- 541.6 MPa, m = 11.9 +/- 19.0, sigma0 = 454.2 +/- 565.2 MPa). No statistically significant difference was found (P = 0.254) in glass infiltrated materials (sigma = 376.9 +/- 405.5 MPa, m = 7.5 +/- 11.5, sigma0 = 393.7 +/- 427.0 MPa). No statistically significant difference was found (P = 0.160) in densely sintered zirconia (sigma = 1,060.8 +/- 1,227.8 MPa, m = 5.8 +/- 7.4, sigma0 = 1,002.4 +/- 1,171.0 MPa). Not all the materials tested fulfilled the requirements for the clinical indications recommended by the manufacturer.


Assessing clinical generalizability in sedation studies of upper GI endoscopy.
Prior endoscopic studies evaluating conscious sedation have recruited only a small proportion of the patients actually approached. The generalizability of such results to an unselected adult ambulatory care population is thus questionable. The objectives of this study were to determine the characteristics of patients who refused inclusion in a randomized controlled trial of sedation and to compare these characteristics to those of patients who agreed to participate. Patients who refused participation in a randomized controlled trial of sedation completed standardized questionnaires addressing demographic data and possible confounding variables, and they also completed a validated anxiety questionnaire. Characteristics associated with refusal to participate in the randomized controlled trial were assessed by using uni- and multivariate analysis. Exploratory comparisons of outcomes between both groups included self-reported satisfaction with level of comfort and technical adequacy. Of 302 patients screened, 203 refused to participate in the randomized controlled trial. The most common reason for refusal was the request for no sedation (135/203). A total of 163 were enrolled in this synchronous study. Patients who refused to participate exhibited 3 distinguishing characteristics: prior treatment for an anxiety disorder (risk difference 9.4%: 95% CI[3%, 17%]), use of analgesic medication (risk difference 10.4%: 95% CI[2%, 19%]), and prior experience with EGD (risk difference 17.9: 95% CI[5%, 30%]). Only upper endoscopy experience was predictive of refusal to participate in the randomized controlled trial. No differences in outcomes existed between patients randomized to sedation and those refusing the randomized controlled trial who chose to receive sedative medication. Patients who refused participation in the randomized controlled trial and who underwent upper endoscopy without sedation were more satisfied than patients randomized to placebo (1.33 vs. 2.58; risk difference -1.25: 95% CI[-0.38, -2.1]). Moreover, the procedure in these patients was more adequate technically (4.86 vs. 4.18; risk difference 0.68: 95% CI[0.21, 1.13]). Characteristics of patients accepting and refusing randomization were highly similar, differing only with regard to upper endoscopy experience. An exploratory analysis of outcomes suggests that randomized controlled trial results may be biased in a direction that may underestimate the benefits of not administering sedative medication in a real-life setting.


Up-regulation of striatal adenosine A(2A) receptors in schizophrenia.
Adenosine A (2A) receptors have been implicated in the pathophysiology of schizophrenia by clinical, anatomical, biochemical and genetic studies. We hypothesized that a genetically determined low number of adenosine A (2A) receptors could be a vulnerability factor for the development of the disease. The density of adenosine A (2A) receptors was investigated in human postmortem striatum of patients with schizophrenia (n = 9) and matched controls ( n= 9) using [ H)CGS 21680 as a radioligand probe. The maximum number of binding sites (B) (max) was 70% higher in patients with schizophrenia than in matched controls (609.4 +/- 259.1 354.0 +/- 156.4 fmol/mg protein, p=0.04). No significant difference could be discerned for the affinity of caffeine for adenosine A receptors between patients and controls. The increase in receptor density correlated with the dose of antipsychotic medication in chlorpromazine equivalents (r =0.61, = 0.014). We failed to provide evidence for a genetically determined reduction of adenosine A 2(A) receptors in schizophrenia. Instead, consistent with findings from animal experiments, our observation supports a role of adenosine A (2A) receptors in the molecular effects of antipsychotic drugs.


[Appearance of proliferative activity in peritoneal macrophages cultured in vitro. Mitotic index values and percent frequency of frequency of mitosis phase].
In vitro culture of rat peritoneal macrophages, cells generally considered devoid of proliferative activity, was found to lead to the appearance of mitosis. Mitotic index and percent phase incidence values were determined for these cells.


Chronic bacterial infection models for BRM screening.
Models of chronic infections have been established to test the therapeutic and prophylactic potency of biological response modifiers (BRM). As an example for a BRM the immunostimulating drug Bestatin was tested. It is of dipeptide nature and was purified from culture supernatants of Streptomyces olivoreticuli. In two chronic bacterial infection models, induced by the inoculation of NRMI mice with Salmonella typhimurium or with a nephropathogenic strain of Escherichia coli, Bestatin acted prophylactically as well as therapeutically. This could be seen from the reduction of bacterial organ colonization and the inhibition of organ lesion formation. Bestatin could be shown to stimulate macrophage activity and to potentiate delayed type hypersensitivity, but not be effective on the humoral immune response.


Lessons to be learnt in managing the breech presentation at term: an 11-year single-centre retrospective study.
The 2000 publication of the Term Breech Trial significantly impacted obstetric practice in Australia with a rapid increase in delivery of term breech singletons by caesarean section. More reassuring data from European centres who continued to offer vaginal breech deliveries to carefully selected women have led to a softening of international guidelines which now support an individualised approach to management. The application of this principle to an Australian population, particularly in the wake of such a major change in obstetric practice, has not previously been demonstrated. To compare short-term neonatal and maternal morbidity for infants with a singleton breech presentation born after 37 weeks, according to planned mode of delivery. Eleven-year single-centre retrospective study with intention-to-treat analysis based on intended mode of delivery. Two hundred and forty-three of 766 (31.7%) eligible women elected for planned vaginal breech delivery. The overall success rate in this group was 58%. Morbidity rates were low and compare favourably with similar international studies. However, there was a nonsignificant trend towards higher rates of short-term serious neonatal and maternal morbidity in the planned vaginal delivery group (1.6 vs 0.4%, P = 0.08 and 8.2 vs 4.8%, P = 0.06, respectively). Attempted vaginal delivery for breech presentation remains an option in carefully selected women under strict obstetric protocols.


Transcriptional profiles of multiple genes in the anterior kidney of channel catfish vaccinated with an attenuated Aeromonas hydrophila.
A total of 22 uniquely expressed sequence tags (ESTs) were identified from channel catfish anterior kidney subtractive cDNA library at 12 h post vaccination with an attenuated Aeromonas hydrophila (AL09-71 N+R). Of the 22 ESTs, six were confirmed to be significantly (P < 0.05) induced by the vaccination. Of 88 channel catfish genes selected from literature, 14 were found to be significantly (P < 0.05) upregulated by the vaccination. The transcriptional levels of the total 20 genes induced by the vaccination were then compared to that induced by the virulent parent A. hydrophila (AL09-71) at different time points. At 3 h post vaccination (hpv) or infection (hpi), Na(+)/K(+) ATPase α subunit was upregulated the most. At 6 and 12 hpv or hpi, hepcidin and interleukin-1β were induced the highest. At 24 hpv or hpi, hepcidin was upregulated the most, followed by lysozyme c. At 48 hpi, lysozyme c and hepcidin were significantly induced. When vaccinated fish were challenged by AL09-71, relative percent of survival of vaccinated fish were 100% at 14 days post vaccination (dpv). Transcriptional levels of toll-like receptor 5 and hepcidin were significantly upregulated in vaccinated fish at 14 dpv. Taken together, our results suggest that vaccination with attenuated A. hydrophila mimics infection by live bacteria, inducing multiple immune genes in channel catfish.


Role of nitric oxide in a progressive neurodegeneration model of Parkinson's disease in the rat.
This study was undertaken to investigate the nitric oxide synthase (NOS) activity in the striatum following 6-hydroxydopamine (6-OHDA) induced neurodegeneration in rats. Constitutive NOS (cNOS) activity remained unaltered at 3, 7 and 14 days after lesion, while a 43% and 45% decrease was observed at 30 and 50 days, respectively. Inducible NOS (iNOS) activity was detected only on the 3rd day after lesion and not in subsequent days or the control striatum. N(G)-nitro-L-arginine methyl ester (L-NAME) pretreatment blocked the amphetamine-induced rotations and inhibited the iNOS activity at the 3rd day after the 6-OHDA injection. L-NAME pretreatment also significantly restored the striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in 6-OHDA treated rats. Thus a possible role of nitric oxide in 6-OHDA induced neurodegeneration is suggested.


[Urea content in the blood serum and fertility in cows].
The interrelation between dietary protein, total protein level and blood serum urea, and conception rate in cows has been studied in the course of two four-month periods on two dairy farms with a total of 150 test cows that were fed on varying rations. It has been demonstrated that the level of serum urea corresponded to the amount of protein in the diet (in percent of dry matter) and could be used in meeting the protein requirements of cows. The content of total protein has not proved to be a suitable index for the same purpose. A weak or moderate negative correlation (from r=-0.07 to r=0.43) has been found to exist between the amount of total protein and that of urea in the serum. The correlation method of Orlov - Dounyov has been used to determine the interrelation between the level of total protein and urea in the blood serum, on the one hand, and the total conception, the conception rate at first insemination, and the cases of anaphrodisia, on the other. It has been found that cows with urea levels closer to the Blowey values (optimal level of 25 mg%) show higher conception rate. The high content of protein in the rations, resp. of urea in the blood serum is an important factor in the etiology of anaphrodisia in cows. No such correlation has been established with regard to total protein.


Towards a comprehensive understanding of the chemical vapor deposition of titanium nitride using Ti(NMe2)4: a density functional theory approach.
A gas phase mechanistic investigation of the chemical vapor deposition (CVD) of titanium nitride (TiN) from the decomposition of Ti(NMe2)4, tetrakis(dimethylamido)titanium (TDMAT) as a single source precursor as well as from the reaction of Ti(NMe2)4 with NH3, i.e., the ammonia assisted mechanism is carried out and reported herein within the framework of density functional theory. Contrary to the theoretical result reported previously for a model TDMAT, metallacycle formation and β-H elimination pathways are found to be the major decomposition pathways responsible for the decomposition of TDMAT, and this finding is in accord with the experimental observation. Interestingly, agostic interaction is found to play a key role in promoting β-H elimination in the decomposition of TDMAT. A new additional pathway of decomposition of TDMAT has been identified theoretically in this present study. Exploration of the complex gas phase mechanism and thereby a detailed identification of the reaction intermediates enable us in realizing the origin of incorporation of carbon contamination in TiN films produced from TDMAT alone and then how the contamination is removed in the presence of ammonia. The ammonia assisted mechanism is found to proceed through the formation of a pre-equilibrium complex. The computed barrier height of 7.3 kcal mol(-1) for the initial transamination process associated with the Ti(NMe2)4 + NH3 reaction is found to be in very good agreement with the experimental activation energy. The total rate constant ktot for the ammonia assisted mechanism is calculated to be 1.28 × 10(-51) cm(3) molecule(-1) s(-1) at 298.15 K.


History of mercury use and environmental contamination at the Oak Ridge Y-12 Plant.
Between 1950 and 1963 approximately 11 million kilograms of mercury (Hg) were used at the Oak Ridge Y-12 National Security Complex (Y-12 NSC) for lithium isotope separation processes. About 3% of the Hg was lost to the air, soil and rock under facilities, and East Fork Poplar Creek (EFPC) which originates in the plant site. Smaller amounts of Hg were used at other Oak Ridge facilities with similar results. Although the primary Hg discharges from Y-12 NSC stopped in 1963, small amounts of Hg continue to be released into the creek from point sources and diffuse contaminated soil and groundwater sources within Y-12 NSC. Mercury concentration in EFPC has decreased 85% from ∼2000 ng/L in the 1980s. In general, methylmercury concentrations in water and in fish have not declined in response to improvements in water quality and exhibit trends of increasing concentration in some cases.


Controlled lumbar drainage in medically refractory increased intracranial pressure. A safe and effective treatment.
A prospective study of lumbar CSF drainage in the setting of raised intra-cranial pressure refractory to medical management and ventriculostomy placement is presented. There have been no controlled trials of its use reported in the literature, to the best of our knowledge. An IRB approved prospective study was conducted. 8 patients with increased intracranial pressure secondary to traumatic brain injury or aneurysm rupture were initially managed with sedation, ventriculostomy placement, mild hyperventilation (pCO2 = 30-35), and hyperosmolar therapy (Na = 150-155). A lumbar drain was placed if ICP continued to be above 20 mmHg despite optimization of medical therapy. After lumbar drain placement, ICP was reduced from a mean of 27 +/- 7.8 to 9 +/- 6.3, an average decrease of 18 mm H2O (p < 0.05). Requirements for hypertonic saline and/or mannitol boluses and sedation to control ICP were also decreased. There were no complications noted. We have shown that controlled lumbar drainage is a safe, efficacious and minimally invasive method for treatment of elevated ICP refractory to medical management. Ventriculostomies are always placed before utilizing lumbar drains to minimize the risk of cerebral herniation. We would advocate making controlled lumbar drainage a standard part of ICP control protocols.


Pyrrolopyrrole aza-BODIPY analogues: a facile synthesis and intense fluorescence.
Pyrrolopyrrole aza-BODIPY analogues were synthesized from diketopyrrolopyrrole and heteroaromatic amines in the presence of titanium tetrachloride. These novel compounds exhibit intense absorption in the visible region and strong emission with high fluorescence quantum yields greater than 0.8.


Severe bronchial synechia after removal of a long-standing bronchial foreign body: a case report to support control bronchoscopy.
The authors report the case of a child who had severe bronchial synechia of the left main bronchus after removal of a pistachio shell embedded in granulation tissue. Histology finding of the removed granulation tissue at initial bronchoscopy showed an Actinomyces bacterial invasion. It was decided not to treat this local contamination and to perform a control bronchoscopy to verify the disappearance of local bacterial invasion. The control bonchoscopy performed 4 weeks after the foreign body (FB) removal disclosed a large central left main bronchus synechia producing a 70% reduction of the lumen, although the child had become asymptomatic except for a slight residual cough. The resection of the synechia restored a normal bronchial lumen. The performance of a systematic control bronchoscopy after removal of long standing FB is discussed and recommended.


Mechanisms of food effects of structurally related antiarrhythmic drugs, disopyramide and bidisomide in the rat.
To determine whether the rat is a good animal model for the food effects observed with bidisomide but not with the structurally similar antiarrhythmic drug, disopyramide in man and to explore a reason for the differences in the food effects of these compounds. The following effects on the absorption of bidisomide and/or disopyramide were examined in the rat: Food effects, gastrointestinal transit time under fasting and nonfasting conditions, pH effects, hypertonic solution effect of NaCl and glucose, bile effects, permeability, inhibitory effects by Gly, Gly-Gly, Gly-Pro, glucose and mannitol and drug binding to food. Remarkable food effects were observed with bidisomide but not with disopyramide. There was no difference in the GI transit time with and without food. The pH effect with and without food was similar. Effect of salt concentrations on bidisomide and disopyramide was similar. There was no bile effect on absorption of both compounds. Binding of bidisomide and disopyramide to food was similarly low. The apparent permeability of bidisomide was much lower than disopyramide especially in the ileum and its absorption was more inhibited by Gly, Gly-Gly and Gly-Pro. In the rat, as previously seen in humans, the food effect was observed with bidisomide but not with disopyramide. This difference was in part due to both lower intestinal permeability of bidisomide compared to disopyramide and greater inhibition of absorption by the amino acid, Gly and the dipeptides, Gly-Gly and Gly-Pro.


Cognitive control in childhood-onset obsessive-compulsive disorder: a functional MRI study.
Failure to resist chronic obsessive-compulsive symptoms may denote an altered state of cognitive control. We searched for the cerebral regions engaged in this dysfunction. Differences in brain regional activity were examined by event-related functional magnetic regional imaging (fMRI) in a group of adolescents or young adults (n = 12) with childhood-onset obsessive-compulsive disorder (OCD), relative to healthy subjects. Subjects performed a conflict task involving the presentation of two consecutive and possibly conflicting prime and target numbers. Patients' image dataset was further analysed according to resistance or non-resistance to symptoms during the scans. Using volume correction based on a priori hypotheses, an exploratory analysis revealed that, within the prime-target repetition condition, the OCD subjects activated more than healthy subjects a subregion of the anterior cingulate gyrus and the left parietal lobe. Furthermore, compared with 'resistant' patients, the 'non-resistant' OCD subjects activated a bilateral network including the precuneus, pulvinar and paracentral lobules. Higher regional activations suggest an abnormal amplification process in OCD subjects during the discrimination of repetitive visual stimuli. The regional distribution of functional changes may vary with the patients' ability to resist obsessions.


Chronic Rapamycin Treatment Improved Metabolic Phenotype but Inhibited Adipose Tissue Browning in High-Fat Diet-Fed C57BL/6J Mice.
Rapamycin (Rap) has been demonstrated to affect lipid metabolism through stimulating lipolysis, inhibiting de novo lipogenesis and reducing adiposity. In the present study, we investigated rapamycin exposure's influence on adipose tissue browning in high-fat diet-induced fatty mice. Four-week old C57BL/6J mice were fed normal chow or high-fat diet for a period of 6 weeks and then divided into three groups: (1) Nor group: mice fed with normal chow; (2) high fat diet (HFD) group: fatty mice fed with high-fat diet; (3) Rap group: high-fat diet-fed fatty mice treated intragastrically with rapamycin at a dose of 2.5 mg/kg per day for 5 weeks. Body weights and food intakes of the mice were recorded weekly. At the end of the study, blood samples were collected for glucose, lipid and insulin evaluations. Adipose tissues were weighed and lipid contents were monitored. Moreover, real-time PCR and Western blotting were applied to detect the expression levels of beige and brown fat marker genes in white adipose tissue (WAT) and brown adipose tissue (BAT). Our data demonstrated that Rap exposure significantly ameliorated metabolic defects including hyperglycaemia, dyslipidaemia and insulin resistance in the fatty mice. Furthermore, Rap treatment led to decreased tissue weights and lipid contents both in WAT and BAT. Remarkably, expression levels of BAT marker genes including uncoupling protein-1 (UCP-1), cell death-inducing DNA fragmentation factor-alpha-like effector A (CIDEA), PR-domain containing protein-16 (PRDM16) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were significantly down-regulated in Rap-treated fatty mice. This report demonstrates Rap exposure is capable of inhibiting adipose tissue browning in high-fat diet-induced fatty mice, and provides evidence for deeper understanding of Rap's influence on lipid homeostasis.


The TIM-barrel fold: a versatile framework for efficient enzymes.
Recent studies on triosephosphate isomerase (TIM)-barrel enzymes highlight the remarkable versatility of the TIM-barrel scaffold. At least 15 distinct enzyme families use this framework to generate the appropriate active site geometry, always at the C-terminal end of the eight parallel beta-strands of the barrel. Sequence and structure comparisons now suggest that many of the TIM-barrel enzymes are evolutionarily related. Common structural properties of TIM-barrel enzymes are discussed.


Immunoperoxidase technique in diagnosis of oral pemphigus vulgaris: an alternative method to immunofluorescence.
Five cases of oral pemphigus vulgaris, diagnosed on the basis of clinical, histopathologic, and immunopathologic criteria, were selected. Sections were stained with the peroxidase antiperoxidase (PAP) technique of immunocytochemical staining. The findings correlated well with those reported by direct immunofluorescence demonstrating the same intercellular substance (ICS) pattern of staining. Because this staining technique is applied to routinely processed and paraffinized tissue, it may be of particular value to the oral pathologist who often receives formalin-fixed material before the need for immunopathologic studies is recognized. In addition, interpretation does not require specialized microscopy and tissue sections can be stored and retrieved for retrospective study.


Multiyear nutrient removal performance of three constructed wetlands intercepting tile drain flows from grazed pastures.
Subsurface tile drain flows can be a major s ource of nurient loss from agricultural landscapes. This study quantifies flows and nitrogen and phosphorus yields from tile drains at three intensively grazed dairy pasture sites over 3- to 5-yr periods and evaluates the capacity of constructed wetlands occupying 0.66 to 1.6% of the drained catchments too reduce nutrient loads. Continuous flow records are combined with automated flow-proportional sampling of nutrient concentrations to calculate tile drain nutrient yields and wetland mass removal rates. Annual drainage water yields rangedfrom 193 to 564 mm (16-51% of rainfall) at two rain-fed sites and from 827 to 853 mm (43-51% of rainfall + irrigation) at an irrigated site. Annually, the tile drains exported 14 to 109 kg ha(-1) of total N (TN), of which 58 to 90% was nitrate-N. Constructed wetlands intercepting these flows removed 30 to 369 gTN m(-2) (7-63%) of influent loadings annually. Seasonal percentage nitrate-N and TN removal were negatively associated with wetland N mass loadings. Wetland P removal was poor in all wetlands, with 12 to 115% more total P exported annually overall than received. Annually, the tile drains exported 0.12 to 1.38 kg ha of total P, of which 15 to 93% was dissolved reactive P. Additional measures are required to reduce these losses or provide supplementary P removal. Wetland N removal performance could be improved by modifying drainage systems to release flows more gradually and improving irrigation practices to reduce drainage losses.


Activation of protein kinase C by ganglioside GM3 in the presence of calcium and 12-O-tetradecanoylphorbol-13-acetate.
Ganglioside GM3 and 12-O-tetradecanoylphorbol-13-acetate activated protein kinase C as substitutes for phosphatidylserine and diacylglycerol. Hydrophobic gangliosides such as GM4 and GM3 were rather more potent activators of protein kinase C than hydrophilic ones such as GD1a and GT1b. Active tumor promoters such as teleocidin, mezerein, phorbol 12,13-acetate and phorbol 12,13-dibenzoate also activated protein kinase C, but not inactive tumor promoters such as phorbol and 4-alpha-phorbol 12,13-didecanoate.


The atypical 16p11.2 deletion: a not so atypical microdeletion syndrome?
One of the recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome (593 kb; ∼29.5 Mb to ∼30.1 Mb), associated with developmental delay, autism spectrum disorder, epilepsy, and obesity. Less frequently reported is a smaller 220 kb deletion, adjacent and distal to this 16p11.2 deletion, which has been referred to as the atypical 16p11.2 deletion (220 kb; ∼28.74 Mb to ∼28.95 Mb). We describe three patients with this deletion and update the manifestations in two sibs who have been described as possibly new entity in this Journal in 1997 [Bakker and Hennekam (1997); Am J Med Genet 70:312-314] and were recently found to have the "atypical 16p11.2 deletion" as well. Patients show a developmental delay, behavioral problems, and unusual facial morphology (prominent forehead, downslanted, and narrow palpebral fissures), and some are obese. We suggest that this "atypical" deletion may turn out to become a microdeletion syndrome that will be recognizable in the future, or at least to show a phenotype that is recognizable in retrospect. As it may no longer be so "atypical," we suggest renaming the entity "distal 16p11.2 deletion," to distinguish it from the common proximal 16p11.2 deletion.


RNA polymerase II CTD modifications: how many tales from a single tail.
Eukaryote's RNA polymerases II (RNAPII) have the feature to contain, at the carbossi-terminal region of their largest subunit Rpb1, a unique CTD domain. Rpb1-CTD is composed of an increasing number of repetitions of the Y1 S2 P3 T4 S5 P6 S7 heptad that goes in parallel with the developmental level of organisms. Because of its composition, the CTD domain has a huge structural plasticity; virtually all the residues can be subjected to post-translational modifications and the two prolines can either be in cis or trans conformations. In light of these features, it is reasonable to think that different specific nuances of CTD modification and interacting factors take place not only on different gene promoters but also during different stages of the transcription cycle and reasonably might have a role even if the polymerase is on or off the DNA template. Rpb1-CTD domain is involved not only in regulating transcriptional rates, but also in all co-transcriptional processes, such as pre-mRNA processing, splicing, cleavage, and export. Moreover, recent studies highlight a role of CTD in DNA replication and in maintenance of genomic stability and specific CTD-modifications have been related to different CTD functions. In this paper, we examine results from the most recent CTD-related literature and give an overview of the general function of Rpb1-CTD in transcription, transcription-related and non transcription-related processes in which it has been recently shown to be involved in.


Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis.
Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.


The influence of a transmembrane pH gradient on protonation probabilities of bacteriorhodopsin: the structural basis of the back-pressure effect.
Bacteriorhodopsin pumps protons across a membrane using the energy of light. The proton pumping is inhibited when the transmembrane proton gradient that the protein generates becomes larger than four pH units. This phenomenon is known as the back-pressure effect. Here, we investigate the structural basis of this effect by predicting the influence of a transmembrane pH gradient on the titration behavior of bacteriorhodopsin. For this purpose we introduce a method that accounts for a pH gradient in protonation probability calculations. The method considers that in a transmembrane protein, which is exposed to two different aqueous phases, each titratable residue is accessible for protons from one side of the membrane depending on its hydrogen-bond pattern. This method is applied to several ground-state structures of bacteriorhodopsin, which residues already present complicated titration behaviors in the absence of a proton gradient. Our calculations show that a pH gradient across the membrane influences in a non-trivial manner the protonation probabilities of six titratable residues which are known to participate in the proton transfer: D85, D96, D115, E194, E204, and the Schiff base. The residues connected to one side of the membrane are influenced by the pH on the other side because of their long-range electrostatic interactions within the protein. In particular, D115 senses the pH at the cytoplasmic side of the membrane and transmits this information to D85 and the Schiff base. We propose that the strong electrostatic interactions found between D85, D115, and the Schiff base as well as the interplay of their respective protonation states under the influence of a transmembrane pH gradient are responsible for the back-pressure effect on bacteriorhodopsin.


Combined use of repetitive task practice and an assistive robotic device in a patient with subacute stroke.
This case report describes a training program comprising repetitive task practice (RTP) and robotic therapy for a patient with subacute stroke and resultant impaired upper-extremity function. A 63-year-old man with right-sided hemiplegia resulting from a hemorrhagic stroke received a combined intervention of RTP and robotic therapy for 4 hours per day for 3 weeks. Clinical and kinetic evaluations were performed before and after intervention. Following the combined intervention, clinical improvements in hand function were observed, maximum grip force decreased slightly, and interlimb coupling decreased. An intervention of RTP with robotic therapy may be an effective method to improve upper-extremity function following stroke. Furthermore, the case suggests that improvements in strength are not necessary for improved dexterous function, provided that a minimal level of strength is present.


[State of the clotting and anticoagulant systems of the blood in children with cerebrovascular insufficiency of congenital etiology].
The author investigated the hemocoagulation system in 59 children with chronic cerebrovascular insufficiency caused by sequelae of natal inadequacy of the cervical division of the vertebral column and vertebral arteries. In children examined, pronounced thromboelastographic changes were noted. These changes pointed to a tendency to hypercoagulation combined with manifestations of hypocoagulation in the third phase of the blood clotting. This is an indication of activation of the secondary anticoagulation mechanism which plays a compensatory role in preventing intravascular thrombosis.


Synthesis and comparative assessment of a labeled RGD peptide bearing two different ⁹⁹mTc-tricarbonyl chelators for potential use as targeted radiopharmaceutical.
During the past decade radiolabeled RGD-peptides have been extensively studied to develop site-directed targeting vectors for integrins. Integrins are heterodimeric cell-surface adhesion receptors, which are upregulated in cancer cells and neovasculature during tumor angiogenesis and recognize the RGD aminoacid sequence. In the present study, we report the synthesis and development of two derivatives of the Nε-Lys derivatized cyclic Arg-Gly-Asp-D-Phe-Lys peptide, namely of cRGDfKHis and cRGDfK-CPA (CPA: 3-L-Cysteine Propionic Acid), radiolabeled via the [(99m)Tc(H(2)O)(3)(CO)(3)](+) metal aquaion at a high yield even at low concentrations of 10-5M (>87%) for cRGDfK-10-5M (>93%) for cRGDfK-CPA. Radiolabeled peptides were characterized with regard to their stability in saline, in His/Cys solutions, as well as in plasma, serum and tissue homogenates and were found to be practically stable. Internalization and efflux assays using αvβ3-receptor-positive MDA-MB 435 breast cancer cells showed a good percentage of quick internalization (29.1 ± 9.8% for (99m)Tc-HiscRGDfK and 37.0 ± 0.7% for (99m)Tc-CPA-cRGDfK at 15 min) and no retention of radioactivity for both derivatives. Their in vivo behavior was assessed in normal mice and pathological SCID mice bearing MDA-MB 435 ανβ3 positive breast tumors. Both presented fast blood clearance and elimination via both the urinary and hepatobiliary systems, with (99m)Tc-His-cRGDfK remaining for a longer time than (99m)Tc-CPA-cRGDfK in all organs examined. Tumor uptake 30 min pi was higher for (99m)Tc-CPAcRGDfK (4.2 ± 1.5% ID/g) than for (99m)Tc-His-cRGDfK (2.8 ± 1.5% ID/g). Dynamic scintigraphic studies showed that the tumor could be visualized better between 15 and 45 min pi for both radiolabeled compounds but low delineation occurred due to high abdominal background. It was finally noticed that the accumulated activity on the tumor site was depended on the size of the experimental tumor; the smaller the size, the higher was the radioactivity concentration.


[Spinal subarachnoid hemorrhage in a case of stenosis of the aorta (author's transl)].
A case of aortic coarctation was reported. This vascular malformation caused a dilatation of the vessels of the thoracic segment of the spinal cord, subarachnoid hemorrhage and paraplegia. These pathological alterations are due to cystic arachnoidal modifications.


[Transfection of human hepatic stimulator substance gene could protect BEL-7402 cells against hepatotoxins].
To investigate protective effects of hHSS transfection against CCl4 or H2O2. cDNA coding for hHSS was constructed into eukaryotic vector of pcDNA3.1 and transfected into BEL-7402 hepatoma cells. The expression of hHSS was analyzed with Northern blot. The growth of the hepatoma cells was remarkably enhanced 24 to 144h after hHSS gene transfection, which suggesting hHSS gene expression could stimulate cells activity. Meantime, incubation of both wild-type and vector-transfected as well as hHSS-transfected cells with CCl4 or H2O2 resulted in severe damage as marked by cell mortality and the rate of apoptosis. However, it appeared that the transfection of hHSS enabled the hepatoma cells to raise obvious resistance against CCl4 and H2O2 injury. Compared the vector cells to the vector-transfected cells, apoptosis ratio were (32.44+/-0.52)% and (25.60+/-0.66)% in which treated with CCl4, while (47.78+/-0.45)% and (37.40+/-0.69)% in which treated with H2O2, t value is 16.82 and 25.20, P<0.01. MAPK phosphorylation was also activated after HSS transfected. The function of hHSS gene expression could be related to proliferation of cell and protection against free radical damage.


Why neutrons and protons are modified inside nuclei.


Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers.
Genistein, an isoflavone and phytoestrogen predominantly found in soy, is considered a potentially safe therapeutic option to prevent postmenopausal bone loss. A novel purified product consisting of 99.4% synthetic genistein aglycone was investigated in a phase 1 clinical study to assess safety and tolerability in healthy volunteers as well as to obtain pharmacokinetic data. Single oral doses of 30, 60, 150, or 300 mg were administered to 40 healthy volunteers in this prospective, randomized, open-label and sequential-group study. Tolerability of the different genistein doses was very good. No clinically significant effects on vital signs, ECG, and clinical laboratory parameters were observed. Genistein was rapidly absorbed and the kinetic profiles revealed a one-peak plasma concentration-time course. Mean Cmax values of 252.0, 605.0, 1518.0, and 1808.0 ng/mL were observed after 4.0 to 6.0 hours. The mean terminal elimination half-lives were calculated to be 7.7, 7.5, 8.1, and 10.2 hours resulting in mean AUCs(0-infinity) of 2761.8, 8022.3, 21655.0, and 27537.8 ngxhr/mL. Linear regression of the dose-normalized AUCs(0-infinity) was not significantly different from zero, whereas the analysis for Cmax showed significance. Based on consecutive administration of single oral doses of genistein, dose linearity was assumed for extent of absorption [AUC(0-infinity)] for all doses (30-300 mg) and for rate of absorption (Cmax) up to 150 mg. At the highest dose the intestinal rate of absorption of genistein seemed to be limited. Genistein was safe and well tolerated in the dose range investigated and showed nearly dose-linear pharmacokinetic characteristics.


Poor repertoire General Movements predict some aspects of development outcome at 2 years in very preterm infants.
Observation of the quality of endogenously generated "General Movements" has been proved to be a reliable and sensitive tool in the assessment of fragile neonates. The absence of fidgety movements at 2-4 months post-term is highly predictive of Cerebral Palsy. On the contrary, the presence of a poor repertoire pattern during the writhing period is not reliable in predicting motor or neurobehavioral disorders at any stage of development. To examine if the presence of a PR pattern at 1 month post-term was associated with lower neurodevelopmental quotients at 2 years. General Movements evaluation at 1 and 3 months and the Griffiths Scales of Mental Development at 2 years were administered to a sample of very preterm infants. Infants were divided into two groups: poor repertoire pattern group and normal pattern group. Student's t Test and Chi squared test and ANOVA were used to compare neonatal variables and results between the two groups. 79 very preterm infants (birthweight≤1500 g or gestational age≤32 weeks), born January 2003 to December 2006 who had a follow-up at 2 years. Griffiths developmental quotient at 2 years. The Poor Repertoire group had lower Gestational Age, lower Birth Weight, lower Apgar scores at birth and lower Developmental Quotient at 2 years. Eye and Hand Coordination (subscale D) was the domain mostly responsible for such a difference. Quality of fidgety movements (normal or abnormal fidgety) at 3 months did not show any correlation with outcome measures at 2 years. The presence of a PR pattern at 1 month post-term seems to predict lower neurodevelopmental scores at 2 years especially in the domain of eye and hand coordination. Longer follow-up is necessary in order to ascertain if such difference will continue to persist at older ages.


A resorbable porous ceramic composite bone graft substitute in a rabbit metaphyseal defect model.
The success of converted corals as a bone graft substitute relies on a complex sequence of events of vascular ingrowth, differentiation of osteoprogenitor cells, bone remodeling and graft resorption occurring together with host bone ingrowth into and onto the porous coralline microstructure or voids left behind during resorption. This study examined the resorption rates and bone infiltration into a family of resorbable porous ceramic placed bilaterally in critical sized defects in the tibial metaphyseal-diaphyseal of rabbits. The ceramics are made resorbable by partially converting the calcium carbonate of corals to form a hydroxyapatite (HA) layer on all surfaces. Attempts have been made to control the resorption rate of the implant by varying the HA thickness. New bone was observed at the periosteal and endosteal cortices, which flowed into the centre of the defect supporting the osteoconductive nature of partially converted corals. The combination of an HA layer and calcium carbonate core provides a composite bone graft substitute for new tissue integration. The HA-calcium carbonate composite demonstrated an initial resorption of the inner calcium carbonate phase but the overall implant resorption and bone ingrowth behaviour did not differ with HA thickness.


An information technology infrastructure to enable evidence-based nursing practice.
The movement toward evidence-based practice (EBP) poses new organizational challenges to provide the necessary infrastructure to promote effective nursing interventions based on the best available evidence. The purpose of this article is to describe a collaborative effort between nursing and library services to provide readily accessible information at the bedside to support nurses using the best available evidence. In collaboration with nursing, the Health Services Librarian created an information resource titled "Research-based Nursing Practice: Finding the Evidence," which enables nursing staff to access the resources at the bedside without having to perform lengthy searches. Every known resource that will educate nurses in defining EBP to providing them with the links to Web sites, published articles, and all the information resources is included in the tool. Much has been written about building the organizational infrastructure to promote EBP and finding the filtered, synthesized research evidence, but to our knowledge, little has been published on building the information technology infrastructure, which will give nurses real-time access at the point-of-care to the research evidence. The research-based nursing practice system is helping bridge the gap between evidence-based resources and practice by compiling the literature in one place and making it easily and readily accessible.


New developments in selenium biochemistry: selenocysteine biosynthesis in eukaryotes and archaea.
We used comparative genomics and experimental analyses to show that (1) eukaryotes and archaea, which possess the selenocysteine (Sec) protein insertion machinery contain an enzyme, O-phosphoseryl-transfer RNA (tRNA) [Ser]Sec kinase (designated PSTK), which phosphorylates seryl-tRNA [Ser]Sec to form O-phosphoseryl-tRNA [Ser]Sec and (2) the Sec synthase (SecS) in mammals is a pyridoxal phosphate-containing protein previously described as the soluble liver antigen (SLA). SecS uses the product of PSTK, O-phosphoseryl-tRNA[Ser]Sec, and selenophosphate as substrates to generate selenocysteyl-tRNA [Ser]Sec. Sec could be synthesized on tRNA [Ser]Sec from selenide, adenosine triphosphate (ATP), and serine using tRNA[Ser]Sec, seryl-tRNA synthetase, PSTK, selenophosphate synthetase, and SecS. The enzyme that synthesizes monoselenophosphate is a previously identified selenoprotein, selenophosphate synthetase 2 (SPS2), whereas the previously identified mammalian selenophosphate synthetase 1 did not serve this function. Monoselenophosphate also served directly in the reaction replacing ATP, selenide, and SPS2, demonstrating that this compound was the active selenium donor. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that contain selenoproteins.


Relationship between cerebral activity and movement frequency of maximal finger tapping.
To examine the cerebral activity of the motor cortex during maximum movement, we measured regional cerebral blood flow (rCBF) in twelve normal volunteers, using near infrared spectroscopy (NIRS). Repetitive tapping of the right index finger was performed at 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 Hz, and during maximum effort (ME). The relative increase rate of rCBF during movement beginning with a resting condition was calculated for each movement condition. The left primary sensorimotor cortex showed significant activation during ME compared to the other frequencies. The rapid increase of rCBF was seen immediately after the initiation of finger tapping at all the tested frequencies but showed no increase following that. However, the rCBF during ME continued to increase until the end of the task. Change of the integrated electromyogram (iEMG) for the frequency and change of rCBF for the frequency at all the tested frequencies showed similar tendencies.


Structural homology of interferon-gamma with B-cell growth factor and its proliferative effect on long term B-cell lines.
In this study, we have demonstrated that recombinant human interferon-gamma (IFN-gamma) acts as a B cell growth factor (BCGF) for long term B cell lines. Immuno dot blot analysis with polyclonal goat antibody against homogenously purified 60K intracellular BCGF (IC-BCGF) was shown to recognize IFN-gamma and IFN-alpha. Out of three E. coli derived recombinant IFN-gamma molecules tested, two containing the complete C-terminal were reactive with antibody and also exhibited BCGF activity, while the third lacking 15 amino acids from C-terminal did not exhibit BCGF activity nor any reaction to anti-IC-BCGF antibodies in immuno dot blot analysis. The proliferative effect of IFN-gamma on long term B cells could be blocked by anti-IC-BCGF antibodies in a dose dependent manner. These results indicated that this BCGF activity may be a result of structural homology between BCGF and C-terminal peptide of IFN-gamma.


Cre Recombinase Gene Transfer In Vitro and Detection of loxP-Dependent Recombination.
INTRODUCTIONAltering the genome of intact cells and organisms by site-specific DNA recombination has become an important gene-transfer methodology. The inclusion of exogenous recombinase target sequences within transferred DNA segments allows subsequent modifications to previously altered genomic structure that increase the utility of gene transfer and enhance experimental design. In this protocol, correctly targeted mouse embryonic stem (ES) cell clones bearing the F[tkneo] allele (containing several loxP sites) are subjected to in vitro Cre gene transfer to generate ES cell subclones bearing either Type 1 (Δ) or Type 2 (F) alleles. Type 2 ES cells are used to generate chimeric mice that are then crossed to germ-line Cre-expressing mice, such as ZP3-Cre transgenic mates. The additional time needed to breed the mice (~2-3 mo) is typically less troublesome than the cost and effort of maintaining multiple clone-derived lines of mice.


Three-dimensional quantitative structure-activity relationship (CoMFA and CoMSIA) studies on galardin derivatives as gelatinase A (matrix metalloproteinase 2) inhibitors.
Three-dimensional quantitative structure-activity relationship models have been derived using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and molecule docking for the training sets of galardin-based matrix metalloproteinase inhibitors (MMPIs). The statistical values for the best models are significant. The models showed that the steric effect near the S1' pocket and hydrogen-bonding effect of the zinc binding group play key roles on the inhibitory activity of gelatinase A. The sets of the training and test proved the models were stable and predictive, and may have a good prediction for the inhibition activities of galardin derivatives as gelatinase A inhibitors. The results not only lead to a better understanding of the molecular mechanisms and structural requirements of gelatinase A inhibitors but also can help to design novel inhibitors against gelatinase A.


Mixed hyperplastic and adenomatous polyp arising from ectopic gastric mucosa of the duodenum.
We report an unusual case of a polyp arising from ectopic gastric mucosa in the duodenum. The polyp demonstrated both hyperplastic and adenomatous proliferation. Adenomatous proliferation in a duodenal polyp arising from ectopic gastric mucosa is, to our knowledge, unique. The areas of adenomatous change were morphologically indistinguishable from those of adenomatous polyps arising in the stomach; hence, the adenomatous change observed in this polyp was regarded as a neoplastic process.


A furnace design for XANES spectroscopy of silicate melts under controlled oxygen fugacities and temperatures to 1773 K.
A controlled-atmosphere furnace has been constructed for X-ray absorption spectroscopy experiments under imposed oxygen fugacities at temperatures up to 1773 K. The use of the furnace is demonstrated in a study of the oxidation state of Cr in a basaltic silicate melt (mid-ocean ridge basalt) by K-edge XANES spectroscopy. This is the first time the Cr(2+)/Cr(3+) ratio has been identified directly in an Fe-bearing melt. At typical terrestrial oxygen fugacities around half the Cr is present as Cr(2+), even though this oxidation state has never been identified in a terrestrial material and only Cr(3+) is observed after quenching to a glass. Cr(2+) oxidizes to Cr(3+) on cooling in the presence of Fe(3+) according to the electron exchange reaction Cr(2+) + Fe(3+) --> Cr(3+) + Fe(2+). This illustrates the importance of the in situ determination of metal oxidation states in melts.


Part 2. Distinguishing physical characteristics and management of brachial plexus injuries.
Brachial plexus injuries (BPI) are usually readily apparent at or shortly after birth. Failure of caregivers to recognize and appropriately treat BPI may contribute to the risk of life-long neuromuscular dysfunction for the infant and represents a serious medical-legal liability for the delivery provider. This article is the second in a series on BPI and provides a standard classification and a systematic guide to physical examination of the infant with suspected BPI. Conditions that mimic BPI are discussed along with diagnostic studies used to confirm this disorder. The natural history and predictors of outcome are presented along with a sample treatment protocol. Pictures and video clips are provided to enhance the reader's understanding of the consequences of this injury and the potential for improvement with surgical treatment. Useful Internet resources for parents, focused discharge planning, and guidelines for appropriate monitoring and follow-up are provided. Advantages of early referral and management by a multidisciplinary team at a brachial plexus specialty center are discussed.


"Endo" and "exo" bicyclo[4.2.0]-octadiene isomers from the electrocyclization of fully substituted tetraene models for SNF 4435C and D. control of stereochemistry by choice of a functionalized substituent.
[reaction: see text] A tandem electrocyclic closure, perceived as the key step in a biomimetic approach to SNF 4435C and D, was tested with 1,1,8-trisubstituted tetraene substrates. The ratio of endo:exo products could be controlled by the choice of the RZ substituent at C-1. On the basis of these results, a short stereoselective route to an advanced SNF 4435 intermediate was devised.


Prevention of esophageal thermal injury during radiofrequency ablation for atrial fibrillation.
Pulmonary vein isolation using radiofrequency ablation is an effective therapy in patients with atrial fibrillation. However, the esophagus descends in close proximity to the posterior wall of the left atrium and renders this structure susceptible to thermal injury. Esophageal ulceration has been hypothesized to be a precursor to left atrial-esophageal fistula, a procedural complication associated with poor prognosis. In this review, we have analyzed and summarized the published data regarding esophageal thermal injury during catheter ablation for atrial fibrillation and strategies to minimize risk of this complication. While esophageal temperature monitoring can be useful, multiple factors such as patient characteristics and specific strategies for radiofrequency energy delivery also merit consideration.


Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis.
This Phase II study was undertaken to assess the activity of methotrexate plus vinblastine in the treatment of patients with inoperable aggressive fibromatosis (AF) and to observe the evolution of the disease after such low-dose chemotherapy. Thirty patients with a median age of 27 years who were affected by primary (20%) or recurrent (80%), advanced, inoperable AF were treated with weekly methotrexate at a dose of 30 mg/m(2) plus vinblastine at a dose of 6 mg/m(2) for a median interval of 1 year. Patients with recurrent disease had received surgery, radiotherapy, tamoxifen, and antracycline-based chemotherapy. Tumor response was assessed in all patients as well as time to disease progression. Eighteen patients (60%) showed stable disease or minor tumor shrinkage along with symptom relief. A partial response was detected in 12 patients (40%). No complete responses were observed, and no patients had tumor progression during treatment. Four patients received fewer than 15 cycles of chemotherapy, mainly because of severe myelotoxicity. One of these patients died of local disease progression 33 months later, and the other three patients were stable. After a median follow-up of 75 months, the 10-year actuarial progression free interval is 67%. Methotrexate plus vinblastine given every 7-10 days for several months is associated with prolonged stable disease in a substantial subset of patients with advanced (inoperable) aggressive fibromatosis.


Systemic immunosuppressive therapy with oral Sirolimus after bare metal stent implantation: the missing alternative in the prevention of coronary restenosis after percutaneous coronary interventions.
In recent years, percutaneous coronary intervention (PCI) with drug eluting stents (DES) to treat de novo coronary lesions has been associated with a significant reduction of neointimal hyperplasia and in-stent restenosis. However, several publications raise concerns about long-term safety of DES, especially with the emerging anxiety with the problem of late stent thrombosis. Different registries with DES reported a growing incidence of stent thrombosis up to three years after stent implantation. In parallel with DES introduction in clinical practice in the last seven years, we identified six reported observational and randomized clinical experiences assessing the potential role of oral Sirolimus therapy in the prevention of coronary restenosis after bare metal stent implantation. Three observational and three randomized studies were performed during these years. Several implications were drawn: First, systemic therapy was given for only 14 days after PCI; minor transient side effects were observed in 25% of patients and were completely relieved after discontinuation of the drug. Secondly, angiographic restenosis and late loss are strongly related with Sirolimus blood concentration during the first week of treatment and were significantly reduced compared to non therapy. Finally, in the last randomized study, oral Sirolimus plus bare metal stent were cost saving compared to drug eluting stents with a trend to better clinical late outcome with the oral immunosuppressive therapy. The manuscript also reviews recent patents with new drugs, combination of drugs and DES designs which would improve safety and efficacy in the restenosis prevention after angioplasty.


Self-regulation and eudaimonic well-being across adulthood.
BACKGROUND/STUDY CONTEXT: The authors developed and tested a model to examine the developmental self-regulatory pathways that lead to optimal eudaimonic well-being across adulthood. Measures of goal adjustment, optimization, possible selves, and well-being were obtained from 590 adults ranging in age from 17 to 94. Structural equation modeling was used to determine the whether there were age-differential pathways among the developmental self-regulatory processes and well-being. The model predicts interactions among age, hoped-for possible selves, age-sensitive developmental processes (i.e., goal adjustment, optimization), and psychological well-being. Results showed direct effects of goal adjustment on well-being and indirect effects of goal adjustment and optimization on well-being through hoped-for possible selves. There were significant age differences in the indirect effects of goal adjustment on possible selves and well-being, such that, by age 55, these pathways disappear, and the role of future self-representations diminish. Findings indicate that the role of possible selves in regulating self-motivated development changes across the adult life span.


Effect of Polypeptides on Cell Proliferation and Apoptosis during Aging.
Polypeptide complexes derived from the bronchi, blood vessels, muscles, kidneys, ovaries, testes, and retina stimulated the processes of cell renewal in organotypic cultures of the corresponding organs of young and old animals. A correlation between the intensity of regeneration and animal' age was revealed. The polypeptide complexes reduced the expression of apoptotic factors p53 and caspase 3 and increased the expression of proliferation protein Ki-67. These results provide the basis for further study of the polypeptide complexes as stimulators of regenerative processes in different tissues during ageing.


Ultrasound of the shoulder.
Ultrasound of the shoulder is a powerful and accurate method for the examination of the rotator cuff, biceps mechanism and the synovium. This article describes the anatomy, standard examination technique, indications, pitfalls and potential errors. It lists suggested imaging algorithms for a range of shoulder pathology.


Heart valve replacement: which valve for which patient?
The ideal heart valve substitute would show no deterioration or thrombogenicity, offer no resistance to blood flow, and be easy to implant. However, such a valve does not exist and we must accept compromises in some of these qualities based on our patients' needs. In selection of cardiac valve prosthesis, valve-related factors such as durability, thrombogenicity, and fluid dynamics should be carefully matched to patient-related factors such as age, size, life expectancy, comorbidities, plans for pregnancy, and lifestyle. In addition, surgeon- or operation-related factors should be considered. Technical aspects of implantation, ease of reoperation, and operative mortalities may tip the risk and benefit balance in a particular direction. We review currently available heart valve prostheses and the clinical factors that are involved in selection of a heart valve substitute.


Lipids of Dietzia sp. A14101. Part II: A study of the dynamics of the release of surface active compounds by Dietzia sp. A14101 into the medium.
Dietzia sp. A14101 isolated from an oil reservoir model column was found to induce a strong decrease of the interfacial tension (IFT) in hydrocarbon-water mixtures in the presence of the intact bacterial cells (Kowalewski et al., 2005). The strain was shown to be able to degrade a wide range of hydrocarbon substrates (Bødtker et al., 2009). Further studies showed that the surface-active compounds tentatively identified as glycolipids were produced by Dietzia sp. A14101 on non- and water-immiscible -hydrocarbon substrates, Part I (Hvidsten et al., 2017). The results suggested that biosurfactant (BS) was a mixture of several isomers. The study presented here is aimed to investigate whether BS are secreted into the aqueous medium, and if so, then at which phase of the culture growth and in which amounts - the dynamics of the BS release in incubations on water-immiscible hydrocarbons. Two methods of BS extraction from the medium were attempted and compared: a liquid-liquid extraction (LLE) and precipitation by acid. For qualitative and semi-quantitative assessment, gas chromatography-mass spectrometry (GC/MS), thin-layer chromatography (TLC), liquid chromatography-mass spectrometry (LC-MS), surface tension measurements (SFT), emulsification (E24) and oil-spreading tests were employed. The results indicated that BS only partially were secreted into the medium. Detectable amounts of glycolipids in media were first identified during the exponential growth phase. However, only a slight decrease of SFT was observed in the cell-free medium. The emulsification index values of the sampled material were lower than those reported for related strains. The results suggested that most of the BS produced by Dietzia sp. A14101 remains cell-bound during the culture development in a batch mode and only a narrow range of the BS isomers can be detected in small amounts in media.


Characterization and differentiation of human embryonic stem cells.
Cell replacement therapies have been limited by the availability of sufficient quantities of cells for transplantation. Human ES (hES) cell lines have recently been generated by several laboratories. When maintained for over 1 year in vitro, they remain karyotypically and phenotypically stable and may therefore provide an excellent source material for cell therapies. Currently, data is available for 26 hES cell lines. Although limited characterization has been performed on most of these lines, there are remarkable similarities in expression of markers. hES cell lines derived in different laboratories show similar expression profiles of surface markers, including SSEA-4, Tra-1-60, and Tra-1-81. In addition, markers associated with pluripotent cells such as OCT-4 are expressed at in all cell lines tested. These cells express high levels of telomerase and appear to have indefinite growth potential. The generation of the large quantities of cells necessary for cell replacement therapies will require a cell population which is stable over long term culture. We have characterized the properties of multiple hES cell lines that have been maintained in culture for extended periods. Quantitative analyses demonstrate that all of the cell lines examined show consistent marker expression and retain a normal karyotype after long-term culture. hES cells have been differentiated into the derivatives of all three germ layers. Specifically this includes cardiomyocytes, neural cells, hepatocyte-like cells, endothelial cells and hematopoietic progenitor cells. These data demonstrating the karyotypic and phenotypic stability of hES cells and their extensive differentiative capacity indicate that they may be an appropriate source of cells for multiple regenerative medicine applications.


Alcohol consumption, risk of injury, and high-cost medical care.
This study examined the effect of alcohol use on the probabilities of injury, inpatient hospital stay, and emergency department visit. Data were obtained from a sample of adults (N = 1219) recruited from a Northern California county. Alcohol use measures included number of drinks, heavy drinking days, and an indicator variable for problem drinking. Models were estimated for men and women separately while controlling for confounders. Results indicate that most alcohol use measures were not significantly related to injury probability or medical care utilization. Among the exceptions, problem drinking was a significant positive predictor of any emergency department visit for both sexes. When drinkers during the past year were divided into light, moderate, and heavy drinking groups and compared to lifetime abstainers, all male drinkers had a higher probability of injury, and light and moderate female drinkers had a lower probability of an emergency department visit.


Improving pharmacy counselling skills: an interdisciplinary model of support for students with English as an additional language.
The pilot project, described in this paper, targeted English as an additional language (EAL) students to facilitate their development of patient counselling communication skills. An interdisciplinary content-based model was developed drawing on an interactional sociolinguistic framework to map language use valued in pharmacy counselling. Evaluation included analysis of successive self-assessments and surveys of students, surveys of teaching staff and final test results. Evaluation indicated that the interdisciplinary model was highly successful in improving EAL students' competency in pharmacy counselling. The model may have possible wider application for education in health professional programmes.


p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3.
Hepatitis C virus (HCV) NS3 protein is known to affect normal cellular functions, such as cell proliferation and cell death, and to be involved, either directly or indirectly, in HCV hepatocarcinogenesis. In this study, we demonstrated that NS3 protein could specifically repress the promoter activity of p21 in a dose-dependent manner. The effect was not cell type-specific and was synergistic when combined with HCV core protein. Repression of the p21 promoter by NS3 was almost completely lost when p53 binding sites present on the p21 promoter were removed. Furthermore, p53 binding sites were sufficient to confer a strong NS3 responsiveness to an heterologous promoter, suggesting that NS3 represses the transcription of p21 by modulating the activity of p53. Although the NS3 protein domain required for the majority of p21 repression was located on the protease domain, the proteinase activity itself does not seem to be necessary for repression. Both transcription and protein stability of p53 were unaffected by NS3, suggesting that NS3 might repress transcription of p21 by inhibiting the regulatory activity of p53 via protein-protein interaction(s). Finally, the growth rate of NS3-expressing cell lines was at least twice as fast as that of the parent NIH 3T3 cells, indicating that the repression of p21 is actually reflected by the stimulation of cell growth.


Headache coding and diagnostic-related groups: a survey of one year's admissions to a neurological department.
In 1995, the introduction of Diagnostic Related Groups (DRGs) within the Italian National Health Service (NHS) significantly changed the mode of payment for hospital admissions. The ICD-IX system is the fundamental instrument by which to identify various clinical entities; however, its codes still refer to an old international classification of diseases. Headache disorders are now diagnosed according to the new classification of the International Headache Society, and their recognition using ICD-IX codes appears to be increasingly inadequate. We evaluated 1-year admissions for "headache" in our Department of Neurology according to the new DRG system, and paid particular attention to the problems related to compilation of the patient discharge schedule. The most common mistakes affecting the definition of DRGs and the admission costs for the NHS were also examined.


Perspectives on replication-incompetent nasal influenza virus vaccines.
Influenza is an emerging as well as resurging contagious disease with a worldwide impact on public health. Although broad administration of the licensed influenza virus (IFV) vaccines has mitigated the disease in many countries over the years, there are intrinsic problems associated with them. The study under evaluation reports that a novel PB2-knockout nonreplicating nasal IFV vaccine has been generated with the capacity to confer protection of mice against live IFV challenges. Moreover, an exogenous gene expressed from the bioengineered PB2-knockout IFV could elicit an immune response against the exogenous protein, showing its potential to deliver transgenes as a vector. The risk-benefit ratio of this new influenza vaccine vector is discussed.


Evidence of age-related variation in plasma vasopressin of normotensive men.
The influence of age on plasma arginine vasopressin was examined in three groups of healthy men, 25 +/- 1 (n = 12), 40 (n = 23) and 50 years of age (n = 13), respectively. The three groups were comparable in body height, weight, blood pressure, heart rate, serum and urine osmolality, electrolytes and endogenous creatinine clearance. Compared to the 25-year olds, the 50-year old men had more than three times higher basal plasma vasopressin (7.8 +/- 1.4 vs. 2.5 +/- 0.6 ng/l, p less than 0.01), only one-third the plasma renin concentration (0.36 +/- 0.05 vs. 1.10 +/- 0.33 G.U. X 10(-4)/ml, p less than 0.01) and a significantly higher plasma noradrenaline (267 +/- 21 vs. 199 +/- 19 ng/l, p less than 0.05) while plasma adrenaline remained essentially unchanged. The 40-year olds had intermediate plasma vasopressin concentrations (4.2 +/- 0.6 ng/l). Thus, age is a variable with a substantial effect on plasma concentrations of vasopressin in addition to the well-known effect on renin and noradrenaline. Age must be taken into account in further clinical studies on vasopressin.


Nanobubbles and the nanobubble bridging capillary force.
Interactions between hydrophobic surfaces at nanometer separation distances in aqueous solutions are important in a number of biological and industrial processes. Force spectroscopy studies, most notably with the atomic force microscope and surface-force apparatus, have found the existence of a long range hydrophobic attractive force between hydrophobic surfaces in aqueous conditions that cannot be explained by classical colloidal science theories. Numerous mechanisms have been proposed for the hydrophobic force, but in many cases the force is an artifact due to the accumulation of submicroscopic bubbles at the liquid-hydrophobic solid interface, the so called nanobubbles. The coalescence of nanobubbles as hydrophobic surfaces approach forms a gaseous capillary bridge, and thus a capillary force. The existence of nanobubbles has been highly debated over the last 15 years. To date, experimental evidence is sound but a theoretical understanding is still lacking. It is the purpose of this review to bring together the many experimental results on nanobubbles and the resulting capillary force in order to clarify these phenomena. A review of pertinent nanobubble stability and formation theories is also presented.


The Focused Assessment With Sonography For Trauma (FAST) Examination And Pelvic Trauma: Indications And Limitations.
Pelvic trauma accounts for only 3% of all skeletal injuries but may have mortality as high as 45% in cases of severe trauma. Significant high-grade-mechanism trauma to the pelvis must always take the abdomen into consideration for evaluation. The focused assessment with sonography for trauma (FAST) examination has been shown to be a valuable tool in assessing the unstable trauma patient with blunt abdominal injury, though its diagnostic utility is much less well-defined than in primary pelvic trauma. This systematic review explores the utility and limitations of the FAST examination in patients with blunt pelvic trauma and discusses the timing for the examination during the trauma survey. Newer techniques for emergency department management of the unstable trauma patient are also addressed.


Association of vitamin D receptor gene polymorphism with susceptibility to Graves' disease in Eastern Croatian population: case-control study.
To evaluate the effect of vitamin D3 receptor (VDR) gene BsmI/ApaI/TaqI restriction fragment length polymorphisms on Graves' disease susceptibility in a subset of patients from Eastern Croatia. Graves' disease patients (n=110) and ethnically matched euthyroid controls (n=99) with no clinical evidence or family history of thyroid or autoimmune diseases were genotyped for VDR gene polymorphisms by BsmI/ApaI/TaqI endonuclease digestion after polymerase chain reaction amplification with sequence-specific primers. Data were analyzed by chi-square-test, and crude odds ratios (OR) with 95% confidence interval (95% CI) were calculated. The ApaI "AA" (14.5% vs 30.3%, patients vs controls, respectively, OR=0.39, 95% CI [0.2-0.77], P=0.01) and BsmI "BB" (7.3% vs 23.2%, OR=0.26 [0.11-0.61], P=0.002) genotypes were significantly underrepresented in patients, whereas ApaI "aa" (28.2% vs 9.1%, OR=3.92 [1.76-8.74], P=0.001) and TaqI "TT" (51.8% vs 31.3%, OR=2.36 [1.34-4.16], P=0.004) genotypes were significantly more frequent in patients than controls. The genotype combination, which conferred the strongest protection against Graves' disease, was "BBAAtt" (2.7% vs 17.2%, OR=0.14 [0.04-0.48], P=0.001). These findings suggest that VDR gene BsmI/ApaI/TaqI polymorphisms are associated with Graves' disease susceptibility in a subset of patients from Eastern Croatia. The ApaI and BsmI "AA" and "BB" genotypes, respectively, as well as combined "BBAAtt" genotype, appeared to confer protection against Graves' disease, whereas ApaI "aa" and TaqI "TT" genotypes were associated with an increased risk for Graves' disease. However, the true mechanisms of association remain to be elucidated.


Cardiorenal Syndrome in Acute Kidney Injury.
Varying degrees of cardiac and kidney dysfunction commonly are observed in hospitalized patients. As a demonstration of the significant interplay between the heart and kidneys, dysfunction or injury of one organ often contributes to dysfunction or injury of the other. The term cardiorenal syndrome (CRS) was proposed to describe this complex organ cross-talk. Type 3 CRS, also known as acute renocardiac syndrome, is a subtype of CRS that occurs when acute kidney injury contributes to or precipitates the development of acute cardiac dysfunction. Acute kidney injury may directly or indirectly produce acute cardiac dysfunction by way of volume overload, metabolic acidosis, electrolyte disorders such as hyperkalemia and hypocalcemia, and other mechanisms. In this review, we examine the definition, epidemiology, pathophysiology, and treatment options for CRS with an emphasis on type 3 CRS.


Recombinant perciform GnRH-R activates different signaling pathways in fish and mammalian heterologous cell lines.
Perciforms have three forms of gonadotropin-releasing hormone (GnRH) in their brain. All three GnRHs are potent secretogogues for luteinizing hormone (LH) from the pituitary. The pivotal role of GnRH-R-GnRH interactions in reproductive homeostasis is well established; however, there is a paucity of information on how a GnRH-R responds to the three endogenous GnRH forms in a perciform species. In this study, a recombinant pituitary GnRH-R from striped bass (stb) was expressed in a mammalian cell line (COS-7) and a fish cell line (CHSE-214). Activation of the signaling pathways was monitored by reporter gene (luciferase) based assays, which were specific for cAMP-PKA or Ca 2+/calmodulin kinase (activated via c-fos promoter) signaling pathways. The stbGnRH-R expressed in two different cell lines triggered different downstream signaling in response to the treatments with chicken (c) GnRH II. Interestingly, when endogenous GnRHs were used in combinations, the luciferase activity was significantly attenuated in transfected CHSE-214 cells.


The Effect of Elbow Extension on the Biomechanics of the Osseoligamentous Structures of the Forearm.
To investigate the hypothesis that elbow extension alters the biomechanics of forearm rotation including force transmission in the distal and proximal radioulnar joints (DRUJ and PRUJ) and the interosseous ligament (IOL). A cadaver model with a custom-designed jig was used to measure forearm pronosupination ranges, transmitted forces and contact areas across the PRUJ and DRUJ, and tension in the 3 main components of the IOL's central band. Testing with applied loads was undertaken throughout pronosupination with the elbow fully flexed (n = 15) and fully extended (n = 11). Elbow extension-flexion affected the range of forearm pronosupination, shifting the arc of rotation such that the forearm supinated maximally with the elbow flexed and pronated maximally with the elbow extended. Elbow extension also increased transmitted forces across the DRUJ and PRUJ while also increasing contact areas within the DRUJ and PRUJ. Elbow extension significantly increased tension in the central band of the IOL when the forearm was maximally pronated. Maximum supination occurred with the elbow flexed. Maximum pronation occurred with it extended. Elbow position altered forearm biomechanics, including force transmission across the PRUJ and DRUJ and transmitted tension in the IOL. The interplay of osseoligamentous forearm structures is such that we would anticipate surgical alteration of any one of them to have effects upon function of the others.


Novel method of preparing acellular cardiovascular grafts by decellularization with poly(ethylene glycol).
We have developed a new method of preparing acellular vascular grafts. Cellular components, including cell membranes and proteins in cytosol, were efficiently extracted from the vessels in a concentrated aqueous solution of poly(ethylene glycol), an amphiphilic biocompatible polymer. The residual DNA was digested by deoxyribonuclease I treatment after extraction with poly(ethylene glycol). The two-step extraction process proved quite effective at removing the cellular components while causing little damage to the extracellular matrices. We did not use any detergent that would damage the extracellular matrices. Therefore, vascular endothelial cells grew well on the acellular vessels after recellularization, promising longi-patent cardiovascular grafts.


Robust Longitudinal Ankle Edema Assessment Using Wearable Bioimpedance Spectroscopy.
We present a robust methodology for tracking ankle edema longitudinally based on bioimpedance spectroscopy (BIS). We designed a miniaturized BIS measurement system and employed a novel calibration method that enables accurate, high resolution measurements with substantially lower power consumption than conventional approaches. Using this state-of-the-art wearable BIS measurement system, we developed a differential measurement technique for robust assessment of ankle edema. This technique addresses many of the major challenges in longitudinal BIS-based edema assessment, including day-to-day variability in electrode placement, positional / postural variability, and inter-subject variability. We first evaluated the hardware in bench-top testing, and determined the error of the bioimpedance measurements to be 0.4Ω for the real components and 0.54Ω for the imaginary components with a resolution of 0.2Ω. We then validated the hardware and differential measurement technique in (1) an ex-vivo, fresh-frozen, cadaveric limb model, and (2) a cohort of 11 human subjects (8 healthy controls and 5 subjects with recently acquired acute unilateral ankle injury). The hardware design, with novel calibration methodology, and differential measurement technique, can potentially enable long- term quantification of ankle edema throughout the course of rehabilitation following acute ankle injuries. This could lead to better-informed decision making regarding readiness to return to activities and / or tailoring of rehabilitation activities to an individual's changing needs.


Search for infectious Epstein-Barr virus-releasing cell lines, with particular reference to a new producer line, NHAd-60.
In a search for infectious Epstein-Barr virus (EBV)-producer cell sources, 36 EBV genome-carrying lymphoblastoid cell lines originating from various sources in Japan were screened. Three cell lines derived from different sources were found to release infectious EBV into the culture fluid. EBV from these 3 lines possessed leucocyte-transformation activity but did not induce early antigen formation. One of the three lines, NHAd-60, originated from an adenoid tissue; it released a relatively large amount of infectious virus (10(2) to 10(3) of 50% of transforming dose of cord leucocytes). The NHAd-60 virus strain was further characterized. Cellular, virological, and immunological properties were described and discussed, and compared with EBV from known producer cell lines.


Criterion validity and inter-rater reliability of a palliative care screening tool for patients admitted to an emergency department intensive care unit.
The use of palliative care (PC) screening criteria to trigger PC consultations may optimize the utilization of PC services, improve patient comfort, and reduce invasive and futile end-of-life care. The aim of the present study was to assess the criterion validity and inter-rater reliability of a PC screening tool for patients admitted to an emergency department intensive care unit (ED-ICU). Observational retrospective study evaluating PC screening criteria based on the presence of advanced diagnosis and the use of two "surprise questions" (traditional and modified). Patients were classified at ED-ICU admission in four categories according to the proposed algorithm.ResultA total of 510 patients were included in the analysis. From these, 337 (66.1%) were category 1, 0 (0.0%) category 2, 63 (12.4%) category 3, and 110 (21.6%) category 4. Severity of illness (Simplified Acute Physiology Score III score and mechanical ventilation), mortality (ED-ICU and intrahospital), and PC-related measures (order for a PC consultation, time between admission and PC consultation, and transfer to a PC bed) were significantly different across groups, more evidently between categories 4 and 1. Category 3 patients presented similar outcomes to patients in category 1 for severity of illness and mortality. However, category 3 patients had a PC consultation ordered more frequently than did category 1 patients. The screening criteria were assessed by two independent raters (n = 100), and a substantial interrater reliability was found, with 80% of agreement and a kappa coefficient of 0.75 (95% confidence interval = 0.62, 0.88).Significance of resultsThis study is the first step toward the implementation of a PC screening tool in the ED-ICU. The tool was able to discriminate three groups of patients within a spectrum of increasing severity of illness, risk of death, and PC needs, presenting substantial inter-rater reliability. Future research should investigate the implementation of these screening criteria into routine practice of an ED-ICU.


Quality of Dried Bacillus NP5 and its Effect on Growth Performance of Tilapia (Oreochromis niloticus).
The main things that need to be considered in the preparation of probiotics are viability during preparation and storage which are the disadvantages of the use of fresh culture probiotics. Dried probiotic can be applied through the feed, easy to be applied and has a long shelf life but application of dried probiotic in aquaculture is still not widely studied. This study aimed to evaluate the quality of dried Bacillus NP5 as the probiotic through in vitro assays and determine the best dose for the growth performance of tilapia. The treatment of in vitro assays including the production of dried probiotic without using of the coating material and dried by spray drying method (NS); freeze drying method (NF); with using of the coating material and dried by spray drying method (WS); freeze drying method (WF). The treatment which showed the best result at in vitro assays was applied for in vivo assays. The in vivo assays containing 4 treatments and 5 replicates which were control (K) and the administration of dried Bacillus NP5 Rf(R) (10(10) CFU g(-1)) in feed with dose of 0.5% (A), 1% (B) and 2% (C). The fish fed 3 times a day by at satiation for 28 days. Probiotic that encapsulated by maltodextrin and dried by spray drying method that stored in room temperature had the higher percentage product, viability after drying process and storage. The administration of 0.5% dried Bacillus NP5 showed the best growth performance in tilapia.


[Histochemical characterization and functional significance of the epidermal gland cells in some invertebrates in phylogenetic aspect].
This paper reviews the basic results of findings on the structure and function of the epidermal gland cells in some invertebrates of different levels of organization. These data are compared with the results on the higher animals. Histochemical affinities of the epidermal gland cells in different animals are considered. The presence of the universal (ancient) cell types also found in mammals and in human is suggested. Marine invertebrate groups considered in this paper are characterized by a presence of a simple ciliated surface epithelium which fulfills different functions: locomotor, secretory, receptor, barrier, protective and absorption. In the process of phylogenesis, the epidermis of chordates underwent structural changes and intensification of protective function took place with the appearance of new protective mechanisms. The conclusion is done that the evolutionary development of surface epithelium is determined by its adaptation to environmental conditions and by the level of general organization; it followed the direction of intensification of protective function with the help of different mechanisms - mucus production, increase of cell layers number, intensive formation of cytoplasmic filaments, appearance of special protective structures in the form of cuticle or corneous layer.


The neural correlates of visual mental imagery: an ongoing debate.
The functional mechanisms and the neural correlates of visual mental imagery (the faculty whereby we can use our "mind's eye" to visualize objects in their absence) are at the centre of a lively debate in cognitive neuroscience. Neurocognitive models have proposed a functional equivalence between visual perception and visual mental imagery, which would be subserved by common neural substrates, such as the retinotopic areas in the occipital lobe. However, brain-damaged patients may demonstrate either impaired imagery and preserved perception, such as the classical Charcot and Bernard case and the patients described by Moro et al. (2008, this issue), or the opposite pattern of performance, consisting of preserved imagery and impaired perception. This double dissociation provides a strong challenge to models postulating a functional and anatomical equivalence of perception and imagery, and suggests that these functions have partly distinct neural correlates.