Datasets:

suolyer

/

pile_pubmed-abstracts

like 0

Long-term neurologic hand complications after radial artery harvesting using conventional cold and harmonic scalpel techniques. The purpose of this study was to determine the incidence of neurologic hand complications after radial artery harvesting and to compare the harmonic scalpel versus conventional cold scalpel technique. From 1995 to 2000, 786 radial arteries were harvested from 782 patients for coronary artery bypass grafting. From 1995 to 1997, the conventional cold scalpel technique was used (422 patients), and from 1998 to 2000, the harmonic scalpel was used (360 patients). Mean follow-up was 4.2 +/- 2.1 years and was 90% complete. Symptoms included thumb weakness or numbness, tingling, or pain in the hand. The incidence of neurologic hand complications was similar with both techniques (11.2% +/- 3.5% cold, 11.0% +/- 3.6% harmonic, p > 0.95), and in 19% (13 of 67 with symptoms) there was complete resolution within 1 year. Symptoms persisted long-term in 9.0% +/- 3.2% cold scalpel and 9.0% +/- 3.3% harmonic scalpel patients (p > 0.81), but were considered a "constant and significant source of discomfort" in only 0.6% +/- 0.9% cold scalpel and 1.4% +/- 1.3% harmonic scalpel patients (p > 0.41). The incidence of adverse neurologic outcomes causing significant long-term discomfort in the hand was low using either the cold scalpel or harmonic scalpel technique. However, a significant number of patients had neurologic hand symptoms in both groups, and this should be included when discussing operative risks with the patient.

Management of shoulder instability in the skeletally immature patient. Several studies have focused on management of shoulder instability in the adolescent and young adult population. However, a paucity of literature exists regarding shoulder dislocation in the skeletally immature population. The presence of an open physis makes the dislocated pediatric shoulder a challenging clinical problem. In general, management includes prompt reduction and sling immobilization. In athletic patients aged ≥14 years with a Bankart lesion, early surgical intervention may be warranted because of the higher risk of recurrent instability. However, the literature on younger skeletally immature patients is less clear in terms of risk of further instability and the necessity of surgical intervention. In the skeletally immature population, a relatively low rate of recurrent instability after primary dislocation has been reported in the recent literature. Surgical intervention should be considered for patients with recurrent instability.

Do patients with late-stage Parkinson's disease still respond to levodopa? Late-stage Parkinson' disease (PD) is dominated by loss of autonomy due to motor and non-motor symptoms which can be marginally corrected by medications adjustments. However, controversy exists on the mechanisms underlying the apparent decrease of benefit from levodopa. To study the response to levodopa in late-stage PD (LSPD). 20 LSPD patients (Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 in MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (DBS) underwent an acute levodopa challenge test. MDS-UPDRS-III and the modified Abnormal Involuntary Movement Scale were evaluated in off and after administration of a supra-maximal levodopa dose. LSPD patients had a median age of 78.8 (IQR: 73.5-82) and median disease duration of 14 years (IQR: 10-19.75). DBS patients had a median age of 66 (IQR: 61-72) and median disease duration of 18 years (IQR: 15-22). LSPD and DBS patients' MDS-UPDRS-III score improved 11.3% and 37% after levodopa, respectively. Rest tremor showed the largest improvement, while axial signs did not improve in LSPD. However, the magnitude of levodopa response significantly correlated with dyskinesias severity in LSPD patients. One third of LSPD and 9% of DBS patients reported moderate drowsiness. LSPD patients show a slight response to a supra-maximal levodopa dose, which is greater if dyskinesia are present, but it is frequently associated with adverse effects. A decrease in levodopa response is a potential marker of disease progression in LSPD.

SIAM, a Novel NMR Experiment for the Determination of Homonuclear Coupling Constants. The simultaneous acquisition of in-phase and antiphase multiplets with high sensitivity and minimum overlap (see section of 2D spectra on the right) is possible in a novel NMR experiment. Based on this method, homonuclear coupling constants such as the 3 J(HN ,Hα ) couplings in peptides and proteins can be determined quantitatively without isotope labeling.

Reproduction and development of Spodoptera exigua from cadmium and control strains under differentiated cadmium stress. The growth and development of living organisms is programmed in genes, but exogenous factors (e.g. cadmium) may modulate endogenous information. Heavy metals may disturb physiological functions and accumulate in the tissues. The insects under prolonged heavy metal stress show some modifications in their metabolism management. The aim of this study was to compare the reproduction and development between individuals of S. exigua from the strain, exposed over 130 generations to sublethal concentration of cadmium (44 mg Cd/kg dry weight of larval diet), and the individuals from the control strain, both additionally exposed to different concentration of cadmium (22-704 mg Cd/kg dry weight of larval diet). The exposure to various cadmium concentrations in the diet revealed survival difference between the cadmium and the control animals at the larvae stage. The differences between adults were not evident. The telomere length (responsible for the duration of a lifespan) in the cadmium strain was shorter in the females than in the males and the individuals from the control strain. TERF1 gene expression (indirectly responsible for the telomere length) was higher in the individuals from the cadmium strain 24 hrs after eclosion. The significant reduction in the larvae body mass was observed in both strains, when the metal concentration was equal to or higher than 264 mg/kg dry weight of larval diet. The EC50 values (defined as of body mass loss), calculated 48 hours after cadmium exposure of individuals from control and cadmium strains, were respectively 632 and 725 mg Cd/kg dry weight of diet. However, some difference in reproduction (the total number of eggs laid and the oviposition time) between the strains appeared only in the groups fed on the uncontaminated diet. The control females laid almost two times more eggs than those from the cadmium strain, and the control ones had more than two times longer oviposition time than the females from the cadmium strain. The fluctuation was also noted in the size of eggs and the hatching success on the following days when both strains were compared, while the hatching success was higher for the insects from the cadmium strain. In conclusion, the insects from the cadmium strain are more resistant to cadmium contamination, as it is evidenced by the EC50 parameter. However, the females from the cadmium strain start laying eggs statistically later, have shorter telomeres and slightly reduced TERF1 gene expression, but hutching success in the strain is significantly higher when compared with the control individuals.

Intraoperative carotid artery duplex scanning in a modern series of 650 consecutive primary endarterectomy procedures. Thromboembolic complications after carotid endarterectomy are frequently associated with technical defects. We analyzed the effect of intraoperative duplex scanning in detection of significant but clinically unsuspected technical defects and residual common carotid artery (CCA) disease as a potential source of postoperative transitory ischemic attack (TIA) and stroke. From April 2000 to April 2003, 650 consecutive primary carotid endarterectomy procedures were performed in 590 patients at a single institution by two vascular surgeons. Patients included 335 men (57%) and 255 women (43%). Indications for surgery were asymptomatic internal carotid artery (ICA) stenosis (>or=70%) in 464 patients (71%). All procedures were performed with the patient under general anesthesia, with synthetic patch angioplasty in 644 (99.1%). Major technical defects at intraoperative duplex scanning (>30% luminal internal carotid artery stenosis, free-floating clot, dissection, arterial disruption with pseudoaneurysm) were repaired. CCA residual disease was reported as wall thickness (0.7-4.8 mm; mean, 1.7 +/- 0.7) and percent stenosis (16%-67%; mean, 32% +/- 8%) in all cases. Postoperative 30-day TIA, stroke, and death rates were analyzed. There were no clinically detectable postoperative thromboembolic events in this series. All 15 major defects (2.3%) identified with duplex scanning were successfully revised. These included 7 intimal flaps, 4 free-floating clots, 2 ICA stenoses, 1 ICA pseudoaneurysm, and 1 retrograde CCA dissection. Diameter reduction ranged from 40% to 90% (mean, 67 +/- 16%), and peak systolic velocity ranged from 69 to 497 cm/s (mean, 250 +/- 121 cm/s). Thirty-one patients (5%) with the highest residual wall thickness (>3mm) in the CCA and 19 (3%) with the highest CCA residual diameter reduction (>50%) did not have postoperative stroke or TIA. Overall postoperative stroke and mortality rates were 0.3% and 0.5%, respectively; combined stroke and mortality rate was 0.8%. One stroke was caused by hyperperfusion, and the other occurred as an extension of a previous cerebral infarct. No patients had TIAs. Two deaths were caused by myocardial infarction, and one death by respiratory insufficiency. We believe intraoperative duplex scanning had a major role in these improved results, because it enabled detection of clinically unsuspected significant lesions. Residual disease in the CCA does not seem to be a harbinger of stroke or TIA.

A mechanistic model of whole-tract digestion and methanogenesis in the lactating dairy cow: model development, evaluation, and application. Dietary intervention to reduce methane emissions from lactating dairy cattle is both environmentally and nutritionally desirable due to the importance of methane as a causative agent in global warming and as a significant loss of feed energy. Reliable prediction systems for methane production over a range of dietary inputs could be used to develop novel dietary regimes for the limitation of feed energy loss to methane. This investigation builds on previous attempts at modeling methanogenesis and involves the development of a dynamic mechanistic model of wholerumen function. The model incorporates modifications to certain ruminal fermentation parameters and the addition of a postruminal digestive element. Regression analysis showed good agreement between observed and predicted results for experimental data taken from the literature (r2 = 0.76, root mean square prediction error = 15.4%). Evaluation of model predictions for experimental observations from five calorimetry studies (67 observations) with lactating dairy cows at the Centre for Dairy Research, in Reading, U.K., shows an underprediction (2.1 MJ/d) of methane production (r2 = 0.46, root mean square prediction error = 12.4%). Application of the model to develop diets for minimizing methanogenesis indicated a need to limit the ratio of lipogenic to glucogenic VFA in the rumen and hindgut. This may be achieved by replacing soluble sugars in the concentrate with starch or substituting corn silage for grass silage. On a herd basis, the model predicted that increasing dietary energy intake per cow can minimize the annual loss of feed energy through methane production. The mechanistic model is a valuable tool for predicting methane emissions from dairy cows.

Alterations in brain norepinephrine metabolism and behavior induced by environmental stimuli previously paired with inescapable shock. After exposure to a single session of inescapable footshock, rats show deficits in escape performance 24 h later when required to lever press on a fixed ratio (FR-3) schedule. Footshock stress produces an immediate increase in brain levels of 3-methoxy-4-hydroxyphenylglycol sulfate (MHPG-SO4), a major metabolite of norepinephrine in rat brain. Twenty-four hours after a single or repeated session(s) of footshock stress, when levels of MHPG-SO4 returned to baseline, increases in brain levels of MHPG-SO4, crouching and defecation behavior were elicited in rats by neutral environmental stimuli that had been previously paired with inescapable footshock stress. These results suggest that sensitization or conditioning of noradrenergic neuronal systems may be induced by environmental stimuli previously paired with stress, and may help to explain, at least in part, the deficits in escape performance observed 24 h after exposure to inescapable shock.

Tracking of Noise Tolerance to Measure Hearing Aid Benefit. The benefits offered by noise reduction (NR) features on a hearing aid had been studied traditionally using test conditions that set the hearing aids into a stable state of performance. While adequate, this approach does not allow the differentiation of two NR algorithms that differ in their timing characteristics (i.e., activation and stabilization time). The current study investigated a new method of measuring noise tolerance (Tracking of Noise Tolerance [TNT]) as a means to differentiate hearing aid technologies. The study determined the within-session and between-session reliability of the procedure. The benefits provided by various hearing aid conditions (aided, two NR algorithms, and a directional microphone algorithm) were measured using this procedure. Performance on normal-hearing listeners was also measured for referencing. A single-blinded, repeated-measures design was used. Thirteen experienced hearing aid wearers with a bilaterally symmetrical (≤10 dB) mild-to-moderate sensorineural hearing loss participated in the study. In addition, seven normal-hearing listeners were tested in the unaided condition. Participants tracked the noise level that met the criterion of tolerable noise level (TNL) in the presence of an 85 dB SPL continuous discourse passage. The test conditions included an unaided condition and an aided condition with combinations of NR and microphone modes within the UNIQUE hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR; directional microphone, no NR; and directional microphone, NR) and the DREAM hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR). Each tracking trial lasted 2 min for each hearing aid condition. Normal-hearing listeners tracked in the unaided condition only. Nine of the 13 hearing-impaired listeners returned after 3 mo for retesting in the unaided and aided conditions with the UNIQUE hearing aid. The individual TNL was estimated for each participant for all test conditions. The TNT index was calculated as the difference between 85 dB SPL and the TNL. The TNT index varied from 2.2 dB in the omnidirectional microphone, no NR condition to -4.4 dB in the directional microphone, NR on condition. Normal-hearing listeners reported a TNT index of -5.7 dB using this procedure. The averaged improvement in TNT offered by the NR algorithm on the UNIQUE varied from 2.1 dB when used with a directional microphone to 3.0 dB when used with the omnidirectional microphone. The time course of the NR algorithm was different between the UNIQUE and the DREAM hearing aids, with the UNIQUE reaching a stable TNL sooner than the DREAM. The averaged improvement in TNT index from the UNIQUE directional microphone was 3.6 dB when NR was activated and 4.4 dB when NR was deactivated. Together, directional microphone and NR resulted in a total TNT improvement of 6.5 dB. The test-retest reliability of the procedure was high, with an intrasession 95% confidence interval (CI) of 2.2 dB and an intersession 95% CI of 4.2 dB. The effect of the NR and directional microphone algorithms was measured to be 2-3 and 3.6-4.4 dB, respectively, using the TNT procedure. Because of its tracking property and reliability, this procedure may hold promise in differentiating among some hearing aid features that also differ in their time course of action.

Transition metals potentiate paraquat toxicity. The involvement of transition metal ions in paraquat toxicity was studied in bacterial model system. We show that the addition of micromolar, or lower, concentrations of copper dramatically enhanced the rate of bacterial inactivation. In contrast, the addition of chelating agents totally eliminated the killing of E. coli. No inactivation was observed under anaerobic exposure to paraquat, both in the absence and presence of copper. However, in the presence of copper, the anaerobic addition of hydrogen peroxide resulted in complete restoration of inactivation as under aerobiosis. Paraquat either produces superoxide ions or directly reduces bound copper ions in a catalytic mode. The reduced cuprous complexes react with hydrogen peroxide to locally form hydroxyl radicals (OH.) which are probably responsible for the deleterious effects. This study indicates the involvement of a site-specific metal-mediated Haber-Weiss mechanism in paraquat toxicity. It is in agreement with earlier observations that copper unusually enhance biological damage induced by either superoxide or ascorbate.

Nutritional and physiological responses of broiler chickens to dietary supplementation with de-oiled soyabean lecithin at different metabolisable energy levels and various fat sources. A 42-d study was conducted to investigate the effects of an emulsifier supplementation (de-oiled soyabean lecithin (DSL)) of diets with different levels of metabolisable energy (ME) and various sources of fat on growth performance, nutrient digestibility, blood profile and jejunal morphology of broiler chickens. Diets were arranged factorially (2 × 2 × 2) and consisted of two concentrations of ME (normal and low), two fat sources (soyabean oil (SO) and poultry fat (PF)) and two levels of DSL supplementation (0 and 1 g/kg). A total of 800 1-d-old male broiler chickens were assigned to eight treatments with five replicates/treatment. The results showed the supplemental DSL caused improvements in the overall feed conversion ratio, fat digestibility and jejunal villus height:crypt depth ratio, but the magnitude of the responses was greater in the PF-containing diets, resulting in significant fat × DSL interactions (P<0·05). Abdominal fat percentage was also reduced by the PF-containing diet, but the response was greater in the normal ME diet, resulting in a significant ME × fat interaction (P = 0·048). Dietary DSL supplementation also increased nitrogen-corrected apparent ME values but decreased blood TAG (P = 0·041) and LDL (P = 0·049) concentrations, regardless of the source of fat used or the ME values in the diet. In conclusion, the present study suggests that the improvements in growth performance, fat digestibility and intestinal morphology that can be achieved with DSL supplementation are highly dependent on the degree of saturation of lipid incorporated into broiler chicken diets.

Stem cells: A path towards improved epilepsy therapies. Despite the immense growth of new anti-seizure drugs (ASDs), approximately one-third of epilepsy patients remain resistant to current treatment options. Advancements in whole genome sequencing technology continues to identify an increasing number of epilepsy-associated genes at a rate that is outpacing the development of in vivo animal models. Patient-derived induced pluripotent stem cells (iPSCs) show promise in providing a platform for modeling genetic epilepsies, high throughput drug screening, and personalized medicine. This is largely due to the ease of collecting donor cells for iPSC reprogramming, and their ability to be maintained in vitro, while preserving the patient's genetic background. In this review, we summarize the current state of iPSC research in epilepsy and closely related syndromes, discuss the growing need for high-throughput drug screening (HTS), and review the use of stem cell technology for the purpose of autologous transplantation for epilepsy stem cell therapy. Although the use of iPSC technology, as it applies to ASD discovery, is in its infancy, we highlight the significant progress that has been made in phenotype and assay development to facilitate systematic HTS for personalized medicine.

Neurochemical and genetic bases of psychopathology: current status. A review, which does not attempt to be exhaustive, is presented. Evidence for the operation of genetic factors in the etiology of mental disorders, including studies of natural families, twins, and adoptees and their biological and adoptive relatives, is briefly summarized and discussed. Environmental influences are also clearly involved, and observations bearing on their nature are described. Certain neurochemical correlates of psychopathology, particularly those related to chemical neurotransmitters, are discussed. Since schizophrenia and the affective disorders are phenomenological syndromes, it is likely that they represent heterogeneous collections of more specific disorders with common symptomatic features. Attempts to delineate more homogeneous subgroups in these disorders on the basis of morphological or biochemical features have achieved some success, and an example of each approach is described.

Lymphocyte replicating ability in individuals exposed to arsenic via drinking water. A human monitoring study was carried out to explore the effect on lymphocyte proliferation of chronic exposure to arsenic (As) via drinking water. Blood and urine samples were taken from volunteers from a town where levels of As in the drinking water averaged 412 micrograms/l, and from a matched group of individuals, with similar socioeconomic status, that drank water with As average levels of 37.2 micrograms/l. Exposure was assessed by questionnaires and by determining the levels of As in urine and water samples. The evaluation of the peripheral blood lymphocyte proliferation was done at different culture times using labelling (LI), mitotic (MI) and replication indexes (RI) as endpoints. No significant differences were seen for either LI or MI, except for MI in 72 h cultures and in LI in males and females with skin lesions vs. those without lesions. Significant differences in RI were seen for exposed females but not for males. Correlations between LI and MI showed that progression from the initial S-to M-phase is altered in exposed individuals. Arsenic exposure as well as lead and mercury affect cellular immune response, making the endpoints of cell proliferation variables of interest in population monitoring study design, since they might provide information in health impairment due to exposure, which is important in risk assessment.

The impact of uncertainties in the CT conversion algorithm when predicting proton beam ranges in patients from dose and PET-activity distributions. The advantages of a finite range of proton beams can only be partly exploited in radiation therapy unless the range can be predicted in patient anatomy with <2 mm accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm accuracy in dose prediction, and proton-induced PET imaging aims at ∼2 mm accuracy in range verification. The latter is done using Monte Carlo predicted PET images. Monte Carlo methods are based on CT images to describe patient anatomy. The dose calculation algorithm and the CT resolution/artifacts might affect dose calculation accuracy. Additionally, when using Monte Carlo for PET range verification, the biological decay model and the cross sections for positron emitter production affect predicted PET images. The goal of this work is to study the effect of uncertainties in the CT conversion on the proton beam range predicted by Monte Carlo dose calculations and proton-induced PET signals. Conversion schemes to assign density and elemental composition based on a CT image of the patient define a unique Hounsfield unit (HU) to tissue parameters relationship. Uncertainties are introduced because there is no unique relationship between HU and tissue parameters. In this work, different conversion schemes based on a stoichiometric calibration method as well as different numbers of tissue bins were considered in three head and neck patients. For Monte Carlo dose calculation, the results show close to zero (<0.5 mm) differences in range using different conversion schemes. Further, a reduction of the number of bins used to define individual tissues down to 13 did not affect the accuracy. In the case of simulated PET images we found a more pronounced sensitivity on the CT conversion scheme with a mean fall-off position variation of about 1 mm. We conclude that proton dose distributions based on Monte Carlo calculation are only slightly affected by the uncertainty on density and elemental composition introduced by unique assignment to each HU if a stoichiometric calibration is used. Calculated PET images used for range verification are more sensitive to conversion uncertainties causing an intrinsic limitation due to CT conversion alone of at least 1 mm.

True MRI assessment of stem cell chondrogenesis in a tissue engineered matrix. Developing a non-invasive method to monitor the growth of tissue-engineered cartilage is of utmost importance for tracking the progress and predicting the success or failure of tissue-engineering approaches. Magnetic Resonance Imaging (MRI) is a leading non-invasive technique suitable for follow-through in preclinical and clinical stages. As complex tissue-engineering approaches are being developed for cartilage tissue engineering, it is important to develop strategies for true non-invasive MRI monitoring that can take into account contributions of the scaffold, cells and extracellular matrix (ECM) using MR parameters. In the current study, we present the preliminary MRI assessment of chondrogenic differentiation of human bone marrow derived stem cells seeded onto a specially designed osteochondral matrix system. We performed water relaxation times (T1 and T2) MRI measurements at 7, 14 and 28 days after cell seeding. The MRI experiments were performed for the tissue-engineered cartilage as well as for acellular scaffolds. We identified that the contribution of the scaffold is the dominant contribution in MR parameters of engineered cartilage and that it hinders observation of the tissue growth. An attempt is made to filter out this contribution, for the first time, in order to make a true observation of tissue growth using MRI.

Establishing differential gene expression in sporulating Bacillus subtilis: phosphorylation of SpoIIAA (anti-anti-sigmaF) alters its conformation and prevents formation of a SpoIIAA/SpoIIAB/ADP complex. Sigma-factor F (sigmaF) is a key transcription factor that initiates prespore development in Bacillus subtilis. Its activity is controlled by an anti-sigma factor, SpoIIAB, which is also a protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. We have examined our earlier prediction that SpoIIAA must undergo a major change in its properties when phosphorylated. Upon gel filtration in the presence of ADP, SpoIIAA-P was eluted from a Superdex column much later than SpoIIAB, whereas SpoIIAA was coeluted with SpoIIAB, indicating the formation of a protein/protein complex. The complex contained ADP, and had two monomers of SpoIIAA to each SpoIIAB dimer. Its dissociation constant was 13 mu M. Gel permeation on high-performance liquid chromatography (HPLC) suggested an apparent molecular mass for SpoIIAA-P which was much higher (23.5 kDa) than that of SpoIIAA (15.8 kDa), but Ferguson plots showed that SpoIIAA-P was not a phosphorylated dimer of SpoIIAA. Our tentative conclusion, that SpoIIAA and SpoIIAA-P differ markedly in conformation, was confirmed by the results of partial digestion with chymotrypsin.

p21 gene polymorphisms in systemic lupus erythematosus. Cyclin-dependent kinase inhibitor 1A (p21) is a negative regulator in the cell cycle. Development of sex-linked lupus-like syndrome in p21-/- mice and reduced p21 gene expression in patients with systemic lupus erythematosus (SLE) compared with those in healthy controls suggested that p21 is a susceptibility gene of SLE. We investigated the same by a case-control association study. Six single nucleotide polymorphisms, p21US G/A, p21DS C/A, p21-1022 G/A, p21C31 C/A, p21In2 G/C and p21UTR T/C, were genotyped in 516 SLE patients and 693 healthy controls. Association of genotypes and alleles with disease, disease phenotypes, haplotypes construction, linkage disequilibrium analysis and p21 mRNA expression were performed. We found a significant association of p21US A allele (OR = 0.23, 95% CI: 0.14-0.38, P < 0.001) and p21-1022 A allele (OR = 1.95, 95% CI: 1.37-2.78, P < 0.001) with SLE. We identified significant differences in the frequencies of haplotypes ht1-ACACCC, which contains p21US A allele, and ht2-GCACCC, which contains p21-1022 A allele, between SLE patients and controls (P < 0.0001). Besides, the p21US GA was associated with SLE patients suffering from arthritis (P = 0.003). We also observed differential p21 mRNA expressions among different genotypes of p21US and p21-1022 which were statistically significant. Our results suggested that the p21US A allele and p21-1022 A allele were both associated with the development of SLE, and the p21US A allele was associated with arthritis in SLE patients.

Proliferation of NG2 cells in the epileptic hippocampus. NG2 cells are oligodendrocyte progenitor cells, and have been shown to receive synaptic input from pyramidal neurons to generate action potentials. Whether any change of these cells occurs after status epilepticus (SE) and subsequent temporal lobe epilepsy remains unknown. In the present study, the expression of NG2 was investigated in the mouse hippocampus after pilocarpine-induced status epilepticus (PISE). We showed that reactive NG2 cells were significantly increased from 1 day to 2 months after PISE. Double immunofluorescence indicated that few NG2 cells differentiated into neurons and astrocytes after PISE, whereas the number of NG2 cells was increased significantly in the stratum lucidum of CA3 area from 1 day onwards after PISE. Our results suggest that the significantly increased reactive NG2 cells from acute to chronic stage after PISE may be involved in epileptogenesis.

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization. This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.

Activation of specific glutamate receptor subtypes increases C-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells. In primary cultures of rat cerebellar granule cells the activation of excitatory amino acid receptors by 1-glutamate enhances the steady state level of c-fos proto-oncogene messenger RNA. This effect is blocked by magnesium (1mM) as well as by the glutamate receptor antagonist 2-amino-5-phosphono-valerate (APV). Among the other excitatory amino acid agonists N-methyl-D-Aspartate (NMDA) and quisqualate also increased c-fos mRNA content, the latter however to a significantly lesser extent, while kainate failed to modify the basal level of c-fos expression. The addition of the muscarinic agonist carbachol or of the inhibitory neurotransmitter GABA did not affect the basal level of c-fos mRNA. This data demonstrate for the first time that activation of signal transduction at a specific excitatory amino acid receptor subtype can increase the steady state level of c-fos proto-oncogene mRNA in primary culture of cerebellar neurons.

Identification of poorly differentiated synovial sarcoma: a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma. Poorly differentiated areas in synovial sarcomas (SS) are known to be associated with a poorer prognosis. The aim of our study was to describe the morphological spectrum of poorly differentiated synovial sarcomas (PDSS) and refine the criteria for their recognition. The clinicopathological features of 28 PDSS were compared with those of 26 classic SS. Common cell types in PDSS included epithelioid, spindle and Ewing sarcoma-like small round cells. Unusual features included presence of desmoplastic small cell tumour-like areas and extraskeletal myxoid chondrosarcoma-like areas. The presence of necrosis (P = 0.002), a mitotic rate over 10/10 high-power fields (P < 0.001), a haemangiopericytomatous vascular pattern (P < 0.001) and vascular invasion (P = 0.003) were significantly associated with PDSS, while mast cells (P < 0.001), calcification (P < 0.001) and hyaline bands (P < 0.001) were significantly associated with classic SS. Poorly differentiated areas showed increased proliferative activity with Ki67. PDSS showed a tendency to be larger (P = 0.008) and to be located in proximal more than distal sites (P = 0.025). Three entirely poorly differentiated tumours were diagnosed by demonstration of the t(X;18)(p11;q11) translocation. PDSS showed additional cytogenetic abnormalities. Poorly differentiated synovial sarcomas show a spectrum of histological features, which may simulate other malignant neoplasms. The diagnosis of entirely poorly differentiated synovial sarcomas requires cytogenetic analysis.

RET S409Y Germline Mutation and Associated Medullary Thyroid Carcinoma. Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.

The relationship between blood glucose excursions and painful diabetic peripheral neuropathy: a pilot study. Peripheral neuropathy affects 30% of Type 1 diabetic patients. Unfortunately, 10-20% of affected patients have disabling symptoms. The aim of this study was to examine the relationship between blood glucose excursions and pain in patients with symptomatic diabetic neuropathy. Twenty Type 1 diabetic patients with peripheral neuropathy (10 painful and 10 painless) wore a continuous glucose monitoring system for 3 days. Symptomatic patients kept a daily pain score diary. The mean amplitude of glycaemic excursions (MAGE) and the M-values (measure of glucose deviations from an arbitrarily selected point) were calculated. Groups were matched for (mean +/- sd) age: 52.0 +/- 11.1 years; duration of diabetes: 24.8 +/- 10.7 years; HbA1c: 9.7 +/- 2.3%; duration of neuropathy: 5.6 +/- 2.6 years; and CGMS performance. The painful group had a greater mean glucose (12.1 +/- 2.9 mmol/l vs. 9.3 +/- 1.9 mmol/l, P = 0.02), a greater M-value (68.4 vs. 31.1, P = 0.02) and more glycaemic excursions (13 vs. 10, P < 0.01), compared with the painless group. However, there was no difference in the MAGE between both groups, and no correlation between the number of glycaemic excursions and the number of painful episodes in the painful group. Patients with painful neuropathy have greater glucose flux and possibly poorer diabetes control, compared with patients with painless neuropathy.

Genotoxic effects of produced waters in mosquito fish (Gambusia affinis). The aim of this study was to assess the potential genotoxic effects of produced water (PW) from an Italian on-shore oil plant. Produced water is a complex mixture containing residual hydrocarbons, trace elements, naturally occurring radioactive material and potentially toxic treatment chemicals such as biocides, dispersants, detergents and scale inhibitors used in oil production. The test organism, mosquito fish (Gambusia affinis), was divided into male and female groups and exposed for 8 days in the laboratory to 50% concentrations of different produced waters: PW before treatment and after settling treatment. The fish were also exposed to lower concentrations (10%) of the same PW for 30 days. DNA damage was evaluated in erythrocytes by single cell gel electrophoresis (Comet assay) and micronucleus test, while an oxidative stress biomarker, was assessed. Polycyclic aromatic hydrocarbons (PAH) metabolites in bile were also evaluated. A higher sensitivity in biomarker responses was found in females in comparison to males. An increase in DNA strand breaks was observed in both genders after 30 days exposure and a statistically significant increase of micronucleated cells was found in females after 8 days exposure. A positive correlation between presence of micronucleated cells and PAH metabolites in bile was also observed.

Disaster Preparedness and Response for the Burn Mass Casualty Incident in the Twenty-first Century. The effective and efficient coordination of emergent patient care at the point of injury followed by the systematic resource-based triage of casualties are the most critical factors that influence patient outcomes after mass casualty incidents (MCIs). The effectiveness and appropriateness of implemented actions are largely determined by the extent and efficacy of the planning and preparation that occur before the MCI. The goal of this work was to define the essential efforts related to planning, preparation, and execution of acute and subacute medical care for disaster burn casualties. This type of MCI is frequently referred to as a burn MCI."

Transient neurologic and ocular manifestations in primary thrombocythemia. We report the presenting neurologic and visual symptoms in 17 patients with primary thrombocythemia. Poorly localizing symptoms occurred in 14 patients: transient unsteadiness in 13, dysarthria in eight, and scintillating scotomata in four. Nine patients had focal symptoms: transient monocular blindness in two patients, transient mono- or hemiparesis in six, and both of these in one patient. The attacks all had a sudden onset, occurred sequentially rather than simultaneously, lasted for a few seconds to several minutes, and were usually associated with a dull or pulsatile headache. A causal platelet-mediated arterial thrombosis was evident in 15 patients. There were no recurrences of thrombotic or ischemic events during long-term treatment of 12 patients with aspirin and during cytostatic reduction of platelet count to normal in seven patients. We conclude that low-dose aspirin and reduction of platelet count to normal are effective, but coumarin is ineffective, in the treatment and prevention of arterial thrombosis in thrombocythemia.

Congenital cardiac disease and contemporary dental care of the pediatric patient: a cardiologist's point of view. Good dental health makes common sense--even more so in patients with underlying cardiac abnormalities. Today, the practising dentist may be confronted by an ever-increasing cohort of patients who have survived complicated repairs of congenital cardiac abnormalities. A basic knowledge of such conditions is useful, primarily to gain an understanding of the physiological abnormalities that may be adversely influenced by dental manipulation. This article reviews some of the important points that practising dentists should know about patients with congenital cardiac disease.

The immunization and vaccine crisis in developing countries. Health care research has shown that immunization can play a crucial role in fighting infectious diseases. A global effort was launched to decrease the incidence of infectious disease worldwide through immunization. This paper highlights many of the problems which have contributed to an immunization crisis, in which developing countries are not receiving the benefits of vaccines due to slow vaccine delivery systems; the increasing cost of vaccines; and vaccine and immunization program deficiencies. Consequences of the crisis, solutions, and the role of health care professionals in supporting immunization programs are presented.

PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2. Development of the cerebral cortex is controlled by growth factors among which transforming growth factor beta (TGFβ) and insulin-like growth factor 1 (IGF1) have a central role. The TGFβ- and IGF1-pathways cross-talk and share signalling molecules, but in the central nervous system putative points of intersection remain unknown. We studied the biological effects and down-stream molecules of TGFβ and IGF1 in cells derived from the mouse cerebral cortex at two developmental time points, E13.5 and E16.5. IGF1 induces PI3K, AKT and the mammalian target of rapamycin complexes (mTORC1/mTORC2) primarily in E13.5-derived cells, resulting in proliferation, survival and neuronal differentiation, but has small impact on E16.5-derived cells. TGFβ has little effect at E13.5. It does not activate the PI3K- and mTOR-signalling network directly, but requires its activity to mediate neuronal differentiation specifically at E16.5. Our data indicate a central role of mTORC2 in survival, proliferation as well as neuronal differentiation of E16.5-derived cortical cells. mTORC2 promotes these cellular processes and is under control of PI3K-p110-alpha signalling. PI3K-p110-beta signalling activates mTORC2 in E16.5-derived cells but it does not influence cell survival, proliferation and differentiation. This finding indicates that different mTORC2 subtypes may be implicated in cortical development and that these subtypes are under control of different PI3K isoforms. Within developing cortical cells TGFβ- and IGF-signalling activities are timely separated. TGFβ dominates in E16.5-derived cells and drives neuronal differentiation. IGF influences survival, proliferation and neuronal differentiation in E13.5-derived cells. mTORC2-signalling in E16.5-derived cells influences survival, proliferation and differentiation, activated through PI3K-p110-alpha. PI3K-p110-beta-signalling activates a different mTORC2. Both PI3K/mTORC2-signalling pathways are required but not directly activated in TGFβ-mediated neuronal differentiation.

Biomechanics during exercise with a novel stairclimber. The current study aimed to investigate the stair-climbing biomechanics related to the lower extremities when subjects used the novel designed stair-climber, which could provide opportunity for both sagittal and frontal movements. 12 volunteers were required to step while either keeping the trunk static (STATIC) or allowing the trunk to shift with weight bearing (SHIFT). A motion analysis system and the 6-axis force and torque sensor embedded in the pedal were used to collect data. Foot contact forces and joint moments were calculated to represent loading characteristics. The joint angle and corresponding moments at the terminal point of the stance phase were computed to serve as the indicator of safety. Significant differences were found in peak foot contact forces, knee extensor moment, and hip abductor moment. At the end of the stance phase, various directions of moment between conditions were found in the knee and the ankle. The knee valgus angle, hip abductor moment, and knee extensor moment were significantly greater in SHIFT than in STATIC. The various stepping strategies caused differences in joint loading characteristics; therefore, these findings need to be given greater consideration in the design of training protocols.

[Respiratory and allergic diseases of children : Temporal trends, urban-rural differences, and in association with environmental tobacco smoke exposure]. Ten years after the establishment of health monitoring units (GME) in Bavaria, temporal trends and urban-rural differences in parent-reported respiratory and allergic diseases as well as environmental tobacco smoke (ETS) exposure in preschoolers were analyzed in an explorative manner. Furthermore, associations between diseases and ETS exposure were studied. Parent questionnaires were used as part of the school entrance examination in two cross sectional studies (S1:2004/2005, n 1 = 6350; S2:2012/2013, n 2 = 5052). Temporal trends and urban-rural-differences were tested by X2 tests. Associations between diseases and exposures were studied using multiple logistic regression analysis. The lifetime prevalence of atopic dermatitis declined from S1-S2 from 12.4 to 11.1 %, whereas those for hay fever, asthma, bronchitis and pseudocroup remained stable. In S1 and S2, bronchitis was less often reported in cities. The other diseases showed no urban-rural differences. The prevalence of children's ETS exposure at home declined from S1-S2 from 14.3 to 7.2 % and was generally higher in cities than in rural regions. There was no positive association between diseases and children's ETS exposure at home. In S2 an association was found between asthma and current parental smoking (OR = 1.60; 95 % CI = (1.10-2.32)). The GME provide important data for regional distribution of respiratory and allergic diseases and ETS exposure of preschoolers in Bavaria. The results of the study are important for further development of questionnaires, which will be used in future GME.

Insight into old and new pure shift nuclear magnetic resonance methods for enantiodiscrimination. Enantiodiscrimination and their quantification using nuclear magnetic resonance (NMR) spectroscopy has always been a subject of great interest. Proton is the nucleus of choice for enantiodiscrimination due to its high sensitivity and ubiquitous presence in nature. Despite its advantages, enantiodiscrimination suffers from extensive signal splitting by the proton-proton scalar couplings, which give complex multiplets that spread over a frequency range of some tens of hertz. These multiplets often overlap, further complicating interpretation of the spectra and quantifications. In the present review, we discuss some of the recent developments in the pure shift 1 H NMR based methods for enantiomer resolution and enantiodiscrimination. We also compare various pure shift methods used for enantiodiscrimination and measurement of enantiomeric excess, considering the fact that conventional 1 H NMR fails to provide any detailed insight.

Nonuniform muscle fiber orientation causes spiral wave drift in a finite element model of cardiac action potential propagation. Reentrant tachyarrhythmias are thought to involve spiral waves of excitation and recovery that may be nonstationary. The effect of muscle fiber curvature on spiral and planar wave propagation was studied using a computational model. Two-dimensional anisotropic cardiac propagation was modeled using a finite element method to solve a modification of the FitzHugh-Nagumo equations. Spiral waves that propagated stably about a fixed core in tissue with a uniform fiber orientation were found to drift at an oblique angle to the fibers when the fibers curved. The drift velocity was linearly related to the fiber angle gradient and was 10% of the longitudinal propagation velocity with a gradient of 4 degree/cm. Planar wavefronts were also affected by fiber curvature. The maximal upstroke rate, propagation velocity, and the action potential amplitude all increased when the fibers curved toward the wavefront and decreased when they curved away. For example, when the fibers curved toward the wavefront with a moderate gradient of 15 degree/cm, maximal upstroke rate increased 74%, transverse propagation velocity increased 65%, and action potential amplitude increased 9%. This phenomenon caused the spiral wave drift: As a spiral wave traverses a cycle, the angle between the wavefront at the wavetip and the fibers changes periodically, thus altering the propagation parameters. These periodic changes affect the instantaneous radius of curvature of the wavetip path, which results in drift. Spiral and planar waves are affected by muscle fiber curvature. The resulting dynamics may be important in determining the lifetime and stability of reentrant arrhythmias.

Restriction fragment length polymorphisms in isolates of Aspergillus fumigatus probed with part of the intergenic spacer region from the ribosomal RNA gene complex of Aspergillus nidulans. Differences in restriction fragment length polymorphisms (RFLPs) have been detected in isolates of Aspergillus fumigatus. Genomic DNA from 11 isolates was digested with EcoRI, separated by electrophoresis, Southern blotted and probed with DNA from the intergenic spacer or non-transcribed spacer region of the rRNA gene complex of Aspergillus nidulans. Three distinct RFLP patterns were detected which differed from the control patterns observed with A. nidulans, Aspergillus flavus and Aspergillus niger hybridized with the same probe. Furthermore, the differences in RFLP patterns in the A. fumigatus isolates were not detected when probed with DNA coding for the rRNA complex in Saccharomyces cerevisiae. These findings may be of use in the study of the epidemiology and pathogenesis of infections caused by A. fumigatus.

The incorporation of the A2 protein to produce novel Qβ virus-like particles using cell-free protein synthesis. Virus-like particles (VLPs) have been employed for a number of nanometric applications because they self-assemble, exhibit a high degree of symmetry, and can be genetically and chemically modified. However, high symmetry does not allow for a single unique modification site on the VLP. Here, we demonstrate the co-expression of the cytotoxic A2 protein and the coat protein of the bacteriophage Qβ to form a nearly monodispersed population of novel VLPs. Cell-free protein synthesis allows for direct access and optimization of protein-synthesis and VLP-assembly. The A2 is shown to be incorporated at high efficiency, approaching a theoretical maximum of one A2 per VLP. This work demonstrates de novo production of a novel VLP, which contains a unique site that has the potential for future nanometric engineering applications.

Feeding oleamide to lactating Jersey cows 1. Effects on lactation performance and milk fatty acid composition. Oleamide was previously reported to resist ruminal biohydrogenation and elevate milk oleic acid concentration when fed to lactating Holstein cows. To determine if Jersey cows responded similarly to oleamide, four lactating Jersey cows (mean 417 kg of body weight and 64 days in milk) were fed four diets in a 4x4 Latin square with 2-wk periods. Diets were total mixed ration containing 47% corn silage and 53% concentrate (dry matter basis) and were supplemented with no added fat (control), or with 3.5% added fat from either higholeic canola oil, a commercial source of oleamide, or oleamide synthesized from oleic acid and urea. The canola oil supplement had no effect on milk yield or composition. Compared to canola oil, the oleamide supplements reduced milk yield, dry matter intake, and milk fat and protein contents. Milk oleic acid concentration increased from 17.4% of total fatty acids for the control diet to 22.1% for the canola oil diet. Both oleamides further increased milk oleic acid to 30.0 and 27.1% of total fatty acids for the commercial and synthesized oleamides, respectively. Milk palmitic acid was reduced and stearic acid was increased by all fat supplements but more so by the oleamides than by the canola oil. Consistent with previous reports that fatty acyl amides resist ruminal biohydrogenation, feeding oleamide to Jersey cows in this study increased milk oleic acid concentration but had negative effects on feed intake and milk yield.

The computed tomographic appearance of subcutaneous nodules occurring in metastatic neuroblastoma. The authors report a case of subcutaneous nodules in a 2-month-old girl with metastatic neuroblastoma; the appearance of the nodules in computed tomography scans is described. Such nodules are sometimes overlooked by clinicians and radiologists, even though they almost always occur in disseminated disease. In patients with neuroblastoma and other neoplasms subcutaneous nodules may be an easily accessible source of samples for histopathologic examination.

Validation of a prediction model to estimate health utilities index Mark 3 utility scores from WOMAC index scores in patients with osteoarthritis of the hip. To examine the validity of a newly developed prediction model translating osteoarthritis (OA)-specific health-related quality of life (HRQL) scores measured using the Western Ontario and McMaster Osteoarthritis Index (WOMAC) into generic utility-based HRQL scores measured using the Health Utilities Index Mark 3 (HUI3). Preintervention data from 145 patients with hip OA and complete WOMAC and HUI3 baseline assessments from the Alberta Hip Improvement Project study were used to validate three utility prediction models. These models were estimated using data from a previous study of knee OA patients. Predictive performance was assessed using the mean absolute prediction error (MAE) criterion and several other criteria. The validation sample appeared healthier (on the basis of the HUI3 and WOMAC) than the subjects used toestimate the prediction models. Nevertheless, the validation sample outperformed the predictive performance of the model sample. The results from the validation sample support the conclusions from the original study in that the primary model identified during model development (a model using WOMAC subscales, their interactions, their square terms, age, OA duration, their square terms, and gender) performed better on the MAE criterion than competing models. These results support the external validity of the prediction model for the retrospective estimation of HUI3 utility scores for use in economic evaluation.

[Familial infantile myofibromatosis]. Infantile myofibromatosis (IM) is the most common fibrous disorder of infancy and childhood. It is characterized by congenital tumours of the skin, striated muscle, bones and viscera. Most cases are sporadic and few familial cases have been reported. We describe a 5-month-old girl presenting with two congenital nodules. The diagnosis of infantile myofibromatosis was based on clinical and histopathological examination. Surgical excision was performed and there was no relapse at six years. The patient's brother presented multiple nodules and toe necrosis at birth due to infantile myofibromatosis. Two months later, the congenital nodules increased in size and new nodules developed. Surgical excision was performed. At 11 months of age, the boy presented with cranial relapse and bone resorption at P3 of the third right toe. The clinical and radiological investigations were normal. Three clinical forms of IM have been described: solitary cutaneous nodules, multiple cutaneous nodules and generalized MI with visceral involvement. The prognosis is good except in generalized MI. All familial cases of MI may be interpreted as autosomal dominant or alternatively there may be genetic heterogeneity. Strict follow-up is recommended to identify potentially life-threatening complications. Spontaneous regression usually occurs but in some cases the treatment of choice is surgical removal.

[Enzyme activity of thiamine pyrophosphate in the rat after oxythiamine administration]. Intraperitoneal injection of hydroxythiamine to rats (1 mmol per kg bw) resulted after 2-4 h in a more than 4-fold decrease in the activity of the oxoglutarate dehydrogenase complex, pyruvate dehydrogenase complex and NADP-dependent isocitrate dehydrogenase in adrenal mitochondria. Inhibition of hyaloplasmic transketolase, 6-phosphogluconate dehydrogenase and NADP-dependent malate dehydrogenase occurred later. Based on the correlation of the time course of enzymatic activity in the adrenals and the decreased concentration of 11-hydroxycorticosteroids in the blood the paramount role in the maintenance of the steroidogenesis among thiamine pyrophosphate-containing enzymes is assigned to the oxoglutarate dehydrogenase and pyruvate dehydrogenase complexes.

Coordinated transformation of the gut microbiome and lipidome of bowhead whales provides novel insights into digestion. Whale digestion plays an integral role in many ocean ecosystems. By digesting enormous quantities of lipid-rich prey, whales support their energy intensive lifestyle, but also excrete nutrients important to ocean biogeochemical cycles. Nevertheless, whale digestion is poorly understood. Gastrointestinal microorganisms play a significant role in vertebrate digestion, but few studies have examined them in whales. To investigate digestion of lipids, and the potential contribution of microbes to lipid digestion in whales, we characterized lipid composition (lipidomes) and bacterial communities (microbiotas) in 126 digesta samples collected throughout the gastrointestinal tracts of 38 bowhead whales (Balaena mysticetus) harvested by Alaskan Eskimos. Lipidomes and microbiotas were strongly correlated throughout the gastrointestinal tract. Lipidomes and microbiotas were most variable in the small intestine and most similar in the large intestine, where microbiota richness was greatest. Our results suggest digestion of wax esters, the primary lipids in B. mysticetus prey representing more than 80% of total dietary lipids, occurred in the mid- to distal small intestine and was correlated with specific microorganisms. Because wax esters are difficult to digest by other marine vertebrates and constitute a large reservoir of carbon in the ocean, our results further elucidate the essential roles that whales and their gastrointestinal microbiotas play in the biogeochemical cycling of carbon and nutrients in high-latitude seas.

Studies on metabolic regulation using NMR spectroscopy. The effects of hypoxia and hypoglycaemia on cerebral metabolism and calcium have been studied using multinuclear magnetic resonance spectroscopy. 13C MRS showed that severe hypoxia did not cause any further increase in metabolic flux into lactate seen in mild hypoxia, but there was a further increase in 13C labelling of alanine and glycerol 3-phosphate. These results are discussed in terms of the ability of lactate dehydrogenase to maintain normal levels of NADH in mild hypoxia, but not in severe hypoxia. We conclude that glycerol 3-phosphate and alanine may provide novel means of monitoring severe hypoxia whereas lactate is a reliable indicator only of mild hypoxia. 19F- and 31P NMR spectroscopy showed that neither hypoxia nor hypoglycaemia alone caused any significant change in [Ca2+]i. Combined sequential insults (hypoxia, followed by hypoxia plus hypoglycaemia), or vice versa, produced a 100% increase in [Ca2+]i, whereas immediate exposure to the combined insult (hypoxia plus hypoglycaemia) resulted in a large 5-fold increase in [Ca2+]i, with severe irreversible effects on the energy state. These results are discussed in terms of metabolic adaptation to the single type of insult, which renders the tissue less vulnerable to the combined insult. The effects of this combined insult are far more severe than those caused by glutamate or NMDA, which throws doubt on the current excitoxic hypothesis of cell damage.

Induction of DNA damage and p21-dependent senescence by Riccardin D is a novel mechanism contributing to its growth suppression in prostate cancer cells in vitro and in vivo. Our previous studies had shown that Riccardin D (RD) exhibited cytotoxic effects by induction of apoptosis and inhibition of angiogenesis and topoisomerase II. Here, we reported that apoptosis is not the sole mechanism by which RD inhibits tumor cell growth because low concentrations of RD caused cellular senescence in prostate cancer (PCa) cells. Low concentrations of RD were used to treat PCa cells in vitro and in vivo, and senescence-associated β-galactosidase activity, DNA damage response markers, and/or colony-forming ability, cell cycle were analyzed, respectively. We then used siRNA knockdown to identify key factor in RD-triggered cellular senescence. RD treatment caused growth arrest at G0/G1 phase with features of cellular senescence phenotype such as enlarged and flattened morphology, increased senescence-associated-beta-galactosidase staining cells, and decreased cell proliferation in PCa cells. Induction of cellular senescence by RD occurred through activation of DNA damage response including increases in the phosphor-H2AX, inactivation of Chk1/2, and suppression of repair-related Ku70/86 and phosphor-BRCA1 in PCa cells in vitro and in vivo. Analysis of expression levels of p53, p21(CIP1), p16(INK4a), p27(KIP1), pRb and E2F1 and genetic knockdown of p21(CIP1) demonstrated an important role of p21(CIP1) in RD-triggered cellular senescence. Involvement of the DNA damage response and p21(CIP1) defines a novel mechanism of RD action and indicates that RD could be further developed as a promising anticancer agent for cancer therapy.

The simultaneous isolation of multiple high and low frequent T-cell populations from donor peripheral blood mononuclear cells using the major histocompatibility complex I-Streptamer isolation technology. Adoptive transfer of donor-derived T cells can be applied to improve immune reconstitution in immune-compromised patients after allogeneic stem cell transplantation. The separation of beneficial T cells from potentially harmful T cells can be achieved by using the major histocompatibility complex (MHC) I-Streptamer isolation technology, which has proven its feasibility for the fast and pure isolation of T-cell populations with a single specificity. We have analyzed the feasibility of the simultaneous isolation of multiple antigen-specific T-cell populations in one procedure by combining different MHC I-Streptamers. First, the effect of combining different amounts of MHC I-Streptamers used in the isolation procedure on the isolation efficacy of target antigen-specific T cells and on the number of off-target co-isolated contaminating cells was assessed. The feasibility of this approach was demonstrated in large-scale validation procedures targeting both high and low frequent T-cell populations using the Good Manufacturing Practice (GMP)-compliant CliniMACS Plus device. T-cell products targeting up to 24 different T-cell populations could be isolated in one, simultaneous MHC I-Streptamer procedure, by adjusting the amount of MHC I- Streptamers per target antigen-specific T-cell population. Concurrently, the co-isolation of potentially harmful contaminating T cells remained below our safety limit. This technology allows the reproducible isolation of high and low frequent T-cell populations. However, the expected therapeutic relevance of direct clinical application without in vitro expansion of these low frequent T-cell populations is questionable. This study provides a feasible, fast and safe method for the generation of highly personalized MHC I-Streptamer isolated T-cell products for adoptive immunotherapy.

Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo. The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the MCvar1 PfEMP1. The in vitro inhibitory effect of PpMC-179 on human dermal microvascular endothelial cells (HDMECs) expressing multiple relevant adhesion molecules was investigated using a parallel-plate flow chamber. Pretreatment of endothelial monolayers with PpMC-179 (2 microM) inhibited the adhesion of infected erythrocytes (IRBCs) from all clinical isolates tested by 84.4% on resting and 62.8% on tumor necrosis factor alpha (TNF-alpha)-stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody 84H10 (5 microg/mL). To determine the in vivo effectiveness of PpMC-179, we used a human/severe combined immunodeficiency (SCID) mouse chimeric model that allowed direct visualization of cytoadherence on intact human microvasculature. In unstimulated skin grafts, PpMC-179 inhibited adhesion by 86.3% and by 84.6% in TNF-alpha-stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBCs by 80.7% and 83.3% on resting and stimulated skin grafts, respectively. The antiadhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadhesion in vivo is feasible and may offer a rapid antimalarial therapy.

Transapical aortic valve implantation at 3 years. Our objective was to analyze the results of transapical aortic valve implantation in high-risk patients with aortic stenosis at up to 3 years after the procedure. A total of 299 patients underwent transapical aortic valve implantation from February 2006 until January 2010 using the Edwards SAPIEN transcatheter xenograft. Mean patient age was 82 ± 6 years and 70% were female. Logistic EuroSCORE and Society of Thoracic Surgeons score predicted risks for mortality were 31% ± 16% and 12% ± 8%, respectively. All patients were treated in a hybrid operative theater by a team of anesthetists, cardiologists and cardiac surgeons. Successful valve implantation was performed in all patients. Transapical aortic valve implantation was uneventful in 267 patients (89.3%), whereas 32 patients (10.7%) required additional interventions. Such interventions included cardiopulmonary bypass support in 18, implantation of a second SAPIEN valve in 15, coronary intervention in 9, conversion to conventional surgery in 6, and annulus perforation in 3 patients (not mutually exclusive). Intraprocedural stroke was not observed in any patient, although 2 (0.7%) patients had a delayed stroke during their hospital stay. Overall survival was 91% at 30 days, 73% at 1 year, 68% at 2 years, and 58% at 3 years. Transapical aortic valve implantation can be performed with good outcomes in high-risk patients with aortic stenosis. Perioperative complications occur in approximately 10% of patients, and a variety of interventions are required for these events. We believe a team approach is therefore essential for the success of transapical aortic valve implantation.

Discriminating rigid from nonrigid motion: minimum points and views. Theoretical investigations of structure from motion have demonstrated that an ideal observer can discriminate rigid from nonrigid motion from two views of as few as four points. We report three experiments that demonstrate similar abilities in human observers: In one experiment, 4 of 6 subjects made this discrimination from two views of four points; the remaining subjects required five points. Accuracy in discriminating rigid from nonrigid motion depended on the amount of nonrigidity (variance of the interpoint distances over views) in the nonrigid structure. The ability to detect a rigid group dropped sharply as noise points (points not part of the rigid group) were added to the display. We conclude that human observers do extremely well in discriminating between nonrigid and fully rigid motion, but that they do quite poorly at segregating points in a display on the basis of rigidity.

Hazards associated with pregnancies and deliveries in lysinuric protein intolerance. Lysinuric protein intolerance (LPI) is an autosomal recessive transport disorder of the dibasic amino acids. The defect leads to deficiency of lysine, arginine, and ornithine and, secondarily, to a functional disorder of the urea cycle. Transient postprandial hyperammonemia and subsequent persistent protein aversion, linked with several other biochemical and clinical characteristics of the disease, suggest an increased risk for maternal and fetal complications during pregnancy and delivery. Our unique material on the outcomes of 18 pregnancies of 9 Finnish mothers with LPI and the follow-up of their 19 children shows that maternal LPI is truly associated with increased risk of anemia, toxemia, and intrauterine growth retardation during pregnancy and bleeding complications during delivery. Successful pregnancies and deliveries can still be achieved with careful follow-up of blood pressure and laboratory values. The children of the mothers with LPI generally develop normally. Special care of maternal protein nutrition and control of ammonemia, anemia, and toxemia during pregnancy are essential. We propose centralization of deliveries to obstetric units with capability to deal with bleeding complications and rare inborn errors of metabolism.

Bioassay of dapsone for possible carcinogenicity. A bioassay of dapsone, 4,4'-sulfonyldianiline, for possible carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered dapsone at one of two doses, either 600 or 1,200 ppm for rats and either 500 or 1,000 ppm for mice. The rats and mice were treated for 78 weeks; the rats were then observed for 26-28 weeks, the mice for 28-30 weeks. Matched controls consisted of groups of 15 untreated rats and 14 untreated mice of each sex, pooled controls, used for statistical evaluation, consisted of the matched controls combined with 30 male and 30 female untreated rats and 29 male and 29 female untreated mice from similarly performed bioassays of two other test chemicals. All surviving rats were killed at 104-106 weeks, all surviving mice at 106-108 weeks. Treated rats and mice had lower mean body weights than the corresponding controls; when treatment was discontinued at week 78, both species showed some increase in body weight. Survival among rats was unaffected by treatment with dapsone; adequate numbers of animals survived for meaningful statistical analyses of the incidences of tumors. Dapsone did not adversely affect the survival of mice, as shown by the test for positive dose-related trend. Suppurative bronchopneumonia was found in some mice in all matched-control and treated groups. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75. Among rats, mesenchymal tumors of the abdominal organs or peritoneal tissues occurred in 13/35 low-dose males and 22/33 high-dose males. None occurred among control males or among control or treated females. The most commonly occurring tumors were fibroma, fibrosarcoma, or sarcoma, NOS (not otherwise specified), of the spleen and the peritoneum. In male rats, these mesenchymal tumors of the spleen occurred in a statistically significant incidence in both treated groups (low-dose 6/34, P=0.006; high-dose 14/32, P<0.001) when compared with pooled controls. In the peritoneum, the incidences of these mesenchymal tumors were significant in both treated groups (low-dose 5/35, P=0.014; high-dose 6/33, P=0.005) when compared with the pooled controls. No tumors related to treatment were found in female rats. Among the mice, there were no tumors that could clearly be related to treatment. It is concluded that under the conditions of this bioassay, dapsone was not carcinogenic for female Fischer 344 rats or B6C3F1 mice of either sex. Dapsone was carcinogenic (sarcomagenic) for male Fischer 344 rats, causing mesenchymal tumors in the spleen and the peritoneum.

Helicobacter pylori and nonsteroidal anti-inflammatory drugs: interaction with proton pump inhibitor therapy for prevention of nonsteroidal anti-inflammatory drug ulcers and ulcer complications--future research needs. Two recently reported studies of nonsteroidal anti-inflammatory drugs (NSAIDs), the Omeprazole versus Misoprostol for NSAID-induced Ulcer Management and the Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment studies, concluded that omeprazole was superior to a subtherapeutic misoprostol or an ineffective dose of ranitidine for the endpoint, prevention of gastroduodenal ulcers in chronic NSAID users. Helicobacter pylori status was collected prospectively but was not reported. We report separate analyses for patients with unequivocal NSAID ulcers (H. pylori negative) and patients whose NSAID use was complicated by the presence of an active H. pylori infection. Omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, omeprazole was not significantly better than a subtherapeutic dose of misoprostol for the prevention of gastroduodenal ulcers in chronic NSAID users. Misoprostol was superior to omeprazole for the prevention of gastric ulcers among those patients with unequivocal NSAID ulcers (8.2% vs 16.6%, respectively; P <0.05). Omeprazole was not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Ranitidine and omeprazole were also not statistically different for the prevention of unequivocal NSAID gastric ulcers (14.6% vs 11.6%, respectively; P = 0.56). That the Misoprostol Ulcer Complications Outcomes Safety Assessment (MUCOSA) trial found full-dose misoprostol to be more effective in ulcer prevention than it was in prevention of ulcer complications suggests that either many of the ulcer complications were related to H. pylori ulcers or that more antisecretory activity than can be provided with misoprostol is needed, or both. The question remains whether the combination of low-dose misoprostol plus an antisecretory drug (either an H(2)-receptor antagonist or a proton pump inhibitor) would provide superior results compared with either alone. That omeprazole was not superior to one half the dose of misoprostol used in the ulcer complication prevention, or MUCOSA, study indicates that it would not be prudent to suggest that ulcer prevention with omeprazole alone would be able to provide similar protection to misoprostol.

Facilitators and barriers related to voluntary counseling and testing for HIV among young adults in Bo, Sierra Leone. In 2012, we interviewed a population-based sample of 285 young adult residents (age 18-35 years) of the city of Bo, Sierra Leone, about their attitudes toward and experience with voluntary testing and counseling (VCT) for HIV. In total, 33% of the participants (44% of women and 25% of men) reported having been tested for HIV at least once. More than 85% of those not previously tested indicated a willingness to be tested in the near future, but untested participants were nearly twice as likely as tested participants to report fears about family/partner rejection, job loss, and other potential consequences of testing. More than 90% of participants expressed a high desire for testing privacy, and the majority reported a preference for VCT at a facility far from home where no one would know them. Social barriers to HIV testing remain a challenge for HIV prevention in Sierra Leone.

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison. Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criteria. Error sensitivity analysis suggested the model that fits three parameters of the gray matter CBF, the gray matter fraction, and the white matter fraction with fixed white matter CBF as the most reliable and suitable for estimating the gray matter CBF. Reproducibility with this model was 11% for estimating the gray matter CBF. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic analysis. However, values were significantly smaller compared with those measured by stereologic analysis by 40%, which can not be explained by the methodologic errors. In conclusion, the partial volume correction was essential in quantitation of regional CBF. The method presented in this article provided the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI derived anatomic information for PVE correction in PET.

An improved profile-level domain linker propensity index for protein domain boundary prediction. Protein domain boundary prediction is critical for understanding protein structure and function. In this study, we present a novel method, an order profile domain linker propensity index (OPI), which uses the evolutionary information extracted from the protein sequence frequency profiles calculated from the multiple sequence alignments. A protein sequence is first converted into smooth and normalized numeric order profiles by OPI, from which the domain linkers can be predicted. By discriminating the different frequencies of the amino acids in the protein sequence frequency profiles, OPI clearly shows better performance than our previous method, a binary profile domain linker propensity index (PDLI). We tested our new method on two different datasets, SCOP-1 dataset and SCOP-2 dataset, and we were able to achieve a precision of 0.82 and 0.91 respectively. OPI also outperforms other residue-level, profile-level indexes as well as other state-of-the-art methods.

The pharmacokinetics of naloxone in the premature newborn. We examined the pharmacokinetic properties of naloxone in a group of premature infants infused with an intravenous bolus of the drug. Ten infants with a mean birth weight of 1,328 +/- 402 g and a gestational age of 29.4 +/- 2.8 weeks were studied at an age of 4.5 +/- 3.2 days of life. Following administration of 0.4 mg/kg of naloxone, we obtained blood samples at specific time intervals, and stored the serum for later analysis by a radioimmunoassay method. Calculations from the serum concentration versus time relationship resulted in an elimination rate constant of 0.75 +/- 0.39/h, a half-life of 70.5 +/- 35.2 min, a systemic clearance of 39.13 +/- 14.53 ml/min/kg, and an apparent volume of distribution of 3.52 +/- 1.20 liters/kg.

Fabrication of poly (trimethylene carbonate)/reduced graphene oxide-graft-poly (trimethylene carbonate) composite scaffolds for nerve regeneration. One of the key challenges for neural tissue engineering is to exploit functional materials to guide and support nerve regeneration. Currently, reduced graphene oxide (rGO), which is well-known for its unique electrical and mechanical properties, has been incorporated into biocompatible polymers to manufacture functional scaffolds for nerve tissue engineering. However, rGO has poor dispersity in polymer matrix, which limits its further application. Here, we replaced rGO with rGO-graft-PTMC. The rGO-graft-PTMC was firstly prepared by grafting trimethylene carbonate (TMC) oligomers onto rGO. Subsequently, PTMC/rGO-graft-PTMC composite fibrous mats were fabricated by electrospinning of a dispersion of PTMC and rGO-graft-PTMC. The loading of rGO-graft-PTMC could reach up to 6 wt% relative to PTMC. Scanning electron microscopy images showed that the morphologies and average diameters of PTMC/rGO-graft-PTMC composite fibrous mats were affected by the content of rGO-graft-PTMC. Additionally, the incorporation of rGO-graft-PTMC resulted in enhanced thermal stability and hydrophobicity of PTMC fibers. Biological results demonstrated that PC12 cells showed higher cell viability on PTMC/rGO-graft-PTMC fibers of 2.4, 4.0 and 6.0 wt% rGO-graft-PTMC compared to pure PTMC fibers. These results suggest that PTMC/rGO-graft-PTMC composite fibrous structures hold great potential for neural tissue engineering.

Network models of dissolution of porous media. We investigate the chemical dissolution of porous media using a 2D network model in which the system is represented as a series of interconnected pipes with the diameter of each segment increasing in proportion to the local reactant consumption. Moreover, the topology of the network is allowed to change dynamically during the simulation: As the diameters of the eroding pores become comparable with the interpore distances, the pores are joined together, thus changing the interconnections within the network. With this model, we investigate different growth regimes in an evolving porous medium, identifying the mechanisms responsible for the emergence of specific patterns. We consider both the random and regular network and study the effect of the network geometry on the patterns. Finally, we consider practically important problem of finding an optimum flow rate that gives a maximum increase in permeability for a given amount of reactant.

Composition and protein efficiency ratio of meat samples partially defatted with petroleum ether, acetone, or ethyl ether. Freeze-dried beef samples were partially defatted with either petroleum ether, acetone, or ethyl ether before determination of protein efficiency ratio (PER) to study the extraction effects on the composition and protein nutritional quality of the extracted beef. Defatting a protein source, such as meat or a meat product, may often be necessary to produce a test diet that contains 10% protein and 8% fat. Amino acid, carnosine, anserine, creatine, creatinine, inosine, and proximate compositions were determined on the extracted samples. Resulting data were compared to the composition and PER data of the beef that had no solvent treatment. Although the chemical analysis data from the study showed some variation between the proteins and other nitrogenous components of the unextracted and the extracted beef, these variations were too small to affect the protein nutritional quality of the beef as measured by PER.

Tug-of-War in a Dynamic Helical Peptide: Solvent-Induced Helix-Helix Transition of a Lactam-Bridged Peptide Composed of Point- and Axial Chiralities Remote from Each Other. The dynamic axial chirality of oligopeptide-bound 2,2'-bipyridine (bpy) residues can be remote-controlled and diastereoselectively locked. A right-handed (P)-310 -helix is first induced in the dynamic helical oligopeptide by an l-valine (l-Val) far from the bpy moiety and the induced axial bpy chirality is diastereoselectively dioxidized. The resulting l-Val-containing linear oligopeptides at the 3,3'-positions retain their (P)-310 -helices independent of the axial chirality (aR or aS) of the N-terminal N,N'-dioxide-bpy unit, while a lactam-bridged dynamic helical oligopeptide exhibits a unique solvent-induced helix-helix transition as a result of competitive helix-inducing biases between the l-Val and (aR) or (aS)-N,N'-dioxide-bpy residues remote from each other along the entire oligopeptide chain in a tug-of-war like manner.

Experience with femoral vein grafts for infra-inguinal bypass. Prosthetic grafts are used for infra-inguinal bypass when autogenous veins, are inadequate but have poorer patency and greater risk of graft infection. We report the use of femoro-popliteal vein (FPV) for such cases. FPV was used in 20 infra-inguinal bypasses (14 combined with other veins). 11 were primary and 9 secondary reconstructions, involving 13 femoro-tibial and 7 femoro-popliteal bypasses. Mean follow up was 78 months. At one year, limb salvage was 83%, primary patency 61%, primary assisted patency 73% and secondary patency 78%. FPV is an acceptable conduit for infra-inguinal bypass when other vein sources are inadequate.

Doxycycline determination in human serum and urine by high-performance liquid chromatography. A reversed-phase high-performance liquid chromatographic method for quantitative doxycycline determination in human serum and urine is described. The drug was extracted from buffered (pH 6.1) serum or urine into ethyl acetate. A structural analog, demeclocycline, was added as the internal standard. A 10-cm X 2-mm i.d., 5-micrometers Lichrosorb RP8 column with acetonitrile-0.1 M citric acid as the eluent was used. The effluent was monitored at 350 nm. The extraction recovery from spiked serum was 87-8 +/- 4.3% (mean +/- SD, n = 11); for urine, a value of 92.2 +/-2.0% (mean +/- SD, n = 10) was found. Within-run and within-day relative standard deviations averaged (x = 2.5 micrograms/ml, n = 10) and 4.75% (x = 2.6 micrograms/ml, n = 9), respectively. The detection limit was estimated at 50 ng/ml of serum. No significant extra peaks were observed in chromatograms obtained on serum or urine extracts, suggesting the probable absence of metabolic processes in vivo.

Histological alterations in the hepatic tissues of Al2O3 nanoparticles exposed freshwater fish Oreochromis mossambicus. Adverse effects of nanoparticles on aquatic environment and organisms have drawn much special attention to many researches. Aluminium oxide nanoparticles (Al2O3-NPs) have potential uses in varied fields and are seen entering into the ecosystem. Their potential toxicity to the freshwater fish is not much studied. Hence this study was framed to investigate the effect Al2O3 NPs on freshwater fish Oreochromis mossambicus in terms of sub lethal toxicity, histological changes and hepato somatic index (HSI) under laboratory conditions. Fishes were exposed to varying concentrations of Al2O3 NPs for 96hr. LC50 value was found to be in between 235 and 245ppm. The findings of the present work showed that the NPs were accumulated in the fish liver and caused major histological anomalies such as structural alterations in the portal vein, necrotic hepatocytes, vacuolation, aggregation of blood cells and melanomacrophages. Significant histological alterations were observed in the highest concentration. Our results evidenced that the Al2O3 NPs in the aquatic environment affects the health condition of the fishes.

Plasmablastic lymphoma of the stomach: an unusual presentation. Plasmablastic lymphoma (PBL) is listed in the World Health Organization (WHO) classification as a subtype of diffuse large B-cell lymphoma (DLBCL). Some morphologic features of PBL are similar to DLBCL; however, PBL has minimal or no expression of CD20 and leukocyte common antigen. Instead, PBL has been characterized by the plasmablastic morphology of the cancer cells, with high mitotic figures. It is believed to be an aggressive lymphoma. We describe a case of a patient who seemed to pose a diagnostic dilemma, and who was later found to have PBL.

Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese. Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease (P range from 4.57×10(-3) to 3.10×10(-6)). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure-related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18-66) and 26% (6-45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the P<0.05). Our data indicate that genetic predisposition to higher blood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure-associated polymorphisms remains to be determined.

Isoflurane induces expression of vascular endothelial growth factor through activating protein kinase C in myocardial cells. Vascular endothelial growth factor (VEGF) plays important roles in establishing collateral circulation of ischemic myocardium. This study aimed to investigate the effect of isoflurane on VEGF expression and the potential intracellular signal transduction pathway in cultured rat myocardial cells in order to further reveal the molecular mechanism of myocardial preservation of isoflurane. Primary myocardial cells of Sprague-Dawley rats were isolated and cultured. They were divided randomly into control group, isoflurane group, protein kinase C (PKC) inhibitor group and PKC inhibitor+isoflurane group where cells were respectively incubated without any treatment, treated by 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC) of isoflurane for 6 hours, by PKC inhibitor calphostin C at a final concentration of 50 nmol/L and by 50 nmol/L calphostin C+1.0 MAC isoflurane for 6 hours. VEGF expression was detected by enzyme-linked immunosorbent assay (ELISA) and the expression levels of PKC isoforms were determined by Western immunoblotting method. Isoflurane increased the VEGF expression in myocardial cells in a dose-dependent way. VEGF levels were significantly higher in 1.0 and 1.5 MAC isoflurane groups than in the control group (both P < 0.01). The effect of isoflurane on upregulating VEGF expression was blocked by PKC inhibitor calphostin C (P < 0.01), but calphostin C did not alter VEGF expression (P > 0.05). Isoflurane induced the activation and translocation of PKCε. Immunoblotting analysis revealed that the immunoreactivity of PKC ε increased significantly in the membrane fractions and deceased significantly in the kytoplasm fractions for cells treated with 1.0 MAC isoflurane as compared with the untreated cells, but not of PKC-α, PKC-δ and PKC-ζ (P less than 0.01). Isoflurane induces myocardial cells to release VEGF through activating PKC-epsilon from the endochylema to the cytomembrane, suggesting a possible novel mechanism of isoflurane protecting myocardial cells.

Simple table for estimating confidence interval of discrepancy frequencies in microbiological safety evaluation. We provide a simple tool to determine discrepancies confidence interval (CI) in microbiology validation studies such as technical accuracy of a qualitative test result. This tool enables to determine exact confidence interval (binomial CI) from an observed frequency when normal approximation is inadequate, that is, in case of rare events. This tool has daily applications in microbiology and we are presenting an example of its application to antimicrobial susceptibility systems evaluation.

Mitotic bypass via an occult cell cycle phase following DNA topoisomerase II inhibition in p53 functional human tumor cells. Cells cycle checkpoints guard against the inapproriate commitment to critical cell events such as mitosis. The bisdioxxopiperazzine ICRF-193, a catalytic inhibitor of DNA topoisomerase II causes a reversible stalling of the exit of cells from G(2) at the decatenation checkpoint (DC) and can generate tetraploidy via the compromising of chromosome segregation and mitotic failure. We have addressed an alternative origin-endocycle entry-for the tetraploidisation step in ICRF-193 exposed cells. Here we show that DC-proficient p53-functional tumor cells can undergo a transition to tetraploidy and subbsequent aneuploidy via an initial bypass of mitosis and the mitotic spindle checkpoint. DC-deficient SV4-tranformed cells move exclusively through mitosis to tetraploidy. In p53-functional tumor cells, escape through mitosis is enhanced by dominant negative p53 co-expression. The mitotic bypass transition phase (termed G(2)(endo)) disconnects cyclin B1 degradation from nuclear envelope breakdown and allows cells to evade the action of Taxol. G(2)(endo) constitutes a novel and alternative cell cycle phase-lasting some 8 h-with distinct molecular motifs at its boundaries for G(2) exit and subsequent entry into a delayed G(1) tetraploid state. The result challenge the paradigm that checkpoint breaching leads directly to abnormal ploidy states via mitosis alone. We further propose that the induction of bypass could: facilitate the covert development of tetraploidy in p53 functional cancers, lead to a misinterpretation of phase allocation during cell cycle arrest and contribbute to tumor cell drug resistance.

Let's talk about health: shoppers' discourse regarding health while food shopping. The present study aimed to examine the role of health in consumers' food purchasing decisions through investigating the nature of people's discourse regarding health while conducting their food shopping. The study employed the think-aloud technique as part of an accompanied shop. All mentions of health and terms relating to health were identified from the data set. Inductive thematic analysis was conducted to examine how health was talked about in relation to people's food choice decisions. Supermarkets in Dublin, Republic of Ireland and Belfast, Northern Ireland. Participants (n 50) were aged over 18 years and represented the main household shopper. Responsibility for others and the perceived need to illicit strict control to avoid 'unhealthy' food selections played a dominant role in how health was talked about during the accompanied shop. Consequently healthy shopping was viewed as difficult and effort was required to make the healthy choice, with shoppers relating to product-based inferences to support their decisions. This qualitative exploration has provided evidence of a number of factors influencing the consideration of health during consumers' food shopping. These results highlight opportunities for stakeholders such as public health bodies and the food industry to explore further ways to help enable consumers make healthy food choices.

Teaching and assessment of professional attitudes in UK dental schools - commentary. The General Dental Council expects professionalism to be embedded and assessed through-out the undergraduate dental programme. Curricula need therefore to accommodate these recommendations. A stroll poll of UK dental schools provided a basis for understanding the current methods of teaching and assessing professionalism. All respondent schools recognised the importance of professionalism and reported that this was taught and assessed within their curriculum. For most the methods involved were largely traditional, relying on lectures and seminars taught throughout the course. The most common form of assessment was by grading and providing formative feedback after a clinical encounter. Whilst clinical skills and knowledge can perhaps be readily taught and assessed using traditional methods, those involved in education are challenged to identify and implement effective methods of not only teaching, but also assessing professionalism. A variety of standalone methods need to be developed that assess professionalism and this will, in turn, allow the effectiveness of teaching methods to be assessed.

Inhibition of tumor promotion by a lecanoric acid analogue. 3',5'-Dichloro-2,4'-dihydroxybenzanilide, an inhibitor of histidine decarboxylase, inhibited skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate in mice.

Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome. Mutations in SLC29A3 lead to pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy plus syndrome. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes, and cardiomyopathy. A 12-year-old girl with PHID syndrome presented with shortness of breath, hepatosplenomegaly, and raised erythrocyte sedimentation rate and C-reactive protein. An echocardiogram showed biventricular myocardial hypertrophy, and cardiac magnetic resonance imaging showed circumferential late gadolinium enhancement of the myocardium. No systemic amyloid deposits were observed on a whole-body serum amyloid P scintigraphy scan. Abdominal ultrasound revealed intra-abdominal fat surrounding the solid organs, suggesting a possibility of evolving lipodystrophy with visceral adiposity. PHID syndrome is a novel monogenic autoinflammatory syndrome (AIS) associated with severe elevation of serum amyloid. Lipodystrophy, cutaneous sclerodermatous changes, and cardiomyopathy were also present in this case. In contrast to other AIS, blockade of interleukin-1 and tumor necrosis-α was ineffective.