Image-guided surgery and medical robotics in the cranial area.
Surgery in the cranial area includes complex anatomic situations with high-risk structures and high demands for functional and aesthetic results. Conventional surgery requires that the surgeon transfers complex anatomic and surgical planning information, using spatial sense and experience. The surgical procedure depends entirely on the manual skills of the operator. The development of image-guided surgery provides new revolutionary opportunities by integrating presurgical 3D imaging and intraoperative manipulation. Augmented reality, mechatronic surgical tools, and medical robotics may continue to progress in surgical instrumentation, and ultimately, surgical care. The aim of this article is to review and discuss state-of-the-art surgical navigation and medical robotics, image-to-patient registration, aspects of accuracy, and clinical applications for surgery in the cranial area.


Cardiovascular effects of environmental noise: research in the United Kingdom.
Although the auditory effects of noise on humans have been established, the non-auditory effects are not so well established. The emerging links between noise and cardiovascular disease (CVD) have potentially important implications on public health and policy. In the United Kingdom (UK), noise from transport is a problem, where more than half of the population is exposed to more than the recommended maximum day-time noise level and just under three-quarters of the population live in areas where the recommended night-time noise level is exceeded. This review focuses on findings from studies conducted in the UK that examined environmental noise and cardiovascular disease. There were statistically no significant associations between road traffic noise and incident ischemic heart disease in the Caerphilly and Speedwell studies, but there was a suggestion of effects when modifying factors such as length of residence, room orientation, and window opening were taken into account. In a sample stratified by pre-existing disease a strongly increased odds of incident ischemic heart disease for the highest annoyance category was found compared to the lowest among men without pre-existing disease (OR = 2.45, 95%1.13 - 5.31), which was not found in men with pre-existing disease. In the Hypertension and exposure to noise near airports (HYENA) study, night time aircraft noise exposure (L night ) was associated with an increased risk of hypertension, in fully adjusted analyses. A 10-dB increase in aircraft noise exposure was associated with an odds ratio of 1.14 (95%CI, 1.01 - 1.29). Aircraft noise was not consistently related to raised systolic blood pressure in children in the road traffic and aircraft noise exposure and children's cognition and health (RANCH) study. There is some evidence of an association among environmental noise exposure and hypertension and ischemic heart disease in the UK studies; further studies are required to explore gender differences, the effects of day and night time exposure, and exposure modifying factors.


Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates.
The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.


Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.
Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.


Distinguishing migration from isolation using genes with intragenic recombination: detecting introgression in the Drosophila simulans species complex.
Determining the presence or absence of gene flow between populations is the target of some statistical methods in population genetics. Until recently, these methods either avoided the use of recombining genes, or treated recombination as a nuisance parameter. However, genes with recombination contribute additional information for the detection of gene flow (i.e. through linkage disequilibrium). We present three summary statistics based on the spatial arrangement of fixed differences, and shared and exclusive polymorphisms that are sensitive to the presence and direction of gene flow. Power and false positive rate for tests based on these statistics are studied by simulation. The application of these tests to populations from the Drosophila simulans species complex yielded results consistent with migration between D. simulans and its two endemic sister species D. mauritiana and D. sechellia, and between populations D. mauritiana on the islands of the Mauritius and Rodrigues. We demonstrate the sensitivity of the developed statistics to the presence and direction of gene flow, and characterize their power as a function of differentiation level and recombination rate. The properties of these statistics make them especially suitable for analyzing high-throughput sequencing data or for their integration within the approximate Bayesian computation framework.


Oridonin Alleviates Visceral Hyperalgesia in a Rat Model of Postinflammatory Irritable Bowel Syndrome: Role of Colonic Enterochromaffin Cell and Serotonin Availability.
The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome (PI-IBS). Rats were randomly divided into five groups: normal control, PI-IBS model, PI-IBS+low-dose oridonin (5 mg/kg), PI-IBS+median-dose oridonin (10 mg/kg), and PI-IBS+high-dose oridonin (20 mg/kg). Rats in control and model groups were orally administered with water by gavage, whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin, and drugs were given for 14 consecutive days. Compared with the control group, the pain threshold pressure was significantly reduced in PI-IBS rats. The colonic enterochromaffin (EC) cell number, serotonin content, and the protein expression of tryptophan hydroxylase (TPH) were markedly increased and the protein expression of serotonin reuptake transporter was significantly decreased in PI-IBS rats. The spleen index in PI-IBS rats was decreased, and the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 in the colon of PI-IBS rats were also markedly decreased. Oridonin treatment dose dependently increased pain threshold pressure, and markedly decreased colon EC cell numbers, TPH expression, and serotonin content in PI-IBS rats. Oridonin treatment also significantly increased the spleen index as well as the levels of TNF-α, IFN-γ, IL-4, and IL-13 in the colon of PI-IBS rats. Results of this study demonstrate that the analgesic effect of oridonin in PI-IBS rats is associated with reduced colonic EC cell hyperplasia and 5-HT availability, the regulatory effect of oridonin on colonic cytokine production may be correlated with its effect on colonic EC cell number.


[Functioning and silent regrouped immunoglobulin genes in the hybridoma genome].
Rearranged genes for heavy and light immunoglobulin chains have been studied in the genomes of hybridoma PTF-02 and parent myeloma P3-X63.Ag8.653. The hybridoma was shown to contain three rearranged allelic variants of the heavy chain gene's locus. Gene H2, responsible for the synthesis of the heavy chain of the antibody to transferrin, was transmitted to the hybridoma cell from a lymphocyte. The structure of the 5'-terminal codons of this gene corresponds to N-terminal amino acid residues of a heavy chain expressed by PTF-02 hybridoma. Two other genes (H1 and H3) were found both in the hybridoma and parent myeloma. Both H1 and H3 genes have serious defects in their structure and do not function. Rearranged k-genes were also identified both in the hybridoma and parent myeloma. A functional (K2) gene appeared in the hybridoma genome from an antigen-stimulated lymphocyte. The fetal mouse Vk gene, which has high homology (96.5%) with the K2 gene, was cloned and sequenced. Both K2 and the Vk fetal gene belong to one subfamily of k-genes. The rearranged gene K1 is nonfunctional because it has lost the Jk locus. This gene was transmitted from myeloma used for fusion. In such a way, the origin of all rearranged heavy and light chain genes in hybridoma PTF-02 was established.


Titration of DnaA protein by oriC DnaA-boxes increases dnaA gene expression in Escherichia coli.
Binding of the DnaA protein to its binding sites, the DnaA-boxes (TTATCCACA), was measured by a simple physiological approach. The presence of extra DnaA-boxes in growing cells leads to a derepression of dnaA gene expression, measured as beta-galactosidase activity of a dnaA-lacZ fusion polypeptide. Different DnaA-boxes caused different degrees of derepression indicating that the DnaA protein requires sequences in addition to the DnaA-box for efficient binding. The DnaA-boxes in oriC might act cooperatively in binding of the DnaA protein. The derepressed levels of DnaA protein obtained in a strain carrying an oriC+-pBR322 chimera were very high and sufficient to activate oriC on the chimeric plasmid, which was maintained at a copy number more than three times that of pBR322.


Effect of dietary IgG source (colostrum, serum, or milk-derived supplement) on the efficiency of Ig absorption in newborn Holstein calves.
This study was designed to compare the absorptive efficiency of IgG from a commercial bovine serum product (bovine serum), cow colostrum (positive control), and two commercial milk-derived IgG supplements (supplement 1 and supplement 2). Newborn Holstein calves, collected at birth and prior to the consumption of colostrum, were allotted to treatment by alternating birth order. Colostrum supplement treatments were fed according to manufacturer's recommendations at birth and again at 12 h. This strategy resulted in varying masses of total IgG being offered to the calves (200, 90, 50, and 60 g of IgG for colostrum, bovine serum, supplement 1, and supplement 2, respectively). Blood samples were collected at 0, 12, and 24 h after the end of treatment administration. Plasma volume was estimated as 9.10% of birth weight. Apparent efficiency of IgG absorption at 24 h was determined. Plasma IgG concentrations at 24 h differed for each treatment (12.1, 6.8, 2.2, and 3.5 g of IgG/L for colostrum, bovine serum, supplement 1, and supplement 2, respectively). Apparent efficiency of IgG absorption was greatest for bovine serum compared with colostrum and supplement 1. No treatment differences were detected on the occurrence of mortality. However, calves fed bovine serum tended to have fewer treatments for illness compared with calves fed colostrum and supplement 1. Calves receiving bovine serum-derived IgG had improved IgG absorption efficiency and a tendency toward fewer medical treatments compared with calves consuming colostrum or a dried colostrum product.


Direct determination of t,t-muconic acid in human urine by two-dimensional liquid chromatography.
The accurate determination of E,E-2,4-hexadiendioic acid (t,t-muconic acid), an important urinary biomarker of benzene exposure, is directly performed in human urine by a new two-dimensional liquid chromatographic method. After a first partial separation of urine components by a reversed-phase mechanism and the focalisation of the anionic analytes on a small anion-chromatographic column, a conventional ion-chromatographic analysis with UV detection is carried out. The analytical procedure is fully controlled by the HPLC instrumentation software using an eight-port switch valve. If compared with conventional one-dimensional procedures, the new method produces chromatograms containing a limited number of well resolved peaks and consequently allows better analytical performances: no interfering peaks, absence of bias, repeatability better than 5% in the concentration range 0.09-5 mg dm-3 and a detection limit of 4.0 micrograms dm-3 (alpha = beta = 0.05) for the analysis of real samples.


Modulational instability windows in the nonlinear Schrödinger equation involving higher-order Kerr responses.
We introduce a complete analytical and numerical study of the modulational instability process in a system governed by a canonical nonlinear Schrödinger equation involving local, arbitrary nonlinear responses to the applied field. In particular, our theory accounts for the recently proposed higher-order Kerr nonlinearities, providing very simple analytical criteria for the identification of multiple regimes of stability and instability of plane-wave solutions in such systems. Moreover, we discuss a new parametric regime in the higher-order Kerr response, which allows for the observation of several, alternating stability-instability windows defining a yet unexplored instability landscape.


Frequency dependent and surface characterization of DNA immobilization and hybridization.
The hybridization of oligomeric DNA was investigated using the frequency dependent techniques of quartz crystal microbalance (QCM) and electrochemical impedance spectroscopy (EIS). Synthetic 5'-amine-terminated single stranded oligonucleotides (ssDNA) were immobilized on the surface of the oxidized platinum driving electrodes of AT-cut quartz QCM crystals using 3-glycidoxypropyl-trimethoxysilane. Similar ssDNA coupling was accomplished on the exposed glass surface between the metallic digits of microlithographically fabricated interdigitated microsensor electrodes (IMEs). Confirmation of this covalent coupling surface chemistry was achieved using Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR). Substantial changes in resonant frequency values (0.012% decrease) and electrochemical impedance values (both real and imaginary components) (35.4 and 42.1% increase in impedance magnitude at 1.0 Hz in buffer and deionized water, respectively) were observed resulting from hybridization of the attached ssDNA upon exposure to its complement under appropriate hybridization conditions. Non-complementary (random) oligomer sequence demonstrated a modest change in resonant frequency and a non-detectable change in impedance. Microarray glass slide surfaces modified with 3-glycidoxypropyltrimethoxysilane (GPS), shown to be advantageous in the design and use of microarrays of amine-terminated ssDNA, is confirmed to arise from direct covalent coupling of the DNA to the surface with little non-specific adsorption. The possibility to detect the binding state of DNA in the vicinity of an electrode, without a direct connection between the measurement electrode and the DNA is hereby reported. The potential for development of label-free, low-density DNA microarrays is demonstrated and is being pursued.


Treatment of Mandibular Angle Fractures with Single Three-Dimensional Locking Miniplates without Maxillomandibular Fixation: How Much Fixation Is Required?
The aim of this simple nonrandomized and observational study was to evaluate the efficacy of single three-dimensional (3D) plate for the treatment of mandibular angle fractures without maxillomandibular fixation. A total of 30 patients with noncomminuted fractures of mandibular angle requiring open reduction and internal fixation were included in the study. All the patients were treated by open reduction and internal fixation using single 3D titanium locking miniplate placed with the help of transbuccal trocar or Synthes 90-degree hand piece and screw driver. 3D locking titanium miniplates used in our study was four-holed, box-shaped plate, and screws with 2 mm diameter and 8 mm length. The following clinical parameters were assessed for each patient at each follow-up visit: pain (visual analog scale: 0-5), swelling (visual analog scale: 0-5), mouth opening, infection, paresthesia, hardware failure (plate fracture), occlusal discrepancies, and mobility between fracture fragments. A significant decrease in pain level was seen during the follow-up visits. No statistically significant changes were seen in swelling, but mouth opening increased in the subsequent visits. Also better results were seen in terms of fracture stability and occlusion in the postoperative period. Two cases of infection and two cases of hardware failure were noted in sixth postoperative week. 3D plating system is an easy to use alternative to conventional miniplates to treat mandibular angle fractures that uses lesser foreign material, thus reducing the operative time and overall cost of the treatment. Better fracture stability and occlusion was also achieved using the 3D plating system.


Parental history of hypertension and parental history of diabetes and microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB IDDM Complications Study.
Diabetic nephropathy clusters in families, suggesting an inherited predisposition. Parental history of hypertension and of Type 2 diabetes mellitus have been associated with nephropathy in offspring with Type 1 diabetes in some studies but not in others. The associations of parental history of hypertension and of diabetes with both albuminuria and proliferative retinopathy were studied in a large cross-sectional study of 3250 patients with Type 1 diabetes, from 16 European countries. Albuminuria was associated with hypertension in a parent (p < 0.01 in men, p < 0.05 in women), adjusted for age. Patients with a parental history of hypertension had a higher prevalence of hypertension (p < 0.001 in men, p < 0.01 in women) and a higher prevalence of parental diabetes (p < 0.001 in men, p < 0.001 in women). The association of albuminuria with parental hypertension was independent of parental diabetes in men but not women (OR = 1.28 in men p = 0.04, OR = 1.25 in women p = 0.09) and was not independent of hypertension in the patient him/herself in either sex. Albuminuria was associated with parental diabetes in women only (OR = 1.36, p = 0.04). This association was independent of both parental hypertension and hypertension in the patient herself. Proliferative retinopathy was not associated with parental hypertension or diabetes. The implications of these data are that both candidate genes for hypertension and Type 2 diabetes should be considered in the search for the genetic determinants of diabetic nephropathy.


Emergency department skull trephination for epidural hematoma in patients who are awake but deteriorate rapidly.
Blunt head trauma patients who have been alert but are deteriorating (talk and deteriorate [T&D]) due to a rapidly expanding epidural hematoma (EDH) usually have poor outcome if they must wait for hospital transfer for evacuation. We therefore have continued to teach skull trephination to emergency physicians (EPs). We are unaware of any literature on EP trephination for EDH in the age of computed tomography (CT) scanning. Patients with EDH from blunt trauma, either in our institution or known to our graduate network, who were T&D with anisocoria despite intubation plus medical therapy, and who had pre-transfer EP trephination, were compared to those who were transferred without trephination. There were 5 patients with blunt trauma and CT-proven EDH who were T&D with anisocoria who underwent Emergency Department (ED) trephination at outlying hospitals before transfer. All 5 had improvement in condition and good outcomes. Three had complete recovery without disability and 2 others had mild disability with good cognitive function. None had complications. Two patients with T&D and anisocoria were transferred without trephination. Both had good neurologic outcomes. The mean time to pressure relief in the trephination group vs. transfer group was 55 vs. 207 min, respectively. In T&D patients with CT-proven EDH and anisocoria, ED skull trephination before transfer resulted in uniformly good outcomes without complications. Time to relief of intracranial pressure was significantly shorter with trephination. Neurologic outcomes were not different.


Grid-wide neuroimaging data federation in the context of the NeuroLOG project.
Grid technologies are appealing to deal with the challenges raised by computational neurosciences and support multi-centric brain studies. However, core grids middleware hardly cope with the complex neuroimaging data representation and multi-layer data federation needs. Moreover, legacy neuroscience environments need to be preserved and cannot be simply superseded by grid services. This paper describes the NeuroLOG platform design and implementation, shedding light on its Data Management Layer. It addresses the integration of brain image files, associated relational metadata and neuroscience semantic data in a heterogeneous distributed environment, integrating legacy data managers through a mediation layer.


Open tension-free Lichtenstein repair of inguinal hernia: use of fibrin glue versus sutures for mesh fixation.
To investigate pain and other complications following inguinal hernioplasty performed by the Lichtenstein technique with mesh fixation by fibrin glue or sutures. Five hundred and twenty patients were enrolled in this 12-month observational multicenter study and received either sutures or fibrin glue (Tissucol(®)/Tisseel(®)) based on the preference of the surgeon. Pain, numbness, discomfort, recurrence, and other complications were assessed postoperatively and at 1, 3, 6, and 12 months. Pain intensity was assessed by a visual analog scale (VAS; 0 [no pain] to 10 [worst pain]). One hundred and seventy-one patients received sutures and 349 received fibrin glue. During the early postoperative phase, 87.4% of patients in the fibrin glue group and 76.6% of patients in the sutures group were complication-free (P = 0.001). Patients who received fibrin glue were also less likely to experience hematoma/ecchymosis than those in the suture group (both P = 0.001). The mean pain score was significantly lower in the fibrin group than the sutures group (2.5 vs. 3.2, P < 0.001). At 1 month, significantly fewer patients in the fibrin glue group reported pain, numbness, and discomfort compared with patients in the sutures group (all P < 0.05). Fibrin glue patients also experienced less intense pain (0.6 vs. 1.2; P = 0.001). By 3 months, the between-group differences had disappeared, except for numbness, which was more prevalent in the sutures group. By 12 months, very few patients reported complications. Tissucol fibrin glue for mesh fixation in the Lichtenstein repair of inguinal hernia shows advantages over sutures, including lower incidence of complications such as pain, numbness, and discomfort, and should be considered as a first-line option for mesh fixation in hernioplasty.


Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds.
Thyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR) in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR) in a field environment. Given the difficulty of measuring metabolic rate in the field-and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements-we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia). Because BMR and daily energy expenditure (DEE) are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR). RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species.


Effects of micronised purified flavonoid fraction on pain, spermiogram and scrotal color Doppler parameters in patients with painful varicocele.
Micronised purified flavonoid fraction (MPFF) is a phlebotropic drug improving venous tone, elasticity and lymphatic drainage, decreasing venous distensibility, venous emptying times, reflux time of venous blood and capillary hyperpermeability, and having antioxidant activities. Since varicocele is a venous pathology, we evaluated the effects of MPFF on pain, spermiogram and color Doppler parameters in patients with painful varicocele. Semen analyses and Doppler sonography were performed in 16 patients (aged 20-62 years, mean 31.2 +/- 10.9) before and after 1,000 mg/day MPFF treatment. Pain change was assessed with visual analogue scale scored between 0 and 10. Patient satisfaction with outcome and side effects were recorded. Mean pain scores at 1, 3, and 6 months were 1.25 +/- 1.34, 0.25 +/- 0.68, and 0.12 +/- 0.34, respectively, all being significantly lower (p < 0.001 for each) than baseline (4.93 +/- 1.77). Mean score at 12 months (0.93 +/- 1.06) was still lower than baseline (p < 0.001) but higher than at 6 months (p = 0.019). Respectively, 14 (87.5%) and 2 (12.5%) patients reported complete and very significant resolution of pain at the 6th month. All patients were very satisfied with the outcome. While semen volume, total sperm count, sperm concentration and morphology did not change significantly, motility increased significantly (p = 0.009) due to decrease of grade 0 sperms (p = 0.006) and increase of grade 3 + 4 sperms (p < 0.001). Reflux time of left spermatic vein during the Valsalva maneuver decreased significantly (p = 0.003). No significant change occurred in reflux time of the right spermatic vein. No side effect was recorded. Results of this preliminary study suggest the safety and efficacy of MPFF in the treatment of varicocele-associated pain. However, no recommendation for the use of MPFF in the treatment of pain associated with varicocele can be made before these preliminary results are confirmed by a randomized placebo-controlled trial.


A 2D multiresolution image reconstruction method in X-ray computed tomography.
We propose a multiresolution X-ray imaging method designed for non-destructive testing/evaluation (NDT/NDE) applications which can also be used for small animal imaging studies. Two sets of projections taken at different magnifications are combined and a multiresolution image is reconstructed. A geometrical relation is introduced in order to combine properly the two sets of data and the processing using wavelet transforms is described. The accuracy of the reconstruction procedure is verified through a comparison to the standard filtered backprojection (FBP) algorithm on simulated data.


An in vivo model of hyperacute rejection: characterization and evaluation of the effect of transgenic human complement inhibitors.
Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after I day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1alpha, IL-1beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase dramatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.


Effect of postactivation potentiation on dynamic knee extension performance.
Six men and four women performed, in separate trials, maximal dynamic knee extensions with loads of 15%, 30%, 45% and 60% of maximal isometric knee extension peak torque (MVC). The dynamic extensions were done after postactivation potentiation (PAP) had been induced with a 10-s MVC, and in a control trial without PAP. PAP, measured as the increase in evoked twitch torque, was 53 (4)% (SE) and 43 (3)% at the time of the first and second extensions with each load. PAP failed to increase the attained peak velocity with any load; on the contrary, there was a trend for peak velocity to decrease in the first extension, which occurred approximately equal to 15 s after the 10-s MVC. The results suggest that fatigue produced by the 10-s MVC suppressed any benefit that could be derived from the induced PAP. A surface electromyogram (EMG) recorded from one muscle of quadriceps femoris gave no indication of activation failure in the first knee extension; however, activation impairment specific to the rate of force development cannot be ruled out. It is concluded that the strategy employed, namely of having knee extensions performed soon after the 10-s MVC to maximize PAP at the time of performance, was unsuccessful because there had been insufficient time for recovery from fatigue. It is possible that a longer recovery time, even at the cost of a diminished PAP, may have proved beneficial.


Is bipolar disorder overdiagnosed?
Bipolar disorder, a serious illness resulting in significant psychosocial morbidity and excess mortality, has been reported to be frequently underdiagnosed. However, during the past few years we have observed the emergence of an opposite phenomenon--the overdiagnosis of bipolar disorder. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we empirically examined whether bipolar disorder is overdiagnosed. Seven hundred psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV (SCID) and completed a self-administered questionnaire, which asked the patients whether they had been previously diagnosed with bipolar or manic-depressive disorder by a health care professional. Family history information was obtained from the patient regarding first-degree relatives. Diagnoses were blind to the results of the self-administered scale. The study was conducted from May 2001 to March 2005. Fewer than half the patients who reported that they had been previously diagnosed with bipolar disorder received a diagnosis of bipolar disorder based on the SCID. Patients with SCID-diagnosed bipolar disorder had a significantly higher morbid risk of bipolar disorder than patients who self-reported a previous diagnosis of bipolar disorder that was not confirmed by the SCID (p < .02). Patients who self-reported a previous diagnosis of bipolar disorder that was not confirmed by the SCID did not have a significantly higher morbid risk for bipolar disorder than the patients who were negative for bipolar disorder by self-report and the SCID. Not only is there a problem with underdiagnosis of bipolar disorder, but also an equal if not greater problem exists with overdiagnosis.


Experience on clinical application of Chinese herbal medicine Yi Guan Jian decoction.
Yi Guan Jian decoction is a traditional Chinese medicine formula noted in Wei Yu-huang's Xu Ming Yi Lei An (Supplement to the Classified Medical Records of Famous Physicians). Acne vulgaris and chronic pelvic inflammation could be successfully treated by the decoction following the principle of formula corresponding to syndromes. The identical characteristics of constitution are found among the patients treated by the decoction, known as the "Yi Guan Jian constitution". It indicates that patients can be treated according to the constitutional characteristics.


Vision Recovery Velocity, Momentum and Acceleration: Advanced Vitreoretinal Analytics as Measure of Treatment Efficacy for Neovascular Age-Related Macular Degeneration.
Currently, varying treatment paradigms and different clinical trial constructs preclude cross-trial comparison between different available vascular endothelial growth factor (VEGF) inhibitors. This study aimed to review the evidence and compare the efficacy of anti-VEGF therapies for neovascular age-related macular degeneration (nAMD), and to develop metrics as a means of facilitating standardized comparison between different anti-VEGF agents within the Advanced VitreoRetinal Analytics (AVRA) model. The study analyzed key outcomes in clinical trials of bevacizumab, ranibizumab, aflibercept, and brolucizumab, including best corrected visual acuity (BCVA), number of injections, and duration of follow-up (minimum follow-up of 48 weeks). The AVRA model includes 1) vision recovery velocity (VRV; letters per unit time), which provides a metric of letters gained or lost over time (or the speed of improvement); 2) injection momentum (InjMom; number of injections multiplied by letters per unit time; units of injections•(letters/time)), which is defined as the number of injections multiplied by VRV and describes the quantity of treatment needed to achieve a vision outcome; and 3) vision recovery acceleration (VRA; letters per unit time squared; units of letters/time2), which denotes final VRV minus initial VRV, per unit time, and describes the rate of change in letters gained or lost over time. AVRA stipulates that the ideal VEGF inhibitor to treat nAMD would have a higher positive VRV (more letters gained per unit time), low InjMom (lower treatment burden requiring fewer interventions for a given visual acuity outcome), and VRA approximating zero (indicating stable vision over time). AVRA allows comparisons across different trials to determine the optimal anti-VEGF agent for the treatment of nAMD.


Estimate of muscle-shortening rate during locomotion.
All skeletal muscle can produce roughly the same maximal cross-sectional force; however, the power (energy X time-1) required to develop and maintain that force increases with increasing contraction velocity. Thus the rate of muscle tension development may be of primary importance in setting the energy demand of contracting muscle. We have estimated the rate of muscle shortening during terrestrial locomotion in mammals as a function of body mass. The rate of muscle shortening of the knee extensors is much faster in small than large mammals, scaling in proportion to the -0.23 power of mass. This exponent suggests a constant body size-independent relation among skeletal muscle: O2 consumption, mitochondria content, myosin ATPase activity, and in vivo shortening velocity.


Strength of Coupling within a mnemonic control network differentiates those who can and cannot suppress memory retrieval.
The ability to direct our thought processes influences not only what we do, but also what we remember later. Here we sought to identify the brain network that supports the ability to control memory retrieval and to understand the neural basis of age-related changes and individual differences in the capacity for mnemonic control. To this end, we collected functional MRI data from 43 children and young adults while they attempted to retrieve or suppress retrieval of previously learned associations. Seed-based functional connectivity analyses revealed a largely right-lateralized dorsolateral prefrontal cortex-cingulate-parietal-hippocampal network that exhibited strongly correlated activity during retrieval suppression. Regardless of age, individuals who were able to suppress memory retrieval exhibited tighter coupling between key nodes in this dorsolateral prefrontal cortex-cingulate-parietal-hippocampal network than individuals who did not. Further, only those capable of mnemonic control exhibited tighter coupling during successful retrieval suppression (intentional forgetting) than during unsuccessful retrieval (unintentional forgetting). Across both children and adults, individual differences in retrieval suppression were best explained by the strength of these network interactions.


Synthesis of ultrabright nanoporous fluorescent silica discoids using an inorganic silica precursor.
The templated sol-gel synthesis of ultrabright fluorescent nanoporous silica particles based on the use of organic silica sources has previously been reported. The use of organosilanes as the main silica precursors has a number of issues, in particular, the low robustness of the synthesis due to instability of the organic silica source. Here we report on a novel synthesis of ultrabright fluorescent nanoporous silica discoids (a specific shape in-between the sphere and disk) of 3.1 ± 0.7 microns in size, which were prepared using a stable inorganic sodium silicate silica source. Organic fluorescent dye Rhodamine 6G (R6G) was physically (non-covalently) entrapped inside cylindrical nanochannels of ∼4-5 nm in diameter. In contrast to the synthesis with organic silica precursors, the obtained particles showed an excessive leakage of dye. To prevent this leakage, we modified the synthesis by adding a small amount of a secondary silica source. The synthesized particles show virtually no leakage, high photostability, and a brightness equivalent to the fluorescence of up to 7 × 10(7) free R6G molecules. This is about 7 times higher than the fluorescent brightness of particles of the same size made of CdSe/ZnS quantum dots, and 420 times higher than the brightness of the same volume of aqueous solution of free R6G dye.


[On sinusitis in swimmers in Lake Constance (author's transl)].
Since the expansion of water-cleaning plants at Lake Constance, the rate of diseases in swimmers, like the sinusitis and otitis in swimmers gradually declined. These sickness almost only occur in teenagers by diving at water temperatures of some 20 degrees centigrade. The rhinogene complications of orbita develop fulminantly.


The Heterotrimeric Transcription Factor CCAAT-Binding Complex and Ca2+-CrzA Signaling Reversely Regulate the Transition between Fungal Hyphal Growth and Asexual Reproduction.
The life cycle of filamentous fungi generally comprises hyphal growth and asexual reproduction. Both growth and propagation processes are critical for invasion growth, spore dissemination, and virulence in fungal pathogens and for the production of secondary metabolites or for biomass accumulation in industrial filamentous fungi. The CCAAT-binding complex (CBC) is a heterotrimeric transcription factor comprising three subunits, HapB, HapC, and HapE, and is highly conserved in fungi. Previous studies revealed that CBC regulates sterol metabolism by repressing several genes in the ergosterol biosynthetic pathway in the human fungal pathogen Aspergillus fumigatus. In the present study, we found dysfunction of CBC caused the abnormal asexual reproduction (conidiation) in submerged liquid culture. CBC suppresses the activation of the brlA gene in the central regulatory pathway for conidiation combined with its upstream regulators fluG, flbD, and flbC by binding to the 5'-CCAAT-3' motif within conidiation gene promoters, and lack of CBC member HapB results in the upregulation of these genes. Furthermore, when the expression of brlA or flbC is repressed, the submerged conidiation does not happen in the hapB mutant. Interestingly, deletion of HapB leads to enhanced transient cytosolic Ca2+ levels and activates conidiation-positive inducer Ca2+-CrzA modules to enhance submerged conidiation, demonstrating that CrzA works with CBC as a reverse regulator of fungal conidiation. To the best of our knowledge, the finding of this study is the first report for the molecular switch mechanism between vegetative hyphal growth and asexual development regulated by CBC, in concert with Ca2+-CrzA signaling in A. fumigatus. IMPORTANCE A precisely timed switch between vegetative hyphal growth and asexual development is a crucial process for the filamentous fungal long-term survival, dissemination, biomass production, and virulence. However, under the submerged culture condition, filamentous fungi would undergo constant vegetative growth whereas asexual conidiation rarely occurs. Knowledge about possible regulators is scarce, and how they could inhibit conidiation in liquid culture is poorly understood. Here, we demonstrated that the transcription factor heterotrimeric CBC dominantly maintains vegetative growth in liquid-submerged cultures by directly suppressing the conidiation-inductive signal. In contrast, calcium and the transcription factor CrzA, are positive inducers of conidiation. Our new insights into the CBC and Ca2+-CrzA regulatory system for transition control in the submerged conidiation of A. fumigatus may have broad repercussions for all filamentous fungi. Moreover, our elucidation of the molecular mechanism for submerged conidiation may support new strategies to precisely control vegetative growth and asexual conidiation in aspergilli used in industry.


The association between physical characteristics of the ankle joint and the mobility performance in elderly people with type 2 diabetes mellitus.
Previous studies showed that older adults with diabetes have a worse mobility performance as compared with those without diabetes. Studies also demonstrated that older adults with diabetes have weakened ankle muscle strength, reduced joint range in ankle dorsiflexion and worsened ankle joint proprioception as compared with control population. The purpose of the present study was to examine the relationship between the physical characteristics of the ankle joint and the mobility performance in older adults with type 2 diabetes. Older adults with type 2 diabetes (n=85) were recruited, and Timed Up and Go test (TUG) for mobility assessment was performed. Active ankle joint repositioning test was used for assessing the ankle joint proprioception sense; peak torque of ankle dorsiflexors and plantar flexors were tested by using a Cybex Norm dynamometer, and weight-bearing lunge test (WBLT) was used for assessing the stiffness of ankle dorsiflexion. Our results showed that age, body mass index (BMI), normalized peak torque of plantar flexors and dorsiflexors, active ankle joint repositioning test errors and the WBLT distance were significantly correlated with the TUG (all p<0.001). These ankle characteristics, together with the demographic data of the subjects, contributed 59.9% of the variance in the TUG by multiple regression analysis. Body mass, ankle plantar flexors strength and ankle joint proprioception are important factors contributing to the physical mobility of the older adults with type 2 diabetes.


Increased withdrawal volume per deposit for pre-operative autologous blood donation in adolescents.
This study was undertaken to assess the feasibility, tolerance, haemodynamic and haematologic effects of an aggressive phlebotomy schedule for autologous blood donation (ABD) in adolescents undergoing major orthopaedic surgery. Twenty adolescents were studied prospectively; 10 patients in group A donated 20% of the circulating blood volume on 2 occasions, whereas 10 patients in group B donated 10% on 4 occasions. The amount of blood donated, subjective tolerance, cardiovascular changes during the procedure and pre-operative haemoglobin level did not differ between the study groups (group A 111+/-16 vs. group B 106+/-10 g/l). The increase in erythropoietin was greater and occurred sooner in group A than in group B. In adolescents ABD is feasible with a reduced number of appointments as they demonstrate tolerance to phlebotomies with a volume which is double the standard per deposit.


Reverse Koebner phenomenon in erythema nodosum leprosum.
Erythema nodosum leprosum (ENL) is an immunologically mediated phenomenon complicating the course of leprosy. Reverse Koebner phenomenon is the term used to describe the sparing of previously injured or diseased skin by new skin lesions of the disease. A middle-aged woman with a known case of lepromatous leprosy for the past year presented with an eruption of reddish painful nodules over her body. The lesions were found to characteristically spare the sites of previous scars. This sparing phenomenon of previous scar sites has been termed reverse Koebner phenomenon, a site of the body that offers greater resistance than the rest of the body to the onset of the disease, seen in various diseases, but it has never been described in ENL. This sparing of scar sites in ENL can be attributed to reverse Koebner phenomenon.


Athletic Engagement and Athletic Identity in Top Croatian Sprint Runners.
The aim of the research was to determine construct validity and reliability for two questionnaires (Athlete Engagement Questionnaire-AEQ and Athletic Identity Measurement Scale-AIMS), applied on elite Croatian athletes-sprinters, as well as the correlations among the dimensions in these measuring instruments. Then, we have determined the differences in the dimensions of sport engagement and sport identity, according to gender, education level and winning medals on international competitions. A total of 71 elite athletes-sprinters (former and still active) are examined, from which 27 (38%) females and 44 (62%) males. The results of factor analyses revealed the existence of dimensions very similar as in the original instruments, which showed moderate to-high reliabilities. A small number of statistically significant correlations have been found between the dimensions of sport engagement and sport identity, mainly in male sprinter runners. Small number of statistically significant differences in the dimensions of sport engagement and sport identity have been found according to the gender, education level and winning medals on the international competitions. The most reasonable explanation of these differences could be given in terms of very similar characteristics of elite athletes on the same level of sport excellence.


Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis.
Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis. mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts. As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.


Metabolic activation of the tobacco carcinogen 4-(methylnitrosamino)-(3-pyridyl)-1-butanone by cytochrome P450 2A13 in human fetal nasal microsomes.
Among human P450s studied to date, P450 2A13 is the most efficient catalyst of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-hydroxylation. This reaction is a key bioactivation pathway in NNK-induced carcinogenesis. P450 2A13 mRNA has been detected in human tissues, but it is unknown whether the enzyme is functional in vivo. Therefore, we studied NNK alpha-hydroxylation in human fetal nasal mucosal microsomes, which have been shown to contain high levels of P450 2A protein, presumed to be a mixture of P450 2A6 and 2A13. The microsomes efficiently catalyzed NNK alpha-hydroxylation at the methylene and methyl carbons, as well as carbonyl reduction. Antibodies against mouse P450 2A5 inhibited alpha-hydroxylation by these microsomes greater than 90%. K(m) and V(max) values for alpha-methylene hydroxylation were 6.5 +/- 1.1 muM and 3.0 +/- 0.1 pmol/min/mg; for alpha-methyl hydroxylation, they were 6.7 +/- 0.8 microM and 0.85 +/- 0.03 pmol/min/mg. The K(m) values agree closely with those for NNK metabolism by P450 2A13. Using a new technique, we separated P450 2A13 from P450 2A6 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Quantitative immunoblot analysis indicated that the level of P450 2A13 in the pooled fetal nasal microsome sample used for kinetic analysis was approximately 1.6 pmol/mg protein. In the same sample, P450 2A6 was not detected (detection limit, 67 fmol/mg protein). These kinetic, immunoinhibition, and immunoblot data confirm that P450 2A13 is a functional enzyme and the catalyst of NNK alpha-hydroxylation in human fetal nasal mucosa. The results are also the first to demonstrate high efficiency NNK alpha-hydroxylation in a human tissue.


Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells.
The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-d,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC. The presence of GAL residues in the polyplexes allows the targeting of HCC cells that express the asialo-glycoprotein receptor (ASGP-R). In these cells, but not in ASGP-R non-expressing cells, PHEA-DETA-PEG-GAL/siE2F1 polyplexes induce the reduction of the mRNA and protein levels of E2F1 and of E2F1-regulated genes, all involved in the promotion of the G1/S phase transition. This results in a decrease of cell proliferation with a G1/G0 phase cells accumulation. Notably, removal of GAL residue almost completely abrogates the targeting capacity of the developed polyplexes. In conclusion, the generated polyplexes demonstrate the potential to effectively contributing to the development of novel anti-HCC therapeutic approaches via a siRNA-targeted delivery.


An assessment of the effectiveness of virginiamycin on liver abscess incidence and growth performance in feedlot cattle: a comprehensive statistical analysis.
The judicious use of commercial products in livestock operations can be part of a sustainable and environmentally friendly production scenario. This study was designed to gather published data of virginiamycin (VM) used in feedlot conditions of the United States and analyze its effectiveness and optimum dosage in reducing the liver abscess incidence (LAI). The dataset contained 26 studies that evaluated more than 7,156 animals of diverse breeds fed in several regions in the United States under different management. Statistical analyses included contingency tables to assess the nonparametric independence of the LAI, meta regression analysis to remove study effects and to evaluate LAI and animal performance, broken-line analysis to determine thresholds of VM dosage on LAI, and residual-based shading mosaic plots to illustrate the contingency analysis. There were 1,391 of 5,430 animals with LAI scores 1, 2, or 3 (LAI1-3) and 651 of 4,690 animals with LAI A+ (score 3). Our analyses suggested that there was a significant dependency (χ2P-value < 0.001) and significant asymmetry (McNemar's test P-value < 0.001) between LAI and VM treatment for both LAI1-3 and LAI A+. For the LAI1-3 group, only 22.5% of the treated animals had liver abscesses compared with 31.7% of the control animals. The metaregression analysis indicated that LAI1-3 was linearly reduced (P < 0.001) by about 0.42% per mg/kg of DM of VM. The lower 95% confidence interval of the intercept for LAI1-3 and LAI A+ obtained with a generalized nonlinear mixed regression was 18.7 and 20.3 mg/kg of DM, respectively. The broken-line regression analysis identified 2 thresholds for LAI (23.9 and 12.3 mg/kg of DM) at which the reduction in total LAI1-3 and LAI A+, respectively, would decrease faster as VM dosage increases (from 2.14% to 6% and from 1.91% to 4.33% per mg of VM per kg of DM, respectively). Additionally, our analyses indicated that after accounting for the study effects, VM significantly increased ADG at 2.08 g BW/d per mg/kg DM compared with 0.92 g BW/d per mg/kg DM for monensin (P < 0.001), suggesting that VM was about 2.3 times more effective in increasing ADG for the same dosage and feeding period length. All analyses yielded consistent results that led us to conclude that VM is effective in reducing LAI when fed between approximately 12 and 24 mg/kg of DM, and the maximum reduction might occur at approximately 24 mg/kg of DM or higher.


Physiological and transcriptomic evidence for a close coupling between chloroplast ontogeny and cell cycle progression in the pennate diatom Seminavis robusta.
Despite the growing interest in diatom genomics, detailed time series of gene expression in relation to key cellular processes are still lacking. Here, we investigated the relationships between the cell cycle and chloroplast development in the pennate diatom Seminavis robusta. This diatom possesses two chloroplasts with a well-orchestrated developmental cycle, common to many pennate diatoms. By assessing the effects of induced cell cycle arrest with microscopy and flow cytometry, we found that division and reorganization of the chloroplasts are initiated only after S-phase progression. Next, we quantified the expression of the S. robusta FtsZ homolog to address the division status of chloroplasts during synchronized growth and monitored microscopically their dynamics in relation to nuclear division and silicon deposition. We show that chloroplasts divide and relocate during the S/G2 phase, after which a girdle band is deposited to accommodate cell growth. Synchronized cultures of two genotypes were subsequently used for a cDNA-amplified fragment length polymorphism-based genome-wide transcript profiling, in which 917 reproducibly modulated transcripts were identified. We observed that genes involved in pigment biosynthesis and coding for light-harvesting proteins were up-regulated during G2/M phase and cell separation. Light and cell cycle progression were both found to affect fucoxanthin-chlorophyll a/c-binding protein expression and accumulation of fucoxanthin cell content. Because chloroplasts elongate at the stage of cytokinesis, cell cycle-modulated photosynthetic gene expression and synthesis of pigments in concert with cell division might balance chloroplast growth, which confirms that chloroplast biogenesis in S. robusta is tightly regulated.


Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat.
Elevated levels of circulating fibroblast growth factor 21 (FGF21) are commonly encountered in type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, all of which share exaggerated postprandial lipemia as a common proatherogenic feature. How FGF21 responds to an oral fat load in man is unknown. We measured liver fat contents and subcutaneous and visceral fat volumes in 47 healthy subjects, who also underwent an oral fat load with measurements of plasma FGF21 and free fatty acid (FFA). Triglyceride (TG), apolipoprotein B-48 (apoB-48), and apoB-100 concentrations were measured in triglyceride-rich lipoprotein (TRL) fractions. When compared with fasting levels, the concentration of FGF21 decreased significantly at 4 h (P < 0.05) and tended to return to fasting levels at 8 h after an oral fat load. Fasting and postprandial FGF21 correlated significantly with liver fat as well as with TRLs in the chylomicron and especially in very low-density lipoprotein 1 (VLDL1) and VLDL2 fractions representing remnant particles, but not with FFA. Subjects with increased liver fat (>5%, n = 12) showed impaired suppression of FGF21 at 4 h (P < 0.05) and at 8 h (P=0.01) and demonstrated higher postprandial TG area under the curve in plasma and TRL fractions (P ≤ 0.032) compared with those with normal liver fat (≤ 5%, n = 35). We observed a significant decrease of FGF21 concentration after an oral fat load. Fasting and postprandial FGF21 levels were closely related to large VLDL and remnants, but not to plasma FFA. Our pilot findings suggest that the postprandial accumulation of TRL remnants and liver fat may modulate postprandial FGF21 levels.


[Mathematic model of the cupuloendolymphatic system for various densities of cupula and endolymph].
This paper presents a mathematical model of time-course variations of the cupulo-endolymphatic system which can be described by the Steinhauzen phenomenological equation for the case of a unidimensional toroid, assuming that the densities of the cupula and endolymph are identical. If the densities are different, the time-course variations of the cupuloendolymphatic system may aggravate and manifest at the powered stages of space flight.


Mycoplasma hominis septicaemia.
Mycoplasma hominis septicaemia occurred in a patient with a malignant lymphoma of lymphoblastic type in leukaemic phase. M hominis was isolated several times from blood cultures with antibody titres against the micro-organism rising to a high level despite severe immunosuppression. M hominis was detected in the blood after subculture of the blood culture bottles despite their macroscopically normal appearance. The patient's pyrexia resolved without treatment with antibiotics effective against M hominis.


Analysis of Monosynaptic Inputs to Thalamic Paraventricular Nucleus Neurons Innervating the Shell of the Nucleus Accumbens and Central Extended Amygdala.
The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral region of central nucleus of the amygdala (CeL). Projection specific modulation of these pathways has been shown to regulate appetitive and aversive behavioral responses. The present investigation applied an intersectional monosynaptic rabies tracing approach to quantify the brain-wide sources of afferent input to PVT neurons that primarily project to the NAcSh, BSTDL and CeL. The results demonstrate that these projection neurons receive monosynaptic input from similar brain regions. The prefrontal cortex and the ventral subiculum of the hippocampus were major sources of input to the PVT projection neurons. In addition, the lateral septal nucleus, thalamic reticular nucleus and the hypothalamic medial preoptic area, dorsomedial, ventromedial, and arcuate nuclei were consistent sources of input. The subfornical organ, parasubthalamic nucleus, periaqueductal gray matter, lateral parabrachial nucleus, and nucleus of the solitary tract were consistent but lesser sources of input. This input-output relationship is consistent with recent observations that PVT neurons have axons that bifurcate extensively to divergently innervate the NAcSh, BSTDL and CeL.


Meningitis due to Stenotrophomonas maltophilia after a Neurosurgical Procedure.
Stenotrophomonas maltophilia is an aerobic, glucose non- fermentative, gram negative bacillus, which is being increasingly recognized as a cause of serious infections such as bacteraemia, urinary tract infections, respiratory tract infections, skin and soft tissue infections, endocarditis, meningitis and ocular infections in hospitalized patients. The treatment of invasive S. maltophilia infections is difficult, as this pathogen shows high levels of intrinsic or acquired resistance to different antibiotics, thus reducing the options which are available for treatment. Meningitiscaused by S. maltophilia is rarely encountered and so its experience is also limited. We are describing here a case of a six months old, male child who developed meningitis caused by Stenotrophomonas maltophilia, after he underwent a neurosurgical procedure.


Knowledge, Attitudes, and Practices among Members of Households Actively Monitored or Quarantined to Prevent Transmission of Ebola Virus Disease - Margibi County, Liberia: February-March 2015.
In early 2015, a patient from a cluster of cases of Ebola Virus Disease (EVD) in Monrovia, Liberia traveled to a rural village in Margibi County, potentially exposing numerous persons. The patient died in the village and post-mortem testing confirmed Ebola Virus infection. Problem The Margibi County Health Team (CHT; Kakata, Margibi, Liberia) needed to prevent further transmission of EVD within and outside of the affected villages, and they needed to better understand the factors that support or impede compliance with measures to stop the spread of EVD. In February-March 2015, the Margibi CHT instituted a 21-day quarantine and active monitoring for two villages where the patient had contact with numerous residents, and a 21-day active monitoring for five other villages where the patient had possible contact with an unknown number of persons. One contact developed EVD and quarantine was extended an additional 12 days in one village. In April 2015, the Margibi CHT conducted a household-based EVD knowledge, attitudes, and practices (KAP) survey of the seven villages. From April 24-29, 2015, interview teams approached every household in the seven villages and collected information on demographics, knowledge of EVD, attitudes about quarantine to prevent the spread of EVD, and their quarantine experiences and practices. Descriptive statistics were calculated. One hundred fifteen interviews were conducted, representing the majority of the households in the seven villages. Most (99%) correctly identified touching an infected person's body fluids and contact with the body of someone who has died from EVD as transmission routes. However, interviewees sometimes incorrectly identified mosquito bites (58%) and airborne spread (32%) as routes of EVD transmission, and 72% incorrectly identified the longest EVD incubation period as ≤seven days. Eight of 16 households in the two quarantined villages (50%) reported times when there was not enough water or food during quarantine. Nine of 16 (56%) reported that a household member had illnesses or injuries during quarantine; of these, all (100%) obtained care from a clinic, hospital, or Ebola treatment unit (ETU). Residents' knowledge of EVD transmission routes and incubation period were suboptimal. Public health authorities should consider assessing residents' understanding of Ebola transmission routes and effectively educate them to ensure correct understanding. Quarantined residents should be provided with sufficient food, water, and access to medical care. Wilken JA , Pordell P , Goode B , Jarteh R , Miller Z , Saygar BG Sr. , Maximore L , Borbor WM , Carmue M , Walker GW , Yeiah A . Knowledge, attitudes, and practices among members of households actively monitored or quarantined to prevent transmission of Ebola Virus Disease - Margibi County, Liberia: February-March 2015. Prehosp Disaster Med. 2017;32(6):673-678.


Avoiding pitfalls when combining multiple imputation and propensity scores.
Overcoming bias due to confounding and missing data is challenging when analyzing observational data. Propensity scores are commonly used to account for the first problem and multiple imputation for the latter. Unfortunately, it is not known how best to proceed when both techniques are required. We investigate whether two different approaches to combining propensity scores and multiple imputation (Across and Within) lead to differences in the accuracy or precision of exposure effect estimates. Both approaches start by imputing missing values multiple times. Propensity scores are then estimated for each resulting dataset. Using the Across approach, the mean propensity score across imputations for each subject is used in a single subsequent analysis. Alternatively, the Within approach uses propensity scores individually to obtain exposure effect estimates in each imputation, which are combined to produce an overall estimate. These approaches were compared in a series of Monte Carlo simulations and applied to data from the British Society for Rheumatology Biologics Register. Results indicated that the Within approach produced unbiased estimates with appropriate confidence intervals, whereas the Across approach produced biased results and unrealistic confidence intervals. Researchers are encouraged to implement the Within approach when conducting propensity score analyses with incomplete data.


Meniscofibular ligament: morphology and functional significance of a relatively unknown anatomical structure.
Purpose. A relatively unknown ligamentous structure of the posterolateral corner of the knee joint, the so-called meniscofibular ligament (MFL), was investigated as regards its macroscopic morphology, its histological features, and its reaction to knee movements. Material and Methods. MFL was exposed on 21 fresh-frozen unpaired knee joints. Its microscopic morphology was examined utilizing for comparison the fibular collateral and the popliteofibular ligament. Results. MFL was encountered in 100% of the specimens as a thin striplike fibrous band extending between the lower border of the lateral meniscus and the head of the fibula. MFL was tense during knee extension and external rotation of the tibia, whereas its histological features were similar to those of fibular collateral and popliteofibular ligament. Discussion. Its precise histological nature is studied as well as its tension alterations during knee movements. The potential functional significance of the MFL with respect to its role in avoidance of lateral meniscus and lateral coronary ligament tears is discussed. Conclusions. MFL presumably provides an additional protection to the lateral meniscus during the last stages of knee extension, as well as to the lateral coronary ligament reducing the possibility of a potential rupture.


The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells.
Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells.


The transliminal brain at rest: baseline EEG, unusual experiences, and access to unconscious mental activity.
Transliminality reflects individual differences in the threshold at which unconscious processes or external stimuli enter into consciousness. Individuals high in transliminality possess characteristics such as magical ideation, belief in the paranormal, and creative personality traits, and also report the occurrence of manic/mystic experiences. The goal of the present research was to determine if resting brain activity differs for individuals high versus low in transliminality. We compared baseline EEG recordings (eyes-closed) between individuals high versus low in transliminality, assessed using The Revised Transliminality Scale of Lange et al. (2000). Identifying reliable differences at rest between high- and low-transliminality individuals would support a predisposition for transliminality-related traits. Individuals high in transliminality exhibited lower alpha, beta, and gamma power than individuals low in transliminality over left posterior association cortex and lower high alpha, low beta, and gamma power over the right superior temporal region. In contrast, when compared to individuals low in transliminality, individuals high in transliminality exhibited greater gamma power over the frontal-midline region. These results are consistent with prior research reporting reductions in left temporal/parietal activity, as well as the desynchronization of right temporal activity in schizotypy and related schizophrenia spectrum disorders. Further, differences between high- and low-transliminality groups extend existing theories linking altered hemispheric asymmetries in brain activity to a predisposition toward schizophrenia, paranormal beliefs, and unusual experiences.


Monteggia fracture-dislocations in children.
Thirty-three Monteggia fracture-dislocations occurring in patients aged 2 to 15 years were reviewed. A follow-up of 2 to 7 years in 25 patients revealed that 88% had good to excellent results and 12% had results which were fair or poor. Closed reduction was successful in 24 of 28 cases and appeared to be very effective. Open reduction was required only for older children or when treatment was begun late. A mild hyperextension deformity at the elbow noted on follow-up of patients with anterior dislocation of the radial head seemed to support the theory that the injury is caused by hyperextension. A new classification of Monteggia fracture-dislocations in children is proposed.


Management of patients with malignant bowel obstruction and stage IV colorectal cancer.
Malignant bowel obstruction (MBO), a serious problem in stage IV colorectal cancer (CRC) patients, remains poorly understood. Optimal management requires realistic assessment of treatment goals. This study's purpose is to characterize outcomes following palliative intervention for MBO in the setting of metastatic CRC. Retrospective review of a prospective palliative database identified 141 patients undergoing surgical (OR; n = 96) or endoscopic (GI; n = 45) procedures for symptoms of MBO. Median patient age was 58 years, median follow-up 7 months. Most (63%) had multiple sites of metastases. Computed tomography (CT) scan findings of carcinomatosis (p = 0.002), ascites (p = 0.05), and multifocal obstruction with carcinomatosis and ascites (p = 0.03) significantly predicted the need for percutaneous or open gastrostomy tube, or stoma. Procedure-associated morbidity for 81 patients with small bowel obstruction (SBO) was 37%; 7% developed an enterocutaneous fistula/anastomotic leak. Thirty-day mortality was 6%. Most (84%) patients were palliated successfully; some received additional chemotherapy (38%) or surgery (12%). Procedure-associated morbidity for 60 patients with large bowel obstruction (LBO) was 25%; 11 patients (18%) required other procedures for stent failure, with one death at 30 days. Symptom resolution was >97%. Patients with LBO had improved symptom resolution, shorter length of stay (LOS), and longer median survival than patients with SBO. Patients with MBO and stage IV CRC were successfully palliated with GI or OR procedures. Patients with CT-identified ascites, carcinomatosis, or multifocal obstruction were least likely to benefit from OR procedures. CT plays an important role in preoperative planning. Sound clinical judgment and improved understanding are required for optimal management of MBO.


Three-Dimensional Printed Shape Memory Objects Based on an Olefin Ionomer of Zinc-Neutralized Poly(ethylene-co-methacrylic acid).
Three-dimensional printing enables the net shape manufacturing of objects with minimal material waste and low tooling costs, but the functionality is generally limited by available materials, especially for extrusion-based printing, such as fused deposition modeling (FDM). Here, we demonstrate shape memory behavior of 3D printed objects with FDM using a commercially available olefin ionomer, Surlyn 9520, which is zinc-neutralized poly(ethylene-co-methacrylic acid). The initial fixity for 3D printed and compression-molded samples was similar, but the initial recovery was much lower for the 3D printed sample (R = 58%) than that for the compression-molded sample (R = 83%). The poor recovery in the first cycle is attributed to polyethylene crystals formed during programming that act to resist the permanent network recovery. This effect is magnified in the 3D printed part due to the higher strain (lower modulus in the 3D printed part) at a fixed programming stress. The fixity and recovery in subsequent shape memory cycles are greater for the 3D printed part than for the compression-molded part. Moreover, the programmed strain can be systematically modulated by inclusion of porosity in the printed part without adversely impacting the fixity or recovery. These characteristics enable the direct formation of complex shapes of thermoplastic shape memory polymers that can be recovered in three dimensions with the appropriate trigger, such as heat, through the use of FDM as a 3D printing technology.


Right posterior approach for pancreaticoduodenectomy: a new technical approach.
The major goals that must be achieved during pancreaticoduodenectomy (PD) include reduction of postoperative hemorrhage and/or operating time. We herein describe a new technique for PD examining right posterior approach PD. From January 2012 to December 2013, 116 patients underwent PD for periampullary or pancreatic disease. Of these 116 patients, 56 cases were surgically treated for pancreas head or periampullary malignancy and were studied for blood loss volume and length of operation. An interesting issue in the present study was related to operating time and intra-operative blood loss. The median blood loss volume and operating time were 349 mL (35-3,636 mL) and 276 min (188-467 min), respectively, in patients who underwent a right posterior-approach PD. The estimated operative blood loss volume and operative time are lower in right posterior approach PD, probably due to clearly detection a route of the inferior pancreaticoduodenal artery from the SMA and following early ligation of the inferior pancreaticoduodenal artery and reduced congestion of the pancreatic head.


Infectious complications of ventricular assist device use in children in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
Infections are frequent in pediatric ventricular assist device (VAD) patients. In this study we aimed to describe infections in durable VAD patients reported to Pedimacs. Durable VAD data from the Pedimacs registry (September 19, 2012 to December 31, 2015) were analyzed. Infections were described with standard descriptive statistics, Kaplan-Meier analysis and competing outcomes analysis. There were 248 implants in 222 patients, with a mean age and a median follow-up of 11 ± 6.4 years and 2.4 patient-months (<1 day to 2.6 years), respectively. Device types were pulsatile flow (PF) in 91 (41%) patients and continuous flow (CF) in 131 (59%) patients. PF patients were younger (4 ± 4 vs 14 ± 4 years; p < 0.0001) and were more likely to have congenital heart disease (25% vs 12%; p = 0.03), prior surgery (53% vs 26%; p < 0.0001) and prior extracorporeal membrane oxygenation (24% vs 7%; p = 0.0003). Infection accounted for 17% (96 of 564) of the reported adverse events (AEs). A non-device infection was most common (51%), followed by sepsis (24%), external pump component infection (20%) and internal pump component infection (5%). Most infections were bacterial (73%) and required intravenous therapy only (77%). The risk of infection in the constant phase was higher in patients with a history of prior infection and in patients with a history of a non-infectious major AEs. Survival was lower after infection only in CF patients (p = 0.008). Infection was the most common AE after pediatric VAD implantation. Non-device infections were most common. The best predictor of a future infection was a past infection. CF patients have higher risk of death after an infection.


PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer.
Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers.


Lack of adverse neonatal neurobehavioral effects of lidocaine.
The effects of epidural anesthesia on the early neonatal neurobehavioral scale (ENNS) following delivery were studied in 22 parturients given 1.5% lidocaine epidural anesthesia during labor and delivery. These results were compared to those obtained in a control group of 17 neonates whose mothers received no analgesics, medications, or local anesthetics for labor or delivery. There was no significant difference in ENNS in the two groups of neonates. Lidocaine as administered in this study has no adverse effects on the early neurobehavioral status of the neonate.


Refinement of the structure of recombinant rat intestinal fatty acid-binding apoprotein at 1.2-A resolution.
The three-dimensional structure of the 131-residue rat intestinal fatty acid-binding protein, without bound ligand (apoI-FABP), has been refined with x-ray diffraction data to a nominal resolution of 1.19 A. The final model has a conventional crystallographic R-factor of 16.9% for 34,290 unique reflections [a root mean square (r.m.s.) deviation for bond length of 0.012 A and a r.m.s. deviation of 2.368 degrees for bond angles]. Ninety-two residues are present as components of the protein's 10 anti-parallel beta-strands while 14 residues are part of its two short alpha-helices. The beta-strands and alpha-helices are organized into two nearly orthogonal beta-sheets. Particular attention has been placed in defining solvent structure and the structures of discretely disordered groups in this protein. Two hundred thirty-seven solvent molecules have been identified; 24 are located within apoI-FABP. The refined model includes alternate conformers for 228 protein atoms (109 main-chain, 119 side-chain) and 63 solvent molecules. We have found several aromatic side-chains with multiple conformations located near, or in, the protein's ligand binding site. This observation, along with the fact that these side-chains have a temperature factor that is relatively higher than that of other aromatic residues, suggests that they may be involved in the process of noncovalent binding of fatty acid. The absence of a true hydrophobic core in I-FABP suggests that its structural integrity may be maintained primarily by a hydrogen bonding network involving protein and solvent atoms.


Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome.
Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (SERT/SLC6A4). SERT deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in early embryonic brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.


[Countermeasures against non-specific reactions in the measurement of beta-glucan in plasma by alkaline treatment, chromogenic automated kinetic assay].
We investigated the detection of non-specific reactions in the measurement of plasma (1-->3)-beta-D-glucan (beta-glucan) and countermeasures against them using alkaline treatment, chromogenic automated kinetic assay (alkaline-kinetic assay). In this study, we reexamined the values of beta-glucan using the alkaline-kinetic assay with and without laminaran oligosaccharides (LO) as a kind of beta-glucan that blocks the Limulus reaction. The materials for this study were 584 plasma samples in which beta-glucan had been measured. These were taken from 232 patients in Kawasaki Medical School Hospital between January 2002 and March 2002. Non-specific reactions were judged by a calculated value under a LO additive condition. Determination as to whether or not the each time course of the Limulus reaction was influenced by a non-specific reaction was also studied by applying a non-specific reaction index set up independently. Non-specific reactions were recognized in 51.9% of the samples (81/156). The amount of non-specific reaction was 9.9 pg/ml or less in major samples. On the other hand, when the cut off value of the index for detection of non-specific reactions was set at 0.5, the sensitivity was 88.9% and specificity was 73.7%. The positive and negative predictive values were 93.5% and 60.9% respectively. Non-specific reactions can be approximately distinguished by applying the non-specific reaction index. By so doing, unnecessary initiation of anti fugal therapy in response to non-specific reactions can be avoided. Further prospective and radical studies of non-specific reactions in the alkaline-kinetic assay are necessary.


Controlled Manipulation of Magic Number Gold-Fullerene Clusters Using Scanning Tunneling Microscopy.
We report controlled manipulation of magic number gold-fullerene clusters, (C60) m-(Au) n, on a Au(111) substrate at 110 K using scanning tunneling microscopy (STM). Each cluster consists of a two-dimensional gold island of nAu atoms confined by a frame of mC60 molecules. Using STM, C60 molecules are extracted from the molecular frame one at a time. The extraction is conducted by driving the STM tip into the cluster, leading to one of the molecules being squeezed out of the frame. Unlike at room temperature, the extracted molecules do not move away from the cluster because of the lack of thermal energy at 110 K; they are found to be attached to the outside of the frame. Reversible manipulation is also possible by pushing an extracted molecule back into the frame. This reversible manipulation is possible only for molecules from the edge of the cluster.


[Visual potentialities of the tick Hyalomma asiaticum asiaticum (Ixodidae)].
Ethological experiments with the desert tick Hyalomma asiaticum asiaticum are conducted. It is shown that tick inhabiting open landscapes discovers his host using his eyes. Since the eyes of this species have a poor resolving possibility, black objects with white strips drawn on it are less attractive for the tick. When the tick scans an area looking for host, the principal optical axis of his eyes is directed not higher than 20 degrees. In allows the tick to discover objects having angular sizes of 5 degrees and greater.


Optical circulator for an in-line-type compact lidar.
The application of an optical circulator is demonstrated for an in-line-type lidar. The lidar's transmitter and receiver are installed in a telescope. The optical circulator of interest here can separate the transmitting laser beam and the echo lights on the same optical axis. It can also divide the echo lights simultaneously into orthogonally polarized components. An insertion loss of 2.2 dB and isolation of >60 dB for the developed optical circulator are obtained in a laser-transmitting situation. This optical circulator makes it possible to measure the polarization ratio caused by cloud phases with a narrow field of view in an in-line-type lidar operation.


Effects of the Cardio First AngelTM on chest compression performance.
Survival rates of out-of-hospital cardiac arrest remain poor. Bystander cardiopulmonary resuscitation (CPR) is crucial for survival and feedback devices could improve its quality. We investigated the quality of chest compression when using the Cardio First AngelTM (CFA) feedback device compared to standard basic life support (BLS). The analysis focused on laymen. Laymen without (n= 43) and with (n= 96) explanation of the device, medical students (n= 128) and medical staff (n= 27) performed 60 seconds of standard versus assisted chest compression using the CFA on a resuscitation manikin. Compression frequency, depth and position were analyzed according to current guidelines. Laymen showed significantly better success rates regarding correct compression depth when using the CFA (23.3% vs. 55.8%, p= 0.004 and 25.0% vs. 52.1%, p< 0.001, laymen without and with explanation of the device, respectively). Medical students likewise improved (22.7% vs. 42.2%, p= 0.004). Hand positioning was 100% correct in all groups with the device. Improvement in frequency yielded by the CFA was more pronounced for probands with fears of contact (p= 0.02). The benefit of using the device did not differ significantly in laymen with or without explanation. Chest compression as performed by laymen was significantly improved with regard to compression depth when using the CFA for guidance and feedback. With the device, no cases of incorrect hand positioning occurred in any group.


Biodegradable Magnetic Molecularly Imprinted Anticancer Drug Carrier for the Targeted Delivery of Docetaxel.
Molecularly imprinted biodegradable polymers are receiving considerable attention in drug delivery due to their ability of targeted recognition and biocompatibility. This study reports the synthesis of a novel fluorescence-active magnetic molecularly imprinted drug carrier (MIDC) using a glucose-based biodegradable cross-linking agent for the delivery of anticancer drug docetaxel. The magnetic molecularly imprinted polymer (MMIP) was characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy, and vibrating sample magnetometry (VSM). The MMIP presented a magnetization value of 0.0059 emu g-1 and binding capacity of 72 mg g-1 with docetaxel. In vitro and in vivo studies were performed to observe the effectiveness of the MIDC for drug delivery. The cell viability assay suggested that the MMIP did not present toxic effects on healthy cells. The magnetic property of the MMIP allowed quick identification of the drug carrier at the target site by applying the external magnetic field to mice (after 20 min of loading) and taking X-ray images. The novel MMIP-based drug carrier could thus deliver the drug at the target site without affecting the healthy cells.


Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3.
Anion and fluid secretion are both defective in cystic fibrosis (CF); however, the transport mechanisms are not well understood. In this study, Cl(-) and HCO(3)(-) secretion was measured using genetically matched CF transmembrane conductance regulator (CFTR)-deficient and CFTR-expressing cell lines derived from the human airway epithelial cell line Calu-3. Forskolin stimulated the short-circuit current (I(sc)) across voltage-clamped monolayers, and also increased the equivalent short-circuit current (I(eq)) calculated under open-circuit conditions. I(sc) was equivalent to the HCO(3)(-) net flux measured using the pH-stat technique, whereas I(eq) was the sum of the Cl(-) and HCO(3)(-) net fluxes. I(eq) and HCO(3)(-) fluxes were increased by bafilomycin and ZnCl(2), suggesting that some secreted HCO(3)(-) is neutralized by parallel electrogenic H(+) secretion. I(eq) and fluid secretion were dependent on the presence of both Na(+) and HCO(3)(-). The carbonic anhydrase inhibitor acetazolamide abolished forskolin stimulation of I(eq) and HCO(3)(-) secretion, suggesting that HCO(3)(-) transport under these conditions requires catalysed synthesis of carbonic acid. Cl(-) was the predominant anion in secretions under all conditions studied and thus drives most of the fluid transport. Nevertheless, 50-70% of Cl(-) and fluid transport was bumetanide-insensitive, suggesting basolateral Cl(-) loading by a sodium-potassium-chloride cotransporter 1 (NKCC1)-independent mechanism. Imposing a transepithelial HCO(3)(-) gradient across basolaterally permeabilized Calu-3 cells sustained a forskolin-stimulated current, which was sensitive to CFTR inhibitors and drastically reduced in CFTR-deficient cells. Net HCO(3)(-) secretion was increased by bilateral Cl(-) removal and therefore did not require apical Cl(-)/HCO(3)(-) exchange. The results suggest a model in which most HCO(3)(-) is recycled basolaterally by exchange with Cl(-), and the resulting HCO(3)(-)-dependent Cl(-) transport provides an osmotic driving force for fluid secretion.


Malignant fibrous histiocytoma of the pulmonary artery.
A patient is reported whose symptoms and clinical features were interpreted as pulmonary embolism. However, the ultimate diagnosis was malignant fibrous histiocytoma of the pulmonary artery, which was made evident at operation. Although extremely rare in the early medical literature, primary sarcoma of the pulmonary artery has been reported more frequently during the last decade. This patient may provide further insight into the clinical, diagnostic, and therapeutic features of primary sarcomas of the pulmonary artery.


The Diminishing Role of Pelvic Stability Evaluation in the Era of Computed Tomographic Scanning.
Pelvic fractures can result in life-threatening hemorrhages or other associated injuries. Therefore, computed tomography (CT) scanning plays a key role in the management of pelvic fracture patients. However, CT scanning is utilized as an adjunct in secondary survey according to traditional Advanced Trauma Life Support (ATLS) guidelines, whereas pelvic x-ray is used as a primary tool to evaluate pelvic stability and the necessity of further CT scanning. In the current study, we attempted to evaluate the role of CT scanning in the era of advanced technology. The significance of pelvic stability was also analyzed. From January 2012 to December 2014, the trauma registry and medical records of pelvic fracture patients were retrospectively reviewed. A 64-slice multidetector CT scanner was used in our emergency department as a standard diagnostic tool for evaluating trauma patients. Pelvic x-ray was used as a primary tool for screening pelvic fractures, and pelvic stability was evaluated accordingly. CT scans were performed in patients with unstable pelvic fractures, suspected associated intra-abdominal injuries (IAIs), or other conditions based on the physicians' clinical judgment. The clinical features of patients with stable and unstable pelvic fractures were compared. The patients with stable pelvic fractures were analyzed to determine the characteristics associated with retroperitoneal hemorrhage (RH) or IAIs. Patients with stable pelvic fractures were also compared based on whether they underwent a CT scan. A total of 716 patients were enrolled in this study. There were 533 (74.4%) patients with stable pelvic fractures. Of these patients, there were 66 (12.4%) and 50 (9.4%) patients with associated RH and IAI, respectively. There were no significant differences between the patients with associated RH based on their primary evaluation (vital signs, volume of blood transfusion, and hemoglobin level). Similarly, the demographics and the primary evaluation results (symptoms, coma scale, and white blood cell counts) of the patients with associated IAIs were also not significantly different from the patients without associated IAIs. Furthermore, the time to definitive hemostasis (surgery or angioembolization) was not significantly different between the unstable patients who underwent a CT scan or those who did not.In the management of pelvic fracture patients, the role of pelvic stability is not significant in the evaluation of associated RH or IAI. Routine CT scanning is suggested for pelvic fracture patients because of the rapid scanning time and sufficient information produced.