Topographic EEG studies of mania.
QEEG findings from 39 hospitalized manic patients were accomplished after a drug free period and following pharmacotherapy with lithium or carbamazepine alone or lithium combined with carbamazepine, haloperidol or risperidone. A subsample of 10 drug-free manic patients was compared with normal controls, which revealed lower qEEG amplitudes in the left anterior and midtemporal regions in the patients. Comparisons of drug therapies showed increased delta amplitudes and total power with lithium compared with carbamazepine. Increased fast frequencies were observed in the lithium and carbamazepine plus lithium groups compared with carbamazepine alone. Comparisons of the three drug combination groups revealed increased alpha and beta 1 amplitudes, most with risperidone and least with carbamazepine. Anterior delta and beta 2 amplitudes and interhemispheric coherence were increased directly proportional to plasma lithium levels. Nonresponders to treatment were identified at baseline by increased generalized theta amplitudes. After treatment, the nonresponders had higher amplitudes in the left temporal areas. Numerous qEEG associations with individual ratings of manic symptoms were found, more at baseline than after treatment. In general levels of psychopathology were negatively correlated with qEEG amplitudes. The qEEG findings appear to implicate dominant temporal lobe dysfunctions in mania.


Development of the Applied Mindfulness Process Scale as a Process Evaluation Measure for Mindfulness Practice in a Chinese Context.
With the rising popularity of mindfulness practice, it is necessary and crucial to evaluate mindfulness using comprehensive and objective measures. The instruments to assess mindfulness in China mainly evaluate mindfulness as a state or trait mode. Few process measures have been developed to clarify effective therapy benefits of the alterations obtained using mindfulness practice. Therefore, this study aims to adapt the Applied Mindfulness Process Scale (AMPS) into Mandarin and explore in detail the reliability and validity of this novel-translated measure. Following cross-cultural modification for original AMPS into Mandarin as per established guidelines, psychometric evaluation was performed on a cohort of 234 Chinese adults. Construct validity was analyzed through exploratory factor analysis (n = 115), together with confirmatory factor analysis (n = 119). Reliability was assessed by internal consistency together with test-retest reliability. Findings indicated that the internal consistency was high, with Cronbach's alpha being 0.936. The principal component analysis led to a three-factor structure that explained 67.374% of all variations. The three-factor model was consistent with the original scale model. Based upon confirmatory factor analyses, all fitting indices satisfied the standard, which showed a close fit to the data. Therefore, the newly multi-culturally modified AMPS has sufficient validity, test-retest reliability, together with internal consistency. Chinese AMPS may offer researchers and clinicians a psychometrically optimized tool for evaluating the application of mindfulness and change process within mindfulness-based interventions (MBIs) in Mainland China.


Large-scale real-world data analysis of source plasma collections using a novel technology-enabled nomogram.
Source plasma collections are needed to satisfy the growing demand for plasma-derived medicinal products. The US plasma collection target volume has been guided by a standard weight-based FDA-issued nomogram (STAN) since 1992. In this research, large-scale US-based real-world data (RWD) were analyzed to confirm the safety and volume gains of a newly introduced personalized nomogram (PERS) that was previously studied in a premarket randomized controlled environment. A non-inferiority (NI) analysis was conducted to compare the novel nomogram's significant hypotensive adverse event (AE) incidence rate with large historical standard nomogram AE datasets. Additionally, the average target volumes and donor return rates were compared for collections following PERS and STAN. A total of 4,816,784 donations (PERS) by 414,957 donors resulted in a rate of 0.0998% (95% CI [0.0970, 0.1027]) significant hypotensive AEs. NI analysis suggested strong non-inferiority of the new technology (Δ = -0.0082%, 95% CI [-0.0113, -0.0050], prespecified NI margin = 0.1080). Average plasma collection target volumes increased by 66.39 mL (8.49%; p < .0001). Consecutive weekly donor return rates were consistent between the two nomograms (PERS: 73.6%, 95% CI [69.6%-76.7%]; STAN: 74.1%, 95% CI [66.1%-77.2%]). This analysis confirms in a large-scale real-world dataset the key safety parameter and collection benefit of a novel, technology-enabled nomogram. The nomogram may help meet the growing demand for plasma-derived therapies by providing approximately 8.5% more plasma per donation on average while maintaining donor safety and return rates.


Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats.
The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca2+-activated K+ channels (BKCa) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.


Surgical management of pulmonary artery sling in children.
Pulmonary artery (PA) sling is a rare vascular anomaly associated with congenital tracheal stenosis. The natural history is poor and these patients often require early surgical intervention. We describe our experience with repair of this condition. From 1984 to 2011, 21 patients with PA sling underwent repair at the Royal Children's Hospital (median age, 5.9 months). PA sling was associated with compression of the trachea in all patients. Tracheal surgery was required in 12 (57.1%) patients. All patients had an echocardiogram, and concomitant repair of coexisting cardiac anomalies was performed in 6 (28.6%, 6/21) patients. Operative mortality was 14.3% (3/21), occurring at 19 days, 4.4 months, and 5 months after surgery. Operative mortality for the first 10 years was 22.2% (1984-1993; 2/9), the next 10 years was 14.3% (1994-2003; 1/7), and 0% for the most recent 7 years (2004-2011; 0/5). All deaths occurred in patients requiring tracheal repair (25%, 3/12). No deaths have occurred since 2004 with introduction of the slide tracheoplasty technique. One (5.6%, 1/18) late death occurred at 8 months after repair. After tracheal repair, intervention for excessive granulations and tracheomalacia was necessary in 6 (50%, 6/12) patients. Median follow-up was 8 years (mean, 8.6 ± 6.4 years; range, 5 months to 20.6 years), and all survivors (100%, 17/17) remain asymptomatic. Children with PA sling who do not require tracheal surgery have excellent outcomes. Mortality is determined by the need for tracheal surgery. However, with the advent of the slide tracheoplasty technique, mortality can be reduced. Survival beyond 1 year after surgery offers excellent prognosis.


Down-regulation of apoptosis after left ventricular aneurysm repair.
Apoptosis is a common feature of the cardiomyopathic process contributing to progressive decline in ventricular function after transmural myocardial infarction. We hypothesized that left ventricular aneurysm repair (LVAR) down-regulates apoptotic potential of cardiomyocytes in the surviving myocardium. In the rat infarct model, LV aneurysms were repaired by pursestring suture 2 weeks after coronary artery ligation. Cardiac function and myocardial infarction size were assessed by echocardiography and transverse heart sections, respectively, before sacrifice 12 weeks later. Cardiomyocytes and TdT-mediated dUTP terminal nick-end labeling (TUNEL) assays of apoptotic nuclei were analyzed adjacent to and remote from the aneurysm (8 in infarction group, 7 in aneurysm group, and 11 in repair group). Biochemical samples for immunoblot were also obtained from surviving myocardium. A statistically significant increase in apoptotic rate was seen in both adjacent and remote areas (p < 0.01) after aneurysm formation. After LVAR, heart function was improved, and TUNEL assays also show significant decrease when compared with aneurysm group. But significant decreases were noted only in activated caspase-9 and increases in Bcl-2 in immunoblot analysis when comparing repair group with aneurysm group. Down-regulation of apoptosis accounts for the change in the long-term benefit after LVAR. To prevent heart failure, LVAR is indicated when it is large enough, and the infarction area should be excluded as much as possible.


Singing-related activity of identified HVC neurons in the zebra finch.
High vocal center (HVC) is part of the premotor pathway necessary for song production and is also a primary source of input to the anterior forebrain pathway (AFP), a basal ganglia-related circuit essential for vocal learning. We have examined the activity of identified HVC neurons of zebra finches during singing. Antidromic activation was used to identify three classes of HVC cells: neurons projecting to the premotor nucleus RA, neurons projecting to area X in the AFP, and putative HVC interneurons. HVC interneurons are active throughout the song and display tonic patterns of activity. Projection neurons exhibit highly phasic stereotyped firing patterns. X-projecting (HVC((X))) neurons burst zero to four times per motif, whereas RA-projecting neurons burst extremely sparsely--at most once per motif. The bursts of HVC projection neurons are tightly locked to the song and typically have a jitter of <1 ms. Population activity of interneurons, but not projection neurons, was significantly correlated with syllable patterns. Consistent with the idea that HVC codes for the temporal order in the song rather than for sound, the vocal dynamics and neural dynamics in HVC occur on different and uncorrelated time scales. We test whether HVC((X)) neurons are auditory sensitive during singing. We recorded the activity of these neurons in juvenile birds during singing and found that firing patterns of these neurons are not altered by distorted auditory feedback, which is known to disrupt learning or to cause degradation of song already learned.


Dependence of Tensile Properties and Fracture Behaviors on the Fractions of Continuous and Discontinuous Precipitates in Peak-Aged AZ80A Magnesium Alloy.
After T5 (forging + aging) and different T6 (forging + solution + aging) heat treatments, the AZ80A Mg alloys exhibited microstructures with different fractions of continuous precipitate (CP) regions and discontinuous precipitate (DP) regions. The effects of the fractions of DP regions and CP regions on the tensile properties and fracture behaviors were investigated using microstructural characterizations and analysis. The results showed that increasing the fraction of DP regions enhanced the yield strength and tensile strength at room temperature. However, at the same high temperature, increasing the fractions of DP regions improved the elongation but deteriorated the tensile strength significantly. The different resultant tensile properties at different temperatures were caused by the different precipitation-strengthening effects in the CP and DP regions. The strengthening contribution of the DP regions was more effective at room temperature but became inferior to the effect brought about by the CP regions at high temperatures. Micro-cracks were usually initiated and propagated in the CP regions at room temperature. At high temperatures, however, micro-voids formed more easily in the DP regions, and the fracture path preferred to locate there.


A light microscopic investigation of the afferent connections of the lateral reticular nucleus in the cat.
The topographical organization of the projections to the lateral reticular nucleus (LRN) of the cat was investigated using the horseradish peroxidase (HRP), silver-impregnation and autoradiographic tracing methods. Following injection of HRP into the LRN, labelled cells were found mainly within Rexed's laminae VII and VIII of the spinal cord, the contralateral red nucleus, the ventro-rostral aspect of the contralateral fastigial nucleus and the contralateral anterior sigmoid and coronal gyri of the cerebral cortex. Animals with injections of tritiated amino acids placed within the pericruciate cortex, red nucleus or fastigial nucleus were processed for autoradiography. In a corresponding series of animals, electrolytic lesions were placed selectively into the above sources of reticular afferents, and terminal degeneration within the LRN was studied by light microscopy. An extensive input from the spinal cord was found to terminate predominantly on the ipsilateral side throughout the rostrocaudal extent of the LRN, except for a small ventromedial area of the rostral parvocellular division and a small rostromedial area of the magnocellular division. The cortical projection terminated diffusely within the middle one-half of the contralateral magnocellular division, while the rubral projection terminated extensively within the contralateral subtrigeminal division and the dorsolateral region of the rostral magnocellular and neighbouring parvocellular divisions. The rubral projection did not overlap the cortical projection. The fastigial nucleus projected sparsely to the contralateral LRN, mainly to the medial aspect of the rostral two-thirds of the magnocellular division, with less to the parvocellular and subtrigeminal divisions. The LRN therefore receives spinal and supraspinal projections within at least its rostral one-half, and these terminate within specific areas in a partially overlapping fashion, whereas the caudal one-half is primarily a spinal receiving region. No convergence of the rubral and sensorimotor cortical projections was evident.


[Progress on distal interlocking screw of cephalomedullary nail for intertrochanteric fractures].
To summarize the progress on the distal interlocking screw of cephalomedullary nail for intertrochanteric fractures. Related literature concerning the distal interlocking screw of cephalomedullary nail was reviewed and analyzed in terms ofbiomechanics, clinical application, operating difficulties, and complications. Distal interlocking screw can provide extra torsional stiffness in both short and long cephalomedullary nail. It is applied in most clinical cases. In long cephalomedullary nail, placing the distal interlocking screw increases the operative time for fixation and the amount of radiation exposure notably. In short cephalomedullary nail, placing the distal interlocking screw can cause adjacent vascular injury, stress concentration, and secondary fracture around the screw. When the fracture is stable (type A1, type A2.1), it can be fixed solidly without the distal interlocking screw, but prefers to use a long nail. In unstable fracture, the distal interlocking screw should be used to prevent rotational displacement of the femur shaft and the failure of the nail.


Chromatographic determination of itopride hydrochloride in the presence of its degradation products.
Two sensitive and reproducible methods are described for the quantitative determination of itopride hydrochloride (IH) in the presence of its degradation products. The first method is based on HPLC separation on a reversed phase Kromasil column [C18 (5-microm, 25 cm x 4.6 mm, ID)] at ambient temperature using a mobile phase consisting of methanol and water (70:30, v/v) adjusted to pH 4.0 with orthophosphoric acid with UV detection at 258 nm. The flow rate was 1.0 mL per min with an average operating pressure of 180 kg/cm2. The second method is based on HPTLC separation on silica gel 60 F254 using toluene:methanol:chloroform:10% ammonia (5.0:3.0:6.0:0.1, v/v/v/v) as mobile phase at 270 nm. The analysis of variance (ANOVA) and Student's t-test were applied to correlate the results of IH determination in dosage form by means of HPLC and HPTLC methods. The drug was subjected to acid and alkali hydrolysis, oxidation, dry heat, wet heat treatment, UV, and photodegradation. The proposed HPLC method was utilized to investigate the kinetics of the acidic, alkaline, and oxidative degradation processes at different temperatures and the apparent pseudo-first-order rate constant, half-life, and activation energy were calculated. In addition the pH-rate profile of degradation of IH in constant ionic strength buffer solutions in the pH range 2-11 was studied.


[The effects of ephedrine and phenylephrine on arterial partial pressure of oxygen during one-lung ventilation].
We investigated the effects of ephedrine (EP) and phenylephrine (PH) on partial pressure of oxygen and intra-pulmonary shunt during one-lung ventilation under general anesthesia with enflurane, fentanyl and oxygen. When systolic blood pressure decreased to less than 80% of the resting values, 30 adult patients who were randomly assigned into 2 groups, received either EP 0.15 mg.kg-1 or PH 2 micrograms.kg-1. In group-EP, PaO2 increased significantly from 187 +/- 112 to 205 +/- 114 mmHg (FIO2 = 1.0, P < 0.05), while in group-PH, PaO2 changed from 209 +/- 129 to 248 +/- 84 mmHg without statistical significance. Intra-pulmonary shunts were essentially unchanged in both groups. Neither dysrhythmia, ST-T changes on electrocardiography, congestive heart failure, nor severe hypoxemia were observed in any patient during the study. These results indicate that EP and PH in above doses can be safely administered to treat arterial hypotension during one-lung ventilation.


The scaling of abundance in consumers and their resources: implications for the energy equivalence rule.
The negative scaling of plant and animal abundance with body mass is one of the most fundamental relationships in ecology. However, theoretical approaches to explain this phenomenon make the unrealistic assumption that species share a homogeneous resource. Here we present a simple model linking mass and metabolism with density that includes the effects of consumer size on resource characteristics (particle size, density, and distribution). We predict patterns consistent with the energy equivalence rule (EER) under some scenarios. However, deviations from EER occur as a result of variation in resource distribution and productivity (e.g., due to the clumping of prey or variation in food particle size selection). We also predict that abundance scaling exponents change with the dimensionality of the foraging habitat. Our model predictions explain several inconsistencies in the observed scaling of vertebrate abundance among ecological and taxonomic groups and provide a broad framework for understanding variation in abundance.


Serum immunoreactive pancreatic phospholipase A2 in patients with various malignant tumors.
The high incidence (40.6%) of elevated serum pancreatic phospholipase A2 (PLA2) was demonstrated in patients with various malignancies. Serum PLA2 was significantly increased in cancer patients compared with healthy sex- and age-matched blood donors (358.4 +/- 168.0 vs. 241.7 +/- 69.0 ng/dl; p less than 0.01). No correlation was observed between serum PLA2 and carcinoembryonic antigen (CEA) in these patients. Although patients with advanced and distantly metastatic cancer of the liver, gallbladder and pancreas showed higher PLA2 levels in serum than those with early cancer, patients with other cancers showed no correlation between serum PLA2 and clinical stage. A combined assay of PLA2 and CEA increased the sensitivity of detection of cancers to 60.8%.


Characterization of regulatory elements in the 5'-flanking region of the rat GPIIb gene by studies in a primary rat marrow culture system.
Glycoprotein (GP)IIb/IIIa, an integrin complex found on the surface of platelets, is a receptor for fibrinogen and other ligands, and is involved in platelet aggregation. Because GPIIb is specifically expressed in megakaryocytes, we have studied the 5'-flanking region of the rat (r) GPIIb gene as a model of a megakaryocyte-specific gene. The studies presented here used a rat marrow expression system, which allows the study of primary cells undergoing terminal differentiation into megakaryocytes. The determination of megakaryocyte-specific expression of DNA constructs was possible by immunomagnetically separating megakaryocytes from total bone marrow cells. Transient expression constructs, containing varying lengths of the 5'-flanking region from -39 to -912 bp, localized a regulatory element between -460 and -439 bp upstream of the transcriptional start site. This region contains a GATA consensus binding element between -457 and -454 (GATA454). Further constructs demonstrated that this GATA binding element was indeed essential for expression. A 25-bp substitution, covering the region -450 to -426 immediately downstream of the GATA454, demonstrated that this region was essential for full expression, which suggests that this region may interact with the GATA454 site in promoting high-level lineage-specific expression. To define regulatory elements between the GATA454 and the transcriptional start site further, we tested additional constructs derived from the original -912 construct; each of which contained the GATA454 but had different 50-bp deletions from -450 to the start site. Virtually all of these constructs continued to show high-level tissue-specific expression. The deleted -150 to -101 construct had twice the level of expression of the full-length wild-type construct; therefore, this region may contain a negative regulatory element. Comparison of our data with expression studies performed with the 5'-region of the human GPIIb gene using HEL cells, a cell line with some megakaryocytic properties, demonstrates significant differences, which may reflect our use of primary rate bone marrow cells. In particular, our study points to the importance of the GATA454 for high levels of GPIIb expression in developing megakaryocytes.


The synthesis and optical properties of ZnO nanocombs.
The ZnO nanocombs were synthesized by chemical vapor deposition method, which the uniform and dense nanotips were along one side of the comb ribbon. The growth mechanism was described as free catalyst self-assembled and vapor-solid model. The optical properties related with the surface states were investigated by Raman and PL spectra. The large redshift of 1LO phonon peak was attributed to the surface and interface states. The normalized PL spectra showed that the deep-level emission decreased for the sample to be annealed in O2 ambient at 500 degrees C. On the contrary, the deep-level emission increased while for the annealed sample in O2 ambient at 600 degrees C. The deep-level emission was attributed to the transition from the shallow donor to the deep acceptor. The XPS analysis showed the existence of oxygen rich and Zn deficient in the ZnO nanocombs annealed at 600 degrees C. The abnormal temperature dependence of integrated PL intensity was attributed to the abundant surface states.


[Thoughts on dying and death in literature].
About 35 novels, stories and poems from some 10 countries were evaluated by the author in order to show how differently the subject of dying and death is treated in such literary works. Special attention is given to both dying in a hospital and to helping people to face death.


Configurational bias Monte Carlo simulation of phase segregation in block copolymer networks.
Cross-linked block copolymers are used as adhesives in fiber-reinforced composite material manufactures for automotive applications. Good adhesion between the polymer matrix and fibers in the interphase region is required for the structural integrity of these materials. Experimental evidence indicates that superior adhesion is obtained when phase segregation occurs between the two matrix phase block copolymers. It is therefore desirable to predict the conditions under which phase segregation is expected to occur. Configurational bias Monte Carlo simulations of two-component, trifunctional block copolymer networks were carried out to investigate phase segregation in these materials. The effects of four principal parameters on phase segregation were examined: the weight fractions of the two components, the cross-link length, the connectivity of the network, and the ratio of the square-well interactions. The molecular simulation results confirmed trends observed in laboratory measurements.


Personality as a predisposing factor for DCI: a pilot study.
This study aimed to identify differences in personality characteristics related to decompression illness (DCI) in recreational scuba divers. A matched control group of nine divers (without DCI) and a research group of nine divers (with DCI) were recruited. Following a chamber dive (control group), or treatment for DCI (study group), three psychometric scales - Locus of Control, Eysenck's Personality Questionnaire - Revised, and Sensation Seeking Scale - were administered together with a diving history questionnaire and questions on motoring. One significant difference was identified and lay between engine sizes, with those experiencing DCI having cars with larger engines (P < 0.01). The data were inconsistent with previous research that suggested a relationship between sensation seeking and risk taking. Further research is needed to elucidate the relationship between diving injury and personality.


Effect of dietary linoleic and linolenic acids on gestation and parturition in the rat.
Six rats fed a basal, purified diet low in essential fatty acids gave birth to a total of twenty-eight pups, of which twenty-six were born dead (range of two to six pups per rat) after a mean gestation of 24 days. A seventh rat carrying ten fetuses had a protracted process of parturition with dystocia. Six rats fed the basal diet supplemented with linoleate gave birth to a total of sixty-one pups of which fifty-seven were born alive (range of two to fourteen pups per rat) after a mean gestation of 21.8 days. Seven rats fed the basal diet supplemented with linolenate and carrying a total of sixty-three fetuses (seven to twelve per rat) had a protracted process of parturition with dystocia, and only one live and one dead pup were born (mean gestation of 22.8 days). At Caesarian operation a marked uterine inertia was noted. In four more rats where the supplement of linolenate was replaced by linoleate from the seventeenth day of gestation, parturition appeared normal and twenty-nine live and four dead pups were born. The occurrence of dystocia appeared to be related to the number of fetuses being carried to term. It is concluded that, in the rat, linolenate satisfies the requirement for the growth of mother rat and of the fetuses but is inadequate for the normal process of parturition, probably through inadequate production of the prostaglandins involved. There appears to be an obligatory requirement for linoleate at parturition.


FG-4592 relieves diabetic kidney disease severity by influencing metabolic profiles via gut microbiota reconstruction in both human and mouse models.
Objective: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is highly associated with devastating outcomes. Hypoxia-inducible factor (HIF), the main transcription factor that regulates cellular responses to hypoxia, plays an important role in regulating erythropoietin (EPO) synthesis. FG-4592 is the HIF stabilizer that is widely used in patients with renal anemia. We investigated the effect of FG-4592 on DKD phenotypes and the pharmacologic mechanism from the perspective of gut microbiota and systemic metabolism. Design: We collected the clinical data of 73 participants, including 40 DKD patients with combined renal anemia treated with FG-4592, and 33 clinical index-matched DKD patients without FG-4592 treatment from The First Affiliated Hospital of Zhengzhou University at the beginning and after a 3-6-month follow-up period. We established DKD mouse models treated by FG-4592 and performed fecal microbiota transplantation from FG-4592-treated DKD mice to investigate the effects of FG-4592 on DKD and to understand this mechanism from a microbial perspective. Untargeted metabolome-microbiome combined analysis was implemented to globally delineate the mechanism of FG-4592 from both microbial and metabolomic aspects. Result: DKD phenotypes significantly improved after 3-6 months of FG-4592 treatment in DKD patients combined with renal anemia, including a decreased level of systolic blood pressure, serum creatinine, and increased estimated glomerular infiltration rate. Such effects were also achieved in the DKD mouse model treated with FG-4592 and can be also induced by FG-4592-influenced gut microbiota. Untargeted plasma metabolomics-gut microbiota analysis showed that FG-4592 dramatically altered both the microbial and metabolic profiles of DKD mice and relieved DKD phenotypes via upregulating beneficial gut microbiota-associated metabolites. Conclusion: FG-4592 can globally relieve the symptoms of DKD patients combined with renal anemia. In the animal experiment, FG-4592 can reconstruct the intestinal microbial profiles of DKD to further upregulate the production of gut-associated beneficial metabolites, subsequently improving DKD phenotypes.


Time-resolved extinction rates of stochastic populations.
Extinction of a long-lived isolated stochastic population can be described as an exponentially slow decay of quasistationary probability distribution of the population size. We address extinction of a population in a two-population system in the case when the population turnover-renewal and removal--is much slower than all other processes. In this case there is a time-scale separation in the system which enables one to introduce a short-time quasistationary extinction rate W1 and a long-time quasistationary extinction rate W2, and to develop a time-dependent theory of the transition between the two rates. It is shown that W1 and W2 coincide with the extinction rates when the population turnover is absent and present, but very slow, respectively. The exponentially large disparity between the two rates reflects fragility of the extinction rate in the population dynamics without turnover.


Implant sizing of the P.F.C. sigma rotating-platform total knee system.
We studied the P.F.C. Sigma rotating-platform total knee arthroplasties performed during 2004 and 2005 to assess implant size variations in men versus women and size variation in bilateral knees. We subsequently studied commercial femoral radiograph templates to compare mediolateral and anteroposterior dimensions. Sixty-four percent of women more frequently had a tibial tray one size smaller with respect to the femur and 63.5% of men had the same-sized femur and tibia. Bilateral knees were the same size in both sides 97% of the time in women, and 90% in men. The template comparison found that the P.F.C. Sigma rotating-platform femur had a mediolateral dimension that was smaller than many knee replacements commercially available.


Population variation in the trophic niche of the Trinidadian guppy from different predation regimes.
Population variation in trophic niche is widespread among organisms and is of increasing interest given its role in both speciation and adaptation to changing environments. Trinidadian guppies (Poecilia reticulata) inhabiting stream reaches with different predation regimes have rapidly evolved divergent life history traits. Here, we investigated the effects of both predation and resource availability on guppy trophic niches by evaluating their gut contents, resource standing stocks, and δ15N and δ13C stable isotopes across five streams during the wet season. We found that guppies from low predation (LP) sites had a consistently higher trophic position and proportion of invertebrates in their guts and assimilate less epilithon than guppies from high predation (HP) sites. Higher trophic position was also associated with lower benthic invertebrate availability. Our results suggest that LP guppies could be more efficient invertebrate consumers, possibly as an evolutionary response to greater intraspecific competition for higher quality food. This may be intensified by seasonality, as wet season conditions can alter resource availability, feeding rates, and the intensity of intraspecific competition. Understanding how guppy diets vary among communities is critical to elucidating the role of niche shifts in mediating the link between environmental change and the evolution of life histories.


[Laparoendoscopic single site (LESS) ureteral reimplantation.]
To present in detail our surgical technique and to show our initial experience with ureteral reimplantation using the transumbilical LESS approach to treat patients with ureteral stenosis secondary to various diseases and surgical complications. We performed 7 ureteral reimplantations from February 2012, using the multichannel Richard- Wolf (KeyPort) platform placed transumbilical by a small 2-2,5 cm transversal incision. We always use a 3.5 mm minilaparoscopy accessory trocar in the right iliac fossa, that is crucial to perform the laparoscopic suturing safely for the patient and in an optimal time. The etiology of ureteral lesions was: 1 endometriosis, 1 symptomatic ureterocele not responding to endoscopic treatment, 1 ureteral lesion after ureteroscopy for lithiasis, 1 ureteral lesion after radical prostatectomy and 3 gynecologic iatrogenic lesions (1 laparoscopically assisted vaginal hysterectomy, 2 radical hysterectomies with double anexectomy for cervix carcinoma). 5 ureteral reimplantations were left and 2 right sides. Before surgery, 5 patients had nephrostomy tubes inserted and the patient with endometriosis had a double J catheter. The patient with ureterocele did not require urinary diversion before the operation and endoscopic intraoperative catheterization was not feasible. We present the operative and postoperative results of the patients undergoing surgery. They had a mean age of 49.3 [28-78] years. Mean intraoperative estimated blood loss was 132.1 [100-250] ml, with no transfusions required. Mean operative time was 127.4 [120-210] minutes, with no conversions to laparoscopic or open surgery required. Mean hospital stay was 2.1 [2-3] days and all patients had drainage removed at 48 hours. There were minor Clavien-Dindo complications in one patient presenting urinary tract infection 10 days after the operation. All patients had double J catheters that were removed with a mean of 34.3 [30-45] days. Mean time for bladder catheter removal was 7.8 [7-10] días. With a mean follow up of 32.6 [14-54] months no ureteral stenosis recurrence has been observed. LESS ureteral reimplantation, in our initial experience, shows a low complication rate, similar to current laparoscopic series, offering less postoperative pain and abdominal wall aggression with great cosmetic results that are perceived by patients very positively, in addition to rapid recovery and return to normal daily life.


Acute oxygen in patients with sleep apnea and COPD.
Nocturnal oxygen administered to patients with disordered breathing ameliorates hypoxemia. As a result, an important chemical stimulus to arousal is diminished. This could cause prolongation of disordered breathing events, worsen respiratory acidosis, and induce potentially harmful cardiac arrhythmias. The presence of chronic obstructive pulmonary disease (COPD) could further aggravate the situation since such patients may have depressed hypercarbic responses. To test this hypothesis, 20 obese men with sleep apnea and COPD were studied polysomnographically on two nights receiving air on one or oxygen at 4 L/min on the other. Supplemental oxygen increased mean DOB event duration from 25.7 to 31.4 seconds (p less than 0.001), increased end apneic PCO2 from 52.8 to 62.3 mm Hg (p less than 0.025), and decreased mean end apneic pH from 7.34 to 7.28 (p less than 0.001). At the same time, it improved mean sleeping and end-apneic oxygen saturation. The number of ventricular extra-systoles (PVCs) per minute of sleep showed small increases in three subjects while breathing oxygen. Complex ventricular arrhythmias were unaffected by oxygen in five subjects. Oxygen eliminated atrioventricular block in two subjects. We conclude that nocturnal supplemental oxygen does not increase ventricular arrhythmias in the majority of patients with COPD and coexisting disordered breathing events. While the clinical significance of an oxygen associated increase in ventricular extrasystoles in three subjects is unclear, nocturnal monitoring by telemetry or ambulatory recorder should be sufficient to detect such patients.


The effectiveness of contrasting protected areas in preventing deforestation in Madre de Dios, Peru.
Accurate monitoring of the effectiveness of protected areas (PAs) in decreasing deforestation is increasingly important given the vital role of forest protection in climate change mitigation. Recent studies on PA effectiveness have used remote-sensing imagery to compare deforestation rates within PAs to surrounding areas. However, remote-sensing data used in isolation provides limited information on the factors contributing to effectiveness. We used landscape-modelling techniques to estimate the effectiveness of ten PAs in Madre de Dios, Peru. Factors influencing PA effectiveness were investigated using in situ key-informant interviews. Although all of the PAs studied had positive effectiveness scores, those with the highest scores were ecotourism and conservation concessions, where monitoring and surveillance activities and good relations with surrounding communities were reported as possible factors in decreasing deforestation rates. Native community areas had the lowest scores, with deforestation mainly driven by internal resource use and population growth. Weak local governance and immigration were identified as underlying factors decreasing the effectiveness of protection, whereas good relations with surrounding communities and monitoring activity increased effectiveness. The results highlight the need to combine remote sensing with in situ information on PA management because identification of drivers and deterrents of deforestation is vital for improving the effectiveness of protection.


Diagnostic value of radionuclide scanning and ultrasonography in thyroid developmental anomaly imaging.
Thyroid is particularly prone to morphogenetic variability. Developmental failure of the thyroid gland is in 85% of cases the underlying cause of congenital hypothyroidism, diagnosed at birth with a frequency of 1:3000-1:4000 newborns. However, the incidence of less severe developmental variants of the thyroid is much higher. Determination of the aetiology of congenital hypothyroidism is crucial for predicting its severity and outcome as well as impacts dose of L-thyroxine during substitution. Thyroid imaging is necessary to establish diagnosis, and it involves mainly thyroid ultrasound examination and scintiscan. Awareness of both the advantages and limitations of sonographic and scintigraphic imaging are central to the successful interpretation of their results and reasonable recommendation of these procedures for patients with thyroid developmental anomalies of different age and clinical picture. Hence, the aim of this review is to provide the most important and up-to-date information on the place of radionuclide scanning and ultrasonography in visualization of different thyroid developmental abnormalities.


Interpretation of mixed-valence compound optical spectra near the class II/III border: dinitrobiphenyl and dinitrophenanthrene radical anions.
The optical spectra of 4,4'-dinitrobiphenyl and other similar 9-bond bridged radical anions show that these mixed-valence compounds are predominantly charge-localized in the high lambda(S) solvent MeCN, charge-delocalized in the low lambda(S) solvent HMPA, and show intermediate behavior in DMF. Hush analysis of the localized charge-transfer band in MeCN allowed the calculation of the electronic coupling between nitro groups (Hab). Hab changes with bridge structure, depending mainly on the twist angle between the two aromatic rings: Hab is higher for the planar 9,9-dimethyl-2,7-dinitrofluorene radical anion (1100 cm(-1)) and about one-half of this value for the more twisted 2,2'-dimethyl-4,4'-dinitrobiphenyl radical anion (540 cm(-1)). The reorganization energy lambda decreases as Hab increases. We suggest that this is due to a decrease of the internal reorganization energy lambda(v) as the Class II/Class III borderline is approached, and that lambda(v) should be zero at the borderline. Subtracting from the experimental spectra the fraction corresponding to the delocalized part (taken as the spectrum in HMPA or THF), we get localized charge-transfer bands that show a significant cutoff effect at the low energy side, as predicted by classical Marcus-Hush theory.


Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.
The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence. Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains. var genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique for the group A var genes The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.


Type 7 adenylyl cyclase-mediated hypothalamic-pituitary-adrenal axis responsiveness: influence of ethanol and sex.
Although ethanol has been considered to be an anxiolytic agent, consumption of ethanol has also been shown to increase plasma adrenocorticotropin and glucocorticoids. The corticotrophin-releasing factor (CRF) receptor 1alpha (CRF-R1) is a G protein-coupled receptor that activates adenylyl cyclase (AC), leading to adrenocorticotropin (and subsequently glucocorticoid) release into the circulation. There are nine members of the membrane-bound AC family, and the type 7 AC (AC7) is most sensitive to ethanol, which enhances the responsiveness of AC7 to G protein-coupled receptor activation. We determined the time course of ethanol's effect on plasma adrenocorticotropin and corticosterone levels in male and female AC7 transgenic (Adcy7(huTG)) mice (in which AC7 is overexpressed in neural tissue) and AC7 heterozygous knockdown [Adcy7(+/-)] mice (in which AC7 is underexpressed in neural tissue), and their respective littermate controls [wild type (WT)]. CRF-R1 mRNA and mRNA and protein for different forms of ACs were measured by using gene expression arrays, quantitative reverse transcription-polymerase chain reaction, and immunoblotting in pituitaries of all animals. Our results demonstrated increased levels of AC7 in pituitary of Adcy7(huTG) mice and decreased levels in pituitary of Adcy7(+/-) mice compared with WT animals. Male and female Adcy7(huTG) mice displayed higher plasma adrenocorticotropin and corticosterone levels than WT and/or Adcy7(+/-) mice after ethanol injection. Female mice displayed higher adrenocorticotropin and corticosterone levels after ethanol injection than males, regardless of genotype. The data provide evidence for an integral role of AC7 in the increase of plasma adrenocorticotropin and corticosterone levels during alcohol intoxication.


Fused-ring pyrazine derivatives for n-type field-effect transistors.
Three new fused-ring pyrazine derivatives end-functionalized with trifluoromethylphenyl groups have been synthesized. The effect of a fused-ring pyrazine core on the thermal, electronic, optical, thin film morphology, and organic field-effect transistor (OFET) properties was investigated both experimentally and theoretically. Electrochemistry measurements and density functional theory calculations suggest that the pyrazine core plays a significant role in tuning the electron affinities of these compounds. The optical absorption and fluorescence properties are also sensitive to the pyrazine core. The OFET devices based on the fused-ring pyrazine compounds exhibit electron mobilities as high as ca. 0.03 cm(2) V(-1) s(-1) under nitrogen, and their performance is sensitive to the pyrazine core. The larger pyrazine core leads to a lower LUMO level and lower reorganization energy, to more ordered thin film morphology with larger grain size, and finally to higher mobilities.


Hürthle cell tumors of the thyroid gland. A clinicopathologic review and long-term follow-up.
We reviewed the pathology and clinical follow-up of 26 patients with H urthle cell adenomas and three patients harboring H urthle cell carcinomas, who were treated at our medical center from 1950 to 1979. Although benign lesions could not be distinguished from malignant tumors by cytologic features alone, other pathologic features allowed differentiation. A total thyroidectomy was performed in only one patient; the remaining patients were treated by less extensive operations. None of the patients with benign adenomas, including those with tumors greater than 2 cm in diameter, experienced recurrent or metastatic disease. The period of observation varied from two to 22 years (mean, 8.5 +/- 7.7 years). We conclude that lobectomy is a satisfactory operation for removal of benign H urthle cell tumors, and reserve total or near-total thyroidectomy for cases displaying pathologic evidence of malignancy.


Acute Coronary Syndrome: Emergency Department Evaluation and Management.
Patients with chest pain who present to emergency departments have a significantly higher incidence of acute coronary syndrome (ACS) than patients with chest pain presenting to outpatient settings, so emergency department clinicians should have a lower threshold for considering ACS as an etiology. Evaluating patients with suspected ACS in the emergency department involves obtaining a history, physical examination, electrocardiograms (ECGs), and cardiac troponin measurements in conjunction with risk calculators. These parameters cannot be used individually because, for example, a normal ECG result does not exclude ACS and troponin levels can be elevated in many conditions. All patients with suspected ACS should receive aspirin, if not contraindicated, as soon as possible. Those with an ST-segment elevation myocardial infarction (STEMI) or those without STEMI who are in unstable condition should be triaged to undergo reperfusion therapy, typically via percutaneous coronary intervention (PCI), within 120 minutes of first medical contact. If that time limit cannot be met because the patient must be transferred to a PCI-capable facility, fibrinolytic therapy should be initiated within 30 minutes of presentation if STEMI is present. (Fibrinolytic therapy is contraindicated for myocardial infarction without STEMI.) Patients also should receive nitroglycerin to relieve angina and beta blockers if not contraindicated.


HCV RNA Testing of Plasma Samples from Cornea Donors: Suitability of Plasma Samples Stored at 4 °C for up to 8 Days.
The HCV RNA testing of potential cornea donors frequently relies on blood samples stored pre mortem. The recommended storage time of maximum 72 h frequently excludes a significant fraction of donors. The influence of storage time of EDTA plasma samples at 4 °C on the viral load measured with the Roche HCV Quantitative Test vs. 2.0 was evaluated for 43 samples from HCV-positive individuals. The mean reduction of the viral load after 4 °C storage for 6-8 days was 0.46 log10 IU/ml (range +0.17 to -1.66 log10 IU/ml). After 1-3 days a mean loss of 0.19 log10 IU/ml (range +0.30 to -1.41 log10 IU/ml) and after 3-5 days of 0.32 log10 IU/ml (range +0.36 to -1.81 log10 IU/ml) was observed. In 23.3% of samples, a viral load reduction ≥ 1 log10 IU/ml (1.0-1.81 log10 IU/ml) was found after prolonged storage (5-8 days). In none of the samples did the HCV load fall below the detection limit. Plasma storage for up to 8 days can quantitatively reduce the HCV RNA load, yet has no influence on the reliability of a qualitative HCV RNA detection by this ultrasensitive test to determine the HCV status of serologically negative cornea donors.


Costs Associated With Intravenous Darbepoetin Versus Epoetin Therapy in Hemodialysis Patients: A Randomized Controlled Trial.
Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies. To compare the cost of DA and EPO and to determine the dose conversion ratio over a 12-month period. Randomized controlled trial. Canadian outpatient hemodialysis center. Eligible patients were adult hemodialysis patients requiring ESA therapy. The primary outcome was ESA cost (Can$) per patient over 12 months. Secondary outcomes included the dose conversion ratio, deviation from target ranges in anemia indices, iron dose and cost, and time and number of dose changes. An open-label randomized controlled trial of intravenous (IV) DA versus EPO was conducted in 50 hemodialysis patients. Participants underwent a minimum 6-week run-in phase followed by a 12-month active study phase. ESA and iron were dosed using a study algorithm. The median cost was $4179 (interquartile range [IQR]: $2416-$5955) for EPO and $2303 (IQR: $1178-$4219) for DA with a difference of $1876 (P = .02). The dose conversion ratio was 280:1 (95% confidence interval [CI]: 197-362:1) at the end of the run-in phase, 360:1 (95% CI: 262-457:1) at the 3-month point of the active phase, and 382:1 (95% CI: 235-529:1) at the 6-month point of the active phase. There were no significant differences between the 2 groups in weekly iron dose, Hb, serum ferritin, or transferrin saturation. The number of dose changes and the time to Hb stability were similar. Results may not be generalizable to hemodialysis units without algorithm-based anemia management, with subcutaneous ESA administration, or to the nondialysis chronic kidney disease population. The effective conversion ratio between EPO and DA is known to increase at higher doses; the Hb targets used in the study were slightly higher than those recommended today so it is possible that the doses used were also higher. Because of this, the cost savings estimated for DA could differ somewhat from the savings realizable in current practice. In this study of hemodialysis patients with comparable anemia management, IV DA cost $1876 less per year per patient than IV EPO. The dose conversion ratio was greater than 350:1 by the 3-month point. ClinicalTrials.gov (NCT02817555).


Cyclosporine-associated nephropathy in patients with heart and bone marrow transplants.
The morphology of kidneys from heart (n = 55) and bone marrow (n = 112) transplant recipients treated either with cyclosporine (CSA) or conventional immunosuppression was investigated at autopsy. The major findings were: In the bone marrow transplant recipients glomerular collapse, tubular atrophy, interstitial fibrosis, striped form, CSA-associated arteriolopathy and thrombi in glomeruli and/or arterioles were more often found in the CSA group as compared to conventional immunosuppression. In the heart transplant recipients glomerular collapse and obsolescence, tubular atrophy and intimal fibrosis in arteries were more frequent in the CSA group. Vascular interstitial toxicity known to be associated with CSA treatment from renal transplant patients was found in 54% (25% severe) of the bone marrow and 19.5% (9.7% severe) of the the heart transplant recipients. The prevalence of vascular interstitial toxicity in bone marrow versus heart transplant recipients is possibly due to higher CSA dosage and pretreatment with cytostatic drugs and irradiation. Analyses of the lesions from early stages to the full picture of vascular interstitial toxicity suggests that CSA causes a form of thrombotic microangiopathy with focal glomerular and/or arteriolar thrombosis followed by typical CSA-associated arteriolopathy which results in interstitial fibrosis with tubular atrophy.


Dynamics of Transgenic Enterobacter cloacae Expressing Green Fluorescent Protein Defensin (GFP-D) in Anopheles stephensi Under Laboratory Condition.
Enterobacter cloacae bacterium is a known symbiont of the most Anopheles gut microflora and nominated as a good candidate for paratransgenic control of malaria. However, the population dynamics of this bacterium within An. stephensi and its introduction methods to the mosquitoes have not yet been explored. Enterobacter cloacae subsp. dissolvens expressing green fluorescent protein and defensin (GFP-D) was used to study transstadial transmission and the course of time, larval habitat, sugar, and blood meal on dynamics of the bacterium in the mosquito life stages in the laboratory condition. The bacterial quantities were measured by plating samples and counting GFP expressing colonies on the Tet-BHI agar medium. The E. cloacae population remained stable in sugar bait at least for eleven days whereas it was lowered in the insectary larval habitat where the bacteria inadequately recycled. The bacterium was weakly transmitted transstadially from larval to adult stage. The bacterial populations increased smoothly and then dramatically in the guts of An. stephensi following sugar and blood meal respectively followed by a gradual reduction over the time. Enterobacter cloacae was highly stable in sugar bait and increased tremendously in the gut of female adult An. stephensi within 24h post blood meal. Sugar bait stations can be used for introduction of the transgenic bacteria in a paratransgenic approach. It is recommended to evaluate the attraction of sugar bait in combination with attractive kairomones as well as its stability and survival rate in the semi-field or field conditions.


Postnatal Increases in Axonal Conduction Velocity of an Identified Drosophila Interneuron Require Fast Sodium, L-Type Calcium and Shaker Potassium Channels.
During early postnatal life, speed up of signal propagation through many central and peripheral neurons has been associated with an increase in axon diameter or/and myelination. Especially in unmyelinated axons postnatal adjustments of axonal membrane conductances is potentially a third mechanism but solid evidence is lacking. Here, we show that axonal action potential (AP) conduction velocity in the Drosophila giant fiber (GF) interneuron, which is required for fast long-distance signal conduction through the escape circuit, is increased by 80% during the first day of adult life. Genetic manipulations indicate that this postnatal increase in AP conduction velocity in the unmyelinated GF axon is likely owed to adjustments of ion channel expression or properties rather than axon diameter increases. Specifically, targeted RNAi knock-down of either Para fast voltage-gated sodium, Shaker potassium (Kv1 homologue), or surprisingly, L-type like calcium channels counteracts postnatal increases in GF axonal conduction velocity. By contrast, the calcium-dependent potassium channel Slowpoke (BK) is not essential for postnatal speeding, although it also significantly increases conduction velocity. Therefore, we identified multiple ion channels that function to support fast axonal AP conduction velocity, but only a subset of these are regulated during early postnatal life to maximize conduction velocity. Despite its large diameter (∼7 µm) and postnatal regulation of multiple ionic conductances, mature GF axonal conduction velocity is still 20-60 times slower than that of vertebrate Aβ sensory axons and α motoneurons, thus unraveling the limits of long-range information transfer speed through invertebrate circuits.


Anthropometric prediction of skeletal muscle cross-sectional area in persons with spinal cord injury.
Finding an accurate and affordable method to quantify muscle size following spinal cord injury (SCI) could provide benefits clinically and in research settings. The purpose of this study was to validate the use of anthropometric measurements vs. magnetic resonance imaging (MRI) to evaluate muscle cross-sectional area (CSA) and develop a field equation to predict muscle CSA specific to the SCI population. Twenty-two men with chronic (>1 yr) motor complete SCI participated in the current study. Anthropometric measurements, including midthigh circumference and anterior skinfold thickness (SFT), were taken on the right thigh. The anthropometric muscle cross-sectional area (muscle CSAanthro) was predicted using the following equation: muscle CSAanthro = π[r - (SFT/2)]2, where r = thigh circumference/2π. MRI analysis yielded whole thigh CSA (thigh CSAMRI), midthigh muscle CSA (muscle CSAMRI), midthigh absolute muscle CSA after subtracting intramuscular fat and bone (muscle CSA-IMFMRI), subcutaneous adipose tissue (SATT) measured at one site as well as at four sites, and bone CSA. Anthropometric measurements were correlated to the thigh CSAMRI [r2 = 0.90, standard error of the estimate (SEE) = 17.6 cm2, P < 0.001]. Muscle CSAanthro was correlated to muscle CSAMRI (r2 = 0.78, SEE = 16.6 cm2, P < 0.001) and muscle CSA-IMFMRI (r2 = 0.75, SEE = 17.6 cm2, P < 0.001). A single SFT was correlated to the polar four-site SATT (r2 = 0.78, SEE = 0.37 cm, P < 0.001). The average femur CSA and average IMF CSA derived from MRI led to the following field equation: muscle CSApredicted = π[(Thighcircum/2π) - (SFT/2)]2 - 23.2. Anthropometric measurements of muscle CSA exhibited a good agreement with the gold standard MRI method and led to the development of a field equation for clinical use after accounting for bone and IMF.NEW & NOTEWORTHY This study used anthropometric measurements and magnetic resonance imaging (MRI) to evaluate muscle cross-sectional area (CSA) and developed a field equation to predict thigh muscle CSA specific to the spinal cord-injured (SCI) population. Anthropometric measurements were correlated to the whole thigh CSA and muscle CSA as measured by MRI. The correlations led to the development of a SCI-specific field equation that accounted for intramuscular fat and bone areas.


[Suppressive effect of methylparaben on the evoked compound action potentials in excised rabbit cervical vagus nerve].
We evaluated the effects of methylparaben on rabbit vagus nerve by measuring the amplitudes and latencies of the evoked compound action potentials during incubation in 0.1% methylparaben containing Ringer's bicarbonate solution. We also evaluated the histological changes of the nerves after incubation in methylparaben-RB solution by means of the electron microscopy. We found that 0.1% methylparaben caused complete suppression of the compound action potentials, which recovered completely after washing in methylparaben-free RB solution. The electron microscopic studies revealed no histological changes of nerves incubated in 0.1% methylparaben containing RB solution. We conclude that methylparaben suppresses nerve excitability dose-dependently, but does not destroy nervous tissues in concentrations up to 0.1%.


Lipopolysaccharides from Porphyromonas endodontalis and Porphyromonas gingivalis promote angiogenesis via Toll-like-receptors 2 and 4 pathways in vitro.
Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4. Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP). The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling. Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.


Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.
The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.


Distinct regions of the Escherichia coli ParC C-terminal domain are required for substrate discrimination by topoisomerase IV.
Type IIA DNA topoisomerases are essential enzymes that use ATP to maintain chromosome supercoiling and remove links between sister chromosomes. In Escherichia coli, the type IIA topoisomerase topo IV rapidly removes positive supercoils and catenanes from DNA but is significantly slower when confronted with negatively supercoiled substrates. The ability of topo IV to discriminate between positively and negatively supercoiled DNA requires the C-terminal domain (CTD) of one of its two subunits, ParC. To determine how the ParC CTD might assist with substrate discrimination, we identified potential DNA interacting residues on the surface of the CTD, mutated these residues, and tested their effect on both topo IV enzymatic activity and DNA binding by the isolated domain. Surprisingly, different regions of the ParC CTD do not bind DNA equivalently, nor contribute equally to the action of topo IV on different types of DNA substrates. Moreover, we find that the CTD contains an autorepressive element that inhibits activity on negatively supercoiled and catenated substrates, as well as a distinct region that aids in bending the DNA duplex that tracks through the enzyme's nucleolytic center. Our data demonstrate that the CTD is essential for proper engagement of both gate and transfer segment DNAs, reconciling different models to explain how topo IV discriminates between distinct DNAs topologies.


Electroantennogram (EAG) responses of Microplitis croceipes and Cotesia marginiventris and their lepidopteran hosts to a wide array of odor stimuli: correlation between EAG response and degree of host specificity?
In order to test whether the electroantennogram (EAG) response spectrum of an insect correlates to its degree of host specificity, we recorded EAG responses of two parasitoid species with different degrees of host specificity, Microplitis croceipes (specialist) and Cotesia marginiventris (generalist), to a wide array of odor stimuli including compounds representing green leaf volatiles (GLVs), herbivore-induced plant volatiles (HIPV), ecologically irrelevant (not used by the parasitoid species and their hosts for host location) plant volatiles, and host-specific odor stimuli (host sex pheromones, and extracts of host caterpillar body and frass). We also tested the EAG responses of female moths of the caterpillar hosts of the parasitoids, Heliothis virescens and Spodoptera exigua, to some of the odor stimuli. We hypothesized that the specialist parasitoid will have a narrower EAG response spectrum than the generalist, and that the two lepidopteran species, which are similar in their host plant use, will show similar EAG response spectra to plant volatiles. As predicted, the specialist parasitoid showed greater EAG responses than the generalist to host-specific odor and one HIPV (cis-3-hexenyl butyrate), whereas the generalist showed relatively greater EAG responses to the GLVs and unrelated plant volatiles. We detected no differences in the EAG responses of H. virescens and S. exigua to any of the tested odor.


Hemorrhagic Reversible Cerebral Vasoconstriction Syndrome: Features and Mechanisms.
To compare hemorrhagic and nonhemorrhagic reversible cerebral vasoconstriction syndromes (RCVS) with a view to understand mechanisms. This single-center retrospective study included 162 patients with RCVS. Clinical, brain imaging, and angiography data were analyzed. The mean age was 44±13 years, 78% women. Hemorrhages occurred in 43% including 21 patients with intracerebral hemorrhage (ICH) and 62 with convexal subarachnoid hemorrhage (cSAH). The frequency of triggers (eg, vasoconstrictive drugs) and risk factors (eg, migraine) were not significantly different between hemorrhagic and nonhemorrhagic RCVS or between subgroups (ICH versus non-ICH, isolated cSAH versus normal scan). Hemorrhagic lesions occurred within the first week, whereas infarcts and vasogenic edema accumulated during 2 to 3 weeks (P<0.001). Although all ICHs occurred before cSAH, their time course was not significantly different (P=0.11). ICH and cSAH occurred earlier than infarcts (P≤0.001), and ICH earlier than vasogenic edema (P=0.009). Angiogram analysis showed more severe vasoconstriction in distal versus proximal segments in all lesion types (ICH, cSAH, infarction, vasogenic edema, and normal scan). The isolated infarction group had more severe proximal vasoconstriction, and those with normal imaging had significantly less vasoconstriction. Multivariable analysis failed to uncover independent predictors of hemorrhagic RCVS; however, female sex predicted ICH (P=0.048), and angiographic severity predicted infarction (P=0.043). ICH and cSAH are common complications of RCVS. Triggers and risk factors do not predict lesion subtype but may alter central vasomotor control mechanisms resulting in centripetal angiographic evolution. Early distal vasoconstriction is associated with lobar ICH and cSAH, and delayed proximal vasoconstriction with infarction.


A telehealth intervention for veterans on antiviral treatment for the hepatitis C virus.
The standard treatment for chronic hepatitis C (pegylated interferon and ribavirin) causes challenging physical and psychological side effects. The current pilot study evaluated the efficacy of a brief, telephone-based, cognitive-behavioral self-management intervention designed to address mood and quality of life within a sample of veterans on antiviral treatment for hepatitis C. Results from this pilot study support the feasibility of this telehealth intervention, showing that veterans were highly satisfied with the content of the intervention and compliant with the telephone calls. Findings further indicate that symptoms of depression and anxiety and mental health quality of life either remained stable or improved in those participants who received the brief telephone intervention, while those receiving usual care showed significant declines in mood and mental health quality of life. The findings from this study provide evidence that a brief, clinician-administered phone intervention may help individuals on antiviral therapy for hepatitis C to cope more effectively with the negative treatment side effects.


Imaging of peritoneal ligament by endoscopic ultrasound.
Double layered peritoneal folds, variously named as ligaments, omenta and mesenteries connect the intraperitoneal organs to the abdominal wall. Some of these ligaments contain blood vessels and lymph nodes while others are avascular. The peritoneal folds not only act as conduits for the passage of blood vessels from the retroperitoneum to reach intraperitoneal organs, but also provide a pathway for the spread of disease processes. It is difficult to identify these normal peritoneal folds at imaging. Computed tomography is the most common imaging modality used to detect diseases of the peritoneum to fully delineate peritoneal anatomy and the extent of disease. The endoscopic ultrasound (EUS) can be used to image peritoneal ligaments with the advantage of lack of ionizing radiation and lower cost. Though EUS is being increasingly used both for diagnostic and interventional purposes in the abdomen, it has not been used to assess the peritoneal ligaments till now. We did this study in 50 patients using linear echo endoscope to delineate various peritoneal ligaments. The technique of evaluation of ligament has been described in this review. The peritoneal ligaments can be delineated with accuracy by EUS.


Vertebral artery dissection in weightlifter with performance enhancing drug use.
This case report describes a transient ischaemic attack secondary to vertebral artery dissection (VAD) in a young male body builder. This occurred following weight training with weights across the back and shoulders. The patient was also known to take multiple performance enhancing agents including anabolic steroids, slimming agents, stimulants and human growth hormone. Cases of VAD have been described with cervical manipulation in the past and an association between the use of anabolic steroids and embolic strokes has been described. To the authors knowledge, this is the first case describing a link between VAD, weight training and anabolic steroids.


Influenza infection causes airway hyperresponsiveness by decreasing enkephalinase.
Ferret tracheal segments were infected with human influenza virus A/Taiwan/86 (H1N1) in vitro. After 4 days, the smooth muscle contractile responses to acetylcholine and to substance P were measured. The response to substance P was markedly accentuated, with a threefold increase in force of contraction at a substance P concentration of 10(-5) M, the highest concentration tested. In contrast, the response to acetylcholine was not affected by viral infection. Histological examination of tissues revealed extensive epithelial desquamation. Activity of enkephalinase (neutral metallo-endopeptidase, EC.22.214.171.124), an enzyme that degrades substance P, was decreased by 50% in infected tissues. Inhibiting enkephalinase activity by pretreating with thiorphan (10(-5) M) increased the response to substance P to the same final level in both infected and control tissues. Inhibiting other substance P-degrading enzymes including kininase II (angiotensin-converting enzyme), serine proteases, and aminopeptidases did not affect the response to substance P. Inhibiting cyclooxygenase and lipoxygenase activity using indomethacin and BW 755c did not affect hyperresponsiveness to substance P. Pretreating tissues with antagonists of alpha-adrenoceptors, beta-adrenoceptors, and H1 histamine receptors (phentolamine 10(-5) M, propranolol 5 X 10(-6) M, and pyrilamine 10(-5) M, respectively) had no effect on substance P-induced contraction. These results demonstrate that infection of ferret airway tissues with influenza virus increases the contractile response of airway smooth muscle to substance P. This effect is caused by decreased enkephalinase activity in infected tissues.


Origin of Conductive Nanocrystalline Diamond Nanoneedles for Optoelectronic Applications.
Microstructural evolution of nanocrystalline diamond (NCD) nanoneedles owing to the addition of methane and nitrogen in the reactant gases is systematically addressed. It has been determined that varying the concentration of CH4 in the CH4/H2/N2 plasma is significant to tailor the morphology and microstructure of NCD films. While NCD films grown with 1% CH4 in a CH4/H2/N2 (3%) plasma contain large diamond grains, the microstructure changed considerably for NCD films grown using 5% (or 10%) CH4, ensuing in nanosized diamond grains. For 15% CH4-grown NCD films, a well-defined nanoneedle structure evolves. These NCD nanoneedle films contain sp3 phase diamond, sheathed with sp2-bonded graphitic phases, achieving a low resistivity of 90 Ω cm and enhanced field electron emission (FEE) properties, namely, a low turn-on field of 4.3 V/μm with a high FEE current density of 3.3 mA/cm2 (at an applied field of 8.6 V/μm) and a significant field enhancement factor of 3865. Furthermore, a microplasma device utilizing NCD nanoneedle films as cathodes can trigger a gas breakdown at a low threshold field of 3600 V/cm attaining a high plasma illumination current density of 1.14 mA/cm2 at an applied voltage of 500 V, and a high plasma lifetime stability of 881 min is evidenced. The optical emission spectroscopy studies suggest that the C2, CN, and CH species in the growing plasma are the major causes for the observed microstructural evolution in the NCD films. However, the increase in substrate temperature to ∼780 °C due to the incorporation of 15% CH4 in the CH4/H2/N2 plasma is the key driver resulting in the origin of nanoneedles in NCD films. The outstanding optoelectronic characteristics of these nanoneedle films make them suitable as cathodes in high-brightness display panels.


Evaluation of candidal colonization and specific humoral responses against Candida albicans in patients with psoriasis.
Psoriasis is an inflammatory skin disease that can considerably affect a patient's quality of life. Environmental and genetic factors, as well as superantigens and toxins from Candida species, may play various roles in the exacerbation and persistence of psoriasis. In the present study, we evaluated candidal colonization and specific humoral responses against Candida albicans in patients with psoriasis. A total of 100 patients with psoriasis vulgaris and 50 healthy control individuals were enrolled in the study. Skin and oral specimens from all participants were cultured on CHROMagar Candida medium. Isolated yeast-like fungi were identified using the sequence of the D1/D2 domain of the 26S rRNA gene. Enzyme-linked immunosorbent assays (ELISAs) were used to detect immunoglobulin M (IgM), IgA, and IgG antibodies against C. albicans in sera of patients and healthy individuals. Candida species were isolated from the skin of 15% of patients and 4% of controls and from oral specimens of 60% of patients and 20% of controls. There was a significant difference in candidal colonization between patients and controls (P < 0.05). Serum IgM, IgA, and IgG levels against C. albicans were significantly lower in patients with psoriasis than in controls (P < 0.05). There was no significant association between serum levels of specific antibodies against C. albicans or the frequency of candidal colonization with the clinical severity of the disease (P > 0.05). The results of the present study show a higher rate of candidal colonization in patients with psoriasis in comparison with controls and a reduction in humoral immune responses in patients.


Point mutation analysis in a mammalian gene: rapid preparation of total RNA, PCR amplification of cDNA, and Taq sequencing by a novel method.
We have developed a very rapid procedure for DNA sequence analysis of induced mutations in a typically large mammalian gene. We are able to determine the nature of chemical carcinogen-induced point mutations in the 25 kb Chinese hamster ovary (CHO) cell dihydrofolate reductase gene within two days starting with 5 to 10 x 10(6) cells. The approach is based on the use of rapidly prepared total RNA from which a 730 bp dhfr cDNA is synthesized by reverse transcriptase and amplified by the polymerase chain reaction (PCR) procedure. Genomic DNA can simultaneously be prepared from the same cells. The amplified double-stranded cDNA is then sequenced directly by the dideoxy method using Taq polymerase in the Thermal Cycler (Perkin Elmer/Cetus). We have previously shown that nonsense codons in the dhfr coding sequence often result in greatly reduced steady-state levels of dhfr mRNA (2). The methods described are suitable for mutants of this type which contain only 1 to 2 copies of mRNA per cell. This approach is readily adaptable to other selectable genes and other cell types provided the necessary primers can be prepared.


Extinction of the estrogen-induced daily signal for LH release in the rat: a role for the proestrous surge of progesterone.
The heightened secretion of estrogen on diestrus-2 is required for the release of an ovulatory amount of LH on the following day, proestrus. Though these surges occur once every 4-5 days in cycling rats, the treatment of ovariectomized rats with a single injection of estrogen results in daily proestrus-like surges of LH. The present study was designed to test the possibility that progesterone, secreted on proestrus, prevents the daily expression of LH surges in cycling animals. The administration of estradiol benzoate (EB, 50 mug) to ovariectomized rats resulted in daily surges of LH secretion for 3 consecutive days. These surges were similar in the timing of onset and duration to the preovulatory surge of LH on proestrus. Serum LH concentrations were not increased on either the second or the third day when 5 mg of progesterone was given at 1600 h on the day of the first surge. These data suggest that progesterone blocks the expression of daily LH surges induced by estrogen. To determine whether this relationship obtains during the estrous cycle, groups of rats were treated with sodium pentobarbital (PB) at 1345 h during proestrus. This treatment postponed the proestrous surges of LH and progesterone for 24 h. When the surge of progesterone was simulated in PB-treated rats by the administration of 5 mg of the steroid at 1400 h during proestrus, a preovulatory surge of LH was not detected during either proestrous, estrus,, or diestrus-1. These data, taken together, suggest that estrogen turns on a "memory center" for the expression of daily LH surges and that one function of the increased secretion of progesterone on proestrus is to limit the expression of the "memory center" to this day.


Posttraumatic and depressive symptoms in victims of occupational accidents.
The present descriptive study was aimed at evaluating posttraumatic and depressive symptoms and their cooccurrence, in a sample of victims of workplace accidents. Also, posttraumatic negative cognitions were assessed. Eighty-five injured workers were evaluated, using the PTSD Symptom Scale, the Beck Depression Inventory II, and the posttraumatic Cognitions Inventory. 49.4% of injured workers reported both depressive and posttraumatic symptoms of clinical relevance. 20% only reported posttraumatic, but not depressive, symptoms, and 30.6% did not report either type of symptoms. The group with both posttraumatic and depressive symptoms displayed greater symptom severity and more negative cognitions about the self and about the world than the other two groups. The obtained findings indicate that workplace accidents can have a major impact upon the mental health of victims. Early interventions should be focused not only on the prevention or reduction of posttraumatic and depressive symptoms but also on restructuring specific maladaptive trauma-related cognitions.


Efficacy and Safety of PARACHUTE® Device: systematic review.
Heart failure due to an acute myocardial infarction is a very frequent event, with a tendency to increase according to improvements in the treatment of acute conditions which have led to larger numbers of infarction survivors. The aim of this study is to synthesize the evidence, through a systematic review, on efficacy and safety of the device in patients with this basic condition. Studies published between January 2002 and October 2016 were analysed, having as reference databases Embase, Medline, Cochrane Library, Lilacs, Web of Science and Scopus. The selection of studies, data extraction and methodological quality assessment of studies were examined by two independent reviewers, with disagreements resolved by consensus. Only prospective studies without control group were identified. Six studies were included, with averages of 34 participants and follow-up of 13 months. Clinical, functional, hemodynamic and quality of life outcomes were evaluated. The highest mortality rate was 8.4% with 12-month follow-up for unspecified cardiovascular reasons, and heart failure rehospitalization was 29.4% with 36-month follow-up. Statistically significant improvements were found only in some of the studies which evaluating changes in left ventricular volume indices, the distance measured by the six-minute walk test, New York Heart Association functional classification, and quality of life, in pre and post-procedure analysis. The present review indicates that no available quality evidence can assert efficacy and safety of PARACHUTE® in the treatment of heart failure after apical or anterior wall myocardial infarction.


Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.
Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P < .05). At a population level, patients treated by providers affiliated with CCOP were no more likely to receive at least 1 of 2 surgical innovations for treatment of their kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care.


Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice.
The CXC chemokine interleukin-8 (IL-8/CXCL8) induces rapid mobilization of hematopoietic progenitor cells (HPCs). Previously we showed that mobilization could be prevented completely in mice by pretreatment with neutralizing antibodies against the beta2-integrin LFA-1 (CD11a). In addition, murine HPCs do not express LFA-1, indicating that mobilization requires a population of accessory cells. Here we show that polymorphonuclear cells (PMNs) serve as key regulators in IL-8-induced HPC mobilization. The role of PMNs was studied in mice rendered neutropenic by administration of a single injection of antineutrophil antibodies. Absolute neutropenia was observed up to 3-5 days with a rebound neutrophilia at day 7. The IL-8-induced mobilizing capacity was reduced significantly during the neutropenic phase, reappeared with recurrence of the PMNs, and was increased proportionally during the neutrophilic phase. In neutropenic mice, the IL-8-induced mobilizing capacity was restored by the infusion of purified PMNs but not by infusion of mononuclear cells. Circulating metalloproteinase gelatinase B (MMP-9) levels were detectable only in neutropenic animals treated with PMNs in combination with IL-8, showing that in vivo activated PMNs are required for the restoration of mobilization. However, IL-8-induced mobilization was not affected in MMP-9-deficient mice, indicating that MMP-9 is not indispensable for mobilization. These data demonstrate that IL-8-induced mobilization of HPCs requires the in vivo activation of circulating PMNs.


Construction of a lipid metabolism-related risk model for hepatocellular carcinoma by single cell and machine learning analysis.
One of the most common cancers is hepatocellular carcinoma (HCC). Numerous studies have shown the relationship between abnormal lipid metabolism-related genes (LMRGs) and malignancies. In most studies, the single LMRG was studied and has limited clinical application value. This study aims to develop a novel LMRG prognostic model for HCC patients and to study its utility for predictive, preventive, and personalized medicine. We used the single-cell RNA sequencing (scRNA-seq) dataset and TCGA dataset of HCC samples and discovered differentially expressed LMRGs between primary and metastatic HCC patients. By using the least absolute selection and shrinkage operator (LASSO) regression machine learning algorithm, we constructed a risk prognosis model with six LMRGs (AKR1C1, CYP27A1, CYP2C9, GLB1, HMGCS2, and PLPP1). The risk prognosis model was further validated in an external cohort of ICGC. We also constructed a nomogram that could accurately predict overall survival in HCC patients based on cancer status and LMRGs. Further investigation of the association between the LMRG model and somatic tumor mutational burden (TMB), tumor immune infiltration, and biological function was performed. We found that the most frequent somatic mutations in the LMRG high-risk group were CTNNB1, TTN, TP53, ALB, MUC16, and PCLO. Moreover, naïve CD8+ T cells, common myeloid progenitors, endothelial cells, granulocyte-monocyte progenitors, hematopoietic stem cells, M2 macrophages, and plasmacytoid dendritic cells were significantly correlated with the LMRG high-risk group. Finally, gene set enrichment analysis showed that RNA degradation, spliceosome, and lysosome pathways were associated with the LMRG high-risk group. For the first time, we used scRNA-seq and bulk RNA-seq to construct an LMRG-related risk score model, which may provide insights into more effective treatment strategies for predictive, preventive, and personalized medicine of HCC patients.


Clinical and immunological effects of vitamin D supplementation during the pollen season in children with allergic rhinitis.
Vitamin D deficiency has been proposed as a potential contributing factor in patients with allergic diseases. We compared the clinical and immunological effects of vitamin D supplementation to placebo during the pollen season in children with allergic rhinitis. Thirty-eight children aged 5-12, sensitive to grass pollen, participated in a prospective, randomized, double-blind, placebo-controlled trial. Children received either vitamin D 1000 IU daily supplementation or placebo. We studied symptoms/medication score, lung function, exhaled nitric oxide concentration (FENO), methacholine bronchial provocation test and serum level of 25(OH)D, as well as; CD4+CD25+Foxp3+ cells, TLR4, IL-1, IL-6, TNF and the IL-10 and transforming growth factor β1 (TGF-β1) levels in cell culture supernatants. Vitamin D therapy was effective in reduction of the symptoms/medication score (p = 0.0371). In vitamin D group an increase in the CD4+CD25+Foxp3+ cells (7.06 vs. 10.5%; p = 0.0013) and serum 25(OH)D concentration (49.6 vs. 96.6 ng/ml; p = 0.0001) and in control group an increase in FENO (15.6 vs. 21 ppb; p = 0.0331) and serum 25(OH)D level were observed (82.9 vs. 100.3 ng/ml; p = 0.0003).We revealed a higher increase from baseline in the percentage of CD4+CD25+Foxp3+ cells in the vitamin D group compared to the control group (p = 0.0058). A significant correlation between CD4+CD25+Foxp3+ cell induction and FENO reduction in the vitamin D group was observed (p = 0.0217). Vitamin D 1000 IU as a supplementary treatment of grass pollen allergy in children with allergic rhinitis during the pollen season significantly reduced the symptoms/medication score. The study revealed an immunological effect of vitamin D.


Performance comparison of two microarray platforms to assess differential gene expression in human monocyte and macrophage cells.
In this study we assessed the respective ability of Affymetrix and Illumina microarray methodologies to answer a relevant biological question, namely the change in gene expression between resting monocytes and macrophages derived from these monocytes. Five RNA samples for each type of cell were hybridized to the two platforms in parallel. In addition, a reference list of differentially expressed genes (DEG) was generated from a larger number of hybridizations (mRNA from 86 individuals) using the RNG/MRC two-color platform. Our results show an important overlap of the Illumina and Affymetrix DEG lists. In addition, more than 70% of the genes in these lists were also present in the reference list. Overall the two platforms had very similar performance in terms of biological significance, evaluated by the presence in the DEG lists of an excess of genes belonging to Gene Ontology (GO) categories relevant for the biology of monocytes and macrophages. Our results support the conclusion of the MicroArray Quality Control (MAQC) project that the criteria used to constitute the DEG lists strongly influence the degree of concordance among platforms. However the importance of prioritizing genes by magnitude of effect (fold change) rather than statistical significance (p-value) to enhance cross-platform reproducibility recommended by the MAQC authors was not supported by our data. Functional analysis based on GO enrichment demonstrates that the 2 compared technologies delivered very similar results and identified most of the relevant GO categories enriched in the reference list.


Fullerene in a metal-organic matrix: design of the electronic structure.
We present a theoretical study of a new hybrid compound, where the C60 molecules are encapsulated in a recently discovered metal-organic framework (MOF). Being placed in a rigid skeleton, the fullerene molecules form a cubic crystal, while the intermolecular distance of the fullerenes is tuned by the choice of appropriate organic linkers of the MOF structure. The resulting C60 crystal shows a density of conduction states considerably higher than any of the fullerene crystals considered so far, which is a key factor influencing the transition temperature of the superconducting state. This constitutes a new approach of tuning the density of states of a fullerene crystal.


Nurses' attitudes and behaviors on patient medication education.
Medication education is vital for positive patient outcomes. However, there is limited information about optimal medication education by nurses during hospitalization and care transitions. Examine nurses' attitudes and behaviors regarding the provision of patient medication education. The secondary objectives were to determine if nurses' medication education attitudes explain their behaviors, describe nurses' confidence in patient medication knowledge and abilities, and identify challenges to and improvements for medication education. A cross sectional survey was administered to nurses servicing internal medicine, cardiology, or medical-surgical patients. Twenty-four nurses completed the survey. Greater than 90% of nurses believed it is important to provide information on new medications and medical conditions, utilize resources, assess patient understanding and adherence, and use open ended question. Only 58% believed it is important to provide information on refill medications. Greater than 80% of nurses consistently provided information on new medications, assessed patient understanding, and utilized resources, but one-third or less used open-ended questions or provided information on refill medications. Most nurses spend 5-9 minutes per patient on medication education and their attitudes matched the following medication education behaviors: assessing adherence (0.57; p<0.01), providing information on new medications (0.52; p<0.05), using open-ended questions (0.51; p<0.01), and providing information on refill medications (0.39; p<0.05). Nurses had higher confidence that patients can understand and follow medication instructions, and identify names and purpose of their medications. Nurses had lower confidence that patients know what to expect from their medication or how to manage potential side effects. Communication, including language barriers and difficulty determining the patient's understanding of the information, was the most common challenge for nurses and they suggested utilization of translator services and patient-friendly drug information resources as a way to improve. Nurses have positive attitudes toward patient medication education. However, their attitudes do not fully explain their behaviors and many nurses are spending limited time with patients on medication education. Enhancements to medication education could include resources on communication and collaboration with pharmacists.