Induction of atrial fibrillation with adenosine during a transesophageal electrophysiology study to risk stratify a patient with asymptomatic ventricular preexcitation.
An asymptomatic adolescent male athlete was incidentally found to have ventricular preexcitation on electrocardiogram during a sports preparticipation physical. A transesophageal electrophysiology study (TEEPS) was performed after an exercise stress test failed to delineate the patient's risk of sudden cardiac death. The TEEPS was favored in this case over a transvenous electrophysiology study due to reduced invasiveness. The goal of the TEEPS was to place the patient into atrial fibrillation (AFib) and evaluate the shortest preexcited RR interval during AFib, thereby assessing the risk of his accessory pathway. Conventional pacing modalities were unable to induce AFib. During atrial burst pacing, adenosine was then administered, which successfully induced AFib. This case highlights adenosine's potential to induce atrial fibrillation during transesophageal electrophysiology studies when atrial pacing alone was unable to do so.


Probability of founder effect in a tribal population.
When an unusually high frequency of an allele is encountered in a population, "founder effect" is often invoked as an explanation. As usually used, the term implies the disproportionate increase through chance (rather than selection) of an allele contributed to the population by a particular ancestor. While genetic theory leaves no doubt this is a possible explanation, problems arise when we try to determine how likely this explanation is for any specific finding in any specific, finite population, i.e., just how rare is this rare event? In this communication we consider the question in the context of Amerindian tribal populations, deriving specific probabilities under defined conditions. Our interest in the question has been whetted by the finding to date of some eight possible examples of a founder effect in studies of twelve different tribes.


The anti-Fn14 antibody BIIB036 inhibits tumor growth in xenografts and patient derived primary tumor models and enhances efficacy of chemotherapeutic agents in multiple xenograft models.
Agonistic antibodies targeting Fn14, the receptor for TWEAK, have demonstrated anti-tumor activity in xenograft models. Herein, we further explore the therapeutic potential of the humanized anti-Fn14 agonistic antibody, BIIB036, as a single agent and in combination with standard of care cancer therapeutics. Pharmacokinetic studies of BIIB036 in tumor-bearing mice revealed a half-life of approximately three days suggesting twice a week dosing would be necessary to maintain efficacy. However, in multiple xenograft models, BIIB036 treatment resulted in extended tumor growth inhibition up to 40-50 d following cessation of dosing, suggesting that frequent administration of BIIB036 may not be necessary to maintain prolonged anti-tumor activity. Subsequent xenograft studies revealed that maximal efficacy was achieved with BIIB036 dosing once every two weeks, by either intraperitoneal or subcutaneous administration. Xenograft tumors that were initially treated with BIBI036 and then re-grew up to 1000 mm³ following cessation of the first cycle of treatment remained sensitive to a second cycle of treatment. BIIB036 was also evaluated in patient derived primary colon tumor models, where efficacy compared favorably with a standard of care agent. Lastly, BIIB036 enhanced the efficacy of several standard of care chemotherapeutics, including paclitaxel in MDA-MBA-231 breast tumor xenografts, paclitaxel or carboplatin in HOP62 non-small cell lung xenografts, and 5-FU in NCI-N87 gastric xenografts, with no overlapping toxicities. These studies thus establish BIIB036 as a promising therapeutic agent with durable anti-tumor activity in human xenografts as well as patient derived primary tumor models, and enhanced activity and tolerability in combination with standard of care chemotherapeutics. Taken together, the data presented herein suggest that BIIB036 warrants evaluation in the clinic.


Measurement of substance abuse treatment outcomes over time.
There are many different ways of calculating the impact of treatment on drug use; percentage of positive drug tests, probability of drug use, percentage of patients abstaining from any use, total number of days of use, daily probability of use and average days till next use, are some examples reported in the literature. We prefer average days till next use because (1) it allows intermittent drug use and relapse; (2) it fits the client's count of drug-free days, and (3) it simultaneously accounts for both tests results and time between tests. We show by way of an example, how conclusions arrived at using average days till next use are likely to be different from other measures in analysis of recent data from impact of online treatment on drug use.


Infant color vision and color preferences: a tribute to Davida Teller.
Almost 40 years ago, Davida Teller developed the forced-choice preferential looking method for studying infant visual capabilities and used it to study infant color vision. About 10 years ago, she used infant looking preferences to study infant color perception. Here, we examine four data sets in which the infant looking preference was measured using a wide range of saturated colors. Three of those data sets, from papers by Marc Bornstein and by Davida Teller and Anna Franklin and their respective collaborators, were fit successfully using MacLeod and Boynton's model of the equiluminant plane in color space, in spite of the varied luminances used in those studies. A fourth data set, from a paper by Zemach, Chang, and Teller, was less well fit by that model. Apparently, infants are able to ignore luminance, and pay attention just to the color of stimuli. These results are discussed in the context of Davida Teller's work on the philosophy of vision science.


[Effects of mineral Chinese medicine Chloriti Lapis on contents of metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) rats].
The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS). The changes in the contents of metal elements were analyzed by SPSS 18. 0. Further,the correlations of differential metal elements( including Cu/Zn ratio) with differential metabolites in plasma,lung tissue and urine of AECOPD rats treated with Chloriti Lapis were analyzed. The results showed that Chloriti Lapis significantly up-regulated the contents of Fe,Al,Mn,Cu,Zn,Sn( P<0. 05),V,Co( P< 0. 01) and Cu/Zn ratio( P< 0. 05),and significantly down-regulated the contents of Ti( P< 0. 05)and Pb( P<0. 05) in the model rat plasma. It significantly increased the content of Be( P<0. 05) and decreased the contents of Mg,Ti and Al( P<0. 01) in model rat lung tissue. The element profiles of normal group,model group and Chloriti Lapis group can be well separated. Chloriti Lapis group and other groups were clustered into two categories. The taurine in plasma and phytosphingosine in lung tissue had the strongest correlations with differential metal elements. The Fe,Al,Mg,Be,Ti,V,Mn,Cu,Zn,Sn,and Co in Chloriti Lapis may directly or indirectly participate in the intervention of AECOPD rats. This group of metal elements may be the material basis of Chloriti Lapis acting on AECOPD rats,and reduce the Cu/Zn value in vivo. It was further confirmed that Chloriti Lapis could interfere with the metabolic pathways of taurine and hypotaurine in plasma and urine as well as the sphingolipid metabolism pathway in lung tissue of AECOPD rats. In addition,this study confirmed that long-term smoking can cause high-concentration Cd accumulation in the lung and damage the lung tissue.


Incident angle of saltating particles in wind-blown sand.
Incident angle of saltating particles plays a very important role in aeolian events. In this paper, the incident angles of sand particles near the sand bed were measured in wind tunnel. It reveals that the incident angles range widely from 0° to 180° and thereby the means of angles are larger than published data. Surprisingly, it is found the proportion that angles of 5°-15° occupy is far below previous reports. The measuring height is probably the most important reason for the measurement differences between this study and previous investigations.


Gamma-ray flash generation in irradiating a thin foil target by a single-cycle tightly focused extreme power laser pulse.
We present a regime where an ultraintense laser pulse interacting with a foil target results in high γ-photon conversion efficiency, obtained via three-dimensional quantum-electrodynamics particle-in-cell simulations. A single-cycle laser pulse is used under the tight-focusing condition for obtaining the λ^{3} regime. The simulations employ a radially polarized laser as it results in higher γ-photon conversion efficiency compared to both azimuthal and linear polarizations. A significant fraction of the laser energy is transferred to positrons, while a part of the electromagnetic wave escapes the target as attosecond single-cycle pulses.


Ultrasensitive photoreversible molecular sensors of azobenzene-functionalized plasmonic nanoantennas.
This Letter describes an unprecedentedly large and photoreversible localized surface plasmon resonance (LSPR) wavelength shift caused by photoisomerization of azobenzenes attached to gold nanoprisms that act as nanoantennas. The blue light-induced cis to trans azobenzene conformational change occurs in the solid state and controls the optical properties of the nanoprisms shifting their LSPR peak up to 21 nm toward longer wavelengths. This shift is consistent with the increase in thickness of the local dielectric environment (0.6 nm) surrounding the nanoprism and perhaps a contribution from plasmonic energy transfer between the nanoprism and azobenzenes. The effects of the azobenzene conformational change and its photoreversibility were also probed through surface-enhanced Raman spectroscopy (SERS) showing that the electronic interaction between the nanoprisms and bound azobenzenes in their cis conformation significantly enhances the intensity of the Raman bands of the azobenzenes. The SERS data suggests that the isomerization is controlled by first-order kinetics with a rate constant of 1.0 × 10(-4) s(-1). Our demonstration of light-induced photoreversibility of this type of molecular machine is the first-step toward removing present limitations on detection of molecular motion in solid-state devices using LSPR spectroscopy with nanoprisms. Modulating the LSPR peak position and controlling energy transfer across the nanostructure-organic molecule interface are very important for the fabrication of plasmonic-based nanoscale devices.


Polarization vortices in germanium telluride nanoplatelets: a theoretical study.
Using first-principles calculations based on density functional theory, we study the properties of germanium telluride crystalline nanoplatelets and nanoparticles. Above a diameter of 2.7 nm, we predict the appearance of polarization vortices giving rise to an unusual ferrotoroidic ground state with a spontaneous and reversible toroidal moment of polarization. We highlight the crucial role of inhomogeneous strain in stabilizing polarization vortices. Combined with the phase-change properties of germanium telluride, the ferrotoroidic properties could be of practical interest for ternary logic applications.


Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep.
Therapeutic hypothermia for hypoxic-ischaemic encephalopathy provides partial white matter protection. Recombinant erythropoietin reduces demyelination after hypoxia-ischaemia, but it is unclear whether adjunct erythropoietin treatment can further improve outcomes after therapeutic hypothermia. Term-equivalent fetal sheep received sham-ischaemia (n = 9) or cerebral ischaemia for 30 min (ischaemia-vehicle, n = 8), followed by intravenous infusion of recombinant erythropoietin (ischaemia-Epo, n = 8; 5000 IU/kg bolus dose, then 833.3 IU/kg/h), cerebral hypothermia (ischaemia-hypothermia, n = 8), or recombinant erythropoietin plus hypothermia (ischaemia-Epo-hypothermia, n = 8), from 3 to 72 h post-ischaemia. Foetal brains were harvested at 7 days after cerebral ischaemia. Ischaemia was associated with marked loss of total Olig2-positive oligodendrocytes with reduced density of myelin and linearity of the white matter tracts (P < 0.01), and microglial induction and increased caspase-3-positive apoptosis. Cerebral hypothermia improved the total number of oligodendrocytes and restored myelin basic protein (P < 0.01), whereas recombinant erythropoietin partially improved myelin basic protein density and tract linearity. Both interventions suppressed microgliosis and caspase-3 (P < 0.05). Co-treatment improved 2',3'-cyclic-nucleotide 3'-phosphodiesterase-myelin density compared to hypothermia, but had no other additive effect. These findings suggest that although hypothermia and recombinant erythropoietin independently protect white matter after severe hypoxia-ischaemia, they have partially overlapping anti-inflammatory and anti-apoptotic effects, with little additive benefit of combination therapy.


Transient signal isotope analysis: validation of the method for isotope signal synchronization with the determination of amplifier first-order time constants.
During transient signal acquisition by Multi-Collection Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS), an isotope ratio increase or decrease (isotopic drift hereafter) is often observed which is related to the different time responses of the amplifiers involved in multi-collection. This isotopic drift affects the quality of the isotopic data and, in a recent study, a method of internal amplifier signal synchronization for isotope drift correction was proposed. In this work the determination of the amplifier time constants was investigated in order to validate the method of internal amplifier signal synchronization for isotope ratio drift correction. Two different MC-ICPMS instruments, the Neptune and the Neptune Plus, were used, and both the lead transient signals and the signal decay curves of the amplifiers were investigated. Our results show that the first part of the amplifier signal decay curve is characterized by a pure exponential decay. This part of the signal decay was used for the effective calculation of the amplifier first-order time constants. The small differences between these time constants were compared with time lag values obtained from the method of isotope signal synchronization and were found to be in good agreement. This work proposes a way of determining amplifier first-order time constants. We show that isotopic drift is directly related to the amplifier first-order time constants and the method of internal amplifier signal synchronization for isotope ratio drift correction is validated.


Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.
The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein.


Survival characteristics of diarrheagenic Escherichia coli pathotypes and Helicobacter pylori during passage through the free-living ciliate, Tetrahymena sp.
Free-living protozoa have been implicated in the survival and transport of pathogens in the environment, but the relationship between non-Shiga toxin-producing Escherichia coli or Helicobacter pylori and ciliates has not been characterized. Six diarrheagenic pathotypes of E. coli and an isolate of H. pylori were evaluated for their susceptibility to digestion by Tetrahymena, an aquatic ciliate. Tetrahymena strain MB125 was fed E. coli or H. pylori, and the ciliate's egested products examined for viable bacterial pathogens by the BacLight(™) LIVE/DEAD (™) assay, a cell elongation method, and by colony counts. All six diarrheagenic E. coli pathotypes survived digestion, whereas H. pylori was digested. Growth of E. coli on agar plates indicated that the bacteria were able to replicate after passage through the ciliate. Transmission electron micrographs of E. coli cells as intact rods vs. degraded H. pylori cells corroborated these results. Scanning electron microscopy revealed a net-like matrix around intact E. coli cells in fecal pellets. These results suggest a possible role for Tetrahymena and its egested fecal pellets in the dissemination of diarrheagenic E. coli in the environment. This bacterial-protozoan interaction may increase opportunities for transmission of diarrheagenic E. coli to mammalian hosts including humans.


Islet transplantation restores normal serum amylase levels in diabetic rats.
Diabetes is associated with a diminution in exocrine pancreatic function. The goal of our study was to investigate whether the altered exocrine pancreatic function of streptozotocin-induced diabetic rats could be ameliorated by islet transplantation. Diabetic rats received either more than 1,000 syngeneic islets intraportally (islet transplantation group) or pancreatic, nonviable insular tissue (sham transplantation group). Plasma amylase and insulin levels in diabetic rats were significantly lower than in normal rats. The exocrine pancreas of streptozotocin-induced diabetic rats showed alterations (decrease of zymogen granules, diminution of endoplasmic reticulum, clusters of ribosomes without organization) in the structure of acinar cells at the electron microscopic level. After islet transplantation, plasma glucose levels were restored to normal values, and those of amylase and insulin gradually increased to normal values. A positive correlation between plasma levels of amylase and insulin was found. Three months after islet transplantation, the islet-transplanted rats did not show morphologic alterations of the acinar cells which were still found in the sham-transplanted rats. It is concluded that alterations of exocrine pancreas in streptozotocin-induced diabetic rats are ameliorated by islet transplantation.


Investigating the binding mechanism of topiramate with bovine serum albumin using spectroscopic and computational methods.
Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), and computational approaches were used to elucidate the molecular aspects of interaction between the antiepileptic drug topiramate and the multifunctional transport protein bovine serum albumin (BSA) under physiological conditions. Topiramate quenched BSA fluorescence in a static quenching mode, according to the Stern-Volmer quenching constant (Ksv ) data derived from fluorescence spectroscopy for the topiramate-BSA complex. The binding constant was also used to calculate the binding affinity for the topiramate-BSA interaction. Fluorescence and circular dichroism experiments demonstrate that the protein's tertiary structure is affected by the microenvironmental alterations generated by topiramate binding to BSA. To establish the exact binding site, interacting residues, and interaction forces involved in the binding of topiramate to BSA, molecular modeling and simulation approaches were used. According to the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) calculations, the average binding energy between topiramate and BSA is -421.05 kJ/mol. Topiramate was discovered to have substantial interactions with BSA, changing the structural dynamic and Gibbs free energy landscape patterns.


The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-phosphate isomerase antibody-positive patients with rheumatoid arthritis.
The pathogenic role of autoantibodies in rheumatoid arthritis (RA) remains elusive. Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are candidates for arthritogenic Abs because they directly induce arthritis in mice. High titers of anti-GPI Abs are found in some RA patients with severe forms. The aim of this study was to analyze the role of IgG, including anti-GPI Abs, in the joints of RA patients. Synovial tissue was obtained from 6 patients with RA (3 anti-GPI Abs- positive and 3 anti-GPI Abs- negative) and compared histologically and immunohistochemically for IgG and C3 deposition. IgG fractions were separated from the sera of anti-GPI Abs-positive RA patients and healthy subjects, and injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. On day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of the C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from the monkeys' joints. The synovia of anti-GPI Abs-positive RA patients showed diffuse infiltration of cells, including mast cells, and strong deposition of IgG and C3. In monkeys, IgG from RA patients, including anti-GPI Abs, resulted in recruitment of granulocytes and mononuclear cells, strong deposition of IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients, including that of anti-GPI Abs, may play a role in the synovitis of RA, although the pathogenesis of human anti-GPI Abs is still uncertain.


Variable pitch reconstruction using John's equation.
We present an algorithm to reconstruct helical cone beam computed tomography (CT) data acquired at variable pitch. The algorithm extracts a halfscan segment of projections using an extended version of the advanced single slice rebinning (ASSR) algorithm. ASSR rebins constant pitch cone beam data to fan beam projections that approximately lie on a plane that is tilted to optimally fit the source helix. For variable pitch, the error between the tilted plane chosen by ASSR and the source helix increases, resulting in increased image artifacts. To reduce the artifacts, we choose a reconstruction plane, which is tilted and shifted relative to the source trajectory. We then correct rebinned fan beam data using John's equation to virtually move the source into the tilted and shifted reconstruction plane. Results obtained from simulated phantom images and scanner images demonstrate the applicability of the proposed algorithm.


Pulmonary infection in the brain injured patient.
Incidence of ventilator associated pneumonia (VAP) in brain injury patient ranges from 28 to 40 %. Brain injury may induce immunosuppression explaining why neurotraumapatients are at higher risk of developing early onset pneumonia. However, occurrence of pneumonia in brain injury patient has not been associated to higher mortality. Many methods such as selective digestive decontamination, early administration of antibiotics, continuous subglottic aspiration, improved initial choice and dosage of antibiotic, may be useful to prevent and treat VAP in brain injury.


A novel multi-stage feature selection method for microarray expression data analysis.
With the development of genome research, finding method to classify cancer and detect biomarkers efficiently has become a challenging problem. In this paper, a novel multi-stage method for feature selection is proposed which considers all kinds of genes in the original gene set. The method eliminates the irrelevant, noisy and redundant genes and selects a subset of relevant genes at different stages. The proposed method is examined on microarray datasets of Leukemia, Prostate, Colon, Breast, Nervous and DLBCL by different classifiers and the best accuracies of the method in these datasets are 100%, 98.04%, 100%, 89.74%, 100% and 98.28%, respectively.


Different dosage regimens of nifedipine, labetalol, and hydralazine for the treatment of severe hypertension during pregnancy: a network meta-analysis of randomized controlled trials.
This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.


Toward a Predictive Framework for Convergent Evolution: Integrating Natural History, Genetic Mechanisms, and Consequences for the Diversity of Life.
A charm of biology as a scientific discipline is the diversity of life. Although this diversity can make laws of biology challenging to discover, several repeated patterns and general principles govern evolutionary diversification. Convergent evolution, the independent evolution of similar phenotypes, has been at the heart of one approach to understand generality in the evolutionary process. Yet understanding when and why organismal traits and strategies repeatedly evolve has been a central challenge. These issues were the focus of the American Society of Naturalists Vice Presidential Symposium in 2016 and are the subject of this collection of articles. Although naturalists have long made inferences about convergent evolution and its importance, there has been confusion in the interpretation of the pattern of convergence. Does convergence primarily indicate adaptation or constraint? How often should convergence be expected? Are there general principles that would allow us to predict where and when and by what mechanisms convergent evolution should occur? What role does natural history play in advancing our understanding of general evolutionary principles? In this introductory article, I address these questions, review several generalizations about convergent evolution that have emerged over the past 15 years, and present a framework for advancing the study and interpretation of convergence. Perhaps the most important emerging conclusion is that the genetic mechanisms of convergent evolution are phylogenetically conserved; that is, more closely related species tend to share the same genetic basis of traits, even when independently evolved. Finally, I highlight how the articles in this special issue further develop concepts, methodologies, and case studies at the frontier of our understanding of the causes and consequences of convergent evolution.


[Retinal vein occlusion. II. Collateral systems].
During the period of 6-12 months, in the majority of patients with occlusion of the branch of the retinal vein, the macular edema regresses and the intraretinal hemorrhages are resorbed. According to the author, this restoration of the circulatory conditions in the retina takes place especially due to the development of the veno-venous collaterals. The author presents an explanation of the mechanism of the regulation of the circulatory conditions in the retina during the development of the collaterals on the basis of the new approach to the explanation of the pathogenesis of the circulatory changes in occlusion of the branch of the retinal vein.


Isolated Lymphomatoid Granulomatosis of the Central Nervous System Mimicking Trigeminal Neuropathy, Bell's Palsy, and Glioblastoma in an Epstein-Barr-Negative Immunocompetent Host: A Case Report.
Lymphomatoid granulomatosis is an Epstein-Barr virus-associated lymphoproliferative B-cell neoplasm that typically involves multiple organ systems. This disease is exceedingly rare when confined to the central nervous system (CNS), usually presenting as a mass lesion or diffuse disease, with no existing standard of care. We present the case of a 67-year-old patient who had a unique and insidious course of isolated CNS lymphomatoid granulomatosis. The disease first presented with cranial neuropathies involving the trigeminal and facial nerves that were responsive to steroids both clinically and radiographically. Two years later, the disease manifested as a parietal mass mimicking high-grade glioma that caused homonymous hemianopsia. The patient underwent craniotomy for resection and was treated with rituximab after surgery. The patient has achieved progression-free survival more than three years after the surgery. Surgical debulking and post-procedural rituximab resulted in favorable survival in a case of isolated CNS lymphomatoid granulomatosis. An intracranial mass preceded by steroid-responsive cranial neuropathies should raise suspicion for lymphoproliferative disorder.


Effects of High-Intensity Ultrasound Pretreatment on Structure, Properties, and Enzymolysis of Soy Protein Isolate.
The objective of this study was to investigate the effects of different high-intensity ultrasonication (HIU) pretreatment on the structure and properties of soybean protein isolate (SPI) as well as enzymatic hydrolysis of SPI by bromelain and antioxidant activity of hydrolysates. The HIU-treated SPI fractions showed a decrease in the proportion of α-helices and β-turns and an increase in the content of β-sheets and random coils based on Fourier-transform infrared spectroscopy. Near-infrared spectra and fluorescence spectra analyses provided support for the changes in secondary and tertiary structures of SPI after ultrasound treatment. The particle size of SPI decreased from 217.20 nm to 141.23 nm and the absolute zeta potential increased. Scanning electron microscopy showed that HIU treatment changed apparent morphology. Dynamic and static light scattering of ultrasonicated samples showed that SPI structure had changed from hard-sphere to hollow-sphere or polydisperse and monodisperse gaussian coils. HIU pretreatment significantly increased the hydroxyl-radical scavenging and the degree of hydrolysis of the SPI hydrolysates.


Relative safety and efficacy of inhaled corticosteroids.
Inhaled corticosteroids are the main treatment for controlling asthma in adults and children. However, there is still some concern over the safety of these drugs when used at high doses and for long periods of time. Hence issues relating to the efficacy and safety of inhaled corticosteroids have been extensively researched over the past 5 years. General considerations, such as use of an appropriate dose of inhaled corticosteroid in an appropriate asthma population, are discussed. Studies comparing the efficacy and safety of fluticasone propionate, beclomethasone dipropionate, and budesonide are highlighted, and a systematic review of these studies suggests that fluticasone propionate has a better efficacy:safety therapeutic ratio than either beclomethasone dipropionate or budesonide.


Relieved or disappointed--experiences of accepted and rejected living kidney donors: a prospective qualitative study.
To investigate the perceived experiences and considerations among potential kidney transplantation donors in relation to acceptance or rejection as donors. Kidney transplantations are successfully performed in all Western countries, but the prevalence of patients waiting for organs from deceased donors far exceeds the number of organs available. This shortfall has promoted donation by living donors, who enter the donation process with feelings of hope, concern and patience to be accepted or rejected for donation. A phenomenological-hermeneutic approach was applied in the study. Semi-structured interviews were conducted with 16 participants. Data were interpreted and discussed in accordance with Ricoeur's theory of interpretation involving: naïve reading, structural analysis, critical interpretation and discussion. Accepted donors experienced relief and delight. Reflections were made on being prepared for donation and on the risks involved. Relationships between donors and recipients became closer. Rejected donors experienced frustration and disappointment, including anxiety about the recipient's prospects. Rejected donors reflected on the reason for rejection, and this could include considerations about changes to their own lifestyle. Reactions from relatives had an impact on donors. The study concluded that both the accepted and rejected donors were vulnerable and in need of attention, engagement, support and care. The study draws attention to the need for healthcare professionals to be open and sensitive to the donors' descriptions of their unique experiences of being accepted or rejected for kidney donation. Nurses should be aware that dialogue with donors, including reflections on experiences, is important to reduce and alleviate vulnerability and to give the best possible support and attention, including the opportunity to promote optimal postdonation outcomes.


Differential expression analysis of miRNA in peripheral blood mononuclear cells of patients with non-segmental vitiligo.
Vitiligo is a common depigmentary skin disease that may follow a pattern of multifactorial inheritance. The essential factors of its immunopathogenesis is thought to be the selective destruction of melanocytes. As a new class of microregulators of gene expression, miRNA have been reported to play vital roles in autoimmune diseases, metabolic diseases and cancer. This study sought to characterize the different miRNA expression pattern in the peripheral blood mononuclear cells (PBMC) of patients with non-segmental vitiligo (NSV) and healthy individuals and to examine their direct responses to thymosin α1 (Tα1) treatment. The miRNA expression profile in the PBMC of patients with NSV was analyzed using Exiqon's miRCURY LNA microRNA Array. The differentially expressed miRNA were validated by real-time quantitative polymerase chain reaction. We found that the expression levels of miR-224-3p and miR-4712-3p were upregulated, and miR-3940-5p was downregulated in the PBMC. The common clinical immune modulator Tα1 changed the miRNA expression profile. Our analysis showed that differentially expressed miRNA were associated with the mechanism of immune imbalance of vitiligo and that Tα1 could play an important role in changing the expression of these miRNA in the PBMC of patients with NSV. This study provided further evidence that miRNA may serve as novel drug targets for vitiligo therapeutic evaluation.


Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.
Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p < 0.001) and disruption of insulin secretion (p < 0.001) associated with of reactive oxygen species (ROS) production and a modulation of pro-oxidant and antioxidant signaling pathway. Cell pre-treatments with extracts considerably increased cell viability (+86% p < 0.001) for simmondsin and +74% (p < 0.001) for aqueous extract and insulin secretion. The extracts also markedly decreased ROS (-69% (p < 0.001) for simmondsin and -59% (p < 0.001) for aqueous extract) and caspase-3 activation and improved antioxidant defense, inhibiting p22phox and increasing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels (+70%, p < 0.001) for aqueous extract. Simmondsin had no impact on Nrf2 levels. The richness and diversity of molecules present in jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.


Kawasaki Disease Associated with SARS-CoV2 in a Pair of Triplets.
The etiology of Kawasaki disease (KD) and its precise genetic basics remain unknown. Genetic variants affecting immunity have been found in some patients. The occurrence of KD in siblings is rare, but KD pedigrees with multiple affected members have been described in Japan and North America. Cases in twins have been documented. We report 2 pairs of trizygotic triplets who developed KD associated with SARS-CoV2 infection from 2 different families. Our cases show that KD is multifactorial in origin, and both infectious etiology (particularly SARS-CoV2 as in our cases) and genetic factors are relevant in the disease.


[The autotransplantation of undescended testes].
A procedure for microsurgical autotransplantation of the undescended testis was proposed, which was different from the well-known ones by the fact that following microvascular anastomoses made between the testicular and lower epigastric vessels, the testis was brought to the scrotum in the clinostatic position through the medial inguinal fossa with prior mobilization of the deferent duct up to the level of the epididymal tail, by straightening the epididymal differential loop. The procedure allows one to provide a relative stretching of the deferent duct at a length equal to the longitudinal axis of the testis, thus achieving the optimal level of scrotal testicular position with initially high retention and a short deferent duct. Biopsies and clinical trials make it possible to recommend the procedure in the surgery of complicated cryptorchidism.


Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson's disease pathogenesis.
Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) are symptomatically characterized by parkinsonism, with the latter presenting additionally a distinctive range of atypical features. Although the majority of patients with PD and APS appear to be sporadic, genetic causes of several rare monogenic disease variants were identified. The knowledge acquired from these genetic factors indicated that defects in vesicular transport pathways, endo-lysosomal dysfunction, impaired autophagy-lysosomal protein and organelle degradation pathways, α-synuclein aggregation and mitochondrial dysfunction play key roles in PD pathogenesis. Moreover, membrane dynamics are increasingly recognized as a key player in the disease pathogenesis due lipid homeostasis alterations, associated with lysosomal dysfunction, caused by mutations in several PD and APS genes. The importance of lysosomal dysfunction and lipid homeostasis is strengthened by both genetic discoveries and clinical epidemiology of the association between parkinsonism and lysosomal storage disorders (LSDs), caused by the disruption of lysosomal biogenesis or function. A synergistic coordination between vesicular trafficking, lysosomal and mitochondria defects exist whereby mutations in PD and APS genes encoding proteins primarily involved one PD pathway are frequently associated with defects in other PD pathways as a secondary effect. Moreover, accumulating clinical and genetic observations suggest more complex inheritance patters of familial PD exist, including oligogenic and polygenic inheritance of genes in the same or interconnected PD pathways, further strengthening their synergistic connection.Here, we provide a comprehensive overview of PD and APS genes with functions in vesicular transport, lysosomal and mitochondrial pathways, and highlight functional and genetic evidence of the synergistic connection between these PD associated pathways.


Ethnic differences in current smoking and former smoking in the Netherlands and the contribution of socioeconomic factors: a cross-sectional analysis of the HELIUS study.
Data exploring how much of the ethnic differences in smoking prevalence and former smoking are explained by socioeconomic status (SES) are lacking. We therefore assessed ethnic differences in smoking prevalence and former smoking and the contribution of both educational level and occupational-related SES to the observed ethnic differences in smoking behaviour. Data of 22 929 participants (aged 18-70 years) from the multiethnic cross-sectional Healthy Life in an Urban Setting study in the Netherlands were analysed. Poisson regression models with a robust variance were used to estimate prevalence ratios. Compared with the Dutch, after adjustment for age and marital status, smoking prevalence was higher in men of Turkish (prevalence ratio 1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women, smoking prevalence was higher in Turkish, similar in African Surinamese but lower in all other ethnic origin groups. All ethnic minority groups, except Ghanaians, had a significantly lower smoking cessation prevalence than the Dutch. Socioeconomic gradients in smoking (higher prevalence among those lower educated and with lower level employment) were observed in all groups except Ghanaian women (a higher prevalence was observed in the higher educated). Ethnic differences in smoking prevalence and former smoking are largely, but not completely, explained by socioeconomic factors. Our findings imply that antismoking policies designed to target smoking within the lower socioeconomic groups of ethnic minority populations may substantially reduce ethnic inequalities in smoking particularly among men and that certain groups may benefit from targeted smoking cessation interventions.


Model for Wireless Magnetoelastic Strain Sensors.
This paper describes a magnetoelastic strain sensor based on the ∆E effect and discusses some materials used in its construction. A polycrystalline Fe-Al-B alloy with good quality magnetoelastic properties was used as the transducer and glued to the test object, either brass plates or rods of SAE 1010 steel. The strain-dependent magnetic field of the transducer changes the operating point of the resonator, a strip of field-annealed Metglas 2826MB3, resulting in a modification of its resonant frequency. A model was developed to simulate the strain-dependent magnetic field acting on the resonator and thus to calculate curves of resonant frequency vs. deformation. With the help of this model, differences in the shape of the frequency vs. strain curve can be understood. For a sensor with resonant frequency of 60.5 kHz glued to a rod of SAE 1010 steel, a total resonant frequency variation ∆f ~7 kHz was observed for a deformation of 1100 ppm. The geometry of this sensor is especially favorable for the remote monitoring of a steel surface, such as the wires of the tensile armor of a marine riser.


Pattern of calbindin-D28k and calretinin immunoreactivity in the brain of Xenopus laevis during embryonic and larval development.
The present study represents a detailed spatiotemporal analysis of the localization of calbindin-D28k (CB) and calretinin (CR) immunoreactive structures in the brain of Xenopus laevis throughout development, conducted with the aim to correlate the onset of the immunoreactivity with the development of compartmentalization of distinct subdivisions recently identified in the brain of adult amphibians and primarily highlighted when analyzed within a segmental paradigm. CR and CB are expressed early in the brain and showed a progressively increasing expression throughout development, although transient expression in some neuronal subpopulations was also noted. Common and distinct characteristics in Xenopus, as compared with reported features during development in the brain of mammals, were observed. The development of specific regions in the forebrain such as the olfactory bulbs, the components of the basal ganglia and the amygdaloid complex, the alar and basal hypothalamic regions, and the distinct diencephalic neuromeres could be analyzed on the basis of the distinct expression of CB and CR in subregions. Similarly, the compartments of the mesencephalon and the main rhombencephalic regions, including the cerebellum, were differently highlighted by their specific content in CB and CR throughout development. Our results show the usefulness of the analysis of the distribution of these proteins as a tool in neuroanatomy to interpret developmental aspects of many brain regions.


The historical experience and practice of fight against tuberculosis in country which is one of the high drug resistant-tuberculosis (DR-TB) burden countries in European Union (EU).
Despite considerable efforts and quite early initiated anti-tuberculosis (TB) actions, Lithuania still remains one of the European Union (EU) countries with the highest tuberculosis rates, especially multidrug-resistant (MDR) TB. According to the European Centre for Disease Prevention and Control, in 2016, 58 994 cases of TB were reported in 30 EU/European Economic Area (EEA) countries. MDR TB was reported for 3.7% of 36 071 cases with drug susceptibility testing results and continues to be highest in the three Baltic countries - Estonia, Latvia and Lithuania. In this article we present the Lithuanian anti-TB action history review and comparison with other countries in this area of action. Literature review was performed by using documents available in the Martynas Mazvydas Library's resource, articles of foreign authors and archival materials. According to archaeological studies, tuberculosis was common in Europe including Lithuania in the Middle Ages. Tuberculosis reporting started in Lithuania in 1926. The first tuberculosis sanatorium in Lithuania was opened in 1891. Patients were treated with sun bathing procedures, fresh air and sunlight. Later the treatment included pneumothorax, toracocaustic, toracoplastic, treatment with gold products and other procedures. Lithuania introduced directly observed treatment, short course therapy (DOTS) in 1999, and since 2007 it has been working in accordance with the requirements of this strategy.


An elderly patient who developed spontaneous spinal epidural hematoma during warfarin therapy.
Spontaneous spinal epidural hematoma (SSEH) is an uncommon but clinically important disease, and delayed diagnosis of this condition can have severe consequences. General physicians should consider the possibility of SSEH when they encounter a patient with a sudden onset of unexplained cervical or back pain or subsequent radicular symptoms during anticoagulant therapy. Immediate magnetic resonance imaging is essential for early diagnosis. In this article, we present a rare case of an 80-year-old man who developed cervical SSEH during warfarin therapy.


Comparative aspects of cell osmoregulation and volume control.
This brief overview considers the mechanisms of adaptation of animal cells to anisosmotic media in the framework of a comparative approach. Successful adaptation of animal cells to abrupt changes in the NaCl content of their environment depends on (1) mechanisms of osmolality and volume control and (2) the use of different organic molecules acting as 'compensatory osmolytes'. Up to now, the importance of this last process has been largely underestimated. It concerns the use of different organic osmolytes, aminocompounds and carbohydrates which can oppose or 'compensate for' the disrupting effects that changes in the intracellular level of inorganic ions can have on the organization and activity of different macromolecular structures. Contrarily to the cells of euryhaline invertebrates, most mammalian cells seem to lack the possibility to regulate effectively their content of organic compensatory solutes. Despite the presence of effective mechanisms of cell volume and osmolality control, they thus adapt only with difficulty to abrupt changes in the NaCl level of their environment. An interesting exception is the kidney medulla in which papillary cells seem to control easily the level of some selected amino compounds and carbohydrates. The use of these compensatory osmolytes enables them to cope with the rapid and sometimes important modifications in the NaCl level they are normally withstanding.


Sub-Doppler infrared spectroscopy of CH2OH radical in a slit supersonic jet: Vibration-rotation-tunneling dynamics in the symmetric CH stretch manifold.
The sub-Doppler CH-symmetric stretch (ν3) infrared absorption spectrum of a hydroxymethyl (CH2OH) radical is observed and analyzed with the radical formed in a slit-jet supersonic discharge expansion (Trot = 18 K) via Cl atom mediated H atom abstraction from methanol. The high sensitivity of the spectrometer and reduced spectral congestion associated with the cooled expansion enable first infrared spectroscopic observation of hydroxymethyl transitions from both ± symmetry tunneling states resulting from large amplitude COH torsional motion. Nuclear spin statistics due to exchange of the two methyl H-atoms aid in unambiguous rovibrational assignment of two A-type Ka = 0 ← 0 and Ka = 1 ← 1 bands out of each ± tunneling state, with additional spectral information obtained from spin-rotation splittings in P, Q, and R branch Ka = 1 ← 1 transitions that become resolved at low N. A high level ab initio potential surface (CCSD(T)-f12b/cc-pvnzf12 (n = 2,3)/CBS) is calculated in the large amplitude COH torsional and CH2 wag coordinates, which in the adiabatic approximation and with zero point correction predicts ground state tunneling splittings in good qualitative agreement with experiment. Of particular astrochemical interest, a combined fit of the present infrared ground state combination differences with recently reported millimeter-wave frequencies permits the determination of improved accuracy rotational constants for the ground vibrational state, which will facilitate ongoing millimeter/microwave searches for a hydroxymethyl radical in the interstellar medium.


Sarcomatoid squamous cell carcinoma of the uterine cervix with osteoclast-like giant cells: report of two cases.
Two postmenopausal women with sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix are described. This report brings the total number of reported SSCCs in the lower female genital tract to 11. The gross and microscopic features of our SSCCs were similar to those of SSCCs in the digestive and upper respiratory tracts with the additional finding of osteoclast-like giant cells in each case. The behaviour and differential diagnosis of these tumors are briefly discussed.


Extracellular Vesicles from Fresh and Dried Plants-Simultaneous Purification and Visualization Using Gel Electrophoresis.
Although animal-derived extracellular vesicles (EVs) are moving increasingly into scientific focus, EVs from other kingdoms remain underestimated and our knowledge of them is still expandable, probably due to the lack of an easy and broadly executable isolation, purification and visualization method. Using differential centrifugation with subsequent agarose gel electrophoresis, we were able to simplify the terms of EV isolation. EVs from Nicotiana tabacum L., Vinca minor L., and Viscum album L. were purified, even though they did not migrate into the gel matrix. If 3,3- Dihexyloxacarbocyanine iodide (DiOC 6 ) is added to the specimen in excess, membranous components can already be detected by eye, or with higher sensitivity, using a UV transilluminator. The sample preparation can be adjusted to the EV species of interest. Moreover, EVs are separated from small charged contaminants and dye excess, because these impurities can pass the gel matrix, while EVs themselves are retained in the pocket. Significantly, we isolated EVs from dried plant material, which is-to our knowledge-the first proof that EVs are stable enough to overcome the drying process of plant material.


Prevalence of serotype and multidrug-resistance of Streptococcus pneumoniae respiratory tract isolates in 265 adults and 36 children in Korea, 2002-2005.
In total, 301 isolates of Streptococcus pneumoniae collected from patients with respiratory tract infections admitted at primary clinics during 2002-2005 were tested for multidrug-resistance (MDR) phenotypes and their serotypes in Korea. The predominant serotypes were 19F, 19A, 23F, 11A, 3, 6A, and 6B, accounting for 67.8% of all isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 73.1% and 39.2%, respectively. For the application of Clinical and Laboratory Standards Institute's new breakpoint for penicillin, the resistance rate of penicillin was 27.9% (but the penicillin resistance was 80.4% based on the previous breakpoint for penicillin of Clinical and Laboratory Standards Institute). Actually, the full resistance rate was only 4.0% (minimum inhibitory concentration >or=8 mg/L). Resistances to erythromycin, clindamycin, and tetracycline were very high (82.9%, 79.4%, and 71.7%, respectively). Especially, 56.1% of all the isolates were MDR, defined as resistant to three or more of the following agents: penicillin, erythromycin, clindamycin, cefotaxime, tetracycline, and levofloxacin. MDR strains were relatively associated with serotypes 19F, 19A, 23F, and 11A, accounting for 58.0% of the isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 79.5% and 45.9%, respectively. Levofloxacin, as a representative fluoroquinolone, was active against 88.2% of all MDR isolates. Of particular concern was the high prevalence of MDR pneumococci in non-PCV7 serotypes with an MDR serotype 19A, 11A, 3, and 6A being mostly responsible. It would be prudent to consider more efficient protective strategies for people at high risk for pneumococcal diseases in regions with a high prevalence of MDR pneumococci.


Digital planning workflow for partial maxillectomy using an osteotomy template and immediate rehabilitation of maxillary Brown II defects with prosthesis.
There is increasing evidence of benefits for the rehabilitation of Brown II defects with prosthesis in surgery. However, the current literature is sparse for maxillary tumour resection using osteotomy templates. To assess the accuracy of maxillectomy using a custom fabricated osteotomy template and to evaluate the prosthesis for surgical accuracy, appearance and functioning (speech, swallowing and occlusal force). Ten patients with Brown II defects caused by tumour resection were treated with precise partial maxillectomy using an osteotomy template. The immediate rehabilitation of the Brown II defect was completed with a prefabricated prosthesis. The post-operative three-dimensional images and the pre-operative virtual images were superimposed, and average deviation and maximum deviation were calculated. Speech intelligibility, swallowing, appearance and University of Washington Quality of Life Questionnaire (UW-QoL) were examined at 1, 3 and 6 months after surgery. Occlusal force was examined post-operatively at 6 months. The maximum deviation between the actual and virtual surgery was 5.12 ± 0.44 mm, with an average of 1.02 ± 0.17 mm. Speech intelligibility, swallowing and UW-QoL improved significantly (P < .05) after wearing the prosthesis. The recovery index of the occlusal force on the affected side was 20.19%-32.28%. The skewed degree of the mouth corner, the difference in the height of the left and right lips, the maximum deviation distance and the change area volume decreased significantly (P < .05). The precise rehabilitation of maxillary Brown II defects can be achieved using a prosthesis fabricated with an osteotomy template. The prosthesis restored appearance and functional capabilities (such as speech and occlusal force).


Workload of official contests, net cost of transport, and metabolic power of Mangalarga Marchador horses of marcha batida or picada gaits.
This study aimed to characterize the maximum heart rate (HR) and the intensity of official marcha contests (OMC) and to compare the cost of transport (COT) and metabolic power (Pmet) of Mangalarga Marchador (MM) horses of marcha batida (MB) and marcha picada (MP) gaits. Twenty-two MM horses participated in this study. The experiment was conducted in 3 phases: 1) maximum effort test (MET), 2) OMC, and 3) standardized marcha test (SMT). To characterize the HR, 19 horses (14 MB and 5 MP) underwent a MET. Of those, 13 (9 MB and 4 MP) were monitored during the OMC, which consisted of 4 stages: marcha, walk, functional trial, and rest. The average heart rate (HR) in each stage of the OMC was related to the HR to determine their relative intensity. The SMT was performed with 14 horses (9 MB and 5 MP), of which 11 had already participated in the previous stages. The COT and Pmet were calculated from the HR values obtained during the SMT. Blood samples were collected to analyze plasma lactate concentration ([Lac]). One-way ANOVA or 1-way repeated-measures ANOVA followed by the Tukey's test ( < 0.05) were used to analyze the results. The average HR was 211 ± 11 and 214 ± 11 beats/min (bpm) for the MB and MP groups, respectively, with no difference ( = 0.7066) between them. The [Lac] increased as a result of the MET ( < 0.05), with no difference between groups ( > 0.05). This indicated that horses of both groups had the same physical fitness levels. The OMC stages defined in our study differed ( < 0.05) regarding the relative intensity of the HR, except for the walk and standing stages, which were similar ( = 0.0875). The MP group presented greater COT ( = 0.0247) and Pmet ( = 0.0193). It can be concluded that the mean HR of MM horses (MB and MP) is 212 ± 11 bpm. The OMC of the MM breed can be characterized as an effort of intermittent and submaximal intensity. In addition, the locomotion of the MB horses is probably more energetically efficient than that of MP horses.


Cognitive Correlates of Developmental Surface Dyslexia: A Single Case Study.
Recently, there have been several reports of developmental analogues of the specific orthographic processing deficits observed in acquired surface dyslexics (Goulandris & Snow ling, 1991; Hanley, Hastie, & Kay, 1992). How ever, very little has been discovered about w hat basic cognitive deficits might be associated w ith this particular kind of reading disorder. This paper describes the case of MI, a 10-year-old boy w ith a high IQ and no known history of neurological impairment. He demonstrates extremely poor performance for his age and reading level on irregular word reading tasks, but performs normally on nonword and regular word tasks. His performance on a series of homophone selection tasks suggests an impairment at the orthographic input level. The results of various tests of associated cognitive abilities conducted on MI suggest that this impairment is not associated either with phonological awareness deficits or with the visual memory problems proposed by Goulandris and Snowling (1991).


Polar expression of tissue factor in human umbilical vein endothelial cells.
Endothelial cells grown on filters developed junctional complexes that reduced diffusional transport and increased electrical resistance over the cell layer. Induction of tissue factor by recombinant interleukin-1 beta led to a highly polarized tissue factor expression on the apical cell surface only. After prolonged growth to allow deposition of matrix, removal of the endothelial cells by collagenase or by 0.1 mol/L NH4OH left behind some cellular material as well as tissue factor, which was only detectable in the upper compartment. A human bladder carcinoma cell line, which does not form tight junctions and expresses tissue factor constitutively, showed essentially no polarity. Endothelial cell secretory compounds like von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 were constitutively released to both sides. The added secretion due to recombinant interleukin-1 beta stimulation of the endothelial cells observed for von Willebrand factor and tissue plasminogen activator was, however, localized to the apical surface. The availability of tissue factor on the luminal surface of endothelial cells, ie, allowing contact with factor VII in the flowing blood, has potentially very significant pathophysiological consequences.


Ground state cooling of an optomechanical resonator assisted by a Λ-type atom.
We propose a ground state cooling scheme for an optomechanical resonator based on the system of one Λ-type three-level atom trapped in an optomechanical cavity. This cooling scheme works in a single-photon coupling, and strong atom-cavity coupling regimes. By investigating the cooling dynamics, we find that there is an EIT-like quantum coherent effect in this system which can suppress the undesired transitions for heating. Moreover, our study shows that the final average phonon number of the optomechanical resonator can be smaller than the one based on the sideband cooling. Furthermore, the ground state cooling of the resonator can still be achieved after thermal fluctuations included. In addition, in comparison with previous cooling methods, there are fewer limitations on the decay rates of both the cavity and the atom in this scheme. As a result, this scheme is very suitable to realize the ground cooling of an optomechanical resonator in the experiment.


Depression Prevalence in Neuropathic Pain and Its Impact on the Quality of Life.
The management of neuropathic pain remains complex, generally because of the psychiatric comorbidity that is often underdiagnosed. The objectives of our work were to determine the link between depression and the characteristics of NP on the one hand and quality of life on the other hand, in a sample of subjects consulting for neuropathic pain (NP) regardless of etiology. We conducted a cross-sectional study involving 61 neuropathic pain consulting patients in whom we assessed five parameters, namely, neuropathic pain based on DN4, pain intensity using EVA, anxiety, and depression according to the HADS and quality of life. The study population mean age was 52.71 ± 14.29 years while the sex ratio (m/f) was 0.52. The neuropathic pain's most common etiologies were postherpetic pain, carpal tunnel syndrome, and diabetic neuropathy. Depression and anxiety prevailed by 65.6% and 73.7%, respectively. The quality of life was impaired with average SF-12 physical and mental scores of 33.76 ± 8.03 and 37.78 ± 11.52, respectively. The overall mean BPI score was 5.53 ± 1.76. Patients with high DN4 scores were significantly more depressed (p=0.025). A significantly positive association was found between the depression score and the pain intensity (p=0.001, r = 0.41). Depressed subjects had a poor quality of life according to SF-12 and BPI. Given the depressive comorbidity impact on the neuropathic pain components as well as the quality of life, screening for this comorbidity should be part of the baseline ND assessment.


[A case of allergic granulomatous angitis with beneficial effects of plasma exchange].
A 54-year-old man had suffered from bronchial asthma, followed by numbness and muscle weakness of the extremities. He was admitted to our department in July, 1994, because of progression of the symptoms. On admission, neurological examination revealed muscle weakness with atrophy and sensory disturbance of multiple mononeuritic type. Blood tests revealed eosinophilia and an increase in rheumatoid factor, IgE levels and P-ANCA. A sural nerve biopsy showed necrotizing vasculitis and inflammation with eosinophil infiltration. The patient was diagnosed as having allergic granulomatous angitis,and treated with steroid pulse therapy without beneficial effect. Plasma exchange was performed twice, which resulted in remarkable improvement in motor and sensory disturbance. The present case suggests that plasma exchange has beneficial effects on severe cases with allergic granulomatous angitis.


Efficient Monitoring of Treatment Response during Youth Psychotherapy: The Behavior and Feelings Survey.
An emerging trend in youth psychotherapy is measurement-based care (MBC): treatment guided by frequent measurement of client response, with ongoing feedback to the treating clinician. MBC is especially needed for treatment that addresses internalizing and externalizing problems, which are common among treatment-seeking youths. A very brief measure is needed, for frequent administration, generating both youth- and caregiver-reports, meeting psychometric standards, and available at no cost. We developed such a measure to monitor youth response during psychotherapy for internalizing and externalizing problems. Across 4 studies, we used ethnically diverse, clinically relevant samples of caregivers and youths ages 7-15 to develop and test the Behavior and Feelings Survey (BFS). In Study 1, candidate items identified by outpatient youths and their caregivers were examined via an MTurk survey, with item response theory methods used to eliminate misfitting items. Studies 2-4 used separate clinical samples of youths and their caregivers to finalize the 12-item BFS (6 internalizing and 6 externalizing items), examine its psychometric properties, and assess its performance in monitoring progress during psychotherapy. The BFS showed robust factor structure, internal consistency, test-retest reliability, convergent and discriminant validity in relation to three well-established symptom measures, and slopes of change indicating efficacy in monitoring treatment progress during therapy. The BFS is a brief, free youth- and caregiver-report measure of internalizing and externalizing problems, with psychometric evidence supporting its use for MBC in clinical and research contexts.


An Integrative Review of the Barriers to Job Acquisition for People With Severe Mental Illnesses.
This integrative review analyses and synthesizes specialized literature of 20 years up to 2017 studying barriers/obstacles to employment for people with severe mental illnesses. The inclusion and exclusion criteria led to 35 experimental and nonexperimental studies. Results of the prospective studies were analyzed with the evidence synthesis method to isolate the most salient obstacles. Six main themes emerged from the findings, grouped into personal and environmental barriers. Environmental barriers were related to disability benefits and other physical resources, to stigma and social support, and to vocational services. Individual barriers included those related to illness, to work experience and skills, and to self-perception, fears, and motivation. The most prominent obstacles are lack of work experience and lack of use of effective strategies toward employment. Systematically identifying barriers to employment for people with severe mental illnesses will enable employment specialists to better support their clients in overcoming them, thus facilitating their work integration.


Impact of surgical ventricular restoration on early and long-term outcomes of patients with left ventricular aneurysm: A single-center experience.
Left ventricular aneurysm (LVA) is a common complication of myocardial infarction. However, the optimal treatment for LVA remains controversial.In this retrospective study, we analyzed the early and long-term clinical consequences of surgical ventricular restoration on 102 patients who had undergone repair between January, 2005 and January, 2015. The LVA repair approaches comprised of patch plasty (n = 28), linear repair (n = 40), and plication repair (n = 34).Patient demographics were 60.8% male, and the mean age was 60.5 ± 7.2 years. The in-hospital mortality rate was 7.8% (8/102), including 6 patients who died from low cardiac output and 2 from multiorgan failure. During the early postoperative period, left ventricular sizes significantly decreased in the patch plasty and linear repair groups compared with the plication group. In addition, all 3 repair techniques greatly ameliorated left ventricular ejection fraction (P < .05), and there was no significant difference in survival rate between groups (P = .25).Surgical ventricular restoration (linear repair, plication repair, and patch plasty) obtained equivalently appreciable outcomes for cardiac function improvement, perioperative mortality, and survival. Selection of a surgical technique for LVA patients should be optimized to individual patient conditions including the morphological characteristics of the aneurysm and ischemic scar.


Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase, bovine alpha-chymotrypsin and subtilisin Carlsberg: thermodynamic study.
The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase (EC 220.127.116.11), bovine alpha-chymotrypsin (EC 22.214.171.124) and subtilisin Carlsberg (EC 184.108.40.206) has been investigated. On lowering the pH from 9.5 to 4.5, values of Ka for eglin c binding to the serine proteinases considered decrease thus reflecting the acid-pK shift of the invariant histidyl catalytic residue (His57 in human leukocyte elastase and bovine alpha-chymotrypsin, and His64 in subtilisin Carlsberg) from congruent to 6.9, in the free enzymes, to congruent to 5.1, in the enzyme:inhibitor adducts. At pH 8.0, values of the apparent thermodynamic parameters for eglin c binding are: human leukocyte elastase - Ka = 1.0 x 10(10) M-1, delta G phi = -13.4 kcal/mol, delta H phi = +1.8 kcal/mol, and delta S phi = +52 entropy units; bovine alpha-chymotrypsin -Ka = 5.0 x 10(9) M-1, delta G phi = -13.0 kcal/mol, delta H phi = +2.0 kcal/mol, and delta S phi = +51 entropy units; and subtilisin Carlsberg - Ka = 6.6 x 10(9) M-1, delta G phi = -13.1 kcal/mol, delta H phi = +2.0 kcal/mol, and delta S phi = +51 entropy units (values of Ka, delta G phi and delta S phi were obtained at 21 degrees C; values of delta H phi were temperature independent over the range explored, i.e. between 10 degrees C and 40 degrees C; 1 kcal = 4184J).(ABSTRACT TRUNCATED AT 250 WORDS)


Joint effect of selection, linkage and partial inbreeding on additive genetic variance in an infinite population.
Under the inifinitesimal model of gene effects, selection reduces the additive genetic variance by inducing negative linkage disequilibrium among selected genes. If the selected genes are linked, the decay of linkage disequilibrium is delayed, and the reduction of additive genetic variance is enhanced. Inbreeding in an infinite population also alters the additive genetic variance through the generation of positive association among genes within a locus. In the present study, the joint effect of selection, linkage and partial inbreeding (partial selfing or partial full-sib mating) on the additive genetic variance was modeled. The recurrence relations of the additive genetic variance between successive generations and the prediction equation of the asymptotic additive genetic variance were derived. Numerical computation showed that although partially inbred populations initially maintain larger genetic variances, the accumulated effect of selection overrides the effect of inbreeding. Stochastic simulation was carried out to check the precision of prediction, showing that the obtained equations give a satisfactory prediction during initial generations. However, the predicted values always overestimate the simulated values, especially in later generations. Based on these results, possible extensions and perspectives of the assumed model were discussed.


A penalty of using anonymous dominant markers (AFLPs, ISSRs, and RAPDs) for phylogenetic inference.
AFLPs (and to a lesser extent ISSRs and RAPDs) are increasingly being used for phylogenetic inference among closely related species. Presence/absence characters for each AFLP allele treat all absences as homologous to one another. With three or more alleles, terminals are grouped by their shared absence of alleles in character-based phylogenetic-inference methods in a manner that is not redundant with their shared presence of an alternative allele. We conducted simulations to quantify how severe the negative effect of using presence/absence characters of individual bands is for phylogenetic inference relative to standard multistate characters. We examined alternative tree topologies, relative branch lengths, numbers of characters, rates of evolution, and numbers of alternative alleles, using both parsimony and Nei-and-Li distance analyses. Multistate parsimony generally outperformed presence/absence parsimony, which in turn outperformed Nei-and-Li distance. Increasing the character-state space (i.e., the number of alternative character states available) was found to be advantageous for all three methods of analysis examined, but was most advantageous for multistate parsimony. However, the advantage of multistate parsimony relative to Nei-and-Li distance decreased when applied to more divergent characters. More parsimony-informative variation generally alleviated the problem associated with scoring multistate characters as presence/absence characters. The ensemble consistency index was lower for presence/absence characters relative to multistate characters.


Iatrogenic Lumbar Vertebral Fracture during Osteosynthesis for a Trochanteric Fracture of the Femur in Diffuse Idiopathic Skeletal Hyperostosis.
Vertebral fractures occur with only slight trauma in patients with diffuse idiopathic skeletal hyperostosis (DISH). However, a lumbar vertebra fracture, due to an intraoperative body position has not been previously reported. An 87-year-old woman with kyphosis sustained a left trochanteric fracture of her femur. The patient was placed in a supine position during the operation. Postoperatively, the patient experienced severe right thigh pain. Magnetic resonance imaging revealed an L4 vertebral fracture. Computed tomography revealed ankylosis from the upper thoracic spine to the sacrum. While in a supine position under general anesthesia, the contact of the patient's lower back with operating table likely created a fulcrum at her lumbosacral spine acting as a long lever arm, bearing the mass of her upper body. We performed L1-S2 posterior stabilization. DISH patients with kyphosis placed in a supine position have an increased risk for lumbar vertebral fracture.


Iron deficiency anemia in pregnancy.
Anemia is the most frequent derailment of physiology in the world throughout the life of a woman. It is a serious condition in countries that are industrialized and in countries with poor resources. The main purpose of this manuscript is to give the right concern of anemia in pregnancy. The most common causes of anemia are poor nutrition, iron deficiencies, micronutrients deficiencies including folic acid, vitamin A and vitamin B12, diseases like malaria, hookworm infestation and schistosomiasis, HIV infection and genetically inherited hemoglobinopathies such as thalassemia. Depending on the severity and duration of anemia and the stage of gestation, there could be different adverse effects including low birth weight and preterm delivery. Treatment of mild anemia prevents more severe forms of anemia, strictly associated with increased risk of fetal-maternal mortality and morbidity.


Behavioral Health Risk Factors for Nonmedical Prescription Opioid Use in Adolescence.
Adolescent nonmedical prescription opioid use is associated with overdose and other adverse outcomes, but its risk factors are poorly understood. Data were drawn from a prospective cohort study of Los Angeles, California, high school students. At baseline (mean age = 14.6 years), students completed self-report screening measures of problem alcohol, cannabis, and drug use and 6 mental health problems (major depression, generalized anxiety, panic disorder, social phobia, obsessive-compulsive disorder, and hypomania or mania). Past 6-month nonmedical prescription opioid use (yes or no) was assessed across 7 semiannual follow-ups. Among baseline never users of nonmedical prescription opioids (N = 3204), average past 6-month prevalence of new nonmedical prescription opioid use across the 42-month follow-up was 4.4% (range 3.5%-6.1%). In a multivariable model co-adjusting for 9 baseline behavioral problems and other factors, major depression, hypomania or mania, cannabis, alcohol, and other drug use problems were associated with increased odds of nonmedical prescription opioid use over follow-ups. Cumulative indices of behavioral health comorbidity showed successively greater odds of subsequent nonmedical prescription opioid use for students with 1 (odds ratio [OR]: 3.74; 95% confidence interval [CI]: 2.79-5.01), 2 (OR: 8.79; 95% CI: 5.95-12.99), or 3 (OR: 9.69; 95% CI: 5.63-16.68) vs 0 baseline substance use problems, and similar increases were associated with increasing number of mental health problems (1 [OR: 1.60; 95% CI: 1.03-2.88] to all 6 [OR: 3.98; 95% CI: 1.09-14.82] vs 0). Behavioral health problems may be associated with increased risk of subsequent nonmedical prescription opioid use during mid to late adolescence, with successively greater risk for those with greater behavioral health comorbidity. In pediatric clinical practice or school-based prevention, behavioral health screeners may be useful for identifying youth at high risk for nonmedical prescription opioid use.


Fatty acid composition in postmortem brains of people who completed suicide.
Cholesterol levels have been reported to be lower in suicidal patients, and alterations in blood levels of polyunsaturated fatty acids have been found in people with depression. Given that the evidence for the link between lipid metabolism and psychopathology thus far has almost exclusively hinged on alterations of these variables in blood, this study aimed to address whether similar alterations in fatty acids would be evident in the brains of people who complete suicide. Using gas chromatography, we measured 49 different fatty acids in the orbitofrontal cortex and the ventral prefrontal cortex of people who had completed suicide with (n = 16) and without (n = 23) major depression and in control subjects (n = 19) with no current psychopathology and whose cause of death was sudden. Comparisons of fatty acids between the 3 groups did not reveal significant differences. Further research is required to better understand the link between fatty acids in the peripheral circulation and those in the central nervous system before determining whether fatty acids play a mediating role in suicidal behaviour.


Implicit multisensory associations influence voice recognition.
Natural objects provide partially redundant information to the brain through different sensory modalities. For example, voices and faces both give information about the speech content, age, and gender of a person. Thanks to this redundancy, multimodal recognition is fast, robust, and automatic. In unimodal perception, however, only part of the information about an object is available. Here, we addressed whether, even under conditions of unimodal sensory input, crossmodal neural circuits that have been shaped by previous associative learning become activated and underpin a performance benefit. We measured brain activity with functional magnetic resonance imaging before, while, and after participants learned to associate either sensory redundant stimuli, i.e. voices and faces, or arbitrary multimodal combinations, i.e. voices and written names, ring tones, and cell phones or brand names of these cell phones. After learning, participants were better at recognizing unimodal auditory voices that had been paired with faces than those paired with written names, and association of voices with faces resulted in an increased functional coupling between voice and face areas. No such effects were observed for ring tones that had been paired with cell phones or names. These findings demonstrate that brief exposure to ecologically valid and sensory redundant stimulus pairs, such as voices and faces, induces specific multisensory associations. Consistent with predictive coding theories, associative representations become thereafter available for unimodal perception and facilitate object recognition. These data suggest that for natural objects effective predictive signals can be generated across sensory systems and proceed by optimization of functional connectivity between specialized cortical sensory modules.


The clinical value of procalcitonin and neopterin in predicting sepsis and organ failure after major trauma.
We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.


Clinical effects with inhibition of multiple coagulative pathways in patients admitted for acute coronary syndrome.
Platelets and the coagulation cascade play key roles in initiation, amplification, and perpetuation of acute coronary syndromes (ACS). In the past few years, there has been great progress in ACS antithrombotic treatment with the introduction of novel anticoagulants (fondaparinux and bivalirudin), more potent P2Y12 inhibitors (prasugrel and ticagrelor) and protease-activated receptor antagonists (vorapaxar). Nonetheless, patients with ACS frequently have recurrent ischemic events despite the use of currently recommended dual antiplatelet therapy, revascularization procedures as appropriate, and other evidence-based secondary preventive measures. This is the rationale beyond intensification of antiplatelet therapy. However, the major downside of intensive antithrombotic therapy is bleeding. When treating ACS patients, clinicians should find the adequate balance between the reduction of thrombotic events by effective drug treatment and the induction of bleeding that is linked to the use of potent or multiple antithrombotic agents. Numerous antithrombotic cocktails including oral anticoagulants with or without aspirin have been tested in large clinical trials with the goal of further reduction of ischemia and bleeding risk. The aim of this review is to discuss clinical outcomes resulting from inhibition of multiple coagulative pathways in patients with ACS in light of evidence from large randomized controlled clinical trials.


An assessment of current HIV treatment adherence services in the UK.
The aim of this study was to examine current approaches to supporting adherence to antiretroviral therapy in UK HIV clinics. One hundred HIV/AIDS/GUM physicians were interviewed: 97% were personally involved in discussing adherence, spending 22% of consultation time on this issue and assessing adherence most commonly by patient self-report (88%). Other personnel involved included nurses (74%), other doctors (56%), health advisers (54%) and pharmacists (48%). Among criteria for achieving treatment success, adherence support ranked fourth after 'treatment fitting well into patient's lifestyle', regular viral load monitoring and the 'experience of the clinician/healthcare team'. A variety of tools were used to support adherence including dosette boxes (53%), written information (44%) and verbal communication (42%). Only 20% of physicians followed adherence protocols or formal guidelines. Three-quarters of physicians had received no training on adherence issues. The most common ways physicians kept informed about adherence matters were by attending conferences (87%), reading literature (71%) and learning from colleagues (51%). Eighty-seven per cent of physicians believed national adherence guidelines would be valuable. In conclusion, there is a need for training and direction within current adherence support services. National guidelines could provide a valuable framework for health care professionals.


Superior Bactericidal Efficacy of Fucose-Functionalized Silver Nanoparticles against Pseudomonas aeruginosa PAO1 and Prevention of Its Colonization on Urinary Catheters.
Pseudomonas aeruginosa, a Gram-negative rod-shaped bacterium is a notorious pathogen causing chronic infections. Its ability to form antibiotic-resistant biofilm has raised the need for the development of alternative treatment approaches. An ideal alternate can be silver nanoparticles known for their strong yet tunable bactericidal activity. However, their use in commercial in vivo medicine could not see the light of the day because of the unwanted toxicity of silver in the host cells at higher concentrations. Thus, strategies which can modulate the bacterial cell-silver nanoparticle interactions thereby reducing the amount of nanoparticles required to kill a typical number of bacterial cells are utmost welcomed. The current work showcases one such strategy by functionalizing the silver nanoparticles with l-fucose to increase their interactions with the LecB lectins present on P. aeruginosa PAO1. The advantage of this approach lies in the higher bactericidal and antibiofilm activity of fucose-functionalized silver nanoparticles (FNPs) as compared to the citrate-capped silver nanoparticles (CNPs) of similar size and concentrations. The superior bactericidal potential of FNPs as demonstrated by fluorescence-assisted cell sorting, confocal laser scanning microscopy, and transmission electron microscopy analyses may be attributed to the higher reactive oxygen species generation and oxidative membrane damage. Additionally, FNPs prevented the formation of biofilms by downregulating the expression of various virulence genes at lower concentrations as compared to CNPs. The practical applicability of the approach was demonstrated by preventing bacterial colonization on artificial silicone rubber surfaces. These results can be extrapolated in the treatment of catheter-associated urinary tract infections caused by P. aeruginosa. In conclusion, the present work strongly advocates the use of antivirulence targets and their corresponding binding residues for the augmentation of the bactericidal effect of silver nanoparticles.


Bioengineered liposome-scaffold composites as therapeutic delivery systems.
The therapeutic potential of liposomes can be amplified when combined with biomaterial scaffolds. Such configurations overcome the convergent demands of therapies by enabling enhanced delivery, environmental responsiveness and potency. Liposomes benefit from the increased physical and mechanical strength, favorable rheological properties and natural environment conducive to improved tissue formation that scaffolds provide, while enabling biocompatible delivery of hydrophilic and lipophilic compounds that can be further functionalized to achieve targeted delivery. Topical, ocular, oral, nasal and vaginal applications have been explored using various polymer- or nanofiber-based scaffolds. Mechanistic and rheological findings on complexation between biomaterials, liposomes and cargo have led to multimodal systems with tremendous clinical potential. A review of the key developments in bioengineered liposome-scaffold composites is presented in this manuscript.


Persistent arteriolar constriction in microcirculation of the terminal ileum following moderate hemorrhagic hypovolemia and volume restoration.
A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.


[Effects of Dissolved Oxygen on Nutrient Removal Performance and Microbial Community in Low Carbon/Nitrogen Municipal Wastewater Treatment Process].
To explore the effects of dissolved oxygen (DO) on the treatment of low carbon/nitrogen municipal wastewater, this study examined the characteristics of the microbial community in a low carbon source environment. The treatment process was conducted with the aeration area having DO concentrations of 2-3, 1-2, and lower than 1 mg·L-1. The results demonstrated that reduced DO concentration in the aeration area increased the efficiency of the nitrogen removal process by 20.23% and 80.54%, for external and internal carbon sources, respectively. Similarly, the efficiency of internal carbon source utilization in the phosphorus removal process increased by 13.89%, thus enhancing the nutrient removal efficiency of the low carbon/nitrogen wastewater treatment system. High-throughput sequencing and RDA analysis showed that reduced oxygen concentration motivated an adjustment in microbial community structure, causing functional microorganisms (i.e., Dechloromonas) to become dominant. In addition, the upregulation of genes associated with energy production and conversion, signal transduction, substrate transport, and metabolism provided favourable nutritional conditions for the proliferation of functional microorganisms in low carbon source conditions. This study provides a theoretical basis for improving the growth of microorganisms involved in the nutrient removal process when treating low carbon/nitrogen municipal wastewater.


Succession of bacterial community structure and diversity in soil along a chronosequence of reclamation and re-vegetation on coal mine spoils in China.
The growing concern about the effectiveness of reclamation strategies has motivated the evaluation of soil properties following reclamation. Recovery of belowground microbial community is important for reclamation success, however, the response of soil bacterial communities to reclamation has not been well understood. In this study, PCR-based 454 pyrosequencing was applied to compare bacterial communities in undisturbed soils with those in reclaimed soils using chronosequences ranging in time following reclamation from 1 to 20 year. Bacteria from the Proteobacteria, Chloroflexi, Actinobacteria, Acidobacteria, Planctomycetes and Bacteroidetes were abundant in all soils, while the composition of predominant phyla differed greatly across all sites. Long-term reclamation strongly affected microbial community structure and diversity. Initial effects of reclamation resulted in significant declines in bacterial diversity indices in younger reclaimed sites (1, 8-year-old) compared to the undisturbed site. However, bacterial diversity indices tended to be higher in older reclaimed sites (15, 20-year-old) as recovery time increased, and were more similar to predisturbance levels nearly 20 years after reclamation. Bacterial communities are highly responsive to soil physicochemical properties (pH, soil organic matter, Total N and P), in terms of both their diversity and community composition. Our results suggest that the response of soil microorganisms to reclamation is likely governed by soil characteristics and, indirectly, by the effects of vegetation restoration. Mixture sowing of gramineae and leguminosae herbage largely promoted soil geochemical conditions and bacterial diversity that recovered to those of undisturbed soil, representing an adequate solution for soil remediation and sustainable utilization for agriculture. These results confirm the positive impacts of reclamation and vegetation restoration on soil microbial diversity and suggest that the most important phase of microbial community recovery occurs between 15 and 20 years after reclamation.


Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy.
Peripheral radiation can have deleterious effects on normal tissues throughout the body, including secondary cancer induction and cataractogenesis. The aim of this study is to evaluate the peripheral dose received by various regions of the body after ocular treatment delivered with the Model C Gamma Knife, proton radiotherapy with a dedicated ocular beam employing no passive-scattering system, or a CyberKnife unit before and after supplemental shielding was introduced. TLDs were used for stray gamma and x-ray dosimetry, whereas CR-39 dosimeters were used to measure neutron contamination in the proton experiments. Doses to the contralateral eye, neck, thorax and abdomen were measured on our anthropomorphic phantom for a 56 Gy treatment to a 588 mm(3) posterior ocular lesion. Gamma Knife (without collimator blocking) delivered the highest dose in the contralateral eye, with 402-2380 mSv, as compared with 118-234 mSv for CyberKnife pre-shielding, 46-255 mSv for CyberKnife post-shielding and 9-12 mSv for proton radiotherapy. Gamma Knife and post-shielding CyberKnife delivered comparable doses proximal to the treatment site, with 190 versus 196 mSv at the thyroid, whereas protons doses at these locations were less than 10 mSv. Gamma Knife doses decreased dramatically with distance from the treatment site, delivering only 13 mSv at the lower pelvis, comparable to the proton result of 4 to 7 mSv in this region. In contrast, CyberKnife delivered between 117 and 132 mSv to the lower pelvis. In conclusion, for ocular melanoma treatments, a proton beam employing no double scattering system delivers the lowest peripheral doses proximally to the contralateral eye and thyroid when compared to radiosurgery with the Model C Gamma Knife or CyberKnife. At distal locations in the pelvis, peripheral doses delivered with proton and Gamma Knife are of an order of magnitude smaller than those delivered with CyberKnife.


Mindfulness-based cognitive therapy in COPD: a cluster randomised controlled trial.
A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) entering pulmonary rehabilitation (PR) report psychological distress, which is often accompanied by poor physical health status. Mindfulness-based cognitive therapy (MBCT) has been shown to improve psychological and physical outcomes in other chronic diseases. We therefore evaluated the efficacy of MBCT as an add-on to a standard PR programme in COPD.COPD patients eligible for PR were cluster randomised to receive either an 8-week, group-based MBCT programme as an add-on to an 8-week PR programme (n=39), or PR alone (n=45). The primary outcomes of psychological distress and physical health status impairment were measured with the Hospital Anxiety and Depression Scale (HADS) and the COPD Assessment Test (CAT) before randomisation (T1), mid- (T2) and post-intervention (T3), and at 3 (T4) and 6 (T5) months' follow-up .A statistically significant time×arm effect was found for the HADS (Cohen's d=0.62, 95% CIs (d)=0.18-1.06, p=0.010). The treatment effect on the CAT failed to reach statistical significance (d=0.42, 95% CIs (d)=-0.06-0.90, p=0.061).MBCT showed a statistically significant and durable effect on psychological distress, indicating that MBCT may be an efficacious add-on to standard PR programmes in COPD.