Assessment of nasalance and nasality in patients with a repaired cleft palate.
In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView®, we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.


Autologous vein transplantation for correction of dermal atrophic changes.
Many filling substances are useful in correcting dermal defects and/or wrinkles. To describe a novel autologous dermal implant. Unwanted leg/hand veins and/or varicose veins are extracted in an ambulatory phlebectomy technique. The veins are then either chopped into pieces and injected into the defect or inserted whole after cellular destruction with 23.4% hypertonic saline. Excellent correction of dermal defect has been obtained with long-lasting and possible permanent results. No complications have occurred. Autologous vein collagen transplantation can correct dermal defects with long-lasting and perhaps permanent results.


The Northwestern University Triplet Study. I: Overview of the international literature.
The international literature on triplet births is surveyed. No definitive work on triplet gestations exists. The relatively few articles on this subject are divided into three categories: 1) national data; 2) local, regional or hospital series; 3) case reports. Clinical concerns, such as prematurity, low birth weight, bed rest, and tocolysis, are discussed with specific reference to literature citations.


Targeted regulation and optimization of multifunctional phase transition materials by novel void occupancy engineering.
As an innovative form of stimulus-response materials, organic-inorganic hybrid phase transition materials have become a wonderful contender in the field of functional electronic equipment due to their versatile structure, intensive functions and straightforward preparation. However, the targeted regulation and optimization of the electrical/optical response, along with the establishment of regular structure-performance relationships, pose significant challenges in meeting the diverse demands of practical applications over an extended period. Herein, we conducted a systematic investigation into the role of lattice void occupancy in regulating phase transition temperature (Tp) and related optical/electrical bistability. By taking hybrid material [TMEA][Cd(SCN)3] featuring a flexible ammonium cation [TMEA]+ (TMEA = ethyltrimethylammonium) as the prototype, we successfully synthesized three phase transition materials, namely [DEDMA][Cd(SCN)3], [TEMA][Cd(SCN)3] and [TEA][Cd(SCN)3] (DEDMA = diethyldimethylammonium, TEMA = triethylmethylammonium, and TEA = tetraethylammonium), and the excellent regulation of the physical properties of these compounds was achieved through subtle engineering of void occupancy. More strikingly, [TEA][Cd(SCN)3] exhibits remarkable bistable properties in terms of dielectric and nonlinear optical responses (with second-harmonic generation intensity reaching 2.5 times that of KDP). This work provides a feasible avenue to reasonably customise organic-inorganic hybrid phase transition materials and finely adjust their intriguing functionalities.


ECOLOGICAL DIVERSIFICATION AND COMMUNITY STRUCTURE IN THE OLD WORLD LEAF WARBLERS (GENUS PHYLLOSCOPUS): A PHYLOGENETIC PERSPECTIVE.
I investigated the historical basis for variation in regional species diversity. I used a molecular phylogenetic analysis within a single genus of birds (the Old World leaf warblers, genus Phylloscopus) in conjunction with ecological studies in Europe, the Himalayas, and Japan to evaluate the importance of historical events in shaping the present constellation of morphology and behavior in the three different regions. The relatively depauperate assemblages have different histories. In Japan, there was invasion of several lineages, which have more closely related species elsewhere in Asia, whereas in Europe there was also limited in situ speciation. Much of the structure of peripheral communities is attributable to invasions from species-rich Asia, with little in situ morphological diversification. Within the Phylloscopus there are several phylogenetic clades with nonoverlapping size distributions. Major ecological and morphological shifts occurred early in the history of diversification within the group, and rarely since.


Human β-Defensin-3 is Associated With Platelet-Derived Extracellular Vesicles and is a Potential Contributor to Endothelial Dysfunction.
While platelets are the essential mediators of hemostasis, they are being increasingly recognized for their potential of contributing to host defenses. Here, using immunofluorescent microscopy, western blot, and ELISA, we found that human β-defensin 3 (hBD-3), an important antimicrobial peptide produced by epithelial cells, can be detected in human platelets and megakaryocytes. Flow cytometry and immuno-electron microscopy revealed hBD-3 on the surface of thrombin activated platelets. Moreover, hBD-3 was also found in platelet derived extracellular vesicles (p-EVs), isolated from platelet poor plasma and from platelet supernatants following thrombin stimulation. Incubation of platelets with hBD-3 peptide resulted in modest platelet activation and pre-incubation of platelets with synthetic hBD-3 prior to exposure to thrombin appeared to increase hBD-3 content in platelet lysates as well as in p-EVs, suggesting that hBD-3 can be initially taken up by platelets, perhaps via their open canalicular system. Interestingly, in vitro exposure of primary human endothelial cells to either hBD-3 peptide or purified p-EVs, caused significant endothelial dysfunction as documented by diminished levels of phosphorylated endothelial nitric oxide synthase (eNOS), Krüppel like factor-2 (KLF-2), and elevated relative expression of von Willebrand Factor (vWF). Pre-incubation of platelets with hBD-3 appeared to augment endothelial dysfunction caused by p-EVs. Overall, the current study provides evidence that hBD-3 enriched EVs can be released by activated platelets and may play a role in positive feedback of platelet activation as well as in endothelial dysfunction. Theoretically, these effects could contribute to both cellular recruitment to the endothelium creating a pro-thrombotic vascular microenvironment which serve as a bridge between innate immunity and hemostasis.


Reversal effect of ginsenoside Rh2 on oxaliplatin-resistant colon cancer cells and its mechanism.
Chemotherapy is an important treatment modality for colon cancer, however, drug resistance is the main factor leading to treatment failure. Ginsenoside Rh2 (G-Rh2), the main bioactive metabolite of ginseng, is known to possess the ability to potently induce cell apoptosis, inhibit cell proliferation and reverse multidrug resistance in a variety of cancer cells. The present study examined the effect of G-Rh2 on oxaliplatin (L-OHP)-resistant colon cancer cells and its potential mechanism. L-OHP-resistant colon cancer cells (LoVo/L-OHP) and LoVo cells were used in the present study. The effect of G-Rh2 on LoVo/L-OHP and LoVo cell proliferation was measured using a 3-(4,5 dimethylthiazol-z-yl)-3,5-diphenyltetrazolium bromide assay. The effects of G-Rh2 on LoVo/L-OHP and LoVo cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis-related genes Bax, Bcl-2 and caspase-3, drug resistance-related genes P-glycoprotein (P-gp) and Smad4, were determined in LoVo/L-OHP and LoVo cells treated with G-Rh2 by reverse transcription-quantitative polymerase chain reaction and western blot analyses. G-Rh2 treatment significantly inhibited the proliferation and induced the apoptosis of LoVo/L-OHP and LoVo cells. In addition, G-Rh2 treatment resulted in a significant increase in pro-apoptotic factors, Bax and caspase-3, and decrease in anti-apoptotic factor Bcl-2 in the LoVo/L-OHP and LoVo cells. Furthermore, G-Rh2 treatment significantly decreased the levels of P-gp and increased the levels of Smad4 in the LoVo/L-OHP and LoVo cells. It was found that L-OHP had no significant effects on LoVo/L-OHP cell proliferation or apoptosis, whereas G-Rh2 + L-OHP treatment significantly inhibited LoVo/L-OHP cell proliferation and induced apoptosis. L-OHP had no significant effects on the expression of P-gp, Smad4, Bcl-2, Bax or caspase-3 in LoVo/L-OHP cells. Treatment with G-Rh2 + L-OHP significantly reduced the expression of P-gp and Bcl-2, and enhanced the expression levels of Smad4, Bax and caspase-3. These findings demonstrated that G-Rh2 reversed the drug resistance of LoVo/L-OHP cells to L-OHP, and this may be mediated by inhibiting cell proliferation and promoting apoptosis and regulating the expression of drug resistance genes. These results suggest that G-Rh2 may function as a potent anticancer drug for drug resistance in colon cancer treatment.


Direct Visualization of Native Defects in Graphite and Their Effect on the Electronic Properties of Bernal-Stacked Bilayer Graphene.
Graphite crystals used to prepare graphene-based heterostructures are generally assumed to be defect free. We report here scanning tunneling microscopy results that show graphite commonly used to prepare graphene devices can contain a significant amount of native defects. Extensive scanning of the surface allows us to determine the concentration of native defects to be 6.6 × 108 cm-2. We further study the effects of these native defects on the electronic properties of Bernal-stacked bilayer graphene. We observe gate-dependent intravalley scattering and successfully compare our experimental results to T-matrix-based calculations, revealing a clear carrier density dependence in the distribution of the scattering vectors. We also present a technique for evaluating the spatial distribution of short-scale scattering. Finally, we present a theoretical analysis based on the Boltzmann transport equation that predicts that the dilute native defects identified in our study are an important extrinsic source of scattering, ultimately setting the charge carrier mobility at low temperatures.


Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs.
Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy.


Surgery on the lateral nasal wall with the operation microscope.
Experiences with operations on the lateral nasal wall and the ethmoid with the operating microscope are reported. 18 suitable cases were operated on according to this technique. For the optimal distance optics with a focal distance of 250 mm are most suitable. Prerequisites for the operations are a self-supporting speculum and special instruments developed for this purpose.


Toxicity of chlorhexidine on odontoblast-like cells.
Chlorhexidine gluconate (CHX) is recommended for a number of clinical procedures and it has been pointed out as a potential cavity cleanser to be applied before adhesive restoration of dental cavities. As CHX may diffuse through the dentinal tubules to reach a monolayer of odontoblasts that underlies the dentin substrate, this study evaluated the cytotoxic effects of different concentrations of CHX on cultured odontoblast-like cells (MDPC-23). Cells were cultured and exposed to CHX solutions at concentrations of 0.06%, 0.12%, 0.2%, 1% and 2%. Pure culture medium (alpha-MEM) and 3% hydrogen peroxide were used as negative and positive control, respectively. After exposing the cultured cells to the controls and CHX solutions for 60 s, 2 h or 60 s with a 24-h recovery period, cell metabolism (MTT assay) and total protein concentration were evaluated. Cell morphology was assessed under scanning electron microscopy. CHX had a dose-dependent toxic effect on the MDPC-23 cells. Statistically significant difference was observed when the cells were exposed to CHX in all periods (p<0.05). Significant difference was also determined for all CHX concentrations (p<0.05). The 60-s exposure time was the least cytotoxic (p<0.05), while exposure to CHX for 60 s with a 24-h recovery period was the most toxic to the cells (p<0.05). Regardless of the exposure time, all CHX concentrations had a high direct cytotoxic effect to cultured MDPC-23 cells.


PbSe quantum dot field-effect transistors with air-stable electron mobilities above 7 cm2 V(-1) s(-1).
PbSe quantum dot (QD) field effect transistors (FETs) with air-stable electron mobilities above 7 cm(2) V(-1) s(-1) are made by infilling sulfide-capped QD films with amorphous alumina using low-temperature atomic layer deposition (ALD). This high mobility is achieved by combining strong electronic coupling (from the ultrasmall sulfide ligands) with passivation of surface states by the ALD coating. A series of control experiments rule out alternative explanations. Partial infilling tunes the electrical characteristics of the FETs.


A heterozygous microdeletion of 20p12.2-3 encompassing PROKR2 and BMP2 in a patient with congenital hypopituitarism and growth hormone deficiency.
Congenital growth hormone deficiency is a rare disorder with an incidence of approximately 1 in 4,000 live births. Pituitary development is under the control of a multitude of spatiotemporally regulated signaling molecules and transcription factors. Mutations in the genes encoding these molecules can result in hypopituitarism but for the majority of children with congenital hypopituitarism, the aetiology of their disease remains unknown. The proband is a 5-year-old girl who presented with neonatal hypoglycaemia and prolonged jaundice. No definitive endocrine cause of hypoglycaemia was identified in the neonatal period. She was born of normal size at 42 weeks but demonstrated growth failure with a progressive reduction in height to -3.2 SD by age 4.5 years and failed a growth hormone stimulation test with a peak growth hormone of 4.2 mcg/L. MRI of the pituitary gland demonstrated a hypoplastic anterior lobe and ectopic posterior lobe. Array CGH demonstrated an inherited 0.2 Mb gain at 1q21.1 and a de novo 4.8 Mb heterozygous deletion at 20p12.2-3. The deletion contained 17 protein coding genes including PROKR2 and BMP2, both of which are expressed during embryological development of the pituitary gland. PROKR2 mutations have been associated with hypopituitarism but a heterozygous deletion of this gene with hypopituitarism is a novel observation. In conclusion, congenital hypopituitarism can be present in individuals with a 20p12.3 deletion, observed with incomplete penetrance. Array CGH may be a useful investigation in select cases of early onset growth hormone deficiency, and patients with deletions within this region should be evaluated for pituitary hormone deficiencies.


Transforming potential of a myc-containing variant of feline leukemia virus in vitro in early-passage feline cells.
We studied a naturally occurring variant of feline leukemia virus (FeLV) in which the oncogene myc has substituted for a portion of the viral structural genes (myc-FeLV). myc-FeLV was rescued by replication in the presence of FeLV as helper, and its biological activity was examined in early-passage feline cells in vitro. Infection of leukocytes from peripheral blood, spleen, or thymus, or of kitten fibroblasts did not immortalize these cells or alter them morphologically. Northern blot (RNA blot) analysis of virion RNA prepared from the supernatant of infected cells demonstrated the 8.2-kilobase genome of FeLV, but did not demonstrate the 5.0-kilobase genome of myc-FeLV. Apparently, the myc-FeLV genome was lost in the absence of the selective pressure of transformation. In contrast, infection of embryonic fibroblasts with myc-FeLV(FeLV) rendered these cells capable of greatly increased, if not infinite, proliferative potential. The cells were morphologically altered compared with controls and were only loosely adherent to the substrate. The cells failed to proliferate in semisolid medium and did not form tumors when inoculated subcutaneously into athymic mice. Blot analyses demonstrated the presence and expression of integrated proviral DNAs of both FeLV and myc-FeLV in these cells. They appear, then, to represent cells partially transformed by infection with myc-FeLV(FeLV). The action of feline v-myc in early-passage cells in vitro was compared to that of avian v-myc.


Human mammalian cell sorting using a highly integrated micro-fabricated fluorescence-activated cell sorter (microFACS).
We demonstrate a high performance microfabricated FACS system with highly integrated microfluidics, optics, acoustics, and electronics. Single cell manipulation at a high speed is made possible by the fast response time (approximately 0.1 ms) of the integrated PZT actuator and the nozzle structure at the sorting junction. A Teflon AF-coated optofluidic waveguide along the microfluidic channel guides the illumination light, enabling multi-spot detection, while a novel space-time coding technology enhances the detection sensitivity of the microFACS system. The real-time control loop system is implemented using a field-programmable-gate-array (FPGA) for automated and accurate sorting. The microFACS achieves a high purification enrichment factor: up to approximately 230 fold for both polystyrene microbeads and suspended human mammalian cells (K562) at a high throughput (>1000 cells s(-1)). The sorting mechanism is independent of cell properties such as size, density, and shape, thus the presented system can be applied to sort out any pure sub-populations. This new lab-on-a-chip FACS system, therefore, holds promise to revolutionize microfluidic cytometers to meet cost, size, and performance goals.


Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: results and clinical implications.
This study attempted to determine the incidence, prognosis and predictability of postoperative left ventricular dysfunction in patients undergoing correction of mitral regurgitation. Left ventricular function in patients with mitral regurgitation is altered by loading conditions and is difficult to assess. Predictive value of preoperative variables on postoperative left ventricular function and the role of echocardiography are uncertain. In 266 patients undergoing correction of mitral regurgitation between 1980 and 1989, left ventricular function was echocardiographically assessed preoperatively (within 6 months) and postoperatively (within 1 year). After correction of mitral regurgitation, left ventricular ejection fraction decreased significantly ([mean +/- SD] 50% +/- 14% vs. 58% +/- 13%, p < 0.0001). Postoperative left ventricular dysfunction (ejection fraction < 50%) was frequent (41% of patients) and carried a poor prognosis (at 8 years survival, 38% +/- 9% vs. 69% +/- 8%, p < 0.0001). Four preoperative echocardiographic variables showed good correlation with postoperative ejection fraction: preoperative ejection fraction (r = -0.70), systolic diameter (r = -0.63), diameter/thickness ratio (r = -0.64) and end-systolic wall stress (r = -0.62) (all p < 0.0001). With multivariate analysis, ejection fraction (p = 0.0001) and systolic diameter (p = 0.0005) were independent predictors of postoperative ejection fraction, and angiographic variables provided no incremental predictive power. In addition to echocardiographic variables, recent regurgitation, functional class and coronary artery disease were also independent predictors of postoperative ejection fraction. After surgical correction of mitral regurgitation, left ventricular dysfunction is frequent and carries a poor prognosis. Postoperative ejection fraction can be predicted by echocardiographic preoperative ejection fraction and systolic diameter. Recent onset of regurgitation, mild or no symptoms, and absence of coronary artery disease are independent and favorable predictors of postoperative ejection fraction. These results should lead to consideration of surgical correction at an earlier stage.


Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth.
ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4.


Enhanced photoluminescence due to lateral ordering of GeSi quantum dots on patterned Si(001) substrates.
Multilayer ordered GeSi quantum dots (QDs) with thin Si spacers were obtained via self-assembly on pit-patterned Si(001) substrates. The lateral ordering of GeSi QDs predetermined by the periodic pit pattern results in remarkably improved size uniformity in comparison with random QDs on flat substrates. A much stronger and narrower photoluminescence (PL) peak from ordered QDs were observed than that from random ones, particularly at high excitation power. Such enhanced PL signal was attributed to the high density of states and the uniform distribution of excitons in the ordered and uniform QDs, which can efficiently suppress the Auger effect and the Coulomb screening effect. Moreover, anomalous narrowing of the PL peak from the ordered QDs with the excitation power was observed, which was explained in terms of distributed feedback associated with the periodic stacked GeSi QDs.


Population Genetic Baseline of the First Plataspid Stink Bug Symbiosis (Hemiptera: Heteroptera: Plataspidae) Reported in North America.
The stink bug, Megacopta cribraria, has an obligate relationship with a bacterial endosymbiont which allows it to feed on legumes. The insect is a pest of soybeans in Asia and was first reported in the Western Hemisphere in October 2009 on kudzu vine, Pueraria montana, in North Georgia, USA. By October 2010 M. cribraria had been confirmed in 80 counties in Georgia actively feeding on kudzu vine and soybean plants. Since the symbiosis may support the bug's ecological expansions, a population genetic baseline for the symbiosis was developed from mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA) gene sequence collected from each insect and its primary g- proteobacterium and secondary a -proteobacterium endosymbionts. A single mitochondrial DNA haplotype was found in all insects sampled in Georgia and South Carolina identified as GA1. The GAI haplotype appears to be rapidly dispersing across Georgia and into contiguous states. Primary and secondary endosymbiont gene sequences from M. cribraria in Georgia were the same as those found in recently collected Megacopta samples from Japan. The implications of these data are discussed.


[Contemporary use of radiosynoviorthesis in chronic polyarthrtitis].
Radiosynoviorthesis is used for local treatment of recurrent joint effusions, leads to necrosis of inflamed synovium due to beta radiation energy served after intraarticular radionuclide administration. The aim of the therapy is destruction and fibrosis of abnormal, hypertrophic synovial membrane and then full recovery of its normal function after local corticosteroids and systemic modifying drugs failure. Radiosynoviorthesis is effective in different type of peripheral arthritis like rheumatoid arthritis, inflammatory spondyloarthtropaties, gout, chondrocalcinosis, pigmented villo-nodular synovitis, recurrent knee effusion after total joint replacement, idiopathic knee joint effusion, osteoarthritis and secondary prevention of intraarticular bleeding in haemophilia. The absolute contraindications are: pregnancy and breastfeeding, uncontrolled coagulation disorders in haemophilic patients, septic skin changes around area of joint puncture, septic arthritis, raptured Baker's cyst. The commonly used radioisotypes in Europe are: 90Yttrium, 186Rhenium, 169Erbium. The favourable results could be reached on average in 60-80% of treated joints regardless of radionuclide used. The efficacy of radiosynoviorthesis is comparable with surgical synovectomy and in some selected situations both methods could be combined. If the primary failure of radiosynoviorthesis appeared procedure could be repeated, good results are obtained very frequently regardless of poor primary effect. Radiosynoviorthesis is safe, effective, simple and patient-friendly procedure, working fast in different type of arthtritis. The team consisted of rheumatologist, orthopedic surgeon and nuclear medicine specialist is essential for proper indications for local radiation therapy.


Profiles of Social Capital and the Association With Depressive Symptoms Among Multicultural Adolescents in Korea: A Latent Profile Analysis.
Low social capital has been reported to be associated with depression in adolescents. In general, adolescents with immigrant backgrounds lack social capital. By employing a latent profile analysis (LPA) for the specification of social capital among multicultural adolescents, depression interventions can be explored through the framework of social capital. The purpose of this study was to identify distinct latent profiles of social capital and explore the depressive symptoms of multicultural adolescents in those profiles. Data of 1,244 adolescents from the Multicultural Adolescents Panel Survey (MAPS) were used, which was conducted for 3rd-year middle school students in 2016. An LPA was used to identify profiles by different social capital classes and Quade's non-parametric ANCOVA was used to confirm the differences in depressive symptoms between profiles. Latent profile analysis indicated four classes. Analysis revealed that there were differences in the level of depressive symptoms according to the social capital sub-profiles (F = 44.42, p < 0.001). Class 1 had the lowest level of depressive symptoms (13.91 ± 4.43) and Class 4 had the highest level (18.07 ± 5.25). The depressive symptoms scores of Classes 2 and 3 were 16.49 ± 5.27 and 16.74 ± 4.95, respectively. These findings provide insight into the interplay between social capital and depressive symptoms among multicultural adolescents. Support in consideration of differences in social capital is needed to reduce depression among multicultural adolescents.


Duration of microbead seeding on endothelial cells significantly affects their response to magnetic excitation.
Our investigation of endothelial cell rheology using optical magnetic twisting cytometry revealed that with time following incubation of ferromagnetic beads on the cells, beads were sinking into the cells and an increasing number of beads demonstrated apparent absurd negative rheological properties. In parallel, the beads' average rheological response changed considerably over time, both in magnitude and in distribution. It was hypothesized that the apparent negative rheological response was related to the above sinking process of seeded beads into the cells, resulting in an elevation of the beads' rotation axis, thus causing a reversal of the beads' lateral movement direction in response to twisting external magnetic excitation. The results suggest that microbead-based rheological characterization of cells should be interpreted with caution, while considering the time of data acquisition.


Inhibitors of mammalian target of rapamycin as novel antitumor agents: from bench to clinic.
Rapamycin and its derivatives, CCI-779 and RAD-001, inhibit the mammalian target of rapamycin (mTOR), downregulating translation of specific mRNAs required for cell cycle progression from G1 to S phase. Preclinically, mTOR inhibitors potently suppress growth and proliferation of numerous tumor cell lines in culture or when grown in mice as xenografts. CCI-779 and RAD-001 are being developed as antitumor drugs and are undergoing clinical trials. Clinically, CCI-779 has shown evidence of antitumor activity but induced relatively mild side effects in patients. Here we discuss potential antitumor mechanisms and resistance mechanisms of mTOR inhibitors, and summarize the current status of these compounds as novel antitumor agents.


Siamese-Twin Porphyrin Goes Platinum: Group 10 Monometallic, Homobimetallic, and Heterobimetallic Complexes.
A series of PtII-based monometallic (H2PtL), homobimetallic (Pt2L), and heterobimetallic (NiPtL and PdPtL) group 10 complexes of the previously established expanded twin porphyrin (H4L) were prepared. Structural characterization of the bimetallic PtII series (Pt2L, NiPtL, and PdPtL) revealed their similar general structures, with slight differences correlated to the ion size. An improvement of the metal-ion insertion process also allowed efficient preparation of the known Pd2L complex, and the novel heterobimetallic NiPdL complex was also structurally characterized. UV-vis spectroscopy, NMR spectroscopy, magnetic circular dichroism (MCD), and (spectro)electrochemistry were used to characterize the complexes; the electronic properties followed largely established lines for metal complexes of the twin porphyrin, except that the PtII-based systems exhibited more complex UV-vis spectral signatures. MCD spectra accompanied by density functional theory (DFT)/time-dependent DFT computations (TDDFT) rationalize the origins of the optical features of the twin porphyrin. The presence of the nonplanar, nonaromatic macrocyclic π system with conjugation pathways confined to each half of the molecule could be visualized. Significant pyrazole(π) → pyrrole(π*) charge-transfer character was predicted for several transitions in the visible region. This study adds to our fundamental understanding of the formation, structure, and electronic structure of bimetallic complexes of this class of expanded metalloporphyrins containing nonpyrrolic moieties.


Internal azomethine ylide cycloaddition methodology for access to the substitution pattern of aziridinomitosene A.
Highly substituted, tethered alkyne dipolarophiles participate in the internal 2 + 3 cycloaddition with azomethine ylides generated by treatment of oxazolium salts with cyanide ion. Starting from oxazole 26, a sequence of N-methylation, cyanide addition, and electrocyclic ring opening of a 4-oxazoline intermediate affords the indoloquinone 31 in a one-pot process. A similar reaction from the protected alkynol derivative 25 affords the sensitive, but isolable, enone 32, and subsequent oxidation affords 31 and the deprotected quinone alcohol 34. Related azomethine cycloaddition methodology via intramolecular oxazolium salt formation from 43 or 46 is also demonstrated and allows the synthesis of quinone 45 and derived structures having the substitution pattern of aziridinomitosene A. Removal of the N-trityl protecting group could not be achieved without aziridine cleavage.


A new catechin derivative from the fruits of Rosa sterilis S. D. Shi.
A new catechin derivative named as sterilin A (1), and three known compounds, (+)-catechin (2), kaji-ichigoside F1 (3) and 2α,3α,19α-trihydroxyurs-12-en-28-oic acid-28-O-β-D-xylopyranosyl-(1 → 2)-β-D-glucopyranoside (4), was isolated from the fresh fruits of Rosa sterilis. Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures.


A comparison of mutagen production in fried ground chicken and beef: effect of supplemental creatine.
Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.


The relationship between magnetic resonance imaging and quantitative electromyography findings in patients with compressive cervical myelopathy.
A retrospective comparison of magnetic resonance imaging (MRI) and quantitative electromyography (EMG) findings in patients with compressive cervical myelopathy (CCM). To investigate which parameters of the EMG motor unit potentials (MUPs) as determined by automatic analysis of 4 muscles in the upper limb are correlated with spinal cord compression observed on MRI in CCM patients and to determine whether electrical and radiologic levels are correlated. Increased mean duration of MUPs has been reported to be a sensitive indicator of disorders of the spinal motor neurons that are accompanied by axonal degeneration and regeneration. MRI findings at each cervical disc level from C3/C4 to C6/C7 and MUPs recorded from 4 muscles (deltoid, biceps brachii, triceps brachii, and abductor digiti minimi) were examined to determine whether there is a statistical correlation between spinal cord compression and abnormal parameters of the MUPs for any combination of disc level and muscle. Significant correlations between increased mean duration of MUPs and radiologic level of cord compression were observed for deltoid and cord compression at C3/C4 (P < 0.01), biceps brachii and cord compression at C3/C4 (P < 0.001) and C4/C5 (P < 0.01), triceps brachii and cord compression at C5/C6 (P < 0.05), and abductor digiti minimi and cord compression at C6/C7 (P < 0.001). Other parameters of MUPs including amplitude, polyphasia and denervation potentials did not show significant correlation with compressive spinal cord lesions on MRI. Quantitative analysis of mean duration of MUPs provides a reliable indicator of physiologic disorder of spinal motor neurons in CCM and may contribute to establishing the site of motor neuron compromise in cases with multilevel spinal canal stenosis.


[Autophagy, autoimmunity and autoimmune diseases].
Autoimmune diseases such as systemic lupus, are the consequence of immunity directed against the organism itself. The immune system abnormally recognizes self-components as foreign and produces antibodies targeting normal cells and tissues. We and others have discovered a number of failures affecting autophagy pathways in the lymphocytes of model mice and patients with lupus. While the current treatments are mainly based on immunosuppressive drugs that can lead to important side effects, the synthetic phosphopeptide P140/Lupuzor, which targets chaperone-mediated autophagy and displays no side effects, holds a lot of promise as a drug candidate. P140, which is currently evaluated in a phase III clinical trial, targets chaperone-mediated autophagy that is hyperactivated in lupus mice, and reduces antigenic peptides presentation to autoreactive helper T cells. Remarkably, we showed in lupus mice that upon treatment with P140, a number of immunological abnormalities affecting the pool of T and B cells as well as many biological and clinical features no longer occur.


[Recurrent low output syndrome after the weaning from mechanical circulatory support for postcardiotomy cardiogenic shock].
We reviewed the cases of recurrent low output syndrome (LOS) after the weaning from mechanical circulatory support for postcardiotomy cardiogenic shock. Twelve patients were divide into 2 groups according to whether low output syndrome recurred or not, consisting of a recurrent low output syndrome (+) group [re-LOS (+) group, n = 6] and a recurrent low output syndrome (-) group [re-LOS (-) group, n = 6]. Between 2 groups, there was no statistical difference in preoperative left ventricular ejection fraction (LVEF), aortic closs-clamping time and cardiac index at the weaning from mechanical circulatory support. Only the LVEF at the weaning in the re-LOS (+) group was significantly less than that in the re-LOS (-) group (0.39 +/- 0.08 vs 0.62 +/- 0.19, p < 0.05). All patients in the re-LOS (-) group survived to discharge, while in the re-LOS (+) group, although 3 patients were re-supported by intra-aortic balloon pumping, 4 of 6 patients died of multiple organ failure and 2 survivors were in New York Heart Association class III. The results suggest that the key to survive to discharge after the weaning from mechanical circulatory support is whether the cardiac contraction could recover or not.


A rapid and safe middle fossa approach to the geniculate ganglion and labyrinthine segment of the facial nerve.
The middle fossa approach provides neurotologic surgical access to lesions of the geniculate ganglion and the labyrinthine portion of the facial nerve as well as to the internal acoustic canal, and therefore helps preserve cochlear function. Although this approach is widely used, surgeons are still not certain which anatomic landmarks are best to locate the facial nerve and internal acoustic canal without causing labyrinthine damage. The purpose of this article is to describe a fast and safe technique to expose the geniculate ganglion and the labyrinthine portion of the facial nerve in two structures of the middle ear: the cochleariform process and the tympanic portion of the facial nerve. We prospectively evaluated 32 patients who underwent surgical facial nerve exploration via the middle fossa approach. Our goal was to determine the incidence of intraoperative difficulties and complications; we found none, and hearing levels could not be maintained in only one of the 32 patients. Our technique allowed us to decompress the first genu and the labyrinthine segment of the nerve. It also allowed us to reach and manipulate its tympanic segment in a very short amount of surgical time.


Multi-Frame SPRITE: a method for resolution enhancement of multiple-point SPRITE data.
The Single Point Ramped Imaging with T1 Enhancement (SPRITE) sequence is well suited for the acquisition of magnetic resonance signals from fast relaxing nuclei and from heterogeneous materials. However, it is time inefficient compared to sequences that are based on frequency encoding because only one single point is acquired per excitation. Multiple-point SPRITE (mSPRITE) mitigates this problem with the acquisition of multiple FID points. mSPRITE images reconstructed from early FID samples suffer from reduced spatial resolution due to the limited extent of its corresponding k-space. In this work we present a new reconstruction algorithm for spatial resolution enhancement that solves this problem without changes to the mSPRITE sequence. The method, called Multi-Frame mSPRITE, substitutes high spatial frequencies from late FID points into k-spaces of limited extent constructed from early FID points. In this way, images of high quality and resolution can be obtained despite a large range of zoom factors used to reconstruct images with the same FOV and resolution.


The inhibition of NOTCH2 reduces UVB-induced damage in retinal pigment epithelium cells.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The pathogenesis of dry AMD remains indistinct and the mechanism of retinal pigment epithelium (RPE) cells death in dry AMD is controversial. The aim of the present study was to investigate the functions of Notch signaling in ultraviolet B (UVB)-induced damage of RPE cells. It was identified that, in RPE cells, UVB increased intracellular reactive oxygen species (ROS) and induced cell apoptosis. In addition, UVB activated Notch signaling in a dose dependent manner. Surprisingly, NOTCH2, but not NOTCH1, was demonstrated to be the major Notch receptor in RPE cells. Under normal conditions, the inhibition of NOTCH2 reduced cell growth and cell migration, but had no impact on intracellular ROS and cell apoptosis. However, in the presence of UVB, the inhibition of NOTCH2, but not NOTCH1, attenuated intracellular ROS and cell apoptosis. The function of Notch signaling involved in UVB damage of RPE cells may not only be significant to understanding the pathogenesis of AMD (especially dry AMD), but also useful for designing effective therapeutic agents for dry AMD.


Role of anisotropy for protein-protein encounter.
Protein-protein interactions comprise both transport and reaction steps. During the transport step, anisotropy of proteins and their complexes is important both for hydrodynamic diffusion and accessibility of the binding site. Using a Brownian dynamics approach and extensive computer simulations, we quantify the effect of anisotropy on the encounter rate of ellipsoidal particles covered with spherical encounter patches. We show that the encounter rate k depends on the aspect ratios xi mainly through steric effects, while anisotropic diffusion has only a little effect. Calculating analytically the crossover times from anisotropic to isotropic diffusion in three dimensions, we find that they are much smaller than typical protein encounter times, in agreement with our numerical results.


Chiral smectic-A and smectic-C phases with de Vries characteristics.
Infrared and dielectric spectroscopic techniques are used to investigate the characteristics of two chiral smectics, namely, 1,1,3,3,5,5,5-heptamethyltrisiloxane 1-[4^{'}-(undecyl-1-oxy)-4-biphenyl(S,S)-2-chloro-3-methylpentanoate] (MSi_{3}MR_{11}) and tricarbosilane-hexyloxy-benzoic acid (S)-4'-(1-methyl-hexyloxy)-3'-nitro-biphenyl-4-yl ester (W599). The orientational features and the field dependencies of the apparent tilt angle and the dichroic ratio for homogeneous planar-aligned samples were calculated from the absorbance profiles obtained at different temperatures especially in the smectic-A* phase of these liquid crystals. The dichroic ratios of the C-C phenyl ring stretching vibrations were considered for the determination of the tilt angle at different temperatures and different voltages. The low values of the order parameter obtained with and without an electric field applied across the cell in the Sm-A^{*} phase for both smectics are consistent with the de Vries concept. The generalized Langevin-Debye model introduced in the literature for explaining the electro-optical response has been applied to the results from infrared spectroscopy. The results show that the dipole moment of the tilt-correlated domain diverges as the transition temperature from Sm-A^{*} to Sm-C^{*} is approached. The Debye-Langevin model is found to be extremely effective in confirming some of the conclusions of the de Vries chiral smectics and gives additional results on the order parameter and the dichroic ratio as a function of the field across the cell. Dielectric spectroscopy finds large dipolar fluctuations in the Sm-A^{*} phase for both compounds and again these confirm their de Vries behavior.


Computational analyses of arteriovenous malformations in neuroimaging.
Computational models have been investigated for the analysis of the physiopathology and morphology of arteriovenous malformation (AVM) in recent years. Special emphasis has been given to image fusion in multimodal imaging and 3-dimensional rendering of the AVM, with the aim to improve the visualization of the lesion (for diagnostic purposes) and the selection of the nidus (for therapeutic aims, like the selection of the region of interest for the gamma knife radiosurgery plan). Searching for new diagnostic and prognostic neuroimaging biomarkers, fractal-based computational models have been proposed for describing and quantifying the angioarchitecture of the nidus. Computational modeling in the AVM field offers promising tools of analysis and requires a strict collaboration among neurosurgeons, neuroradiologists, clinicians, computer scientists, and engineers. We present here some updated state-of-the-art exemplary cases in the field, focusing on recent neuroimaging computational modeling with clinical relevance, which might offer useful clinical tools for the management of AVMs in the future.


Performance of a knotless four-strand flexor tendon repair with a unidirectional barbed suture device: a dynamic ex vivo comparison.
With increased numbers of reports using barbed sutures for tendon repairs we felt the need to design a specific tendon repair method to draw the best utility from these materials. We split 30 sheep deep flexor tendons in two groups of 15 tendons. One group was repaired with a new four-strand barbed suture repair method without knot. The other group was repaired with a conventional four-strand cross-locked cruciate repair method (Adelaide repair) with knot. Dynamic testing (3-30 N for 250 cycles) and additional static pull to failure was performed to investigate gap formation and final failure forces. The barbed suture repair group showed higher resistance to gap formation throughout the test. Additionally final failure force was higher for the barbed suture group compared with the conventional repair group. When used appropriately, barbed suture materials could be beneficial to use in tendon surgery, especially with regard to early loading of the repair site and gap formation.


Further evidence to suggest that microbodies do not exist as individual entities.
Male wild-type mice (Cs(a) strain) were treated with ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and induces rapid and significant increase in the number of microbody (peroxisome) profiles in liver cells. Numerous microbody profiles, several of them appearing in clusters and retaining membranous continuities, were observed in liver cells of CPIB-treated mice. They showed a significant variation in size and configuration, and the presence or absence of the nucleoid or core did not appear to bear any relation to the size or shape of microbody profiles. Nucleoids were encountered frequently in microbody profiles measuring as small as 0.1 mu in diameter. Numerous continuities between two or more anucleoid and/or nucleoid-containing microbody profiles of different sizes and shapes were seen. These findings are inconsistent with the concept that the smaller peroxisomes are the possible precursors or progenitors of their larger counterparts. Detailed examination of numerous electron micrographs revealed irregular dilatations and tortuosities of the endoplasmic reticulum (ER) containing electron-opaque peroxisomal material displaying the characteristic appearance of matrix and usually containing irregular cores. Transitions of rough ER to smooth ER in which microbody proteins accumulated were also apparent. Numerous continuities between several microbody profiles and continuities between microbody profiles and ER are interpreted as accumulations of peroxisomal proteins in dilated tortuous channels of ER. These observations strongly suggest that the microbody proteins constitute a common pool, circulating constantly in the dilated ER channels. The size, shape and number of microbody profiles appear to reflect the amount of peroxisomal proteins present in the pool. These observations clearly suggest that the microbodies do not exist as individual entities.


[Management of varus knee arthrosis by high tibial osteotomy].
Authors made a follow-up of 69 varsus knee arthrosis treated with high tibial osteotomy. Beside the general results the effect of the severeness of the arthrosis before the correction and that of the gain of the axial correction on the result were also investigated. 56 (81 per cent) of the reexamined patient reported excellent or good results. The ratio of the successful operations was even higher in cases in which the femorotibial axis was corrected to physiological valgus (95 per cent). The best prognosis of the osteotomy is in the early stage of arthrosis (Ahlbäck 0-II). In cases of the more advanced process the ratio of the unsuccessful cases increases. In consequence it is stated that the best results can be expected after osteotomies performed in the early stage and leading to the physiological femorotibial valgus position.


Computational Study of Hemodynamic Changes Induced by Overlapping and Compacting of Stents and Flow Diverter in Cerebral Aneurysms.
Purpose: The flow diversion effect of an intracranial stent is closely related to its metal coverage rate (MCR). In this study, the flow diversion effects of Enterprise and low-profile visualized intraluminal support (LVIS) stents are compared with those of a Pipeline flow diverter, focusing on the MCR change. Moreover, the changes in the flow diversion effect caused by the additional manipulations of overlapping and compaction are verified using computational fluid dynamics (CFD) analysis. Methods: CFD analysis was performed using virtually generated stents mounted in an idealized aneurysm model. First, the flow diversion effects of single Enterprise, LVIS, and Pipeline devices were analyzed. The Enterprise and LVIS were sequentially overlapped and compared with a Pipeline, to evaluate the effect of stent overlapping. The effect of compacting a stent was evaluated by comparing the flow diversion effects of a single and two compacted LVIS with those of two overlapped, uncompacted LVIS and uncompacted and compacted Pipeline. Quantitative analysis was performed to evaluate the hemodynamic parameters of energy loss, average velocity, and inflow rate. Results: Statistically significant correlations were observed between the reduction rates of the hemodynamic parameters and MCR. The single LVIS without compaction induced a reduction in all the hemodynamic parameters comparable to those of the three overlapped Enterprise. Moreover, the two overlapped, uncompacted LVIS showed a flow diversion effect as large as that induced by the single uncompacted Pipeline. Compacted stents induced a better flow diversion effect than uncompacted stents. The single compacted LVIS induced a flow diversion effect similar to that induced by the two uncompacted LVIS or single uncompacted Pipeline. Conclusions: The MCR of a stent correlates with its flow diversion effect. Overlapping and compaction can increase the MCR of an intracranial stent and achieve a flow diversion effect as large as that observed with a flow diverter.


Influence of Tinnitus on Auditory Spectral and Temporal Resolution and Speech Perception in Tinnitus Patients.
Although cochlear damage is believed to trigger the perception of tinnitus in the central auditory system, its pathophysiological mechanism is still unclear. We aimed to investigate the pathophysiology of tinnitus using psychoacoustic assessments of auditory spectral and temporal resolution and speech perception in noise. Human subjects with tinnitus and symmetric hearing thresholds were divided into three groups: nine unilateral tinnitus subjects with normal hearing thresholds (Group 1), 12 unilateral tinnitus subjects with hearing loss (HL; Group 2), and nine bilateral tinnitus subjects with HL. Fifteen normal-hearing subjects without tinnitus were also tested as a control group. Four different tests were administered: (1) the spectral-ripple discrimination (SRD) test, (2) the temporal modulation detection (TMD) test, (3) the Schroeder-phase discrimination (SPD) test, and (4) the speech recognition threshold (SRT) in noise test. There were no significant differences in SRD, TMD, and SPD between the tinnitus-affected ears (TEs) and non-tinnitus ears (NTEs) in Groups 1 and 2 (p > 0.05). In contrast, the TEs showed poorer SRTs than the NTEs in these two subject groups (p = 0.022 and 0.049). No inferiority of spectral/temporal resolution in TEs compared with NTEs suggests that there may be no more outer hair cell (OHC) damage on the tinnitus side given that damaged OHCs are associated with broadening the auditory filters. The decoupling of the SRT results from the spectral/temporal resolution data could imply that the occurrence of tinnitus does not depend upon the degree of damage to the OHCs, but rather upon different plastic changes in the central auditory system after cochlear damage. We can easily find unilateral tinnitus patients who have symmetric hearing thresholds. Our research question was what kind of difference would be responsible for the tinnitus in the tinnitus-affected ears but not in the non-tinnitus ears of subjects with symmetric hearing thresholds. The answer to this fundamental question could help us to understand the pathophysiology of tinnitus. We evaluated the potential influence of tinnitus upon the subjects' auditory spectral and temporal resolution and speech perception in noise by comparing these psychoacoustic performances between tinnitus-affected ears and non-tinnitus ears in the same subjects.


Spatial relative risk mapping of pseudorabies-seropositive pig herds in an animal-dense region.
This paper describes a new approach for spatial relative risk mapping as a tool for geographical risk assessment. The spatial epidemiological analysis is based on geographically referenced data about pseudorabies (Aujeszky's disease) virus infections at farm level in a region of high animal density in Germany at the beginning of the national eradication project. On the basis of serological findings 186 farms were classified as positive out of a total of 482 investigated farms listed in veterinary administrative registers. Geographical cluster analysis was used to identify two areas of high risk (RR = 2.4 and 3.3). Non-parametric density estimation was used to estimate the proportion of infected farms per square kilometre. Furthermore, the spatial relative risk function was approximated through the prevalence ratio defined by the ratio of the local prevalence and the overall prevalence of the farms outside the cluster regions. The corresponding approximated relative risk map indicates and quantifies a clear spatial pattern of disease frequency.


Three cases of Wegener's granulomatosis treated with an antimicrobial agent.
Sulfamethoxazole-trimethoprim, an antimicrobial agent, was used to treat three cases of cytotoxic agent-resistant Wegener's granulomatosis; one case was refractory to a regimen consisting of azathioprine and prednisolone, and in another two cases the therapy was insufficient to control the disease. By the introduction of sulfamethoxazole-trimethoprim, which has an advantage of fewer side effects compared with the conventional agents, into the regimen, the disease condition was markedly improved in all cases within four months. Sulfamethoxazole-trimethoprim is thus considered as one of the most promising drugs to treat, especially, cytotoxic agent-resistant Wegener's granulomatosis. The possible underlying mechanism of the effect of sulfamethoxazole-trimethoprim is also described.


Recurrent Syncope following Substance Abuse; a Case Report.
Drug abuse is considered as the most common poisoning in the world. Stimulants agent especially amphetamines and methamphetamines are among important abused substances. Different types of neurologic, psychiatric, respiratory, gastrointestinal, and cardiogenic complications have been reported to be related to methamphetamine consumption. Some of these substances could cause dysrhythmias which is the most prevalent etiology of cardiogenic syncope. Ecstasy, as one of the most commonly abused drugs, is known as a cause of cardiac dysrhythmias. Here we report a young boy who was admitted into the emergency department following three syncope attacks. All cardiac and neurologic assessments were normal; and finally ecstasy abuse was detected as the main etiology of syncopes.


Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers.
The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67-2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25-1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23-1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84-4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63-0.67)]. We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients.


Components of a Measure to Describe Organizational Culture in Academic Pharmacy.
Objective. To develop a measure of organizational culture in academic pharmacy and identify characteristics of an academic pharmacy program that would be impactful for internal (eg, students, employees) and external (eg, preceptors, practitioners) clients of the program. Methods. A three-round Delphi procedure of 24 panelists from pharmacy schools in the U.S. and Canada generated items based on the Organizational Culture Profile (OCP), which were then evaluated and refined for inclusion in subsequent rounds. Items were assessed for appropriateness and impact. Results. The panel produced 35 items across six domains that measured organizational culture in academic pharmacy: competitiveness, performance orientation, social responsibility, innovation, emphasis on collegial support, and stability. Conclusion. The items generated require testing for validation and reliability in a large sample to finalize this measure of organizational culture.


Sequence-specific impairment of learning by c-jun antisense oligonucleotides.
Hybridization studies revealed a differential accumulation of c-jun and jun B mRNA in the hippocampus and cerebral cortex of rats trained on a foot-shock-motivated brightness discrimination. Supposing that early gene expression is functionally significant for plastic changes in the brain, we used antisense phosphorothioate oligodeoxynucleotides (S-ODN) in vivo to study effects of specific inhibition of c-jun and jun B gene expression on learning and memory formation in rat brain. Discrimination performance of rats was impaired after intrahippocampal injection of anti-c-jun S-ODN but not of anti-jun B S-ODN. These results imply that topically injected antisense oligonucleotides affect processes involved in learning and memory in a sequence-specific manner.


High-risk drinking among college fraternity members: a national perspective.
This survey, with its 85% response rate, provides an extensive profile of drinking behaviors and predictors of drinking among 3,406 members of one national college fraternity, distributed across 98 chapters in 32 states. Multiple indexes of alcohol consumption measured frequency, quantity, estimated blood alcohol concentration levels (BACs), and related problems. Among all members, 97% were drinkers, 86% binge drinkers, and 64% frequent binge drinkers. On the basis of self-reports concerning the 4 weeks preceding the time of survey, the authors found that members drank on an average of 10.5 days and consumed an average of 81 drinks. Drinkers had an average BAC of 0.10, reaching at least 0.08 on an average of 6 days. These fraternity members appear to be heavier drinkers than previously studied fraternity samples, perhaps because they were more representative and forthright. All 6 preselected demographic attributes of members and 2 chapter characteristics were significantly related to the drinking behaviors and levels of risk, identifying possible targets for preventive interventions.


Analysis of indoor particles and gases and their evolution with natural ventilation.
The air composition and reactivity from outdoor and indoor mixing field campaign was conducted to investigate the impacts of natural ventilation (ie, window opening and closing) on indoor air quality. In this study, a thermal desorption aerosol gas chromatograph (TAG) obtained measurements of indoor particle- and gas-phase semi- and intermediately volatile organic compounds both inside and outside a single-family test home. Together with measurements from a suite of instruments, we use TAG data to evaluate changes in indoor particles and gases at three natural ventilation periods. Positive matrix factorization was performed on TAG and adsorbent tube data to explore five distinct chemical and physical processes occurring in the indoor environment. Outdoor-to-indoor transport is observed for sulfate, isoprene epoxydiols, polycyclic aromatic hydrocarbons, and heavy alkanes. Dilution of indoor species is observed for volatile, non-reactive species including methylcyclohexane and decamethylcyclopentasiloxane. Window opening drives enhanced emissions of semi- and intermediately volatile species including TXIB, DEET, diethyl phthalate, and carvone from indoor surfaces. Formation via enhanced oxidation was observed for nonanal and 2-decanone when outdoor oxidants entered the home. Finally, oxidative depletion of gas-phase terpenes (eg, limonene and α-pinene) was anticipated but not observed due to limited measurement resolution and dynamically changing conditions.


Development of postural stability in children with autism spectrum disorder: a cross-sectional study.
The purpose was to investigate the effects of age on postural stability for children with autism spectrum disorder (ASD). Twenty-nine children with mild ASD were assigned into one of the three groups: 6-8 years (U8), 9-11 years (U11) and 12-14 years (U14). Participants stood barefoot with both feet on a force platform and maintained stationary for 15 seconds during eyes-open and eyes-closed conditions. Center of pressure data were collected and variables were calculated, including displacements, total distances, sway areas, and sample entropy. The variables were compared among the three groups using a mixed-model ANOVA. The age group effect was significant for mediolateral center of pressure displacement (p = 0.04) and sway distance (p = 0.02). Post-hoc comparisons revealed that U8 exhibited greater mediolateral displacement and total distance compared to U14, regardless of test conditions. The U14 group exhibited improved mediolateral postural stability compared to U8, whereas no differences were found between U8 and U11 or between U11 and U14. This may suggest that children with ASD could slowly develop postural stability but only demonstrate significant changes over a long period of time. Early intervention programs aimed to improve complexity of postural control could be beneficial.


The dexamethasone suppression test in patients with presenile and senile dementia of the Alzheimer's type.
The dexamethasone suppression test (DST) was performed on 18 patients with presenile and senile dementia of the Alzheimer's type. Objective cognitive testing showed that 13 patients were mildly to moderately impaired and five were moderately to severely impaired. The Hamilton Depression Scale yielded normal results in all patients. The DST results were abnormal in only one of the mildly impaired patients but in four of the five moderately impaired patients. These data suggest that the DST may be a useful clinical tool in mildly impaired patients with Alzheimer's disease but is likely to be confounded by disease in moderately to severely impaired patients.


The effects on lipid serum levels of a 2-year adjuvant treatment with exemestane after tamoxifen in postmenopausal women with early breast cancer.
The third-generation aromatase inhibitor exemestane represents a new development in the treatment of estrogen-positive breast cancer. The aim of this study was to evaluate the effects on lipid profile and body composition of the shift from tamoxifen to exemestane. After 2-3 years of tamoxifen adjuvant treatment, 68 postmenopausal women were randomly assigned to either continue tamoxifen 20 mg/day (n = 35) or to switch to exemestane 25 mg/day (n = 33). No significant changes in lipid profile were found in patients continuing on tamoxifen. In the exemestane group, serum HDL-cholesterol (HDL-C) and triglycerides (TG) decreased significantly (p < 0.01) and serum LDL-cholesterol (LDL-C) increased significantly (p < 0.05) with respect to baseline. The difference between the two groups was significant. Moreover, in the exemestane group, fat mass (FM) and fat-free mass (FFM) showed an opposite trend, which determined a progressive and significant increase in the FFM/FM ratio. This study shows that the choice of first-line treatment or adjuvant therapy for breast cancer should also take the individual lipid and body composition profile into account.


Corticosteroid and cytokines synergistically enhance toll-like receptor 2 expression in respiratory epithelial cells.
Respiratory epithelial cells play important roles not only in host defense mechanisms, but also in inflammatory responses. Inhaled corticosteroids are widely used for the treatment of patients with inflammatory lung disorders, including asthma, chronic obstructive pulmonary disease, and sarcoidosis. Corticosteroids effectively reduce the production of inflammatory mediators, such as cytokines and chemokines. Although these molecules are also essential for host defense responses, there is no convincing evidence that inhaled corticosteroids increase susceptibility to lower respiratory tract infections. To test the involvement of Toll-like receptor (TLR) family molecules in this phenomenon, we examined the effects of various cytokines and corticosteroid on the expression of TLRs in human respiratory epithelial cells. Among the TLRs tested, TLR2 expression was significantly enhanced after stimulation with a combination of tumor necrosis factor-alpha and interferon-gamma. Dexamethasone synergistically enhanced TLR2 expression in combination with tumor necrosis factor-alpha and interferon-gamma in terms of both mRNA and protein levels. Furthermore, increased cell-surface TLR2 was functional, judging from the remarkable induction of interleukin-6, interleukin-8, and beta-defensin-2 after stimulation with peptidoglycan. These results provide evidence for a novel function of corticosteroids in airway inflammatory disorders, and indicate that the use of inhaled corticosteroids in such disorders may have a beneficial role in host defense mechanisms.


Contamination of apple orchard soils and fruit trees with copper-based fungicides: sampling aspects.
Accumulations of copper in orchard soils and fruit trees due to the application of Cu-based fungicides have become research hotspots. However, information about the sampling strategies, which can affect the accuracy of the following research results, is lacking. This study aimed to determine some sampling considerations when Cu accumulations in the soils and fruit trees of apple orchards are studied. The study was conducted in three apple orchards from different sites. Each orchard included two different histories of Cu-based fungicides usage, varying from 3 to 28 years. Soil samples were collected from different locations varying with the distances from tree trunk to the canopy drip line. Fruits and leaves from the middle heights of tree canopy at two locations (outer canopy and inner canopy) were collected. The variation in total soil Cu concentrations between orchards was much greater than the variation within orchards. Total soil Cu concentrations had a tendency to increase with the increasing history of Cu-based fungicides usage. Moreover, total soil Cu concentrations had the lowest values at the canopy drip line, while the highest values were found at the half distances between the trunk and the canopy drip line. Additionally, Cu concentrations of leaves and fruits from the outer parts of the canopy were significantly higher than from the inner parts. Depending on the findings of this study, not only the between-orchard variation but also the within-orchard variation should be taken into consideration when conducting future soil and tree samplings in apple orchards.


Human T-cell receptor V alpha gene polymorphism.
Polymorphism in the germline repertoire of T-cell receptor (TCR) variable alpha and beta (V alpha and V beta) genes could alter the relative abilities of individuals in a population to respond to particular antigens. Variation in the number of germline V alpha and V beta gene segments has been reported in wild mice and in different inbred mouse strains. A previous study of the human V beta gene germline repertoire failed to reveal a similar degree of polymorphism in the numbers of V beta gene segments. We have now carried out a survey of 10 different V alpha gene segment subfamilies containing approximately 23 V alpha gene segments in a panel of 120 unrelated individuals by hybridization and failed to find any evidence for V alpha repertoire polymorphism. To determine if significant germline polymorphism does occur in humans at the level of individual V gene segments, we determined the nucleotide sequences of eight copies of the V alpha 21 gene segment derived from seven unrelated individuals. Polymorphic differences between these sequences defined three different alleles. One of these alleles contains a frameshift mutation which would cause premature termination of the protein product. The presence of this null allele among the eight sequences determined suggests that functionally relevant germline polymorphism of human TCR V gene segments may occur by mechanisms other than gene duplication or deletion.


Assessment of horse owners' ability to recognise equine laminitis: A cross-sectional study of 93 veterinary diagnosed cases in Great Britain.
Use of owner-reported data could further epidemiological knowledge of equine laminitis. However, owner recognition of laminitis has not previously been assessed. The primary objective was to establish whether cases of owner-suspected laminitis would be confirmed as laminitis by the attending veterinary surgeon. Secondary objectives were to compare owner- and veterinary-reported information from veterinary-confirmed cases of equine laminitis. Cross-sectional study. Twenty-five British veterinary practices were invited to submit laminitis reporting forms (LRFs) for active laminitis cases attended between January 2014 and October 2015; detailing 27 clinical signs, 5 underlying conditions and 7 risk factors associated with laminitis. Owners were invited to independently complete a modified LRF if reason for the veterinary visit was suspicion of laminitis. Differences between paired veterinary and owner LRFs, and between cases where owners did and did not recognise laminitis, were assessed using McNemar's and Fisher's Exact tests, respectively. Veterinary LRFs were received for 93 veterinary-diagnosed laminitis cases. All 51 owner-suspected cases were confirmed by veterinary diagnosis, with the remaining 42 (45.2%) not recognised as laminitis by owners. Undefined lameness, foot abscesses, colic and stiffness were common reasons for owner-requested veterinary visits in owner-unrecognised cases. 'Divergent growth rings' (prevalence difference: +27.3%, P = 0.01) and 'breed type' (prevalence difference: +21.2%, P = 0.04) were more commonly reported by veterinary surgeons in owner-recognised compared to owner-unrecognised cases. 'Difficulty turning', 'shifting weight' and risk factor 'body condition' were more frequently reported by veterinary surgeons whilst 'increased hoof temperature' was reported more frequently by owners. The limited clinical data restricted statistical inferences regarding the secondary objectives. All owner-suspected laminitis cases were confirmed upon veterinary examination, showing validity for the inclusion of owner-reported cases in future epidemiological studies. However, failure of laminitis recognition by owners highlights further need for evidence-based education to ensure early disease detection.


ZBTB16 is a sensitive and specific marker in detection of metastatic and extragonadal yolk sac tumour.
Accurate histological diagnosis and classification of germ cell tumours (GCTs) is key to informing successful therapeutic and surveillance strategy. The modern therapeutic approach for yolk sac tumour (YST) is highly curative. Because YST takes on a large morphological spectrum, it can be confused for other GCT subtypes as well as somatic carcinomas, particularly when YST presents in an extragonadal or a metastatic setting. Currently available immunohistochemical markers are limited by suboptimal sensitivity and specificity. We reported recently that ZBTB16 is a sensitive and specific marker for testicular YST. ZBTB16 is absent in other GCTs and in most common somatic carcinomas, including those of gastrointestinal, pancreatobillary, respiratory, genitourinary and gynaecological tracts. The purpose of this study is to investigate the diagnostic utility of ZBTB16 in the settings of metastatic and extragonadal YST. We studied 32 archived metastatic and four extragonadal primary YSTs as well as 51 somatic malignancies for their immunohistochemical expression of ZBTB16. For comparison, α-fetoprotein (AFP) and glypican-3 were also studied in parallel. Our results demonstrated an overall sensitivity of 91.6% for ZBTB16 in detecting metastatic and extragonadal YSTs. The non-YST elements (teratoma and embryonal carcinoma) in 15 YST-containing metastatic mixed GCTs were non-reactive. With the exception of occasional myoepithelial cells of salivary gland carcinoma, all the 51 somatic malignancies were negative for ZBTB16. ZBTB16 is a sensitive and specific marker for YST and is diagnostically superior to AFP and glypican-3 in metastatic and extragonadal settings.


Dirac Cones in two-dimensional conjugated polymer networks.
Linear electronic band dispersion and the associated Dirac physics has to date been limited to special-case materials, notably graphene and the surfaces of three-dimensional (3D) topological insulators. Here we report that it is possible to create two-dimensional fully conjugated polymer networks with corresponding conical valence and conduction bands and linear energy dispersion at the Fermi level. This is possible for a wide range of polymer types and connectors, resulting in a versatile new family of experimentally realisable materials with unique tuneable electronic properties. We demonstrate their stability on substrates and possibilities for doping and Dirac cone distortion. Notably, the cones can be maintained in 3D-layered crystals. Resembling covalent organic frameworks, these materials represent a potentially exciting new field combining the unique Dirac physics of graphene with the structural flexibility and design opportunities of organic-conjugated polymer chemistry.


How is the patient's nutrition after a stroke?
Neurological conditions usually cause altered levels of consciousness or swallowing mechanisms which make artificial nutritional support necessary. International guidelines recommend nutritional screening to detect malnutrition in patients with neurological diseases. Dysphagia is a common problem after a stroke, however, it is a treatable pathology, and swallowing rehabilitation allows for improving patients' nutritional status. Awareness of this problem is required among healthcare professionals both for its diagnosis and for the implementation of nutritional intervention measures. Patients should be tested for dysphagia within the first 24 hours of the stroke onset; this swallowing assessment as well as malnutrition screening should never be delayed by more than 72 hours. The present study addresses diagnostic and therapeutic approaches, the indications of the different nutritional treatments available and the transition to oral feeding in patients who have had a stroke episode.


[A case of aortitis syndrome with left coronary ostial stenosis treated by aorto-coronary bypass grafting].
A 22 years-old woman who was suffered from effort angina caused by aortitis syndrome was hospitalized. The coronary arteriogram showed the left main trunk stenosis more than 99% with the visualization of the left anterior descending and left circumflex through the co-lateral vessels from right coronary artery. After successful sequential aorto-coronary bypass grafting to left anterior descending artery, the patient has been free from anginal pain.


If times change, should we throw away the hearthstone? Exploring (Dis) continuities in autonomy and decision-making in the lives of Ghanaian women.
This paper attempts to investigate continuities and discontinuities between traditional and modern representations of womanhood and female gender roles focusing primarily on family and work settings. Using approaches informed by Sociology, Cultural Psychology, and African Studies, the paper explores traditional views of womanhood encapsulated in (and also transmitted intergenerationally) through proverbs. This customary perspective is contrasted with the results of the Everyday Lives Survey from the Pathways of Women's Empowerment Ghana project. The survey investigated the nature of everyday life- education, work, decision making, access to institutions, and autonomy in relationships-in six hundred (600) adult women in both rural and urban communities in three regions of Ghana. We argue that although the times are changing, there have only been modest disruptions in the lives of Ghanaian women as far as issues of autonomy and decision-making in are concerned.


Different bulk and active bacterial communities in cryoconite from the margin and interior of the Greenland ice sheet.
Biological processes in the supraglacial ecosystem, including cryoconite, contribute to nutrient cycling within the cryosphere and may affect surface melting, yet little is known of the diversity of the active microbes in these environments. We examined the bacterial abundance and community composition of cryoconite over a melt season at two contrasting sites at the margin and in the interior of the Greenland ice sheet, using sequence analysis and quantitative polymerase chain reaction of coextracted 16S rDNA and rRNA. Significant differences were found between bulk (rDNA) and potentially active (rRNA) communities, and between communities sampled from the two sites. Higher concentrations of rRNA than rDNA were detected at the interior site, whereas at the margin several orders of magnitude less rRNA was found compared with rDNA, which may be explained by a lower proportion of active bacteria at the margin site. The rRNA communities at both sites were dominated by a few taxa of Cyanobacteria and Alpha- and/or Betaproteobacteria. The bulk alpha diversity was higher in the margin site community, suggesting that local sources may be contributing towards the gene pool in addition to long distance transport.


Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.
To systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels. Meta-analysis of cross sectional data from the United States. Five cohort studies. 16 760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. β values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R2 values, were used to quantitate associations. Seven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ≤0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation. In contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.


Stochastic modeling and optimization of phage display.
Phage display, SELEX and other methods of combinatorial chemistry have become very popular means of finding ligands with high affinities to given targets. Despite their success, they suffer from numerous sources of error and bias, such as very low initial concentrations of species, non-specific binding, and the sampling of only a tiny fraction of the library at the end of an experiment. To understand the interaction of these errors and to better devise molecular search strategies that take the errors into account, I devise and analyze a highly detailed model of phage display. The model is specifically designed to study the influence of the stochastic nature of each laboratory step. The model includes phage multivalency, multiple classes of targets, and solid-phase equilibrium and washing, yet it is amenable to analytic results and rapid computer simulation. With both analytic and simulation approaches, I: (1) describe the effects of target concentration, phage valency, degree of background binding and other laboratory parameters on the probabilities of phage binding and of being selected; (2) show the effects of an increasing selection stringency strategy and how it results in a tradeoff between rapid library enrichment and high probability of sampling the best ligands; and (3) show how the number of phage sampled for detailed study at the end of a search alters search success. The work concludes with several practical suggestions for the control of selection stringency.


"Bitten By Shyness": Menstrual Hygiene Management, Sanitation, and the Quest for Privacy in South Africa.
Little is known about how menstruation is managed in low-income settings and whether existing sanitation systems meet women's needs. Using the 'Photovoice' method with 21 women in participatory workshops and in-depth interviews, we collected data on menstrual hygiene management in three sites in Durban, South Africa. All women reported using disposable sanitary pads. Although they were aware that disposable pads were nonbiodegradable, incompatible with waterborne flush systems, and fill up pit latrines, they had little experience with reusable products. Considerable energy was devoted to concealing and containing 'menstrual waste,' and women expressed concern about inadequate privacy during menstruation. All sites lacked discreet disposal options and reliable water access, while outdoor sanitation facilities were considered unsafe. Findings highlight the need for advocacy to improve safety and privacy of facilities for women in this setting.


Reactive anti-predator behavioral strategy shaped by predator characteristics.
Large mammalian herbivores use a diverse array of strategies to survive predator encounters including flight, grouping, vigilance, warning signals, and fitness indicators. While anti-predator strategies appear to be driven by specific predator traits, no prior studies have rigorously evaluated whether predator hunting characteristics predict reactive anti-predator responses. We experimentally investigated behavioral decisions made by free-ranging impala, wildebeest, and zebra during encounters with model predators with different functional traits. We hypothesized that the choice of response would be driven by a predator's hunting style (i.e., ambush vs. coursing) while the intensity at which the behavior was performed would correlate with predator traits that contribute to the prey's relative risk (i.e., each predator's prey preference, prey-specific capture success, and local predator density). We found that the choice and intensity of anti-predator behaviors were both shaped by hunting style and relative risk factors. All prey species directed longer periods of vigilance towards predators with higher capture success. The decision to flee was the only behavior choice driven by predator characteristics (capture success and hunting style) while intensity of vigilance, frequency of alarm-calling, and flight latency were modulated based on predator hunting strategy and relative risk level. Impala regulated only the intensity of their behaviors, while zebra and wildebeest changed both type and intensity of response based on predator traits. Zebra and impala reacted to multiple components of predation threat, while wildebeest responded solely to capture success. Overall, our findings suggest that certain behaviors potentially facilitate survival under specific contexts and that prey responses may reflect the perceived level of predation risk, suggesting that adaptive functions to reactive anti-predator behaviors may reflect potential trade-offs to their use. The strong influence of prey species identity and social and environmental context suggest that these factors may interact with predator traits to determine the optimal response to immediate predation threat.


Updated ACVIM consensus statement on leptospirosis in dogs.
Since publication of the last consensus statement on leptospirosis in dogs, there has been revision of leptospiral taxonomy and advancements in typing methods, widespread use of new diagnostic tests and vaccines, and improved understanding of the epidemiology and pathophysiology of the disease. Leptospirosis continues to be prevalent in dogs, including in small breed dogs from urban areas, puppies as young as 11 weeks of age, geriatric dogs, dogs in rural areas, and dogs that have been inadequately vaccinated for leptospirosis (including dogs vaccinated with 2-serovar Leptospira vaccines in some regions). In 2021, the American College of Veterinary Internal Medicine (ACVIM) Board of Regents voted to approve the topic for a revised Consensus Statement. After identification of core panelists, a multidisciplinary group of 6 experts from the fields of veterinary medicine, human medicine, and public health was assembled to vote on the recommendations using the Delphi method. A draft was presented at the 2023 ACVIM Forum, and a written draft posted on the ACVIM website for comment by the membership before submission to the editors of the Journal of Veterinary Internal Medicine. This revised document provides guidance for veterinary practitioners on disease in dogs as well as cats. The level of agreement among the 12 voting members (including core panelists) is provided in association with each recommendation. A denominator lower than 12 reflects abstention of ≥1 panelists either because they considered the recommendation to be outside their scope of expertise or because there was a perceived conflict of interest.


Endoscopic brow lifts uber alles.
Innumerable approaches to the ptotic brow and forehead have been described in the past. Over the last twenty-five years, we have used all these techniques in cosmetic and reconstructive patients. We have used the endoscopic brow lift technique since 1995. While no one technique is applicable to all patients, the endoscopic brow lift, with appropriate modifications for individual patients, can be used effectively for most patients with brow ptosis. We present the nuances of this technique and show several different fixation methods we have found useful.


Fate of the Urinary Tract Virus BK Human Polyomavirus in Source-Separated Urine.
Human polyomaviruses are emerging pathogens that infect a large percentage of the human population and are excreted in urine. Consequently, urine that is collected for fertilizer production often has high concentrations of polyomavirus genes. We studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus (BKPyV) in hydrolyzed source-separated urine with infectivity assays and quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine for long periods of time (T90 [time required for 90% reduction in infectivity or gene copies] of >3 weeks), the viruses were rapidly inactivated (T90 of 1.1 to 11 h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA bacteriophage surrogate T3 (T90 of 24 to 46 days) was much more persistent than that of BKPyV, highlighting a major shortcoming of using bacteriophages as human virus surrogates. Pasteurization and filtration experiments suggest that BKPyV virus inactivation was due to microorganism activity in the source-separated urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is concurrent with inactivation. Our results imply that stored urine does not pose a substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA surrogate do not accurately depict BKPyV fate, and that microbial inactivation is driven by structural elements of the BKPyV capsid.IMPORTANCE We demonstrate that a common urinary tract virus has a high susceptibility to the conditions in hydrolyzed urine and consequently would not be a substantial exposure route to humans using urine-derived fertilizers. The results have significant implications for understanding virus fate. First, by demonstrating that the dsDNA (double-stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity lasting for hours to days, our work highlights the shortcomings of using qPCR to estimate risks from unculturable viruses. Second, commonly used dsDNA surrogate viruses survived for weeks under the same conditions that BK polyomavirus survived for only hours, highlighting issues with using virus surrogates to predict how human viruses will behave in the environment. Finally, our mechanistic inactivation analysis provides strong evidence that microbial activity drives rapid virus inactivation, likely through capsid disassembly. Overall, our work underlines how subtle structural differences between viruses can greatly impact their environmental fate.


Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial.
Systemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts. Relate systemic levels of those proteins to forced expiratory volume in 1 s (FEV1) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV1 of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial. Participants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV1 decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender. Systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV1, FEV1 decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months. In COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV1 decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD. NCT01313676.


Gastrointestinal leishmaniasis in human immunodeficiency virus-infected patients: report of five cases and review.
We describe five cases of gastrointestinal leishmaniasis in patients with human immunodeficiency virus infection and review 10 additional cases reported in the literature. All of the patients had CD4+ cell counts of < 200/mm3, and AIDS had been previously diagnosed for 12 patients. Fever and splenomegaly were present in 46% of cases. Thirteen patients had digestive symptoms; these symptoms included diarrhea (6), dysphagia and/or odynophagia (6), abdominal pain (2), epigastric pain (2), gastrointestinal hemorrhage (1), and rectal discomfort (1). The regions of the digestive tract most frequently affected by Leishmania organisms were the duodenal mucosa (90%) and the gastric mucosa (75%). Endoscopy showed normal-appearing mucosa in 45% of cases. In 10 cases the diagnosis of visceral leishmaniasis was first made by biopsy of the gastrointestinal mucosa. In most cases treatment with antimonial agents was not effective.