[Severe course of a rare non-tuberculous Mycobacteriosis (M. haemophilum) of the hand - case report and strategic comments].
Mycobacterium haemophilum belongs to the group of atypical mycobacteria and is rarely reported as a cause of upper extremity and hand infections. It is of low virulence. The bacterium seems to be ubiquitous. Sources and mechanism of infection are poorly defined. A 48-year-old female patient was admitted with chronic flexor tendon synovitis of the left palm and distal forearm site. Three debridements were carried out and wound swabs were taken. No proof of bacterial colonisation was found. Histologically a granulomatous infection with Langerhans cells was revealed. Effectively calculated monotherapy with ciprofloxacin was begun. Six weeks postoperatively Mycobacterium haemophilum was cultivated in a colaboration with the National Reference Centre for Mycobacteria in Borstel. Medication was changed to triple therapy with clarithromycin, ethambutol and rifabutin. The patient could carry out her daytime job three months postoperatively. One year after first admission functional impairment needed to be treated by scar excision and radical flexor tendon tendolysis. The palmar defect was resurfaced by using a transmetacarpal DMCA 2 flap at the same time. An almost full range of motion was achieved with intensive hand and physiotherapy after a total treatment period of 15 months. Patients with upper extremity infections caused by atypical Mycobacteria need qualified hand-surgical care. The decision about need and kind of medicamentous treatment is based on germ differentiation and should be made in cooperation with the National Reference Centre for Mycobacteria in Borstel. To shorten the diagnostic gap between first admission and detection of Mycobacteria in hand infections with a non-typical course of disease we suggest a standardised approach.


Changing prescription patterns: impact on costs.
The cost of treating hypertension is high. In the Federal Republic of Germany the total sales of antihypertensive compounds increased, from 1981 to 1984, from 1075 million to 1525 million DM per year, corresponding to 7.4 and 9.1%, respectively, of total drug expenditure. Economists have calculated that about two-thirds of this increase is caused by structural changes within the market, i.e. changing prescription patterns. The proportion of prescribed daily doses of reserpine combinations dropped from 52 to 34% whereas that of most other compounds increased. The approximate daily costs of treatment vary from 0.5 DM (reserpine combinations) to 2.5 DM [angiotensin converting enzyme, (ACE) inhibitors], but the decline of the cheaper compounds and their substitution by newer and more expensive drugs has resulted in additional costs of 309-328 million DM. The higher prices of the new drugs should be justified by greater benefits compared with conventional compounds. Assessment of new antihypertensive drugs should include potency, efficacy, number and quality of adverse effects, and impact on quality of life. The evaluation should be performed separately for mild and for more severe forms of hypertension. Some advantages or drawbacks of the newer drugs may be important for small subgroups only.


[Early prognostic assessment using evoked potentials in severe craniocerebral trauma].
103 patients in acute posttraumatic coma were assessed during 72 hours following severe head injury by clinical examinations (documented with a modified Glasgow-Coma-Score and a brain-stem-score and brainstem auditory evoked potentials (BAEP) as well as short latency somatosensory evoked potentials (SEP). Patient outcomes were classified at 6 months or more, according to the following categories: good recovery, severely disabled or vegetative, and brain dead. Patients who had died by systemic complications were excluded from the study. The Glasgow-Coma-Score was reliable in forecasting a favorable outcome, but tended to produce false-pessimistic predictions. The brainstemscore and the BAEPs were reliable predictors of an unfavorable but not a favorable outcome. SEP data however, performed well as a prognostic indicant in predicting an unfavorable as well as a favorable outcome. Using the BAEP, the amplitude ratio Wave V/Wave I is more sensitive to detect a lesion than the interpeak-latency Wave I-Wave V, and--using the SEP--the amplitude ratio N20/N13b (over C2) is more sensitive than the central conduction time (N13a (over C7)--N20).


Patent ductus arteriosus in adults: surgical experience in Ivory-Coast.
Patent ductus arteriosus surgery is well documented. Hospital Mortality has reduced to almost 0%. Yet, with adults, this surgical cure is likely to be difficult and require some technical skills A retrospective study of surgical procedures and results after surgery of patent ductus arteriosus (PDA) in adults. Since 1978 to 2000 we have reported 16 operated cases. The average age was 22.5 years. There was female predominance with a sex ratio of 2.3/1. All patent ductus arteriosus had been confirmed by two dimensional echocardiography (2D echocardiography) and cardiac catheterization. All hemodynamic types of Nadas classification were observed. Double or triple ligation supported on Teflon felt was the most frequent technique used (69%). This technique gave good results in view of the absence of hospital mortality and only 1 case of recanalisation after a long follow up of all patients from 1 - 7 years (mean 5 years). Double or triple ligation on Teflon felt according to Wright technique is a good technique.


Cryoinsolubility of peanut agglutinin. Effect of saccharides and neutral salts.
Peanut agglutinin (PNA) has been shown to be insoluble at low temperatures. This cryoinsolubility has been studied by means of absorption spectroscopy, fluorescence, circular dichroism, and analytical ultracentrifugation. It was found to be dependent on pH, temperature, and protein concentration. No effects on dimer-tetramer equilibrium could be determined nor any conformational changes provoked by exposure of the PNA preparation to low temperatures. The dimer half-molecule apparently does not precipitate. The cryoinsolubility was partially reversible and totally inhibited in the presence of galactosides, the specific ligands of PNA. Their efficacy as inhibitors of cryoinsolubility was related to their affinity for the lectin. The effects of neutral salts and particularly inhibition of the insolubility by strongly chaotropic salts indicate that charge-charge interactions are of little importance and that hydrogen bonds and/or van der Waals interactions are most probably responsible for the formation of the cryoprecipitate.


Laboratory method for measuring small amounts of tissue glycogen.
A procedure is reported which is well applicable for the quantitative determination of glycogen, especially in cases of a small glycogen content in a small amount of tissue. The method consists of extraction of glycogen by boiling potassium hydroxide, precipitation with ethanol, hydrolysis with sulphuric acid, and determination of the glycogen in form of glucose obtained with orthotoluidine.


Temporal Changes Rather than Long-Term Repeated Burning Predominately Control the Shift in the Abundance of Soil Denitrifying Community in an Australian Sclerophyll Forest.
To understand the temporal dynamics of soil bacterial denitrifying community in response to long-term prescribed burning and its resilience and recovery following a fire, a wet sclerophyll forest study site under two treatments (2 yearly burning (2YB) and no burning (NB)) and with 40-year-old burning history was used. Similar temporal patterns in the abundance of total (16S rRNA) and denitrifying (narG, nirK, nirS, nosZ) bacteria between two burning treatments revealed strong temporal influences. The magnitude of burning impacts on the abundance of 16S rRNA and denitrification genes was smaller compared with the impact of sampling time, but significant burning and temporal impacts were recorded for all (P < 0.001)-except for the nirS gene. Impacts of prescribed fire on the abundance of soil denitrifying community could be observed immediately after fire, and this impact diminished over a 24-month period prior to the next prescribed burning event. In conclusion, temporal changes govern the fluctuations of the abundance of soil denitrifying genes over the sampling period and the denitrifying community can recover after fire, suggesting that this community is resilient to the effects of prescribed burning. A combination of biotic and abiotic factors may account for the different temporal dynamics of denitrification gene abundance.


Postoperative complications in patients with obstructive sleep apnea: a meta-analysis.
To determine whether a diagnosis of obstructive sleep apnea (OSA) imparts an increased risk of postoperative respiratory failure, cardiac events, and intensive care unit (ICU) transfer than patients with no OSA diagnosis. Systematic review and meta-analysis. Academic Veterans Affairs Medical Center. PubMed, EMBASE, CINAHL, and ISI Web of Knowledge databases were searched through April 2013 for studies that examined the relationship between OSA and postoperative respiratory and cardiac complications among adults. Either fixed or random-effects models were used to calculate the pooled risk estimates. Sensitivity analysis was conducted to examine the robustness of pooled outcomes. Seventeen studies with a total of 7,162 patients were included. Overall, OSA was associated with significant increase in risk of respiratory failure [odds ratio (OR) 2.42; 95% confidence intervals (CI) 1.53 - 3.84; P = 0.0002] and cardiac events postoperatively (OR = 1.63; 95% CI 1.16 - 2.29; P = 0.005). Heterogeneity was low for these outcomes (I(2) = 5% and 0%, respectively). ICU transfer occurred also more frequently in patients with OSA (OR 2.46; 95% CI 1.29 - 4.68; P = 0.006). These results did not materially change in the sensitivity analyses according to various inclusion criteria. Surgical patients with OSA are at increased risk of postoperative respiratory failure, cardiac events, and ICU transfer.


Control of quantal transmitter release at frog's motor nerve terminals. II. Modulation by de- or hyperpolarizing pulses.
Quanta of transmitter were released from motor nerve terminals of the frog by a depolarizing 'releasing pulse'. 'Modulating pulses' were subthreshold for release; pre-pulses were added directly before and post-pulses directly after the releasing pulse. Modulating depolarization pulses enhanced release up to 20-fold, and such hyperpolarizations suppressed release up to 10-fold. Pre- and post-pulses were about equally effective. In a wide range these modulations did not affect the facilitation of a test-EPSC by the preceding releasing pulse; modulation thus is not mediated by changes in Ca-inflow. It is suggested that phasic release is largely controlled by an 'activator' which is generated by depolarization, and that modulating pulses increase this activator when depolarizing, and decrease this activator below its resting level if hyperpolarizing. If an interval was interposed between pre- and releasing pulse, the modulating effect decreased very steeply with increasing interval for the first 2 ms, and much slower for longer intervals. Distributions of delays of quantal releases showed a time course of decay very similar to the decay of modulation with increasing interval. Both decays may reflect the exponential decay of activator. Depolarizing post-pulses increased the minimal synaptic delay and the delay of maximal release, and hyperpolarizing ones had the opposite effects. They are interpreted to modulate the generation and decay of a 'repressor', which is produced by depolarization and is responsible for the minimal synaptic delay and the delayed maxima of release. A speculative scheme of interactions of [Ca]i, activator and repressor is discussed.


Organisation of bone morphogenetic proteins in renal development.
Bone morphogenetic proteins (BMPs) comprise the largest subfamily of the transforming growth factor-beta (TGF-beta) superfamily of secreted proteins. Evidence for the involvement of BMPs in metanephric development emerged recently when renal phenotypes were observed in BMP7 null mutant mice. Since then, several other BMPs, BMP receptor serine/threonine kinases and BMP signal transduction molecules (Smads) have been implicated in mammalian metanephric development. It appears that particular BMPs have pivotal roles in specific aspects of metanephric development. Current knowledge and evidence of specific roles of particular BMPs are presented in this review.


Genetic mapping of meander tail, a mouse mutation affecting cerebellar development.
The meander tail mouse harbors a recessive mutation on chromosome 4 that affects the anterior lobes of the cerebellum and the caudal vertebrae. Examination of the mea/mea cerebellum reveals that the complete disorganization of all cell types seen in the anterior lobes is separated by a sharp and consistent boundary from the normal cytoarchitecture of the posterior lobes. In the absence of any biochemical information regarding the affected gene product, attempts to clone the gene must rely on the strategy of reverse genetics. As an initial step in this process we have constructed a genetic linkage map spanning 68 cM of chromosome 4 using an intersubspecific phenotypic backcross. The loci included in this analysis are Calb, Ggtb, Lv, b, Ifa, mea, D4Rp1, Glut-1, Lck, Lmyc-1, and Eno-1. This analysis positions the mea phenotypic locus in the interval between Ifa and Glut1. These results also further define regions of homology between mouse chromosome 4 and human chromosomes 8, 1, and 9. This linkage map provides the means to evaluate candidate genes, and to identify tightly linked markers useful for cloning the meander tail locus.


[Reye's syndrome. Discussion of a clinical case].
A case of Reye's syndrome in an unweaned child aged 5 1/2 months is reported. The boy presented ingravescent neurological symptomatology accompanied by sporadic gastrointestinal signs and by marked renal impairment, with total, or nearly total absence of pathognomonic laboratory data. The diagnosis was confirmed by autopsy.


Serum cholesterol levels in patients with familial hypercholesterolemia confirmed by tissue culture.
Sixty-two subjects from 23 families were evaluated by serum lipid analyses and tissue culture biochemistry in skin fibroblasts. In 53 cases from 19 families with proven familial hypercholesterolemia (FHC), fibroblast cultures were successful. In 45 of these cases (85%) the clinical diagnosis of hyper- or normocholesterolemia was in accordance with the tissue culture findings. Four patients 2-38 years old, had hypercholesterolemia but normal tissue culture results. Four patients, 18-44 years old, had normal serum cholesterol levels for their age and sex, but were heterozygotes according to tissue culture results. In the remaining four families only the propositus had hypercholesterolemia. All members of the families including the propositus had normal tissue culture determinations indicating that not all cases of idiopathic hypercholesterolemia are due to the Goldstein-Brown mechanism of defective LDL receptor function.


Cisapride improves gastric emptying in mechanically ventilated, critically ill patients. A randomized, double-blind trial.
We conducted a randomized, double-blind, placebo-controlled trial in mechanically ventilated intensive care unit (ICU) patients to evaluate the effect of cisapride on gastric emptying using an acetaminophen absorption model. We enrolled 72 patients expected to remain in the ICU for more than 48 h; 39% were female; the average age was 54.0 +/- 19.1 yr; 47% were postoperative, 83% were receiving narcotics, and the mean simplified acute physiology score (SAPS) was 9.5 +/- 3.0. Within 72 h of admission to ICU, 1.6 g of acetaminophen suspension was administered via a nasogastric tube into the stomach (Day 1). Blood samples were drawn at baseline, 30, 60, 90, 120, and 180 min for measurement of plasma acetaminophen levels. The following morning (Day 2), patients were randomized to receive 20 mg of cisapride or placebo and gastric emptying was again assessed. The difference (Day 2-Day 1) in the maximal plasma concentration was 49.1 mumol/L in the cisapride groups compared with 12.3 mumol/L in the placebo group (p = 0.005) and the time to reach maximal concentration was significantly shorter in the cisapride group (-40.8 min versus -4.2 min, p = 0.02). The difference in area under the time-acetaminophen concentration curve was also greater in the patients receiving cisapride (5,534 versus 2,832, p = 0.09). We conclude that cisapride enhances gastric emptying in critically ill patients. Studies to examine the effect of cisapride on tolerance to enteral nutrition, infectious morbidity, and other clinically important outcomes are warranted.


A method for purification and characterisation of Mycobacterium avium subsp. paratuberculosis from the intestinal mucosa of sheep with Johne's disease.
Mycobacterium avium subsp. paratuberculosis, the cause of Johne's disease in ruminants, cannot be cultured in large quantities from affected sheep in Australia. A method is described for the purification of the organism from the intestinal mucosa of sheep with multibacillary Johne's disease in order to undertake restriction fragment length polymorphism (RFLP) analysis for epidemiological purposes. Using sucrose and potassium chloride as separation media for differential and density gradient centrifugation, yields of approximately 90 mg dry weight M. avium subsp. paratuberculosis per 5 g intestinal mucosa were obtained. The preparations of purified M. avium subsp. paratuberculosis were visually free of non-acid fast bacteria and contained 10(2)-10(3) aerobic/ facultatively anaerobic organisms per gram wet weight. DNA extracted from purified M. avium subsp. paratuberculosis was examined by hybridisation with an IS900 probe after digestion with BstEII and RFLP patterns distinct from isolates from cattle were obtained. The RFLP pattern of purified M. avium subsp. paratuberculosis from five sheep matched that obtained previously from organisms cultured from sheep in studies in New Zealand, indicating that the purification and RFLP method is robust.


Morphology engineering of Aspergillus oryzae for l-malate production.
Aspergillus oryzae is a competitive natural producer for organic acids, but its production capacity is closely correlated with a specific morphological type. Here, morphology engineering was used for tailoring A. oryzae morphology to enhance l-malate production. Specifically, correlation between A. oryzae morphology and l-malate fermentation was first conducted, and the optimal range of the total volume of pellets in a unit volume of fermentation broth (V value) for l-malate production was 120-130 mm3 /ml. To achieve this range, A. oryzae morphology was improved by controlling the variation of operational parameters, such as agitation speed and aeration rate, and engineered by optimizing the expression of cell division cycle proteins such as tyrosine-protein phosphatase (CDC14), anaphase promoting complex/cyclosome activator protein (CDC20), and cell division control protein 45 (CDC45). By controlling the strength of CDC14 at a medium level, V value fell into the optimal range of V value and the final engineered strain A. oryzae CDC14(3) produced up to 142.5 g/L l-malate in a 30-L fermenter. This strategy described here lays a good foundation for industrial production of l-malate in the future, and opens a window to develop filamentous fungi as cell factories for production of other chemicals.


Influence of salt depletion and hydralazine-induced vasodilatation on accuracy of selective renal vein sampling in patients with essential hypertension and renal artery stenosis.
The diagnostic accuracy of renal vein renin (RVR) analyses was evaluated in 63 hypertensive patients treated with sodium depletion and/or hydralazine prior to selective renal vein sampling. A positive RVR study (i.e., lateralization of RVR) was defined as a ratio greater than or equal to 1.5 when RVR from the kidney with renal artery stenosis was compared to RVR from the contralateral kidney. Approximately 40% of patients with essential hypertension had positive RVR studies. Among patients with renal artery stenosis, surgical outcome was correctly predicted in 5 of 8 patients (63%) treated with sodium depletion, whereas outcome was accurately predicted in 11 of 12 patients (92%) treated with hydralazine. These observations demonstrate that a high percentage of patients with essential hypertension have positive RVR studies despite arteriographically normal renal vasculature. Results obtained in patients with renal artery stenosis suggest that stimulation of renin secretion by hydralazine may be of particular advantage prior to renal vein sampling. However, additional data are required to confirm whether activation of specific mechanisms for renin release improves the reliability of the RVR test.


The implicit influence of a negative mood on the subliminal mere exposure effect.
Despite numerous studies on the mere exposure effect, it is still not clear why it occurs. The present study examined whether a negative mood would enhance or inhibit the effects. Fifty-two participants (30 men, 22 women; M age = 20.5 yr.) were assigned to one of two mood-induction groups (negative and neutral), and were exposed to a photograph 20 times after the mood induction. Thereafter, a single-category Implicit Association Test was conducted to measure their implicit attitudes toward the photograph. There was a significant interaction, with exposed stimuli evaluated more favorably than unexposed stimuli in the neutral condition, but not in the negative condition. This result suggests that a negative mood inhibited the mere exposure effect, implying that people could use their emotional states as cues to evaluate ambiguous objects that they have been repeatedly exposed to.


A rare nosological entity: the perforated solitary cecal diverticulum. Research article.
To describe three cases of solitary cecal diverticulum, and trying to evaluate the better method of diagnosis and treatment with analysis of the literature. Description of three cases of solitary cecal diverticulum's perforation admitted in the Department of General and Oncologic Surgery, Santa Maria della Misericordia Hospital, Perugia, during the period January 2011 - January 2012. In all patients the clinical presentation was very similar to that of acute appendicitis. Preoperative diagnosis was achieved in one case through abdominal CT scan, other two cases were identified at final pathology. At one year from the treatment all patient are still alive. Cecal diverticulum is a rare condition, often diagnosed either casually or because of inflammatory or perforative complications. The highest incidence is found in Western population. Because of the clinical presentation, very similar to the appendicitis, and the inflammatory reaction involving the colon and its surrounding tissues, the pre- and intra-operative diagnosis are very difficult. The diagnosis is almost always histological. The treatment may vary from simple expectant medical management, carried out with bowel rest, parenteral support and antibiotics as for left-sided diverticulitis, to surgical approach, performed through simple diverticulectomy or by classical right hemicolectomy. Pre-surgical and, also intra-operative, diagnosis of perforated solitary cecal diverticulum is clearly difficult. CT scan represents the gold standard for the differential diagnosis. Right hemicolectomy is an effective and safe approach, allowing accurate control, preventing complications and recurrences, and it represents the optimal management of the disease.


Interphase cytogenetics in oncocytic adenomas and carcinomas of the thyroid gland.
Follicular neoplasms of oncocytic type in the thyroid gland frequently cause diagnostic problems and prognostic uncertainties. To identify numerical chromosomal aberrations of possible pathogenetic importance, we determined chromosome copy numbers in situ in interphase nuclei of 31 oncocytic adenomas and 25 oncocytic carcinomas. Archival formaldehyde-fixed, paraffin-embedded tumor samples and normal control thyroid tissues were arranged in arrays and analyzed by fluorescence in situ hybridization (FISH). We used pericentromeric or locus specific probes for chromosomes 1, 7, 8, 9, 11, 12, 17, 18, 22, and X as well as for the oncogenes Her2/neu, cyclin D1, N-myc, and c-myc. The average number of aneusomies per nucleus was significantly higher in carcinomas than in adenomas, and in both, monosomies were more frequent than polysomies. Loss of chromosome 22 was found in 8 of 21 (38%) carcinomas; in 5 cases, it was associated with chromosome 2 monosomy. Conversely, chromosome 2 aberrations were not found in adenomas. Monosomies for chromosome 8 and X were detected in most adenomas and carcinomas. The most common gains in adenomas and carcinomas were for chromosome 7 (13.8% and 32.0% of the cases, respectively), chromosome 12 (9.6% and 12.0%), and chromosome 17 (19.3% and 32.0%). None of the adenomas with trisomy 17 was associated with gains for chromosomes 7 and 12. None of the analyzed oncogenes was found to be amplified by FISH analysis. Our results indicate that numerical chromosomal aberrations in oncocytic follicular tumors of the thyroid gland are common findings and suggest that different patterns of aberrations may occur in these neoplasms.


Spinal anesthesia for cesarean section in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disorder of the peripheral nervous system with progressive or relapsing signs in more than one limb, ending in prolonged periods of disability. There are no guidelines for anesthesia in this uncommon paralyzing disease. This report features a 19-year-old woman with CIDP scheduled for an elective cesarean section who had prolonged recovery of motor function after the administration of spinal anesthesia. Although a partial neural block in both feet persisted for 1 day, we conclude that spinal anesthesia is acceptable for cesarean delivery in CIDP-patients when reasonable precautions have been taken.


Design, fabrication, and testing of convex reflective diffraction gratings.
The convex reflective diffraction grating is an essential optical component that lends itself to various applications. In this work, we first outline the design principles of convex diffraction gratings from wavefront quality and efficiency perspectives. We then describe a unique fabrication method that allows for the machining of convex diffraction gratings with variable groove structure, which is extendable to rotationally non-symmetric convex diffraction grating substrates. Finally, we demonstrate two quantitative wavefront measurement methods and respective experimental validation.


Midbrain raphe hypoechogenicity in migraineurs: An indicator for the use of analgesics but not triptans.
Introduction The involvement of the serotonergic system of the brainstem raphe in the pathogenesis of migraine is discussed. Here we studied brainstem alterations in migraineurs using transcranial sonography and examined their relation to clinical features and self-medication. Methods We investigated 51 migraineurs (11 men, 40 women, mean age 29.7 ± 11.9 years) and 32 healthy individuals without history of headache or depressive disorder (eight men, 24 women, mean age 34.4 ± 13.0 years). Transcranial sonography was performed in an investigator-blinded fashion. Midbrain raphe echogenicity was quantified using digitized analysis. Migraine characteristics and the use of analgesics were evaluated by applying validated questionnaires. Eight migraineurs underwent neurophysiologic evaluation of contingent stimulus-related cortical potentials. Results Echo-reduced midbrain raphe was detected in 27 (53%) migraineurs, but only six (19%) control subjects (odds ratio = 4.87, p = 0.002). Lower raphe echogenicity correlated with both higher amplitude of terminal contingent negative variation (Spearman test, r = 0.76, p = 0.028) and higher use of analgesic drugs ( r = -0.45, p = 0.011), but not with use of triptans or with migraine frequency or severity (all p > 0.2). Compared to migraineurs without aura, migraineurs with aura had enlarged third ventricles (t-test, p = 0.014), while the lateral ventricle widths did not differ ( p = 0.62). Conclusions Midbrain raphe alteration is frequent in migraineurs and relates to self-medication behavior. This alteration may reflect the dysfunction of serotonergic raphe nuclei.


Novel P-T Phase Diagram of the Multiorbital Mott Insulator Sr2VO4.
The electrical and optical properties of the Mott insulator Sr2VO4 are investigated under high pressure on a phase pure polycrystalline sample. The system undergoes a pressure-driven insulator to metal transition (IMT) with a crossover between 20 and 24 GPa. The effect of pressure on the thermally driven electronic changes resulting from spin-orbital ordering transitions is studied. A multiorbital analysis of the low frequency optical conductivity spectra suggests a bandwidth-controlled and orbital selective nature of the Mott IMT transition. Dramatic enhancement of the low energy spectral weight in the high pressure correlated metallic phase is explained in terms of the formation of a quasiparticle peak in the spectral function of the narrow and degenerate d(yz,zx) orbitals. Our results overall establish a novel electronic phase diagram of tetragonal Sr2VO4.


Inhibitory effects of plasma from uraemic patients on human mononuclear phagocytes cultured in vitro.
Human mononuclear phagocytes were cultured in plasma from uraemic patients. The presence of uraemic plasma during the engulfment or digestion of 125I-labelled Candida albicans did not inhibit these functions in mononuclear phagocytes cultured for 8 days under normal condition. When normal human macrophages were cultured in the presence of uraemic plasma for 2-4 days, a marked detachment of the cells from the glass coverslips was registered. The phagocytic function of the remaining cells was impaired. Creatinine, urea and methylguanidine in concentrations higher than those usually measured in plasma from uraemic patients did not influence the functional properties of the cells. The inhibitory effect of uraemic plasma on the mononuclear phagocytes is suggested as an explanation for the increased frequency of infections in uraemic patients.


Activity of certain fractions of Tribulus terrestris fruits against experimentally induced urolithiasis in rats.
An ethanolic extract of the fruits of T. terrestris showed significant dose dependent protection against uroliths induced by glass bead implantation in albino rats. On subsequent fractionation of the ethanol extract, maximum activity was localised in the 10% aqueous methanol fraction. It provided significant protection against deposition of calculogenic material around the glass bead. It also protected leucocytosis and elevation in serum urea levels. Further, fractionation lead to decreased activity. This could be either due to loss of active compounds during fractionation, or the antiurolithiatic activity of T. terrestris being a combined effect of several constituents present in the methanolic fraction.


A mouse-attenuated envelope protein variant of Murray Valley encephalitis virus with altered fusion activity.
A neutralization escape variant of Murray Valley encephalitis virus (MVE), of low neuroinvasiveness in mice and with low haemagglutination activity, had a reduced rate of replication in cultured cells during the early phase of infection compared to wild-type MVE. The variant was internalized by Vero cells at a similar rate to wild-type MVE at pH 7.4, but had reduced pH-dependent membrane fusion activity. In fusion-from-within experiments in infected mosquito (C6/36) cells, the variant had a lowered pH threshold for induction of fusion, which occurred at a reduced rate and to a lesser extent than for wild-type virus. Fusion was inhibited by monoclonal antibodies specific for envelope protein epitopes E-5 and E-8, which were implicated as determinants of fusion. These observations are discussed in relation to the regulation of MVE replication by fusion of the viral envelope with endosome membranes and, in turn, how rates of replication may affect neuroinvasion.


Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity: Differential regulation of COX-2/PGE2 pathway.
To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100mg/kg) for 14days. In independent groups, lithium chloride (4meq/kg/day i.p.) was administered at day 4 of the experiment for 10days, with or without GRb1. Li+ caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+ also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+ significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+ levels by about 50% in serum, urine and brain and by 35% in the kidney. Interestingly, Li+ had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway, as it significantly increased COX-2 expression and PGE2 level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+ suppressed COX-2/PGE2 pathway in both kidney and brain compared to Li+ alone. In conclusion, GRb1 can alter Li+ pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2 pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.


Anatomically flexible, computer-assisted reporting system for coronary angiography.
A computer-assisted method for reporting coronary arteriographic findings has been developed. A videographic display with a touch input system permits finger pointing to designate arterial segments, lesion locations, graft insertion points and collateral vessels. The coronary diagram is flexible to accommodate variations in dominance and in the size and length of the left coronary system branches. Lesion severity, type and length of lesions, distal vessel anatomy, collateral circulation and coronary bypass grafts (including Y or jump grafts) are displayed pictographically. A tabular summary and graphic output provide a completed coronary report eliminating the need for narrative dictation. An edit mode provides capability for teaching and review. The computer-assisted reporting method has the advantage of automatic data encoding in formats suitable for data base storage and subsequent retrieval.


Maternal obesity and risk for birth defects.
Several studies have shown an increased risk for neural tube defects associated with prepregnancy maternal obesity. Because few recent studies have examined the relation between maternal prepregnancy obesity and overweight and other birth defects, we explored the relation for several birth defects and compared our findings with those of previous studies. We conducted a population-based case-control study of several selected major birth defects using data from the Atlanta Birth Defects Risk Factor Surveillance Study. Mothers who delivered an infant with and without selected birth defects in a 5-county metropolitan Atlanta area between January 1993 and August 1997 were interviewed. Maternal body mass index (BMI) was calculated from self-reported maternal prepregnancy weight and height. Women with known preexisting diabetes were excluded. The risks for obese women (BMI > or =30) and overweight women (BMI 25.0-29.9) were compared with those for average-weight women (BMI 18.5-24.9). Obese women were more likely than average-weight women to have an infant with spina bifida (unadjusted odds ratio [OR]: 3.5; 95% confidence interval [CI]: 1.2-10.3), omphalocele (OR: 3.3; 95% CI: 1.0-10.3), heart defects (OR: 2.0; 95% CI: 1.2-3.4), and multiple anomalies (OR: 2.0; 95% CI: 1.0-3.8). Overweight women were more likely than average-weight women to have infants with heart defects (OR: 2.0; 95% CI: 1.2-3.1) and multiple anomalies (OR: 1.9; 95% CI: 1.1-3.4). Our study confirmed the previously established association between spina bifida and prepregnancy maternal obesity and found an association for omphalocele, heart defects, and multiple anomalies among infants of obese women. We also found an association between heart defects and multiple anomalies and being overweight before pregnancy. A higher risk for some birth defects is yet another adverse pregnancy outcome associated with maternal obesity. Obesity prevention efforts are needed to increase the number of women who are of healthy weight before pregnancy.


Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.
Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)


Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and body mass index: clinical correlates of prostate volume among Black men.
To examine the relationship between insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and body mass index and prostate volume, as a surrogate marker for benign prostatic hyperplasia, in a community-based sample of black men. Epidemiologic studies examining the role of IGF-1 and IGFBP-3 suggest that increased levels of serum IGF-1 and decreased levels of serum IGFBP-3 are associated with an increased risk of prostate cancer. Few studies have examined these factors with respect to benign prostatic hyperplasia, and these have been limited to white men. The study population consisted of a sample of 364 black men, 40 to 79 years of age, residing in Genesee County, Michigan. Men with prostate cancer or prior prostate surgery were excluded. All subjects completed a clinical examination, which included a complete urologic examination with transrectal ultrasonography, anthropometric measurements, and serum assays for IGF-1 and IGFBP-3. Multivariable regression models demonstrated that prostate volume increased with increasing age (P <0.0001) and body mass index (P = 0.03). IGFBP-3 rather than IGF-1 was positively associated with increasing prostate volume (P = 0.003). This is the largest study describing the relationships between IGF-1, IGFBP-3, and body mass index and prostate volume, and the only study in black men. Although earlier studies demonstrated an association between IGF-1 and prostate cancer risk, our findings indicate that IGFBP-3 is more relevant for prostate enlargement, suggesting that IGF-1 and IGFBP-3 may play different pathophysiologic roles in benign and malignant prostatic conditions.


Inhibition of IK,ACh current may contribute to clinical efficacy of class I and class III antiarrhythmic drugs in patients with atrial fibrillation.
Inward rectifier potassium currents I(K1) and acetylcholine activated I(K,ACh) are implicated in atrial fibrillation (AF) pathophysiology. In chronic AF (cAF), I(K,ACh) develops a receptor-independent, constitutively active component that together with increased I(K1) is considered to support maintenance of AF. Here, we tested whether class I (propafenone, flecainide) and class III (dofetilide, AVE0118) antiarrhythmic drugs inhibit atrial I(K1) and I(K,ACh) in patients with and without cAF. I(K1) and I(K,ACh) were measured with voltage clamp technique in atrial myocytes from 58 sinus rhythm (SR) and 35 cAF patients. The M-receptor agonist carbachol (CCh; 2 microM) was employed to activate I(K,ACh). In SR, basal current was not affected by either drug indicating no effect of these compounds on I(K1). In contrast, all tested drugs inhibited CCh-activated I(K,ACh) in a concentration-dependent manner. In cAF, basal current was confirmed to be larger than in SR (at -80 mV, -15.2 +/- 1.2 pA/pF, n = 88/35 vs. -6.5 +/- 0.4 pA/pF, n = 194/58 [myocytes/patients]; P < 0.05), whereas CCh-activated I(K,ACh) was smaller (-4.1 +/- 0.5 pA/pF vs. -9.5 +/- 0.6 pA/pF; P < 0.05). In cAF, receptor-independent constitutive I(K,ACh) contributes to increased basal current, which was reduced by flecainide and AVE0118 only. This may be due to inhibition of constitutively active I(K,ACh) channels. In cAF, all tested drugs reduced CCh-activated I(K,ACh). We conclude that in cAF, flecainide and AVE0118 reduce receptor-independent, constitutively active I(K,ACh), suggesting that they may block I(K,ACh) channels, whereas propafenone and dofetilide likely inhibit M-receptors. The efficacy of flecainide to terminate AF may in part result from blockade of I(K,ACh).


The anti-photoaging effect of antioxidant collagen peptides from silver carp (Hypophthalmichthys molitrix) skin is preferable to tea polyphenols and casein peptides.
Applying antioxidants to attenuate skin photoaging has received great attention. In this study, antioxidant collagen peptides (ACPs) with different activities were prepared using different proteases, called high (HCP), medium (MCP) and low antioxidant collagen peptides (LCP). The effects of ACPs, tea polyphenols (TP) and casein peptides (CP) on the photoaged skin of mice were evaluated and compared. Ingestion of ACPs significantly alleviated UV-induced abnormal alterations of skin components and antioxidative indicators in both serum and skin (p < 0.05). In addition, HCP had the best effect on protecting skin from photoaging among the three collagen peptides, with no significant differences between MCP and LCP (p > 0.05). TP and CP, with higher antioxidant activity in vitro, only significantly increased hydroxyproline content (only in the TP group) and CAT activity and decreased protein carbonyl content at week 2, showing a much weaker effect than that of the ACP groups. The histological analysis result further demonstrates that ACPs exerted a stronger beneficial effect on normalizing skin structure and collagen arrangement than TP and CP. Accordingly, ACPs have potential for nutraceuticals as anti-skin-photoaging ingredients.


[Arterial blood gas and electrolytes in severe pulmonary tuberculosis with respiratory failure: analysis of 50 cases].
To study the characteristics of arterial blood gas and electrolytes in patients with severe pulmonary tuberculosis with respiratory failure. In 50 patients with severe pulmonary tuberculosis, the arterial blood gas and electrolytes were measured after the onset of respiratory failure to define the types of respiratory failure and acid-base imbalance. Severe pulmonary tuberculosis with respiratory failure was characterized by development of hypoxia, and the degree of hypercapnia may vary; more extensive tuberculous involvement or longer disease course suggest greater chance of type II respiratory failure. Increment of the anion gap occurred irrespective of the pH value. Analysis of arterial blood gas and electrolytes may help monitor the progression of severe pulmonary tuberculosis and provides valuable information for implementing treatment and making prognostic decisions.


Influence of hyperthermia, pH and culturing conditions on the electrical parameters of Chinese hamster V79 cells.
Conductivity measurements in the frequency range 10 kHz-100 MHz have been performed on Chinese hamster fibroblasts V79 exposed to hyperthermia in different experimental conditions. The membrane electrical conductivity is decreased when cells are heated for 1 h at 44 degrees C or 3 h at 43 degrees C at pH 7.25. This effect has not been observed on cell samples following heating for 1 h at 43 degrees C at pH 7.25. However, if the pH of the culture medium is adjusted to 6.50 or 6.0 before hyperthermic exposure, a substantial decrease of membrane conductivity is observed. In cells maintained in partially spent medium before heating, a 3 h treatment at 43 degrees C at pH 7.25 does not produce any effect on membrane conductivity. The results of all these experiments seem to indicate that some alteration of the energy-driven mechanisms involved in active transport across the plasma membranes may be responsible for the observed effects.


[A primary study using the method of average positive stained area percentage to measure the immunohistochemistry results].
With the help of computer image analysis system, we used the method of average positive stained area percentage APSAP to evaluate the slice immunohistochemistry result. Then we compared the evaluation result with the result of manual counting. Conformity between the two methods was verified. These data indicated that the method of was in accord with manual counting to a great extent. Moreover, the theory basis, advantages and disadvantages of the method were discussed in this paper.


[Correlation between skinfold thickness and ultrasonography in the study of subcutaneous adipose tissue in females].
The aim of this study was to verify if there is a 1:2 correlation between subcutaneous adipose tissue thickness measured by ultrasonography and skinfold caliper and if this correlation varies in function of the degree of obesity, subcutaneous fat thickness, and the area evaluated. Forty women (age 27.9 +/- 11.7 years, body mass index 28.75 +/- 5.40 Kg/m2, waist to hip ratio 0.77 +/- 0.06) underwent ultrasonographic measurement of subcutaneous adipose tissue and skinfold caliper measurement at nine different sites (bicipital, tricipital, subscapular, suprailiac, epigastric umbilical, hypogastric, gluteal, and femoral). Data analysis confirmed a significant correlation between measurements made by ultrasonography and skinfold plicometry at all sites when the patients were not subdivided according to body mass index or skinfold thickness. When they were subdivided on the basis of body mass index, a significant correlation was found for subjects with a body mass index < 30; when the index was > 30, the correlation was observed at only the subscapular and suprailiac sites, and to a lesser degree at the tricipital and femoral sites. Moreover, a highly significant correlation was found only at sites at which ultrasonographic thickness was not > 20 mm (p < 0.001) with an r value decreasing progressively from 0.685 (thickness < 10 mm) to 0.248 (thickness > 40 mm). Given the great variability of this correlation, we suggest that ultrasonography is preferable to plicometry for the measurement of fat.


Management of neonatal and infancy-onset diabetes mellitus.
Diabetes mellitus is a rare disorder during the first 2 years of life, amounting to about 3-5% of all cases diagnosed before the fifteenth birthday. However, in spite of low numerical values, this is an important diagnosis, since we are dealing with a vulnerable age group with major and special problems related to diagnosis, treatment and psychosocial follow-up. Efforts should be made to establish a molecular genetic diagnosis as early as possible (e.g. homozygous glucokinase deficiency, defects of the ATP-sensitive potassium channel, chromosome 6 imprinting abnormalities). This is particularly important, since patients with Kir6.2 and SUR1 defects can now be treated with oral sulfonylureas. Major advancements have been obtained and continue to be made with respect to diagnosis and classification. Differentiation between transient and permanent neonatal diabetes can only be done after long-term follow-up. Patients should be scrutinized for comorbidity (e.g. celiac disease, Wolcott-Rallison syndrome). Type 1 diabetes is probably the most prevalent subtype, particularly after the first year of life. Insulin treatment in infancy continues to represent major technical, medical and psychological challenges. Family support is mandatory and close attention should be paid to psychosocial issues.


Enzyme histochemistry and thyroid neoplasia.
The authors have examined the enzyme histochemical staining of surgically removed human thyroid tissue in an attempt to identify markers that might be useful in the histopathologic diagnosis of thyroid neoplasms. Fresh thyroid glands and other tissues were fixed in cold (4 degrees C) 4% paraformaldehyde and embedded in glycol methacrylate. Forty-two specimens were studied in thin sections, which gave excellent histologic detail and enzyme preservation. Cytologic detail was similar to that in Papanicolaou-stained smears, with good definition of nuclear inclusions and grooves, particularly in cases of papillary carcinoma. The enzyme histochemical reactions studied were as follows: adenosine triphosphatase, alkaline and acid phosphatases, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Thyroid epithelial cells and the benign neoplasms derived from them were typically positive for 5'-nucleotidase, alpha-naphthyl acetate esterase, and acid phosphatase, and negative for adenosine triphosphatase and alkaline phosphatase. Staining for adenosine triphosphatase was present in papillary and follicular carcinomas and was seen in benign glands only under certain circumstances such as Graves' disease. The adenosine triphosphatase reaction therefore appears to be helpful in distinguishing between benign and malignant neoplasms derived from thyroid epithelium in humans and may be a useful adjunct to routine morphology.


Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations.
This work demonstrates that extracellular Na(+) modulates the cloned inwardly rectifying K(+) channels Kir4.1 and Kir4.1-Kir5.1. Whole-cell patch clamp studies on astrocytes have previously indicated that inward potassium currents are regulated by external Na(+). We expressed Kir4.1 and Kir4.1-Kir5.1 in Xenopus oocytes to disclose if Kir4.1 and/or Kir4.1-Kir5.1 at the molecular level are responsible for the observed effect of [Na(+)](o) and to investigate the regulatory mechanism of external cations further. Our results showed that Na(+) has a biphasic modulatory effect on both Kir4.1 and Kir4.1-Kir5.1 currents. Depending on the Na(+)-concentration and applied voltage, the inward Kir4.1/Kir4.1-Kir5.1 currents are either enhanced or reduced by extracellular Na(+). The Na(+) activation was voltage-independent, whereas the Na(+)-induced reduction of the Kir4.1 and Kir4.1-Kir5.1 currents was both concentration-, time- and voltage-dependent. Our data indicate that the biphasic effect of extracellular Na(+)on the Kir4.1 and Kir4.1-Kir5.1 channels is caused by two separate mechanisms.


Effects of chronic spinalization on ankle extensor motoneurons. I. Composite monosynaptic Ia EPSPs in four motoneuron pools.
1. We examined the effects of 6-wk chronic spinalization at the L1-L2 level on composite monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded in medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus (SOL), and plantaris (PL) motoneurons. Amplitudes, rise times, and half-widths of composite monosynaptic Ia EPSPs evoked by low-strength electrical stimulation of peripheral nerves were measured in barbiturate-anesthetized cats and compared between unlesioned and chronic spinal preparations. 2. The mean amplitude of homonymous composite Ia EPSPs evoked by 1.2 times threshold (1.2T) stimulation and recorded in all four ankle extensor motoneuron pools increased 26% in chronic spinal animals compared with unlesioned controls. There was also an increased incidence of large-amplitude, short-rise time EPSPs. When the same data were separated according to individual motoneuron species, homonymous EPSP amplitudes in MG motoneurons were found to be unchanged. EPSPs recorded in LG motoneurons and evoked by stimulation of the combined LG and SOL nerve were increased by 46%. Mean EPSP amplitudes recorded in both SOL and PL motoneurons were larger after spinalization but statistical significance was only achieved when values from SOL and PL were combined to produce a larger sample size. 3. In LG motoneurons from chronic spinal animals, all EPSPs evoked by 1.2T stimulation of the LGS nerve were > or = 0.5 mV in amplitude. In unlesioned preparations, one fourth of the LG cells had EPSPs that were < or = 0.2 mV. 4. The mean amplitude of heteronymous EPSPs evoked by 2T stimulation of LGS and MG nerves and recorded in MG and LG motoneurons, respectively, doubled in size after chronic spinalization. Because homonymous EPSP amplitudes were unchanged in MG motoneurons, synaptic mechanisms and not passive membrane properties are likely responsible for increased heteronymous EPSP amplitudes in MG. 5. The mean 10-90% rise time of homonymous composite Ia EPSPs in pooled data from all motoneurons decreased 21% in 6-wk chronic spinal animals. Unlike EPSP amplitude, significant rise time decreases were found in all four motoneuron pools. Compared with the other motoneuron species, the mean homonymous rise time recorded in MG motoneurons was shortest and decreased the least in chronic spinal animals. Rise times of heteronymous Ia EPSPs in MG and LG motoneurons also decreased. The maximum rate of rise of homonymous EPSPs increased in all four motoneuron species. 6. The mean half-widths of Ia composite EPSPs decreased in 6-wk spinalized preparations in all motoneuron species.(ABSTRACT TRUNCATED AT 400 WORDS)


Three attempts to replicate the behavioral sunk-cost effect: a note on cunha and caldieraro (2009).
Cunha and Caldieraro (2009) investigated whether sunk-cost effects, which are well documented in hypothetical situations involving monetary investments, also occur in choice situations with purely behavioral investments. Their results suggest that decision makers indeed fall prey to behavioral sunk-cost effects under certain circumstances. I have been unable to replicate their pattern of results in three separate investigations. In these studies, I attempted to recover the effect using two other behavioral effort manipulations in addition to the manipulation used by Cunha and Caldieraro. This failure to replicate the pattern of results calls into question the robustness of the initial findings.


The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning.
Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.


The long-term cancer survivor: a challenge for nurse practitioners.
For approximately 8 million Americans alive today, the words "cancer" and "survival" are no longer mutually exclusive. As advances are made in the early detection and treatment of cancer, the numbers of survivors who are recovering from their illnesses or living longer with cancer as a chronic disease are increasing. With this extended survival comes a new set of responsibilities and standards for follow-up care that include the following: (1) the recognition of chronic or potential problems, (2) the need for life-long surveillance, and (3) continued access to quality health care. Long-term follow-up care for cancer survivors can be a specialty unto itself. The development of clinics or programs that specialize in caring for this expanding population have a history within pediatric oncology. The challenge in the current health care market is to dedicate energy and resources to do the same within the adult oncology community. Nurse practitioners are ideal candidates to create holistic programs that focus on the special needs, both biomedical and psychosocial, of long-term cancer survivors.


Phosphorylation of an actin.tropomyosin.troponin complex from human skeletal muscle.
A human skeletal actin.tropomyosin.troponin complex was phosphorylated in the presence of [gamma-32 P]ATP, Mg2+, adenosine 3':5'-monophosphate (cyclic AMP) and cyclic AMP-dependent protein kinase (protein kinase). Phosphorylation was not observed when the actin complex was incubated in the absence of protein kinase or 1 microM cyclic AMP. In the presence of 10(-7) M Ca2+ and protein kinase 0.1 mole of [32P]phosphate per 196 000 g of protein was incorporated. This was two-fold higher than the [32P]phosphate content of a rabbit skeletal actin complex but two-fold lower than that of a bovine cardiac actin complex. At high Ca2+, 5.10(-5) M, little change in the phosphorylation of a human skeletal actin complex occurred. Phosphoserine and phosphothreonine were identified in the [32P]phosphorylated actin complex. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that 60% of the label was associated with the tropomyosin binding component of troponin. The inhibitory component of troponin contained 16% of the bound [32P]phosphate. Increasing the Ca2+ concentration did not significantly decrease the [32P]phosphate content of the phosphorylated proteins in the actin complex. No change in the distribution of phosphoserine or phosphothreonine was observed. Half maximal calcium activation of the ATPase activity of reconstitute human skeletal actomyosin made with the [32P] phosphorylated human skeletal actin complex was the same as a reconstituted actomyosin made with an actin complex incubated in the absence of protein kinase at low or high Ca2+.


Correction.
29 April (p.734) and 13 May (p. 911) issues of Science The talk being given by Dr. Harold Varmus at the Science/HUGO Human Genome 1994 meeting on Monday, 3 October, in Washington, D.C., is entitled "Manipulating Cancer Genes in the Mouse."


Constitutional pericentric inversion of chromosome 9 and hematopoietic recovery after allogeneic stem cell transplantation.
Recent reports suggest that hemopoietic stem cells with constitutional pericentric inversion of chromosome 9 [inv(9)] may be related to delayed engraftment or hemopoietic defect after stem cell transplantation (SCT). We conducted a retrospective study on five allogeneic SCT in which constitutional inv(9) was detected either in the donor or the recipient. The results showed that hematologic recovery was within the expected time range for all our patients. However, one patient exhibited decreasing blood counts between day +45 and +272 after transplantation, possibly due to protracted cytomegalovirus (CMV) infection and gansiclovir and imatinib treatment. Our findings suggest that constitutional inv(9) may not be associated with delayed hemopoietic recovery after SCT.


Total aerobic destruction of azo contaminants with nanoscale zero-valent copper at neutral pH: promotion effect of in-situ generated carbon center radicals.
In this study, nanoscale zero-valent copper (nZVC) was synthesized with a facile solvothermal method and used for the aerobic removal of azo contaminants at neutral pH for the first time. We found that both Cu(I) and OH generated during the nZVC induced molecular oxygen activation process accounted for the rapid total destruction of azo contaminants in the nZVC/Air system, where nZVC could activate molecular oxygen to produce H2O2, and also release Cu(I) to break the -NN- bond of azo contaminants via the sandmeyer reaction for the generation of carbon center radicals. The in-situ generated carbon center radicals would then react with OH produced by the Cu(I) catalyzed decomposition of H2O2, resulting in the generation of low molecular weight organic acids and their subsequent mineralization. The indispensible role of Cu(I) catalyzed sandmeyer reaction and the promotion effect of in-situ generated carbon center radicals on the rapid total destruction of azo contaminants in the nZVC/Air system were confirmed by gas chromatography-mass spectrometry analysis. This study can deepen our understanding on the degradation of organic pollutant with molecular oxygen activated by zero valent metal, and also provide a new method to remove azo contaminants at neutral pH.


Torsade de pointes ventricular tachycardia. A complication of disopyramide shared with quinidine.
Two cases of documented torsade de pointes ventricular tachycardia in association with the use of disopyramide are described. One patient had previously experienced an episode suggestive of quinidine induced ventricular tachycardia while the other developed ventricular tachycardia during quinidine treatment which was later exacerbated and sustained by the administration of disopyramide. Both patients exhibited a prolonged QTc or QUc interval at the time of the arrhythmia. These cases suggest that a propensity of ventricular arrhythmias induced by quinidine may identify individuals who are likely to develop similar arrhythmias disopyramide treatment as well.


A case of carotid body tumor.
A thirty-five-year-old woman had an asymptomatic, slow growing mass that pushed the right tonsilla palatina and was pulsatile in the oropharyngeal region. Magnetic resonance imaging showed a vascular mass at the carotid bifurcation, causing displacement of the external and internal carotid arteries. The diagnosis of a carotid body tumor was confirmed by magnetic resonance angiography. Surgery included a subadventitial dissection at the carotid bifurcation, preserving the hypoglossal and vagal nerves. The patient developed loss of function of the tenth cranial nerve postoperatively. After a year follow-up period, there was no change in the function of the tenth cranial nerve.


Isatin Derivatives and Their Antiviral Properties Against Arboviruses: A Review.
Arboviruses have been spreading rapidly throughout the Western Hemisphere in recent decades. Among the arboviruses with high morbidity and mortality are the members of the Alphavirus and Flavivirus genera. Within the first genus, Chikungunya Virus (CHIKV) is considered one of the most challenging human arboviral infection worldwide, against which there is no specific antivirals. Flaviviruses are some of the main viruses responsible for encephalitis, haemorrhagic disease and developmental defects. Dengue virus (DENV), Japanese Encephalitis Virus (JEV), West Nile Virus (WNV) and Zika Virus (ZIKV) are examples of flaviviruses without clinically approved antiviral agents. Thus, the search for new antivirals becomes highly important. One of the strategies that can be employed to obtain new drugs is the identification and utilization of privileged structures. Isatin is an example of a privileged molecular framework, displaying a broad spectrum of biological activities, including antiviral action. Obtaining and studying the antiviral properties of isatin derivatives have helped to identify important agents with potential activity against different arboviruses. This article reviews some of these isatin derivatives, their structures and antiviral properties reported against this important group of viruses.


Prolonged infusion gemcitabine: a clinical phase I study at low- (300 mg/m2) and high-dose (875 mg/m2) levels.
Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- (300 mg/m2) and high-dose (875 mg/m2) GEM, administered on days 1, 8 and 15 at 4-week intervals in a step-wise escalation of duration (> or = 33%) at a starting level of 60 minutes. At least 3 patients entered each infusion-level step and 3 more cases were treated in the presence of significant toxicity. Conservative criteria for toxicity were employed, including treatment delay until recovery with infusion de-escalation in the subsequent course. Forty-seven patients (29 at low- and 18 at high-dose GEM levels) with various solid tumors, including 9 (taken as a reference) who had received the same dose levels over 30 min. entered the study. All but 9 patients (with pancreatic cancer) had been previously treated with chemotherapy and all had extensive visceral disease. A striking infusional-effect relationship was observed at both GEM dose levels. Four escalation steps were required to define the maximum tolerated infusion time (MTIT) at 6 hours for 300 mg/m2 GEM, with leucopenia being dose-limiting. At 875 mg/m2, although no limiting toxicity was observed (in spite of increased severity of leucopenia), no escalation was attempted following the 1-hour infusion, due to the limiting rate (58% of 12 patients) of toxic delay requiring shorter infusions. Toxicity was usually mild (no grade 4 event was recorded) showing the usual profile, although there was a trend towards increased non-hematologic toxicity (i.e. LFT abnormalities) as compared with the MTD previously defined using a 30-min. infusion schedule (1,370 mg/m2). Eight patients achieved a PR: 1 with NSCLC, 1 with gastric and 2 with bladder cancer at 300 mg/m2 (1 with a 3- and 3 with a 6-hour infusion) and 2 with pancreatic, 1 with cervical and another with bladder cancer at 875 mg/m2 (all but one with a 1-hour infusion). These data clearly suggest that the infusion duration is an important independent factor that influences the clinical effects of GEM. The present study not only defined the toxic profiles and the MTITs of the selected dose levels but demonstrated that GEM retained the antitumor activity at doses as small as 300 mg/m2 when given as a prolonged infusion. Further studies should clarify the underlying mechanism(s) responsible for the erratic dose-effect dose-effect relationships of GEM and establish the optimal dose-infusion level in the treatment of solid tumors.


Cell adhesion and EGFR activation regulate EphA2 expression in cancer.
EphA2 is frequently overexpressed in cancer, and increasing amounts of evidence show that EphA2 contributes to multiple aspects of the malignant character including angiogenesis and metastasis. Several aspects of the regulation and functional significance of EphA2 expression in cancer are still largely unknown. Here we show that the expression of EphA2 in in vitro cultured cells, is restricted to cells growing adherently and that adhesion-induced EphA2 expression is dependent upon activation of the epidermal growth factor receptor (EGFR), mitogen activated protein kinase kinase (MEK) and Src family kinases (SRC). Moreover, the results show that adhesion-induced EGFR activation and EphA2 expression is affected by interactions with extracellular matrix (ECM) proteins working as integrin ligands. Stimulation with the EphA2 ligand, ephrinA1 inhibited ERK phosphorylation and cancer cell viability. These effects were however abolished by activation of the EGF-receptor ligand system favoring Ras/MAPK signaling and cell proliferation. Based on our results, we propose a regulatory mechanism where cell adhesion induces EGFR kinase activation and EphA2 expression; and where the effect of ephrinA1 mediated reduction in cell viability by inhibiting EphA2 expression is overruled by activated EGFR in human cancer cells.


Evidence for activity-dependent modulation of sensory-terminal excitability in spindles by glutamate release from synaptic-like vesicles.
Sensory terminals of muscle spindles and similar mechanosensory neurons contain large numbers of 50 nm, "synaptic-like" vesicles (SLVs), about whose role very little is known. Using fluorescence microscopy, immunocytochemistry and electrophysiological recording, we present evidence that SLVs undergo a recycling process, and that they release glutamate that has an autogenic excitatory effect on mechanosensory transduction, probably involving a metabotropic receptor linked to phospholipase D. The rate of recycling of SLVs is activity dependent, at least in part, as shown by an increased rate of destaining of preparations labelled with FMI-43 during high-frequency, small-amplitude vibration. Immunogold labelling showed levels of glutamate-like reactivity in the sensory terminals at least as great as in probable Ia presynaptic terminals in the spinal cord. Exogenously applied glutamate has an excitatory effect on the spindle's response to stretch, which is blocked by 3,5-dihydroxyphenylglycine.


Structure-function analysis of the active site tunnel of yeast RNA triphosphatase.
Cet1, the RNA triphosphatase component of the yeast mRNA capping apparatus, catalyzes metal-dependent gamma phosphate hydrolysis within the hydrophilic interior of a topologically closed 8-strand beta barrel (the "triphosphate tunnel"). We used structure-guided alanine scanning to identify 6 side chains within the triphosphate tunnel that are essential for phosphohydrolase activity in vitro and in vivo: Arg393, Glu433, Arg458, Arg469, Asp471 and Thr473. Alanine substitutions at two positions, Asp377 and Lys409, resulted in partial catalytic defects and a thermosensitive growth phenotype. Structure-function relationships were clarified by introducing conservative substitutions. Five residues were found to be nonessential: Lys309, Ser395, Asp397, Lys427 Asn431, and Lys474. The present findings, together with earlier mutational analyses, reveal an unusually complex active site in which 15 individual side chains in the tunnel cavity are important for catalysis, and each of the 8 strands of the beta barrel contributes at least one functional constituent. The active site residues fall into three classes: (i) those that participate directly in catalysis via coordination of the gamma phosphate or the metal; (ii) those that make critical water-mediated contacts with the gamma phosphate or the metal; and (iii) those that function indirectly via interactions with other essential side chains or by stabilization of the tunnel structure.


[Adenoma of the pituitary gland in the ophthalmologist's out-patient practice].
Authors describe eye and general symptoms in five patients with the adenoma of the pituitary gland, detected on the results of the ophthalmological examination. Identical symptoms in all patients were the decrease of central visual acuity or visual field defects. The general somatic manifestations of the disease were different.


Separation of morphine and its oxidation products by capillary zone electrophoresis.
Separation of morphine and its oxidation products (10-S-hydroxymorphine, pseudomorphine and morphine N-oxide) by capillary zone electrophoresis in Tris-borate buffer in the presence of cyclodextrins was studied. Pyridoxine was used as an internal standard.


Three new species, two newly recorded species and one newly recorded genus of Lithocolletinae (Lepidoptera: Gracillariidae) from China.
The Chinese representatives of the genera Chrysaster Kumata and Cameraria Chapman (Gracillariidae: Lithocolletinae) were studied. Chrysaster is recorded for the first time in China. Three species belonging to Cameraria, C. diplodura Bai, sp. nov., C. rhynchophysa Bai, sp. nov. and C. jiulianshanica Bai, sp. nov., are described as new. Chrysaster hagicola Kumata and Cameraria magnisignata Kumata are new records for China. Adults and genitalia of the five species are illustrated. A key to the Chinese species of Cameraria is provided.


Primary hepatocellular carcinoma developing in a female patient on long term oral contraceptives--a case report.
The association between hepatic tumours and oestrogen and progestogen therapy is well established. The risk of developing primary hepatocellular carcinoma (PHC) is small. In Africa and Asia where hepatitis B virus (HBV) infections are common, the development of PHC is also high. The presence of Hepatitis B core antibody indicates previous exposure to HBV and carries a risk of developing PHC by more than 34 times of non-infected normal. A Chinese female 29 years who had been on oral oestrogen and progestogen contraceptives continuously for 8 years developed PHC. She had no known illness due to HBV but was found to have concomitantly positive Hepatitis B core antibody in her sera. The presence of this HB core antibody and the long term consumption of oestrogen/progesterone derivatives may have been responsible for the early presentation of PHC in this patient. It is the first report in this country of PHC developing in a pill consumer since the introduction of oral contraceptives a decade ago In view of the prevalence of Hepatitis B in the region, this case finding warrants further study to determine whether (a) there is a higher frequency in pill consumers (b) an earlier age of presentation of hepatic malignancy. Meanwhile, it may be prudent to recommend alternative methods of birth control in individuals known to have been previously exposed to HBV infection, clinically or otherwise.


A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea.
In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments.


Modeling extended sources of event-related potentials using anatomical and physiological constraints.
For the study of functional organization and reorganization of the human cortex by means of electromagnetic source imaging, a measure of the location and spatial extent of neural sources is of interest. This study evaluates the cortical patch method (CPM), an iterative procedure introduced by Lütkenhöner et al. [1995] that models EEG/MEG activity by means of extended cortical patches. Anatomical information is used to constrain estimates of location and extent of neural sources that generate the measured evoked potential. Whereas minimum norm approaches use mathematical constraints to solve the ambiguity of the inverse problem, the CPM introduces constraints based on anatomical and physiological knowledge about neural mass activity. In order to test the proposed method, the simulated activity in an artificial sulcus was subjected to the CPM. The results show that even activity on opposing walls of a sulcus can be well reconstructed. The simulations demonstrate the usefulness and limits of the CPM in estimating the spatial extent of neural sources in the cerebral cortex. As an example, an application of the method on experimental somatosensory evoked potentials is presented in the Appendix.


Port-access bilateral internal mammary artery grafting for left main coronary artery disease: canine feasibility study.
To extend the applications of minimal access cardiac surgery, an endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia delivery and cardiac venting was used to perform bilateral internal mammary artery (IMA) bypass grafting in six dogs. The left IMA (LIMA) was taken down thoracoscopically from three left lateral chest ports, followed by the right IMA (RIMA) from the right side. One left-sided port was extended medially 5 cm with or without rib resection, to expose the pericardium. Both IMAs were divided and exteriorized through the left anterior mediastinotomy. Flow and pedicle length were satisfactory in all cases. Femoral-femoral bypass was used and the heart arrested with antegrade delivery of cardioplegic solution via the central lumen of a balloon catheter inflated to occlude the ascending aorta. All anastomoses were made through the mediastinotomy under direct vision. In five studies the RIMA was attached to the left anterior descending artery (LAD) and the LIMA to the circumflex, and in one study the RIMA was tunneled through the transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was 108 +/- 27 minutes (mean +/- SD) and the clamp duration was 54 +/- 10 minutes. Preoperative and postoperative cardiac outputs were 2.9 +/- 0.71/min and 2.4 +/- 0.31/min, respectively (p = NS), and corresponding pulmonary artery occlusion pressures were 6 +/- 3 mmHg and 7 +/- 2 mmHg, respectively (p = NS). All 12 grafts were demonstrated to be fully patent. Postmortem examination revealed well aligned pedicles and correctly grafted target vessels. This canine model demonstrates the potential for a less invasive approach to the surgical management of left main coronary artery disease in humans.


Aging curve of neuromotor function by pronation and supination of forearms using three-dimensional wireless acceleration and angular velocity sensors.
We have developed an evaluation system for pronation and supination of forearms. The motion of pronation and supination of the forearm is used as a diagnosis method of developmental disability, etc. However, this diagnosis method has a demerit in which diagnosis results between doctors are not consistent. It is hoped that a more quantitative and simple evaluation method is established. Moreover it is hoped a diagnostic criteria obtained from healthy subjects can be established to diagnose developmental disorder patients. We developed a simple and portable evaluation system for pronation and supination of forearms. Three-dimensional wireless acceleration and angular velocity sensors are used for this system. In this study, pronation and supination of forearms of 570 subjects (subjects aged 6-12, 21-100) were examined. We could obtain aging curves in the neuromotor function of pronation and supination. These aging curves obtained by our developed system, has the potential to become diagnostic criteria for a developmental disability, etc.


Angina bullosa hemorrhagica: report of 7 cases and analysis of 199 cases from the literature.
Angina bullosa hemorrhagica (ABH) is a condition characterized by blood blisters in the oral or oropharyngeal mucosa. Typically, the first presentation of ABH is acute, and rupture of the blisters occurs after a few hours or days. Although its etiology is unclear, ABH is assumed to be associated with predisposing factors such as local trauma or chronic use of inhaled steroids. The diagnosis is defined clinically, based on the presentation and evolution of the lesions. The recommended treatment is symptomatic, but extensive lesions may present a risk of airway obstruction and may require surgical excision. This case series reports 7 cases of ABH and reviews 199 cases published in the English-language literature. The possible etiologic factors, predisposing factors, and differential diagnoses are discussed.


Free-field correction values for Interacoustics DD 45 supra-aural audiometric earphones.
This paper reports free-field correction values for the Interacoustics DD 45 audiometric earphone. The free-field correction values for earphones provide the loudness based equivalence to loudspeaker presentation. Correction values are especially used for the calibration of audiometric equipment for speech audiometry performed with headphones. Calibration values may be found in, e.g. the ISO 389 series of standards. The free-field correction values were determined by means of loudness balance measurements of one-third octave noises (centre frequencies 125 Hz to 8000 Hz) presented alternately from a loudspeaker in a free field and from the earphones. The procedure was essentially in accordance with the free-field frequency response procedure described in IEC 60268-7: Headphones and earphones. Four earphones and 14 test subjects. Free field correction values are reported for the acoustic coupler IEC 60318-3 (NBS 9-A) and for the ear simulator IEC 60318-1. The results are in good agreement with the results of another independent investigation. The reported free-field correction values may be used as part of the basis for future standardization of the DD 45 earphone.


Atherosclerosis: the eicosanoid connection.
This bird's eye view presents connections between the metabolically short-lived local hormones (collectively known as eicosanoids) and atherosclerotic cardiovascular disease. The discussion will be centered around an overview of coronary atherosclerosis with an emphasis on the sequences involved in the formation of atherosclerotic lesions; structure and historical background of oxygenated fatty acids cyclooxygenase and lipoxygenase products--eicosanoids; the generation of free radicals during the formation of endoperoxides by cyclooxygenase; the involvement of eicosanoids in the atherosclerotic inflammatory process, and finally, the effects of non-steroidal and steroidal anti-inflammatory drugs on the synthesis of eicosanoids and experimental atherosclerosis. Little is known about the exact role of eicosanoids in the genesis of atherosclerosis.


Development of the Curvex toothbrush.
This is a first-hand narrative of the steps in developing a new toothbrush from concept through initial marketing. The design seeks to provide the softest bristles consistent with effective plaque removal. Patent protection, incremental design and testing, and accurate market analysis have been essential steps in the process.


Controversial issues in treating the dental patient with autism.
The author conducted a literature review to investigate concerns that parents of a child with an autism spectrum disorder may have when oral health care is provided to the child. The author conducted a search of PubMed using the terms "mercury," "fluoride," "nitrous oxide," "antibiotics," "gluten," "casein," "acetaminophen" and "dentistry" each with the term "autism." He identified controlled studies and literature reviews in both medical and alternative medical literature that were related to areas of importance to oral health care workers. The use of mercury, fluoride, nitrous oxide, antibiotic agents and acetaminophen all are sources of controversy between dentistry and the parents of children who have autism. The author found that patients who have autism frequently also have allergies, immune system problems, gastrointestinal disturbances and seizures. Dental health care workers must be aware of these comorbid conditions so they can provide optimal care to the children with autism spectrum disorders. The author found two distinct theories as to what causes autism: one that focuses on genetic causes, and one that focuses on the impact of the environment. He found that the interpretation of these theories might affect parents' concerns about various dental treatments. Dentists treating patients who have autism may need to provide more than standard patient care, as the use of time-tested dental treatment and prevention modalities may be questioned or refused by parents.


Protein family classification using sparse Markov transducers.
In this paper we present a method for classifying proteins into families using sparse Markov transducers (SMTs). Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Because substitutions of amino acids are common in protein families, incorporating wildcards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. We also present efficient data structures to improve the memory usage of the models. We evaluate SMTs by building protein family classifiers using the Pfam database and compare our results to previously published results.


Age effects on the P300 potential and the corresponding fMRI BOLD-signal.
Age has been reported to influence amplitude and latency of the P300 potential. Nevertheless, it is not yet fully understood which brain regions are responsible for these effects. The aim of this study was to investigate age-effects on the P300 potential and the simultaneously acquired BOLD signal of functional MRI. 32 healthy male subjects were investigated using an auditory oddball paradigm. The functional MRI data were acquired in temporal synchrony to the task. The evoked potential data were recorded during the intervals in between MR image acquisitions in order to reduce the influence of the scanner noise on the presentation of the tones and to reduce gradient artifacts. The age-effects were calculated by means of regression analyses. In addition, brain regions modulated by the task-induced amplitude variation of the P300 were identified (single trial analysis). The results indicated an age effect on the P300 amplitude. Younger subjects demonstrated increased parietal P300 amplitudes and increased BOLD responses in a network of brain regions including the anterior and posterior cingulate cortex, the insula, the temporo-parietal junction, the superior temporal gyrus, the caudate body, the amygdala and the parahippocampal gyrus. Single trial coupling of EEG and fMRI indicated that P300 amplitudes were predominantly associated with neural responses in the anterior cingulate cortex, the putamen and temporal brain areas. Taken together, the results indicate diminished neural responses in older compared to younger subjects especially in frontal, temporo-parietal and subcortical brain regions.


The relationship between body composition and knee structure in patients with human immunodeficiency virus.
Obesity is a risk factor for osteoarthritis. Antiretroviral therapy (ART)-treated HIV-infected patients are frequently affected by overweight and obesity, and may be at increased risk of osteoarthritis. BMI however is a measure which does not discriminate adipose from non-adipose body mass, or fat distribution, which may have different effects. This study aimed to examine relationships between body composition and knee cartilage volume, as assessed by magnetic resonance imaging in HIV infection. 35 ART-treated HIV-infected men aged 51.7 years (mean) 7.9 (SD) and 18 healthy men aged 49.5 years (mean) 6.4 (SD) participated. Cartilage volume was measured on magnetic resonance imaging of the dominant knee using validated methods. Body composition was measured using dual x-ray absorptiometry. HIV-infected participants had less total body and gynoid fat (kg) (p = 0.04 and p = 0.007, respectively) and more percent android fat mass and percent trunk fat mass (p = 0.001 and p < 0.001, respectively) than controls. In HIV-infected participants there was an inverse association between total body fat mass and average tibial cartilage volume (R = -8.01, 95% CI -15.66, -0.36). Also, in HIV-infected participants there was an inverse association between android fat mass and average cartilage volume (R = -90.91, 95% CI -158.66, -23.16). This preliminary study found that both total body and android fat mass were inversely related to average knee cartilage volume in ambulant, ART-treated HIV-infected adults. These findings are features of early knee osteoarthritis and this may be of future significance in HIV.


Glucocorticoid receptor in patients with lupus nephritis: relationship between receptor levels in mononuclear leukocytes and effect of glucocorticoid therapy.
We investigated the clinical significance of glucocorticoid receptor determination in 20 patients with systemic lupus erythematosus (SLE) who afterwards developed nephrotic syndrome. Glucocorticoid receptor concentrations in mononuclear leukocytes (MNL) in these patients were comparable with those in both other patients with SLE and healthy persons. Improvement in urinary protein excretion and in disease activity, which was scored according to the SLE Disease Activity Index system of the University of Toronto, closely related to the glucocorticoid receptor concentrations in MNL isolated from the corresponding patients. In summary, glucocorticoid receptor determination in patients with lupus nephritis may be a predictive clue for assessing responsiveness to glucocorticoid therapy.


Ultrasound-assisted emulsification microextraction coupled with high-performance liquid chromatography for the simultaneous determination of fragrance allergens in cosmetics and water.
A simple, inexpensive, and environmentally friendly method based on ultrasound-assisted emulsification microextraction followed by solidification of floating organic drop and high-performance liquid chromatography coupled to diode array detection was developed for the simultaneous determination of 18 potentially allergenic fragrance substances. Several parameters affecting the microextraction process were investigated in detail by the "one-variable-at-a-time" approach. Optimal conditions were the following: 50 μL of 2-dodecanol as extraction solvent, 10 mL of sample containing 150 g/L of salt, and 5 min of sonication at 35°C. Under the optimized conditions, method showed good linearity in the selected ranges, with squared correlation coefficients ranging from 0.948 to 0.999. Limits of detection ranged from 0.001 to 0.154 μg/mL and enrichment factors from 9 to 237. Precision of the method, expressed as relative standard deviation, was checked at two levels obtaining good results (3.3-14.4%). Recovery studies were made in baby bath water and in eau de cologne showing acceptable accuracy. Finally, the developed method was successfully applied to different commercial cosmetic and water samples. The most commonly found analyte was linalool followed by cinnamal and lilial. Most of the analyzed samples contained at least one of the target compounds.


Unusual cisternal coil migration in the follow-up period after aneurysm perforation during endovascular coiling.
A 61-year-old woman suffered cisternal coil migration in the follow-up period after endovascular coil embolization for a ruptured cerebral aneurysm. She presented with sudden onset of headache. Computed tomography demonstrated diffuse subarachnoid hemorrhage, and cerebral angiography disclosed a left anterior choroidal artery aneurysm. The aneurysm was treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure, the microcatheter perforated the aneurysm. For direct closure of the perforation site with coils, the microcatheter was withdrawn and coils were deployed partially in the subarachnoid space and partially in the aneurysm sac. The coil mass was spread in the subarachnoid space around the aneurysm immediately after embolization. The patient was discharged with no neurological deficit. Three months later, follow-up radiography demonstrated obvious reduction in the size and compaction of the coil mass. Magnetic resonance angiography and digital subtraction angiography demonstrated stable occlusion of the aneurysm. The coil mass probably spread in the cistern around the aneurysm and was compacted by the shape memory of the coils and pulsation of the brain and vessels, as the subarachnoid clots around the aneurysm had disappeared. This case suggests that cisternal coil migration should be considered in the follow up of intracranial aneurysm treated with detachable coils.


Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism: all-atom representation study of protein L.
Experimental and theoretical results suggest that, since proteins are energetically minimally frustrated, the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble and on-pathway intermediate states in protein folding. Although the central role of native state topology in determining the folding mechanism is thought to be a quite general result-at least for small two-state folding proteins-there are remarkable exceptions. Recent experimental findings have shown that topology alone cannot always determine the folding mechanism, and demonstrated that the balance between topology and energetics is very delicate. This balance seems to be particularly critical in proteins with a highly symmetrical native structure, such as proteins L and G, which have similar native structure topology but fold by different mechanisms. Simplified, C(alpha)-atom only protein models have shown not be sufficient to differentiate these mechanisms. An all-atom Gō model provides a valuable intermediate model between structurally simplified protein representations and all-atom protein simulations with explicit/implicit solvent descriptions. We present here a detailed study of an all-atom Gō-like representation of protein L, in close comparison with the experimental results and with the results obtained from a simple C(alpha)-atom representation of the same protein. We also perform simulations for protein G, where we obtain a folding mechanism in which the protein symmetry is broken exactly in the opposite way to protein L as has been observed experimentally. A detailed analysis for protein L also shows that the role of specific residues is correctly and quantitatively reproduced by the all-atom Gō model over almost the entire protein.


Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic Review and Meta-analysis.
Depression is common in individuals with mild cognitive impairment (MCI) and may confer a higher likelihood of progression to dementia. Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision. To provide a precise estimate of the prevalence of depression in individuals with MCI and identify reasons for heterogeneity in the reported results. A search of literature from database inception to March 2016 was performed using Medline, Embase, and PsycINFO. Hand searching of all included articles was performed, including a Google Scholar search of citations of included articles. Articles were included if they (1) were published in English, (2) reported patients with MCI as a primary study group, (3) reported depression or depressive symptoms using a validated instrument, and (4) reported the prevalence of depression in patients with MCI. All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. The overall prevalence of depression in patients with MCI was pooled using a random-effects model. Heterogeneity was explored using stratification and random-effects meta-regression. The prevalence of depression in patients with MCI, reported as a percentage with 95% CIs. Estimates were also stratified by population source (community-based or clinic-based sample), method of depression diagnosis (clinician-administered, informant-based, or self-report), and method of MCI diagnosis (cognitive vs global measure and amnestic vs nonamnestic). Of 5687 unique abstracts, 255 were selected for full-text review, and 57 studies, representing 20 892 patients, met all inclusion criteria. The overall pooled prevalence of depression in patients with MCI was 32% (95% CI, 27-37), with significant heterogeneity between estimates (I2 = 90.7%). When stratified by source, the prevalence of depression in patients with MCI in community-based samples was 25% (95% CI, 19-30) and was 40% (95% CI, 32-48) in clinic-based samples, which was significantly different (P < .001). The method used to diagnose depression did not significantly influence the prevalence estimate, nor did the criteria used for MCI diagnosis or MCI subtype. The prevalence of depression in patients with MCI is high. A contributor to heterogeneity in the reported literature is the source of the sample, with greater depression burden prevalent in clinic-based samples.