Living Anisotropic Structural Color Hydrogels for Cardiotoxicity Screening.
Environmental toxins can result in serious and fatal damage in the human heart, while the development of a viable stratagem for assessing the effects of environmental toxins on human cardiac tissue is still a challenge. Herein, we present a heart-on-a-chip based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured living anisotropic structural color hydrogels for cardiotoxicity screening. Such anisotropic structural color hydrogels with a conductive parallel carbon nanotube (CNT) upper layer, gelatin methacryloyl (GelMA) interlayer, and inverse opal bottom layer were fabricated by a sandwich replicating approach. The inverse opal structure endowed the anisotropic hydrogels with stable structural color property, while the parallel and conductive CNTs could induce the hiPSC-CMs to grow in a directional manner with consistent autonomous beating. Notably, the resultant hiPSC-CM-cultured hydrogel exhibited synchronous shifts in structural color, responding to contraction and relaxation of hiPSC-CMs, offering a visual platform for monitoring cell activity. Given these features, the hiPSC-CM-cultured living anisotropic structural color hydrogels were integrated into a heart-on-a-chip, which provided a superior cardiotoxicity screening platform for environmental toxins.


Delta-Notch signaling induces hypochord development in zebrafish.
Different cell types that occupy the midline of vertebrate embryos originate within the Spemann-Mangold or gastrula organizer. One such cell type is hypochord, which lies ventral to notochord in anamniote embryos. We show that hypochord precursors arise from the lateral edges of the organizer in zebrafish. During gastrulation, hypochord precursors are closely associated with no tail-expressing midline precursors and paraxial mesoderm, which expresses deltaC and deltaD. Loss-of-function experiments revealed that deltaC and deltaD were required for her4 expression in presumptive hypochord precursors and for hypochord development. Conversely, ectopic, unregulated Notch activity blocked no tail expression and promoted her4 expression. We propose that Delta signaling from paraxial mesoderm diversifies midline cell fate by inducing a subset of neighboring midline precursors to develop as hypochord, rather than as notochord.


Temporal Trends in Use of Biologic DMARDs for Rheumatoid Arthritis in the United States: A Cohort Study of Publicly and Privately Insured Patients.
Ten biologic disease-modifying antirheumatic drugs (bDMARDs) are available as treatment for rheumatoid arthritis (RA), but relatively little is known about population-level time trends in the use of these agents. To describe time trends in the use of bDMARDs in RA patients with private or public insurance in the United States. Claims data from private (Optum Clinformatics, 2004-2015) and public (Medicaid Analytic eXtract [MAX], 2000-2010) insurance programs were used. Patients with RA diagnosis codes and continuous health plan enrollment for 1-year baseline and 1-year follow-up periods were identified into 2 separate cohorts: (1) patients not using any bDMARD or (2) patients using a single bDMARD during the baseline period. Initiation of the first bDMARD from group 1 and switch to a second bDMARD from group 2 was identified as the outcome of interest during the 1-year follow-up period. Using mixed-effects regression models, we calculated yearly rates of initiation and switch for bDMARDs, adjusted for case-mix. We also described the proportion of all initiations and switches accounted for by each agent. There were 113,031 RA patients with public insurance and 97,751 RA patients with private insurance who were included in the study. The rates of initiation of bDMARDs (per 100 patients) increased significantly over time in Medicaid data for incident RA patients (from 1.1 to 3.1, P = 0.0006) and prevalent RA patients (from 4.6 to 10.9, P = 0.008). In Optum Clinformatics data, the rates were stable, with 7.7 to 8.3 per 100 incident RA patients (P = 0.10) and 11.0 to 11.5 per 100 prevalent RA patients (P = 0.12). The rates of switching (per 100 patients) increased over time from 6.4 to 16.0 (P = 0.04) in Medicaid data and 9.1 to 17.0 (P = 0.00003) in Optum Clinformatics data. Use of etanercept as the most common first-line agent was stable at approximately 50% of all biologic initiations, but use of infliximab decreased and the use of newer agents increased. More RA patients used bDMARDs in recent years, and use of newer agents, including certolizumab, golumumab, and tocilizuamab, is rising, which highlights a need for further comparative safety and effectiveness research of these agents to better guide evidence-based decision making. This study was supported by an investigator-initiated research grant from Pfizer. The study was conducted by the authors independent of the sponsor. The sponsor was given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and determined the final wording. Solomon receives salary support through research support to his hospital from Amgen, Pfizer, AstraZeneca, Genentech, Lilly, Bristol-Myers Squibb, and CORRONA. Kim receives research grants from AstraZeneca, Lilly, Pfizer, Bristol-Myers Squibb, and Genentech. Desai receives research grants from Merck. Study concept and design were contributed by Desai and Kim. Liu took the lead in data collection, along with Jin, Desai, and Kim. All authors contributed equally in the interpretation of the results. The manuscript was written and revised primarily by Desai, along with Kim and the other authors.


Origin of the monolayer Raman signature in hexagonal boron nitride: a first-principles analysis.
Monolayers of hexagonal boron nitride (h-BN) can in principle be identified by a Raman signature, consisting of an upshift in the frequency of the E2g vibrational mode with respect to the bulk value, but the origin of this shift (intrinsic or support-induced) is still debated. Herein we use density functional theory calculations to investigate whether there is an intrinsic Raman shift in the h-BN monolayer in comparison with the bulk. There is universal agreement among all tested functionals in predicting the magnitude of the frequency shift upon a variation in the in-plane cell parameter. It is clear that a small in-plane contraction can explain the Raman peak upshift from bulk to monolayer. However, we show that the larger in-plane parameter in the bulk (compared to the monolayer) results from non-local correlation effects, which cannot be accounted for by local functionals or those with empirical dispersion corrections. Using a non-local-correlation functional, we then investigate the effect of finite temperatures on the Raman signature. We demonstrate that bulk h-BN thermally expands in the direction perpendicular to the layers, while the intralayer distances slightly contract, in agreement with observed experimental behavior. Interestingly, the difference in in-plane cell parameter between bulk and monolayer decreases with temperature, and becomes very small at room temperature. We conclude that the different thermal expansion of bulk and monolayer partially 'erases' the intrinsic Raman signature, accounting for its small magnitude in recent experiments on suspended samples.


Amniotic membrane as a biological scaffold for dental pulp stem cell transplantation in ocular surface reconstruction.
To evaluate the ability of human immature dental pulp stem cells, which are mesenchymal stem cells of neural crest origin, to differentiate into the corneal epithelium for purposes of corneal transplantation and tissue engineering when cultured on de-epithelized amniotic membranes. We compared the immunophenotypes (ABCG2, K3/12, and vimentin) of cells grown on amniotic membranes or plastic surfaces under serum-free conditions or in culture media containing serum or serum replacement components. Immature dental pulp stem cells grown on amniotic membranes under basal conditions are able to maintain their undifferentiated state. Our data also suggest that the culture medium used in the present work can modulate the expression of immature dental pulp stem cell markers, thus inducing epithelial differentiation of these cells in vitro. Our results suggest that the amniotic membrane is a good choice for the growth and transplantation of mesenchymal stem cells, particularly immature dental pulp stem cells, in clinical ocular surface reconstruction.


Incoherent white light solitons in logarithmically saturable noninstantaneous nonlinear media.
We analytically demonstrate the existence of white light solitons in logarithmically saturable noninstantaneous nonlinear media. This incoherent soliton has elliptic Gaussian intensity profile, and elliptic Gaussian spatial correlation statistics. The existence curve of the soliton connects the strength of the nonlinearity, the spatial correlation distance as a function of frequency, and the characteristic width of the soliton. For this soliton to exist, the spatial correlation distance must be smaller for larger temporal frequency constituents of the beam.


Treatment options and considerations for hypertensive patients to prevent dementia.
Dementia is a worldwide health concern, which leads to loss of autonomy. To date no curative treatment is available so focus on modifiable risk factors is of particular interest. Hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia including vascular dementia (VAD) and Alzheimer disease (AD). In this context, antihypertensive treatments might have a preventive effect. The objective of this review was to examine the relationship between antihypertensive therapy and cognitive decline or dementia. Areas covered: A literature search was conducted using PUBMED and the COCHRANE LIBRARY for publications from 1990 onwards mentioning cognitive decline, AD, Vad, mixed dementia, vascular cognitive impairment, hypertension and antihypertensive therapy. Thirty-nine relevant publications including 20 longitudinal studies, 10 randomized-controlled trials and 9 meta-analyses were taken into account. Expert opinion: Most observational studies have suggested a potential preventive effect of antihypertensive therapies on cognitive decline and dementia, particularly calcium channel blockers and renin-angiotensin system blockers. Randomized clinical trials and meta-analyses provided more conflicting results potentially due to methodological issues. In conclusion, antihypertensive therapies may reduce cognitive decline and incidence of dementia. Further randomized clinical trials conducted in populations at higher risk of cognitive decline, with longer periods of follow-up and cognition as the primary outcome are still needed.


Rapid Identification Method of Omphalotus japonicus by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
Omphalotus japonicus is a poisonous mushroom that grows in Japan. It can be mistaken for edible mushrooms (Shiitake, Hiratake and Mukitake), and if ingested, it causes food poisoning within 30 min to 1 hr. We established a rapid detection method using PCR-RFLP to identify O. japonicus by restriction digestion of the amplified ITS region. By using Sau96I, Bpu10I, SfcI or DrdI/HincII as a restriction enzyme, it was possible to rapidly identify and discriminate O. japonicus based on the fragment length. This study also provided a short PCR-RFLP system comprising amplification and digestion of a short 200-bp DNA fragment within the ITS region. The system could identify and discriminate O. japonicus after in vitro gastric digestion of native and heated mushroom samples as a model of food poisoning. In addition, a confirmatory assay using real-time PCR was developed to achieve more sensitive detection of O. japonicus.


Underwater optical wireless communications: depth-dependent beam refraction.
Global refractive gradients in seawater cause pointing problems for optical wireless communications. A refractive index depth profile of the Pacific Ocean was calculated from measured salinity, temperature, and pressure, determining the end points of a refracted and nonrefracted 200 m communication link. Numerical ray tracing was used with a point source for angles between 10° and 80° and transmission wavelengths of 500-650 nm; the maximum end-point difference found was 0.23 m. A 500 nm laser with a 0.57° full-angle FOV was traced; the nonrefracted receiver location was outside the FOV for all links angled >15° to the vertical. However, most pointing issues underwater are unlikely to be significant with suitable FOV choice and natural scattering of the source.


Comparative study on the regeneration of flue-gas desulfurizing agents by using conventional electrodialysis (ED) and bipolar membrane electrodialysis (BMED).
Piperazine is an ideal desulfurizing agent but the heat-stable salts formed in desulfurization have caused secondary pollution and waste of resources. In the previous paper, a method was reported to regenerate piperazine by using BMED. To find the variety of that regeneration process, we performed experiments on the regeneration of piperazine by using ED. In comparison, ED has higher piperazine yield and current efficiency, and much lower voltage drop and energy consumption. However, its process cost is higher than that of BMED due to an extra expenditure for the base and its tank and pumps. The process cost is estimated to be 0.96 dollar/kg Pz for BMED and 1.14 dollar/kg Pz for ED. Notably, BMED has more environmental benefits and will be more economically attractive as the control on secondary pollution is strengthened and the bipolar membrane cost decreases.


A validation study: simulations as a measure of nurse practitioners' problem-solving skills.
A national sample of 79 masters- and certificate-prepared family and adult nurse practitioners completed six instruments designed to validate one type of clinical simulation, patient management problems (PMPs). The instruments were: a self-chart audit, self-evaluation rating scale, colleague evaluation rating scale, multiple-choice examination. PMP simulation, and demographic questionnaire. Use of a multitrait-multimethod correlation matrix, a multivariate analysis of covariance, and a stepwise multiple regression analysis provided modest evidence to support the claim that the PMP simulation is a valid measure of the construct clinical problem solving. In fact, a multiple-choice examination appeared to be an equal, if not superior, instrument.


Evidence for the cognitive mediational model of cognitive behavioural therapy for depression.
Although empirical support for the efficacy of cognitive behavioural therapy (CBT) as a treatment for major depressive disorder (MDD) is well established, its mechanism of action is uncertain. In this investigation, we examined evidence for the cognitive mediational model in a randomized control trial involving CBT, interpersonal therapy (IPT) and pharmacotherapy (PHT) in patients with MDD. One hundred and thirty participants diagnosed with MDD were treated with CBT, IPT or PHT. Participants completed the Hamilton Depression Rating Scale, Beck Depression Inventory-II and Dysfunctional Attitudes Scale prior to and following treatment. The cognitive mediational model, in which dysfunctional attitudes are proposed to mediate depressive symptom reduction in response to treatment, provided a good fit to the data when contrasting CBT v. IPT, with results supporting a mediational role for dysfunctional attitude change in depressive symptom reduction. The complication model, in which dysfunctional attitudes are proposed to be a consequence of depressive symptom reduction, provided a good fit to the data when contrasting CBT v. PHT, with results supporting a mediational role for depressive symptom reduction in dysfunctional attitude change. There was no evidence for a mediational role for dysfunctional attitude change in IPT. Changes in dysfunctional attitudes accompanied both CBT and PHT; however, empirical evidence suggests that the role of attitudes in treatment outcome may differ between these two treatments.


Looking through the Glass Ceiling: A Qualitative Study of STEM Women's Career Narratives.
Although efforts have been directed toward the advancement of women in science, technology, engineering, and mathematics (STEM) positions, little research has directly examined women's perspectives and bottom-up strategies for advancing in male-stereotyped disciplines. The present study utilized Photovoice, a Participatory Action Research method, to identify themes that underlie women's experiences in traditionally male-dominated fields. Photovoice enables participants to convey unique aspects of their experiences via photographs and their in-depth knowledge of a community through personal narrative. Forty-six STEM women graduate students and postdoctoral fellows completed a Photovoice activity in small groups. They presented photographs that described their experiences pursuing leadership positions in STEM fields. Three types of narratives were discovered and classified: career strategies, barriers to achievement, and buffering strategies or methods for managing barriers. Participants described three common types of career strategies and motivational factors, including professional development, collaboration, and social impact. Moreover, the lack of rewards for these workplace activities was seen as limiting professional effectiveness. In terms of barriers to achievement, women indicated they were not recognized as authority figures and often worked to build legitimacy by fostering positive relationships. Women were vigilant to other people's perspectives, which was costly in terms of time and energy. To manage role expectations, including those related to gender, participants engaged in numerous role transitions throughout their day to accommodate workplace demands. To buffer barriers to achievement, participants found resiliency in feelings of accomplishment and recognition. Social support, particularly from mentors, helped participants cope with negative experiences and to envision their future within the field. Work-life balance also helped participants find meaning in their work and have a sense of control over their lives. Overall, common workplace challenges included a lack of social capital and limited degrees of freedom. Implications for organizational policy and future research are discussed.


An ATP2B4 polymorphism protects against malaria in pregnancy.
Polymorphisms of ATP2B4 encoding an ubiquitous Ca(2+) pump protect against severe childhood malaria. We assessed the influence of a main polymorphism (rs10900585) on malaria among 834 delivering Ghanaian women. In homozygous primiparae, the odds of placental Plasmodium falciparum infection were reduced by 64%. No influence of the polymorphism on parasite density, low birth weight, or preterm delivery was discernible. However, malarial anemia was greatly reduced in primiparous carriers of the variant allele, paralleling the reduced impact of malaria on hemoglobin levels in this group. A common ATP2B4 polymorphism protects against malaria in pregnancy and related maternal anemia, suggesting ATP2B4 variant associated protection not to be limited to severe childhood malaria.


Epigenetic silencing in transgenic plants.
Epigenetic silencing is a natural phenomenon in which the expression of genes is regulated through modifications of DNA, RNA, or histone proteins. It is a mechanism for defending host genomes against the effects of transposable elements and viral infection, and acts as a modulator of expression of duplicated gene family members and as a silencer of transgenes. A major breakthrough in understanding the mechanism of epigenetic silencing was the discovery of silencing in transgenic tobacco plants due to the interaction between two homologous promoters. The molecular mechanism of epigenetic mechanism is highly complicated and it is not completely understood yet. Two different molecular routes have been proposed for this, that is, transcriptional gene silencing, which is associated with heavy methylation of promoter regions and blocks the transcription of transgenes, and post-transcriptional gene silencing (PTGS), the basic mechanism is degradation of the cytosolic mRNA of transgenes or endogenous genes. Undesired transgene silencing is of major concern in the transgenic technologies used in crop improvement. A complete understanding of this phenomenon will be very useful for transgenic applications, where silencing of specific genes is required. The current status of epigenetic silencing in transgenic technology is discussed and summarized in this mini-review.


Diagnosis of Pediatric Foreign Body Ingestion: Clinical Presentation, Physical Examination, and Radiologic Findings.
(1) To describe clinical and radiologic findings in patients with esophageal foreign bodies. (2) To examine the sensitivity and specificity of history, physical examination, and radiologic studies in children with suspected foreign body ingestion. A retrospective cohort study was performed evaluating all children who underwent esophagoscopy for suspected foreign body ingestion at our institution from 2006 to 2013. Five hundred forty-three patients were included (54% male). Average age was 4.7 years (SD = 4.1 years). Foreign bodies were identified on esophagoscopy in 497 cases (92%). Ingestion was witnessed in 23% of cases. Most common presenting symptoms were choking/gagging (49%), vomiting (47%), and dysphagia/odynophagia (42%). Most patients with foreign bodies had a normal exam (76%). Most foreign bodies were radiopaque (83%). In 59% of patients with normal chest radiographs, a foreign body was present. Sensitivity and specificity of 1 or more findings on history, physical examination, and imaging were 99% and 0%, 21% and 76%, and 83% and 100%, respectively. Most patients with esophageal foreign bodies are symptomatic. Although many patients will have a normal physical examination, an abnormal exam should increase suspicion for a foreign body. Most esophageal foreign bodies are radiopaque, but a normal chest radiograph cannot rule out a foreign body.


Characterisation of inflammatory processes in Helicobacter pylori-induced gastric lymphomagenesis in a mouse model.
Gastric MALT lymphoma (GML) can be induced by Helicobacter pylori infection in BALB/c mice thymectomised at day 3 post-birth (d3Tx). This represented a unique opportunity to investigate the inflammatory process involved in the recruitment, proliferation and structuration of lymphoid infiltrates in the gastric mucosa of mice developing GML. Complementary molecular and proteomic approaches demonstrated that Th1 and Th2 cytokines were upregulated, along with activators/regulators of the lymphoid response and numerous chemokines. Interleukin-4, interferon γ, lymphotoxin-α and -β were significantly upregulated and correlated with the inflammatory scores for all the d3Tx mice. GML lesions in d3Tx mice infected with H. pylori were associated with the presence of the inflammatory response. The dysregulation of numerous members of the tumour necrosis factor superfamily was also evident and suggests that they could play an important role in GML pathology, especially in light of their ability to promote and control lymphocyte proliferation.


Analytic formula for leading-order nonlinear coherent response in stochastic resonance.
The response of an overdamped bistable system driven by a Gaussian white noise and perturbed by a weak monochromatic signal is studied analytically. The perturbation theory is employed to calculate the nonlinear coherent response in the leading order of the amplitude of the weak signal. Simple analytic formulas for the linear and the nonlinear responses have been derived in low noise and low-frequency regime and the results based on the derived formulas are compared with the numerical results.


Pictures, images, and recollective experience.
Five experiments investigated the influence of picture processing on recollective experience in recognition memory. Subjects studied items that differed in visual or imaginal detail, such as pictures versus words and high-imageability versus low-imageability words, and performed orienting tasks that directed processing either toward a stimulus as a word or toward a stimulus as a picture or image. Standard effects of imageability (e.g., the picture superiority effect and memory advantages following imagery) were obtained only in recognition judgments that featured recollective experience and were eliminated or reversed when recognition was not accompanied by recollective experience. It is proposed that conscious recollective experience in recognition memory is cued by attributes of retrieved memories such as sensory-perceptual attributes and records of cognitive operations performed at encoding.


Radionuclide evaluation of liver transplants.
Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.


Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury.
AMP-activated protein kinase (AMPK) is activated by increases in the intracellular AMP-to-ATP ratio and plays a central role in cellular responses to metabolic stress. Although activation of AMPK has been shown to have anti-inflammatory effects, there is little information concerning the role that AMPK may play in modulating neutrophil function and neutrophil-dependent inflammatory events, such as acute lung injury. To examine these issues, we determined the effects of pharmacological activators of AMPK, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and barberine, on Toll-like receptor 4 (TLR4)-induced neutrophil activation. AICAR and barberine dose-dependently activated AMPK in murine bone marrow neutrophils. Exposure of LPS-stimulated neutrophils to AICAR or barberine inhibited release of TNF-alpha and IL-6, as well as degradation of IkappaBalpha and nuclear translocation of NF-kappaB, compared with findings in neutrophil cultures that contained LPS without AICAR or barberine. Administration of AICAR to mice resulted in activation of AMPK in the lungs and was associated with decreased severity of LPS-induced lung injury, as determined by diminished neutrophil accumulation in the lungs, reduced interstitial pulmonary edema, and diminished levels of TNF-alpha and IL-6 in bronchoalveolar lavage fluid. These results suggest that AMPK activation reduces TLR4-induced neutrophil activation and diminishes the severity of neutrophil-driven proinflammatory processes, including acute lung injury.


New Echocardiographic Protocol for the Assessment of Experimental Myocardial Infarction in Rats.
The rat infarct model was used extensively to study the pathophysiology of myocardial infarction and to evaluate different therapies. Transthoracic echocardiography is used in rats in order to assess cardiac anatomy and function, being a safe and reliable non-invasive technique. However, studies combining conventional with new echo techniques, such as tissue Doppler imaging (TDI) and speckletracking echocardiography (STE), are lacking. To validate a protocol using the available conventional and new echocardiographic techniques (TDI and STE) for a comprehensive assessment of cardiac remodelling and function, after myocardial infarction in rats. Ten Wistar (W) and five Sprague Dawley (SD) male rats (aged 21±2 weeks, mean weight 355±43 g) were evaluated by echocardiography, before and 24 hours post-ligation of the left coronary artery, with previous anaesthesia. Left ventricular (LV) structure was assessed by end-diastolic and endsystolic anterior wall thickness and LV diameters (from the SAX view), while LV function by fractional shortening (FS) and ejection fraction (EF) (by area-length formula), septal mitral annular plane systolic excursion (MAPSE), cardiac output (CO), myocardial performance index (MPI), septal mitral annular systolic velocity (S', by TDI), and global circumferential and radial systolic strain (GCS, GRS) and strain rate (GCSr, GRSr) by STE, from the SAX view at the level of papillary muscles. Feasibility of measuring the above mentioned parameters was 100%. Twenty-four hours after myocardial infarction, rats had lower heart rate (373±44 vs. 351±32 bpm, p<0.05) and thinner LV anterior wall, while LV diameters and volumes were significantly higher. FS (54±7 vs. 33±9%), EF (72±9vs. 47±10%), septal MAPSE (2.02±0.17 vs. 1.44±0.22 mm), CO (76±15 vs. 48±12 ml/min), MPI (0.33±0.11 vs. 0.50±0.14), S' (5.58±1.20 vs. 3.84±1.06 cm/s), and LV strain and strain rate (GCS: -23.52±2.44 vs. -13.33±1.51% and GRS: 50.45±13.11 vs. 17.27±5.2%, GCSr: -8.42±0.85 vs. -4.68±0.53; and GRSr: 11.93±2.39 vs. 4.89±1.18 1/s) were significantly lower, all p<0.01. Our echocardiographic protocol of experimental myocardial infarction in rats is feasible. The impact of myocardial infarction in rats could be more extensively assessed using a comprehensive echocardiographic protocol of conventional and specific myocardial parameters, measured by TDI and STE, in order to quantify better the LV structure and function. Therefore, we suggest that this protocol may be used in order to assess the effect of different regenerative therapies in experimental myocardial infarction in rats.


Effects of granulocyte-macrophage colony-stimulating factor and colony-stimulating factor-1 on the proliferation and differentiation of murine alveolar macrophages.
Murine alveolar macrophages (AM) were shown to have proliferative ability and to form colonies in vitro. The factors in lung-conditioned medium (CM) and L929-CM which stimulate the proliferation of AM were considered to be granulocyte-macrophage colony-stimulating factor (GM-CSF) and CSF-1, respectively, because recombinant murine (rm)GM-CSF and recombinant human (rh)CSF-1 could replace the activities of lung-CM and L929-CM, respectively. The phenotype of the cells in the colonies formed by AM incubated with rmGM-CSF or lung-CM was AM-like; more than 90% of the cells were stained by anti-asialo GM1 but not by FITC-LPS, and had AM-like morphology. Expression of Mac-1 Ag determined by M1/70HL in these cells as well as original AM was low. However, the phenotype of the cells in the colonies formed by AM incubated with rhCSF-1 or L929-CM was peritoneal macrophage (PM)-like; more than 90% of the cells were stained by FITC-LPS and M1/70HL, but not by anti-asialo GM1, and showed PM-like morphology. The cells in the colonies formed by AM incubated with rmGMCSF changed their phenotype after treatment with rhCSF-1; the percentage of cells stained by anti-asialo GM1 decreased, and that of cells stained by FITC-LPS increased. The cells in the colonies formed by AM incubated with rhCSF-1 never changed their phenotype after incubation with rmGM-CSF. In contrast to AM, more than 90% of the cells in all colonies formed by PM incubated with either rmGM-CSF, rhCSF-1, lung-CM, or L929-CM were stained by FITC-LPS but not by anti-asialo GM1. These results show that although AM and PM can proliferate, AM, in contrast to PM, are bipotential cells that can differentiate into two types of macrophages responding to distinct types of CSF, and that one of the molecular mechanisms controlling macrophage heterogeneity may be based on the type of CSF produced at distinct tissues.


Effects of contrast media on renal function and subcellular morphology in the dog.
The effects of intravenous contrast media (CM) on renal excretory function and subcellular morphology are examined in this animal investigation. A decrease in GFR (12.0 +/- 1.6 vs. control 30.2 +/- 2.5 ml/min) was observed when renal function was evaluated by means of the artero-venous extraction method with Tc99m DTPA and the anticipated inverse relationship to urinary flow (Vml/min) noted. An artifactual increase in GFR (43.5 +/- 10.0 vs. control 39.1 +/- 3.8 ml/min) was observed using the timed urinary clearance of inulin. V(ml/min) increased four-fold (0.6 +/- 0.16 control vs. 2.7 +/- 0.7 ml/min; P less than .05) over the first five minutes after injection of CM. Urine osmolality initially approached isotonicity and then returned toward preinjection values. Osmolal clearance (Cosm) rose 2.5 times (1.4 +/- 0.3 control vs. 3.7 +/- 1.0 ml/min; P less than .05). The fractional excretion of both Na+ (FENa+) and K+ (FEK+) increased. A comparison of urinary osmolality vs. time after injection of CM confirms a nonspecific osmotic effect on tubular (and hence total urine) flow. The hemodynamic effects of CM on the kidney via the i.v. route reflect a predominant and nonspecific osmotically mediated vasodilation. No significant light or electron microscopic changes were observed. These findings suggest that the major renal physiologic actions of hypertonic CM are a nonspecific response to agent osmolality.


Fms related tyrosine kinase 1 (Flt1) functions as an oncogene and regulates glioblastoma cell metastasis by regulating sonic hedgehog signaling.
Studies have shown that the abnormal expression of Fms related tyrosine kinase 1 (Flt1) is associated with multiple malignancies, yet its role in glioblastoma pathology remains to be elucidated. In this study, we investigated the role of Flt1 in regulating proliferation, migration and invasion of glioblastoma cells by establishing glioblastoma cell strains with constitutively silenced or elevated Flt1 expression. We demonstrate that ectopic expression of Flt1 promotes glioblastoma cells migration, invasion through cell scratching and Transwell assays. Further study has indicated that Flt1 knockdown prevents the spread of glioblastoma cells in vivo. Conversely, we also show that suppression of Flt1 expression inhibits migration and invasion of glioblastoma cells. Finally, our findings demonstrate that Flt1 promotes invasion and migration of glioblastoma cells through sonic hedgehog (SHH) signaling pathway. Our study suggests that galectin-1 represents a crucial regulator of glioblastoma cells metastasis. Thus, the detection and targeted treatment of Flt1-expressing cancer serves as a new therapeutic target for glioblastoma.


ALAD-YOLO:an lightweight and accurate detector for apple leaf diseases.
Suffering from various apple leaf diseases, timely preventive measures are necessary to take. Currently, manual disease discrimination has high workloads, while automated disease detection algorithms face the trade-off between detection accuracy and speed. Therefore, an accurate and lightweight model for apple leaf disease detection based on YOLO-V5s (ALAD-YOLO) is proposed in this paper. An apple leaf disease detection dataset is collected, containing 2,748 images of diseased apple leaves under a complex environment, such as from different shooting angles, during different spans of the day, and under different weather conditions. Moreover, various data augmentation algorithms are applied to improve the model generalization. The model size is compressed by introducing the Mobilenet-V3s basic block, which integrates the coordinate attention (CA) mechanism in the backbone network and replacing the ordinary convolution with group convolution in the Spatial Pyramid Pooling Cross Stage Partial Conv (SPPCSPC) module, depth-wise convolution, and Ghost module in the C3 module in the neck network, while maintaining a high detection accuracy. Experimental results show that ALAD-YOLO balances detection speed and accuracy well, achieving an accuracy of 90.2% (an improvement of 7.9% compared with yolov5s) on the test set and reducing the floating point of operations (FLOPs) to 6.1 G (a decrease of 9.7 G compared with yolov5s). In summary, this paper provides an accurate and efficient detection method for apple leaf disease detection and other related fields.


Autogenous Shrinkage, Microstructure, and Strength of Ultra-High Performance Concrete Incorporating Carbon Nanofibers.
The mix design of ultra-high performance concrete (UHPC) is complicated by the presence of many "ingredients." The fundamental packing density allows a simpler mix design with fewer ingredients to achieve optimum packing density and dense microstructure. The optimum particle grading increases the flowability of UHPC and eliminates entrapped air. This study presents a simplified particle grading design approach that positively influences the strength, autogenous shrinkage, and microstructure characteristics of UHPC. Carbon nanofibers (CNFs) of superior mechanical properties were added to enhance the strength of UHPC and to reduce its autogenous shrinkage. In addition, ground granulated blast-furnace slag (GGBS) was used as a cement replacement material to reduce the amount of cement in UHPC mixes. Test results showed that the presence of homogeneously dispersed CNF increased the compressive strength and compensated the autogenous shrinkage of UHPC. The findings indicated that an ideal particle distribution, which is close to the modified Andreasen and Andersen grading model, contributed to achieving high compressive strength and CNFs were capable of providing nano-bridges to compensate the shrinkage caused by GGBS.


Risk of steroid withdrawal in pediatric renal allograft recipients (a 5-year follow-up).
Withdrawal of steroid therapy in renal allograft recipients remains controversial despite the many side effects of this treatment. We have previously presented data on 16 pediatric renal transplant recipients in whom prednisone was withdrawn 6 months or later post-transplantation. To assess the impact of steroid withdrawal, we retrospectively compared this group of patients (Group 1) with a group of 12 patients (Group 2) with renal transplants who continued on prednisone. The groups were compared as to age, sex, ethnicity, source of graft, number of HLA-DR mismatches and incidence of ATN in the immediate postoperative period. The only significant difference was that Group 2 was older. Group 1 had significantly fewer episodes of early acute rejection in the first 6 months post-transplantation than the control group (3/16 vs 8/12, p = 0.009) but nevertheless, without prednisone, had significantly more late acute rejections (11/16 vs 3/12, p = 0.03). Acute rejections occurred as late as 4 years after withdrawal of steroids. Only 5 of the 16 patients in Group 1 have maintained stable graft function without steroids. All of these patients are now alive more than 5 years after steroid withdrawal. In comparing these patients to the other 11, who failed a trial of steroid withdrawal, we found that a serum creatinine of less than 1.7 mg/dl at the time of withdrawal of steroids was predictive of a successful outcome (p = 0.03). In conclusion, withdrawing steroids in pediatric renal allograft recipients has a high risk of late acute rejection and subsequent graft loss, especially for those who have higher baseline creatinine levels.


Glucose metabolism in brain tumours can be estimated using [18F]2-fluorodeoxyglucose positron emission tomography and a population-derived input function scaled using a single arterialised venous blood sample.
The aim of this study was to assess simplified methods for deriving input functions for estimating glucose metabolism using 18F-FDG-PET. Nine glioma patients underwent paired 18F-FDG-PET scans as part of a phase II study and the data used to estimate the metabolic rate of glucose (MRGlu) using a population-derived input function (arterial data from 14 scans) scaled using a single arterial blood sample taken at 20 min. Paired studies were performed in four further glioma patients with stable disease at least four months following radiotherapy to determine whether scaling the population-derived input function using a 20-min arterialised venous or venous sample further simplified the method. The heated hand method was used to obtain arterialised venous blood that approximated arterial blood. In the 9 phase II glioma patients, there was a good, statistically significant correlation between the MRGlu values estimated using the individual arterial input functions and the single arterial sample scaled population-derived input functions (r(2)=0.88, p<0.001, n=36). Blood samples collected during three scans on two of the stable disease patients showed no significant difference between the arterialised venous and arterial plasma concentrations of 18F (p>0.1, n=15) when the degree of arterialisation of the blood was monitored and maintained using a thermocouple. A significant difference was found between the plasma arterial and venous levels of 18F. There was an excellent correlation between MRGlu estimated using an arterial input function and a population-derived input function scaled using a single arterialised venous blood sample (r(2)=0.98, n=12). The method was reproducible with less than 4.4% variation between repeat tumour scans. Therefore, a population-derived input function scaled using a single arterialised venous blood sample at 20 min can be used for estimating MRGlu using 18F-FDG PET in glioma patients.


HOW is required for stem cell maintenance in the Drosophila testis and for the onset of transit-amplifying divisions.
The mechanisms by which germline stem cells (GSCs) in the Drosophila testis undergo asymmetric division to regenerate a stem cell as well as a daughter (gonialblast) that will only undergo a further four mitotic divisions prior to entering premeiotic S phase and differentiating into a cyst of spermatocytes are not fully resolved. Here we demonstrate that the HOW RNA-binding protein is required for maintenance of CycB and therefore mitotic progression in GSCs and gonialblasts as well as determining the timing of the spermatogonial divisions. HOW is normally expressed in a complementary pattern to Bam in the germline and bam mRNA is bound by HOW in vivo. Ectopic expression of the HOW(L) isoform is associated with a delay in accumulation of Bam to the level required for differentiation, resulting in extra mitotic divisions. Spatiotemporal regulation of HOW expression is therefore required to specify the four spermatogonial transit-amplifying divisions.


Frequent inconsistency of parsimony under a simple model of cladogenesis.
Although the conditions under which the parsimony method becomes inconsistent have been studied for almost two decades, the probability that the parsimony method would encounter conditions causing inconsistency under simple models of cladogenesis is unknown. Here, we examine the statistical behavior of the parsimony method under a birth-death model of cladogenesis, when the molecular clock holds. The parsimony method can become inconsistent a high proportion of the time even under this simple model of cladogenesis. When taxon sampling is poor or rates of evolution are high, the probability that parsimony will become inconsistent increases.


Systematic analysis of secondary life cycle inventories when modelling agricultural production: A case study for arable crops.
Analysis of agricultural production with life cycle based methodologies is data demanding. To build comprehensive life cycle inventories, secondary datasets are commonly used when primary data are not available. However, different inventory data and modelling approaches are used to populate secondary datasets, leading to different results. The present study analyses the features of twelve secondary datasets to support datasets selection and proper interpretation of results. We assess twelve datasets for arable crop production in France, as modelled in three databases often used in the LCA field (Agri-footprint, ecoinvent and AGRIBALYSE). First, we compared system boundaries and general assumptions. Second, we focused on foreground systems comparing, inventory data, data sources and modelling approaches. Third, we performed a contribution analysis of impact assessment results to identify modelling choices that contribute most to differences in the results. Nine relevant elements were identified and assessed: definition of system boundaries and modelling of agricultural practices, characteristics of inventory data, agricultural operations, fertiliser application and fate, plant protection products application and fate, heavy metals inputs to the agricultural system and fate, irrigation assumptions, land use and transformation. The datasets differ greatly with respect to these elements. Hence, recommendations are drawn from the datasets comparison, supporting the selection of the datasets coherently with the goal and scope of a study and interpretation of results.


Anticoagulants for cancer-associated ischemic stroke.
Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism.


Atopic dermatitis.
A) Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy. B) Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl. C) Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.


ALDH2 Expression, Alcohol Intake and Semen Parameters among East Asian Men.
Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.


Discourses on sex differences in medieval scholarly Islamic thought.
This study explores how medical authorities in medieval Islamic society understood and analyzed Greek authorities on the differences between men and women and their mutual contributions to the process of reproduction. As this research illustrates, such thinkers' interpretations of sex differences did not form a consistent corpus, and were in fact complex and divergent, reflecting, and contributing to, the social and cultural constructs of gender taken up by European authors in the Middle Ages. While some scholars have argued for a "one sex" view of human beings in the medieval period, a close reading of Islamic medical authors shows that the plurality and complexity of ideas about sex differences and the acceptance of the flexibility of barriers between the sexes make it difficult to assume that the biological knowledge about sex differences formed a unitary ideological foundation for a system of gender hierarchy. It is clear, however, that whatever their differences, medieval Islamic discussions of sex differences implicitly or explicitly emphasized the inferiority of the female body.


Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells.
ZnO@polymer core-shell nanoparticles are assembled into novel capsule shells with diameters of about 100 nm to load isotretinoin (ISO) with a capacity as high as 34.6 wt %. Although ISO, a widely used drug for acne treatment, by itself is not suitable for treating cancer because of its hydrophobicity, our ZnO-ISO composite showed much stronger anticancer activity. The improved cytotoxicity is ascribed to the synergistic effects of the ZnO@polymer and ISO, where the ZnO@polymer helps in the accumulation of ISO in cancer cells on the one hand, and on the other hand, ISO is released completely through ZnO decomposition under acidic conditions of cancer cells. Such a pH-triggered drug-delivery system exhibits a much improved killing of cancer cells in vitro in comparison with the benchmarks, Nintedanib and Crizotinib, two commercial drugs clinically applied against lung cancer.


Minimally invasive procedures and medical management-their relative merits in treating lower urinary tract symptoms of benign prostatic hyperplasia.
Evidence is reviewed supporting the safety and efficacy of minimally invasive transurethral microwave thermotherapy and medical management in patients with benign prostatic hyperplasia. Recent data indicate more pronounced long-term beneficial effects of microwave treatment. alpha-Blockade, however, offers more rapid onset of action than does microwave treatment. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement in patients undergoing microwave treatment. Compared with medical management, microwave treatment also appears to possess greater versatility, allowing patients who fall within a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success.


[THE SCALP AS A SPLIT-THICKNESS GRAFT DONOR IN THE TREATMENT OF A MASSIVE THERMAL INJURY].
We are presenting our initial experience with the utilization of the scalp as a donor for split thickness skin grafting in the treatment of massive thermal injuries. Rapid donor reepithelization, absence of hypertrophic scarring in the donor area, inconspicuous donor area and a large area for the procurement of grafts in the pediatric population are the advantages that are emphasized in the literature. The outcome in a 3-year-old boy who suffered a burn injury from an open fire in the family house on the 57% of his total body surface area (48% full thickness burn) showed that the "take rate", in the absence of a massive local infection, was around 80% and that the scalp can be utilized again as a donor area after a period of 14 days. Folliculitis and alopecia are complications that should be kept in mind when using this technique.


Linking physiological parameters to perturbations in the human exposome: Environmental exposures modify blood pressure and lung function via inflammatory cytokine pathway.
Human biomonitoring is an indispensable tool for evaluating the systemic effects derived from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. The aim of this study was to explore consequences of environmental exposures to diesel exhaust (DE) and ozone (O3) and ultimately to interpret these parameters from the perspective of in vitro to in vivo extrapolation. In particular, the objective was to use cytokine expression at the cellular level as a biomarker for physiological systemic responses such as blood pressure and lung function at the systemic level. The values obtained could ultimately link in vivo behavior to simpler in vitro experiments where cytokines are a measured parameter. Human exposures to combinations of DE and O3 and the response correlations between forced exhaled volume in 1 second (FEV1), forced vital capacity (FVC), systolic and diastolic blood pressure (SBP and DBP, respectively), and 10 inflammatory cytokines in blood (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) were determined in 15 healthy human volunteers. Results across all exposures revealed that certain individuals displayed greater inflammatory responses compared to the group and, generally, there was more between-person variation in the responses. Evidence indicates that individuals are more stable within themselves and are more likely to exhibit responses independent of one another. Data suggest that in vitro findings may ultimately be implemented to elucidate underlying adverse outcome pathways (AOP) for linking high-throughput toxicity tests to physiological in vivo responses. Further, this investigation supports assessing subjects based upon individual responses as a complement to standard longitudinal (pre vs. post) intervention grouping strategies. Ultimately, it may become possible to predict a physiological (systemic) response based upon cellular-level (in vitro) observations.


Controlling spin exchange interactions of ultracold atoms in optical lattices.
We describe a general technique that allows one to induce and control strong interaction between spin states of neighboring atoms in an optical lattice. We show that the properties of spin exchange interactions, such as magnitude, sign, and anisotropy, can be designed by adjusting the optical potentials. We illustrate how this technique can be used to efficiently "engineer" quantum spin systems with desired properties, for specific examples ranging from scalable quantum computation to probing a model with complex topological order that supports exotic anyonic excitations.


Nanoparticle conversion to biofilms: in vitro demonstration using serum-derived mineralo-organic nanoparticles.
Mineralo-organic nanoparticles (NPs) detected in biological fluids have been described as precursors of physiological and pathological calcifications in the body. Our main objective was to examine the early stages of mineral NP formation in body fluids. A nanomaterial approach based on atomic force microscopy, dynamic light scattering, electron microscopy and spectroscopy was used. The mineral particles, which contain the serum proteins albumin and fetuin-A, initially precipitate in the form of round amorphous NPs that gradually grow in size, aggregate and coalesce to form crystalline mineral films similar to the structures observed in calcified human arteries. Our study reveals the early stages of particle formation and provides a platform to analyze the role(s) of mineralo-organic NPs in human tissues.


Effects of haemorrhage on the distribution of the peripheral blood flow in the rabbit.
1. The effects of bleeding unanaesthetized rabbits by 26% of their blood volume on the blood flow in the portal, renal, muscle and skin beds were investigated in normal animals, in animals without functioning autonomic effectors, and in animals with section of the carotid sinus and aortic nerves.2. In animals without functioning autonomic effectors there was progressive vasodilatation during the 4 hr following haemorrhage, which differed markedly in the different regional beds studied. The dilatation was greatest in the portal bed, followed by kidney and skin, but there was no significant change in the vascular resistance in muscle.3. In normal animals with intact reflexes the vascular resistance either increases or remains at control values, suggesting that reflex constrictor effects oppose locally acting dilator mechanisms. During the 4 hr following haemorrhage reflex vasoconstrictor effects were greatest in kidney, followed by muscle, portal bed and skin.4. In animals with section of the carotid sinus and aortic nerves reflex constrictor effects were absent in the portal, muscle and skin beds, but significant vasoconstriction was still evident in the renal bed, though of smaller magnitude than in normal animals. The results suggest that the arterial baroreceptors are a major source of reflex activity following haemorrhage, but that other reflexogenic zones contribute to the renal effects in normal animals.


Serum asymmetric dimethylarginine (ADMA), homocysteine, vitamin B(12), folate levels, and lipid profiles in epileptic children treated with valproic acid.
Recent reports have demonstrated elevated serum homocysteine (Hcy) levels in children receiving valproic acid (VPA) therapy. Elevated Hcy levels might play a potential role in the resistance to antiepileptic drugs, and might lead to an increased risk for a vascular disease. It has been reported that elevated total homocysteine (tHcy) levels are associated with elevated asymmetric dimethylarginine (ADMA) levels, which are factors that may be better indicators of endothelial dysfunction compared to serum homocysteine levels, because they are less sensitive to changes, such as fasting status, physical activity, and other factors. In this study, we aim to evaluate serum ADMA, Hcy, lipid, folate, and vitamin B₁₂ levels in epileptic children, receiving VPA monotherapy. Forty-four epileptic children, receiving VPA monotherapy for at least 6 months and 28 healthy children aged between 4 and 16 years, were recruited. Serum lipids, lipoproteins, folate, vitamin B₁₂, Hcy, and ADMA levels were analyzed in both study groups. Serum Hcy, ADMA, and vitamin B₁₂ levels were higher in patients than in controls (p < 0.001 for tHcy and ADMA levels; p < 0.05 for vitamin B₁₂ levels); however, serum lipid, lipoprotein, and folate levels were similar. According to the duration of epilepsy, serum tHcy, ADMA, and triglyceride (TG) levels were higher in patients with epilepsy for ≥ 2 years than in patients with epilepsy for < 2 years (p < 0.001 for serum ADMA levels, p < 0.01 for tHcy levels, and p < 0.05 for serum TG levels). Similarly, with respect to the duration of VPA therapy, serum tHcy, ADMA, and TG levels were higher in patients who had received VPA therapy for more than 2 years (p < 0.001 for serum ADMA levels, p < 0.05 for serum tHcy levels, p < 0.01 for TG levels). Serum ADMA levels were significantly higher in patients receiving VPA at the dose of 25-30 mg/kg/day than in those receiving 20 mg/kg/day (p < 0.01). In conclusion, our study found increased serum ADMA levels and increased tHcy levels in epileptic children receiving VPA monotherapy. Increased serum ADMA levels were demonstrated in epileptic children who have had a seizure history greater than 2 years, and have used VPA therapy for more than 2 years, and have received higher doses of VPA. Routine monitoring of serum ADMA and tHcy levels might have beneficial effects for patients receiving long-term VPA therapy, especially in children who have other potential risk factors for vascular diseases. Further studies are needed to investigate serum ADMA and Hcy levels, and the presence of vascular disease, as well as the potential interactions between serum ADMA levels and seizure control.


Individuals Experiencing Homelessness: A Systematic Review of Otolaryngology-Related Health Needs and Community-Based Interventions.
Access to and use of physician services is limited for those experiencing homelessness. Homelessness may predispose patients to several Otolaryngology-Head and Neck Surgery (OHNS) health conditions and barriers to care may leave these unaddressed. The aim of this review was to synthesize the literature on OHNS health needs and community-based interventions for patients experiencing homelessness. English literature was searched in MEDLINE, EMBASE, and CINAHL. Studies were included if they reported on OHNS-related conditions in patients experiencing homelessness and/or interventions related to providing OHNS care to this patient population. Twelve hundred and one articles were screened, and 12 articles were included. Most studies reported on otologic conditions (n = 8) and head and neck-related conditions (n = 6). Nasal trauma, chronic rhinosinusitis, dysphonia, hearing loss, and cancerous/precancerous head and neck lesions were common OHNS conditions reported in this patient population. Identified barriers to care included lack of transportation, financial considerations, and lower health literacy. Three articles on community-based interventions were included. Most of these interventions were single visits to shelters, and ensuring adequate follow-up was identified as a challenge. The current literature brings attention to certain OHNS diseases that are prevalent in this unique patient population and identifies unique barriers these patients experience when accessing care. Future studies should focus on further delineating the impact of OHNS diseases in patients experiencing homelessness and screening interventions that can be employed to mitigate the impact of diseases of the head and neck.


Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts.
Vitamin K-dependent proteins in vascular tissue affect vascular stiffness and calcification, which is associated with cardiovascular disease (CVD) and all-cause mortality. To determine the association of circulating vitamin K concentrations with CVD and all-cause mortality by conducting a participant-level meta-analysis. We obtained individual participant-level data from the Health, Aging, and Body Composition Study, the Multi-Ethnic Study of Atherosclerosis, and the Framingham Offspring Study, known cohorts with available measures of fasting circulating phylloquinone (vitamin K-1) and confirmed CVD events and mortality. Circulating phylloquinone was measured in a central laboratory from fasting blood samples and categorized as ≤0.5 nmol/L, >0.5-1.0 nmol/L, and >1.0 nmol/L. Multivariable Cox proportional hazard regression with multiple imputations was used to evaluate the association of circulating phylloquinone with incident CVD and all-cause mortality risk. Among 3891 participants (mean age 65 ± 11 y; 55% women; 35% nonwhite), there were 858 incident CVD events and 1209 deaths over a median of 13.0 y. The risk of CVD did not significantly differ according to circulating phylloquinone [fully adjusted HR (95% CI) relative to >1.0 nmol/L: ≤0.5 nmol/L, 1.12 (0.94, 1.33); >0.5-1.0 nmol/L, 1.02 (0.86, 1.20)]. Participants with ≤0.5 nmol/L circulating phylloquinone had an adjusted 19% higher risk of all-cause mortality compared with those with >1.0 nmol/L [fully adjusted HR (95% CI): 1.19 (1.03, 1.38)]. Mortality risk was similar in participants with >0.5-1.0 nmol/L compared with >1.0 nmol/L [fully adjusted HR (95% CI): 1.04 (0.92, 1.17)]. Low circulating phylloquinone concentrations were associated with an increased risk of all-cause mortality, but not of CVD. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of increased phylloquinone intake on cardiovascular and other health outcomes in individuals with low vitamin K status.


Accumulation of mono-glycosylated form-rich, plaque-forming PrPSc in the second atypical bovine spongiform encephalopathy case in Japan.
The recent identification of several atypical cases of bovine spongiform encephalopathy (BSE) has raised the possibility of the existence of distinct strains of BSE agents, arguing against the previous notion that BSE is caused by a single strain. To date, at least, two atypical types (L and H) of agent have been reported based on the molecular sizes of the proteinase K-resistant forms of prion protein (PrP(Sc)). These atypical agents were identified first in Japan, Italy, France, and Germany, and later in other European countries. Here, we have identified a case of BSE in a 169-month-old cow (designated as BSE/JP24), in which predominant deposition of the mono-glycosylated form of PrP(Sc) was observed by Western-blot analysis, and plaques of PrP(Sc) were detected in the brain by immunohistochemical analysis. The glycoform ratio of PrP(Sc) was different from that of the typical BSE agent, in which the di-glycosylated form is dominant; instead, the ratio resembled that of type-2 human sporadic Creutzfeldt-Jakob disease and that reported for the L-type BSE. The characteristic glycoform ratio and plaques of PrP(Sc) suggested that the agent in BSE/JP24 was relevant, if not identical, to the agent in bovine amyloidotic spongiform encephalopathy (BASE), an L-type BSE identified in Italy. It was of interest that at the level of the obex, the medulla oblongata was devoid of plaques of PrP(Sc), and a pathological phenotype similar to that of typical BSE specimens with vacuolations and coarse granular/linear deposition of PrP(Sc) were observed.


Minimal influence of traditional surgical risk factors on mortality in contemporary aortic valve replacement.
Transcatheter aortic valve implantation is increasingly presented as an alternative to aortic valve replacement in the high risk surgical candidate. We review the outcomes of isolated aortic valve replacement to identify contemporary results of aortic valve replacement in such high risk patients. Retrospective analysis of 846 patients (mean age 68.7 ± 11.8 years) who underwent aortic valve replacement in a single institution from 1999 to 2008. We considered 10 risk factors as follows: female gender (395 patients, 46.7%), age, left ventricular ejection fraction, New York Heart Association Class, preoperative creatinine clearance, body mass index, peripheral vascular disease (49 patients, 5%), cerebrovascular disease (42 patients, 4.9%), chronic obstructive pulmonary disease (87 patients,10.2%), and redo surgery (53 patients, 6.2%). Twenty-five patients died (2.9%). Age (P=0.032; OR 1.07 per each year increase) was the only significant independent predictor of mortality. Length of stay in the hospital was correlated with age (P<0.0001), New York Heart Association Class (P<0.0001) creatinine clearance (P=0.005) and redo surgery (P=0.006). Contemporary aortic valve replacement is a low risk procedure for most patients. Historical risk factors which have been used to define high risk and inoperability, such as pulmonary disease, reoperations, decreased left ventricular ejection fraction and vascular disease, may not be relevant in the current era. This observation should be considered if such criteria are used to define patients for transcatheter aortic valve implantation.


Quantitative proteomic profiling of host-pathogen interactions: the macrophage response to Mycobacterium tuberculosis lipids.
Mycobacterium tuberculosis (M. tuberculosis) is an intracellular pathogen possessing a complex mixture of cell wall lipids that are thought to modulate the activities of host macrophages. In this study, we employed two state-of-the-art quantitative proteomic approaches, metabolic labeling SILAC and chemical isobaric tagging iTRAQ, to study changes in macrophage protein expression in response to exposure to M. tuberculosis lipids. From a total of 1286 proteins identified, 463 were discovered by both isotope-labeling strategies at a high consistency, and the rest of proteins were detected by only one of the two approaches. Upon exposure to mycobacterial cell wall lipids, 166 macrophage proteins showed differential expression. These included proteins involved in the immune response, oxidation and reduction, and vesicle transport, as well as other cellular processes. The response of the macrophage proteome to M. tuberculosis lipids reflects the cell's innate defense mechanisms as well as lipid-induced processes that may benefit the pathogen.


Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo.
Klotho is originally discovered as an anti-aging gene and knock-out of klotho accelerates aging in mice. Subsequent studies support the anti-carcinogenesis role of klotho in a variety of human malignancies. The present study investigated the role of klotho on growth and metastasis of osteosarcoma cells. The osteosarcoma cells were transduced with lentivirus particles encoding klotho or scramble control. The reconstructed osteosarcoma cells were injected into the femoral medullary cavity of nude mice to establish a xenograft animal model. The anti-tumor properties of klotho were evaluated in terms of tumor growth, apoptosis, glycogen production, and pulmonary metastasis. Lentivirus-mediated overexpression of klotho significantly decreased tumor volume and weight in osteosarcoma mice. Determination of PCNA and Ki67 expression revealed that overexpression of klotho inhibited cell proliferation in tumor tissues obtained from osteosarcoma xenografts. PAS staining also showed that overexpression of klotho significantly decreased the production of glycogen in osteosarcoma. Moreover, TUNEL positive cells were significantly increased after lentivirus-mediated overexpression of klotho. Furthermore, lentivirus-mediated upregulation of klotho reduced the number of pulmonary metastatic lesions in mice compared to control mice. These findings demonstrated that elevated klotho could inhibit osteosarcoma cell growth and pulmonary metastasis in vivo, suggesting that klotho may be a valuable therapeutic target for osteosarcoma.


Application of Displacement-Current-Governed Triboelectric Nanogenerator in an Electrostatic Discharge Protection System for the Next-Generation Green Tire.
Electrostatic discharge (ESD), a universal phenomenon derived from tribocharging and electrostatic induction, has always been regarded as a negative effect because it may cause various types of damage, such as gas explosions, wildfires, failure of integrated circuits, and so on. Normally, ESD is avoided by conducting those harmful charges through the surface or the whole bulk, by means of improving the conductivity of dielectrics or directly using conductive materials. However, the first approach compromises other performances at the same time, whereas the second one can be applied in only a few circumstances. In this Article, we analyzed the working principle of the triboelectric nanogenerator from the perspective of the time variation of the surface-charge-introduced polarization density ∂Ps∂t , the second term of Maxwell's displacement current. Then, we demonstrated an electrostatic protective system by implanting a conductive layer under the tribocharging surface to form a triboelectric nanogenerator (TENG). Theoretical derivation, finite element analysis, and experimental results prove that this system can efficiently prevent ESD without sacrificing any other performance. Finally, we applied it to the next generation of the green tire, which can save >10% of fuel but still cannot be commercialized due to the potential ESD risk. This research work reveals a way to prevent ESD and shows great potential in the field of engineering.


Indicators and outcome of liver transplantation in acute liver decompensation after flares of hepatitis B.
Non-cirrhotic patients having acute liver decompensation in flares of hepatitis B can recover spontaneously or die without liver transplantation. Criteria for identifying patients in need of liver transplantation are lacking. Fifty-one non-cirrhotic patients having acute liver decompensation in flares of hepatitis B were retrospectively reviewed. The patients were divided into three groups: group A patients (n=18) recovered from acute liver decompensation spontaneously; group B patients (n=22) died of acute liver failure; and group C patients (n=11) had liver transplantation. Model of end-stage liver disease (MELD) scores were evaluated to identify the criteria for liver transplantation. The cut-off point of MELD scores for liver transplantation was evaluated by receiver operating characteristic (ROC) curve. Comparing group A and B patients, MELD score was an independent factor to predict prognosis. By analysing ROC curve, a MELD score>30 was the most optimal cut-off point to indicate liver transplantation; however, the false positive rate was 11.1%. By weekly measurement of MELD scores, subsequent increase in MELD scores could help to avoid false positives. Moreover, a MELD score>34 yielded 0% false positive rate and indicated the necessity of definite liver transplantation. For group C patients, ten of 11 patients were saved by liver transplantation. In conclusion, for the patients having acute liver decompensation in flares of hepatitis B, liver transplantation is definitely indicated by MELD scores>34. Liver transplantation is also indicated if the MELD score increases in the subsequent 1-2 weeks. Liver transplantation has a good outcome if performed on time.


Narcolepsy and other hypersomnias in children.
We provide an update on the pathogenesis, diagnosis, assessment (clinical and laboratory), and treatment options for children with narcolepsy and other hypersomnias of central origin in order to raise awareness of these diseases and to highlight the clinical findings that should make the pediatrician suspect the diagnosis. Narcolepsy is a chronic rapid eye movement sleep disorder. Accumulating evidence indicates that signs of narcolepsy may start during childhood. Recent data suggest that a deficiency in the hypothalamic orexin/hypocretin system underlies the pathogenesis of narcolepsy with cataplexy. Confirmatory tests such as polysomnography, multiple sleep latency test, and actigraphy, along with referral to a sleep physician, maybe necessary in appropriate cases. Laboratory tests such as human leukocyte antigen typing and cerebrospinal fluid hypocretin-1 analysis are useful as adjuncts. Modafinil is now considered the first-line treatment for excessive sleepiness in adult patients with narcolepsy. Sodium oxybate is currently approved by the Food and Drug Administration for the treatment of narcolepsy with cataplexy in patients aged more than 16 years. Awareness of the extent of hypersomnia in children will allow physicians to effectively screen every child; once identified, further assessment should be performed in order to diagnose and treat the underlying cause. Better understanding of pathogenesis, availability of newer therapies with different mechanism of effect, and appropriately designed randomized clinical trials should allow improved management of children with narcolepsy.


The Relation of HPV Infection and Expression of p53 and p16 Proteins in Esophageal Squamous Cells Carcinoma.
GOAL: To investigate the HPV prevalence and characterize the expression of potential molecular surrogate markers of HPV infection in esophageal squamous cell carcinoma. MATERIALS AND METHODS: The prevalence of HPV in individuals with and without esophageal cancer (EC) was determined by using multiplex PCR; p16 and p53 protein levels were assessed by immunohistochemistry (IHC). RESULTS: High-risk HPV (hr-HPV) was found in the same frequency (13.8%) in esophageal squamous cell carcinoma (ESCC) and in healthy individuals. The p53 expression was positive in 67.5% of tumor tissue, 20.0% of adjacent non-tumoral tissue and 1.8% of normal esophageal tissue. p16 was positive in 11.6% of esophageal cancer cases and 4.7% of adjacent non-tumoral tissue. p16 was undetectable among control group samples. p53 and p16 levels were not significantly associated with the HPV status. CONCLUSIONS: These results suggest that hr-HPV types are not associated with the development of ESCC and that p53 and p16 protein expression have no relationship with HPV infection in normal or cancerous esophagus.


[Preparation and identification of polyclonal antibodies against Moraxella catarrhalis UspA1].
To prepare polyclonal antibodies (PcAb) against UspA1 of Moraxella catarrhalis (Mc), we used bioinformatic analysis to determine the surface exposed region in this protein that holds the antigen epitopes. Then the corresponding coding sequences for this fragment was artificially synthesized according to the codon usage of Escherichia coli. The gene fragment was then subcloned into the prokaryotic expression vector pET-28a(+) and expressed in E. coli rosseta (DE3), and then the recombinant UspA1-His proteins were purified. Two New Zealand white rabbits were immunized with this protein to prepare antiserum. The resulting PcAb was then purified from the antiserum with Protein A affinity column. The results of fluorescence antibody assay, enzyme linked immunosorbent assay and Western blotting analysis showed that the PcAb could specifically recognize the surface exposed region of UspA1 on Mc. The preparation of the PcAb laid a foundation of further development of rapid detection technique for M. catarrhalis.


Fluctuation of riding passengers induced by chaotic motions of shuttle buses.
We study the fluctuation of the number of riding passengers in a few shuttle buses that pass each other freely. We present a dynamical model of the shuttle buses that takes into account the maximum capacity of a bus. The dynamics of the buses is expressed in terms of a coupled nonlinear map with noise. The number of passengers carried by a bus and the time headway between buses exhibit complex behavior with varying trips. It is found that the behavior of the buses exhibits deterministic chaos even if there is no noise. The chaotic motion depends on the loading parameter, the maximum capacity of a bus, the bus's speed, and the number of buses. When the loading parameter is larger than a threshold value, each bus carries a full load of passengers throughout its trip. The dependence of the threshold (transition point) on both capacity and speed is clarified.


Dopaminergic modulation of axon collaterals interconnecting spiny neurons of the rat striatum.
Dopamine is a critical modulator of striatal function; its absence produces Parkinson's disease. Most cellular actions of dopamine are still unknown. This work describes the presynaptic actions of dopaminergic receptor agonists on GABAergic transmission between neostriatal projection neurons. Axon collaterals interconnect projection neurons, the main axons of which project to other basal ganglia nuclei. Most if not all of these projecting axons pass through the globus pallidus. Thus, we lesioned the intrinsic neurons of the globus pallidus and stimulated neostriatal efferent axons antidromically with a bipolar electrode located in this nucleus. This maneuver revealed a bicuculline-sensitive synaptic current while recording in spiny cells. D1 receptor agonists facilitated whereas D2 receptor agonists depressed this synaptic current. In contrast, a bicuculline-sensitive synaptic current evoked by field stimulation inside the neostriatum was not consistently modulated, in agreement with previous studies. The data are discussed in light of the most recent experimental and modeling results. The conclusion was that inhibition of spiny cells by axon collaterals of other spiny cells is quantitatively important; however, to be functionally important, this inhibition might be conditioned to the synchronized firing of spiny neurons. Finally, dopamine exerts a potentially important role regulating the extent of lateral inhibition.


The Natural History of Antibiotic-Treated Lower Limb Cellulitis: Analysis of Data Extracted From a Multicenter Clinical Trial.
Although cellulitis is a relatively common skin infection, there remains uncertainty about management, particularly the length and route of antimicrobials required. Further information on the symptomatology and biomarker changes associated with cellulitis over time would guide clinicians and patients as to the expected natural history. We extracted data from a randomized clinical trial (NCT01876628) of clindamycin as adjunctive therapy in cellulitis to illustrate the evolution of local parameters (pain, swelling, local erythema, and warmth) and the resolution of biomarkers over time. Data from 247 individuals with mild to moderate unilateral lower limb cellulitis, who attended at least 1 face-to-face interview following recruitment, were used to examine response dynamics. Although there was a local improvement in swelling, warmth, erythema, and pain by day 5 compared with baseline, some individuals still had evidence of local inflammation at 10 days. Most biomarkers demonstrated a return to normal by day 3, although the initial fall in albumin only returned to baseline by day 10. Although there was initial resolution, a significant number of individuals still had local symptoms persisting to day 10 and beyond. Clinicians can use these data to reassure themselves and their patients that ongoing local symptoms and signs after completion of antibiotic treatment do not indicate treatment failure or warrant extension of the initial antibiotic treatment or a change in antibiotic class or mode of administration.


A toughening mechanism of the strain rate-optimal chain length on polymer-modified calcium silicate hydrates (CSH).
Polymers are known to effectively improve the toughness of inorganic matrices; however, the mechanism at the molecular level is still unclear. In this study, we used molecular dynamics simulations to unravel the effects and mechanisms of different molecular chain lengths of polyacrylic acid (PAA) on toughening calcium silicate hydrate (CSH), which is the basic building block of cement-based materials. Our simulation results indicate that an optimal molecular chain length of polymers contributes to the largest toughening effect on the matrix, leading to up to 60.98% increase in fracture energy. During the uniaxial tensile tests along the x-axis and z-axis direction, the configuration evolution of the PAA molecule determines the toughening effect. As the polymer unfolds and its size matches the defects of CSH, the stress distribution of the system becomes more homogeneous, which favors an increase in toughness. Furthermore, based on our simulation results and a mathematical model, we propose a theory of "strain rate/optimal chain length". This theory suggests that the optimal toughening effect can be achieved when the molecular chain length of the organic component is 1.3-1.5 times the largest defect size of the inorganic matrix. This work provides molecular-scale insights into the toughening mechanisms of an organic/inorganic system and may have practical implications for improving the toughness of cement-based materials.


Depressive attributions: selection of different causes or assignment of dimensional meanings?
Attributional models of depression suggest that depression is associated with internal, stable, and global causal explanations of events. However, the models do not specify whether the depressive attributional process involves the selection of certain causes, the assignment of dimensional meanings to those causes, or both. A distinction between these two processes was suggested by the findings that the choice of causes does not reliably indicate the perceived dimensions and that there is poor convergence between existing methods that assess causes and those that assess dimensions. When causes and dimensions were each measured in a manner that avoided confounding by the other, each made a unique contribution to the prediction of depression scores. Cause ratings alone were significantly associated with depression scores, but the optimal prediction of depression included both causes and dimensions. The implications of the distinction between these two processes for experimental manipulations of attributions and for reattribution training programs are discussed.


Polyploid evolution: The ultimate way to grasp the nettle.
Polyploidy is one of the major forces of plant evolution and widespread mixed-ploidy species offer an opportunity to evaluate its significance. We therefore selected the cosmopolitan species Urtica dioica (stinging nettle), examined its cytogeography and pattern of absolute genome size, and assessed correlations with bioclimatic and ecogeographic data (latitude, longitude, elevation). We evaluated variation in ploidy level using an extensive dataset of 7012 samples from 1317 populations covering most of the species' distribution area. The widespread tetraploid cytotype (87%) was strongly prevalent over diploids (13%). A subsequent analysis of absolute genome size proved a uniform Cx-value of core U. dioica (except for U. d. subsp. cypria) whereas other closely related species, namely U. bianorii, U. kioviensis and U. simensis, differed significantly. We detected a positive correlation between relative genome size and longitude and latitude in the complete dataset of European populations and a positive correlation between relative genome size and longitude in a reduced dataset of diploid accessions (the complete dataset of diploids excluding U. d. subsp. kurdistanica). In addition, our data indicate an affinity of most diploids to natural and near-natural habitats and that the tetraploid cytotype and a small part of diploids (population from the Po river basin in northern Italy) tend to inhabit synanthropic sites. To sum up, the pattern of ploidy variation revealed by our study is in many aspects unique to the stinging nettle, being most likely first of all driven by the greater ecological plasticity and invasiveness of the tetraploid cytotype.


[Nephrureterectomy with endoscopic resection of the urinary bladder, ureteral ostium and terminal part in papillary tumors of the upper urinary tracts].
Short- and long-term results of endoscopically assisted nephrureterectomy were studied in 15 patients (7 males and 8 females aged 31-79 years) with papillary tumours of the upper urinary tracts (UUT). Of them, 11 patients have undergone transurethral endoresection of the urinary bladder, ostium and terminal part of the ipsilateral ureter followed by nephrureterectomy from the lumbotomic approach (technique 1) and 4 patients had nephrureterectomy followed by endoscopic intervention (technique 2). Results of standard open nephrureterectomy with resection of the bladder were analyzed retrospectively for 25 patients with papillary tumors of the UUT taken as control. It was found that transurethral endoscopic resection of the bladder, ostium and terminal part of the ipsilateral ureter in nephrureterectomy for papillary tumors of the UUT facilitates the performance, decreases duration and aggression of surgical intervention, diminishes number of complications, shortens hospital stay of the patients and their rehabilitation. Technique 1 is thought more ablastic and simple in performance.


On-axis and off-axis primary dose component in high energy photon beams.
The depth dose of the primary dose component, on axis and off axis of six different x-ray beams, has been determined from transmission measurements in narrow beam geometry with and without flattening filter using a Perspex column of a cross section large enough to ensure electronic equilibrium. In order to derive the primary photon fluence, a correction for the scatter from the column has been applied according to the following method: A number of spectra taken from the literature have been used for computing a scatter coefficient Sc at different depths by convolution of dose spread arrays. Using the relationship between Sc and the single attenuation coefficient mu i to represent each entire spectrum, it has been possible to correct the experimental transmission curves iteratively, until the corresponding values of mu were stabilized and representative of the primary. The measured attenuation coefficients were found to have a linear increase as a function of the distance from the central axis for all the energies and types of linear accelerators. For the same nominal energy, this increase is different from one accelerator to another. The same phenomenon was observed for the attenuation coefficients obtained without the flattening filter in the same experimental conditions. The results are tentatively interpreted considering the angular variation of bremsstrahlung energy spectra with and without a flattening filter as calculated by a Monte Carlo method and they are consistent and useful to take accurately into account the softening of the beam as the off-axis distance increases.


Chronic Oral Administration of Aluminum Hydroxide Stimulates Systemic Inflammation and Redox Imbalance in BALB/c Mice.
The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.


[Cytosteatonecrosis of the newborn infant].
Cytosteatonecrosis of the newborn (CSNN) is an acute hypodermatitis that appears within the first four weeks of life. It essentially develops in infants born at term or postmature, and following a difficult delivery. THE LESIONS: The lesions are more or less extended sub-cutaneous nodules or inflammatory plaques on the body that regress spontaneously, without after effects, within one to four months. A cutaneous biopsy, rarely required for diagnosis, reveals a granulomatous reaction to a foreign body in a necrosed subcutaneous adipose tissue. Although the progression is generally benign, it may be complicated by the occurrence of hypercalcemia. The management of these infants justifies the regular monitoring of blood calcium levels and treatment of an eventual hypercalcemia.


The effect of electrochemical regeneration upon the enzymatic catalysis of a thermodynamically unfavorable reaction.
The association between enzymatic and electrochemical reactions, enzymatic electrocatalysis, had proven to be a very powerful tooth in both analytical and synthetic fields. However, most of the combinations studied have involved enzymatic catalysis of irreversible or quasi-irreversible reaction. In the present work, we have investigated the possibility of applying enzymatic electrocatalysis to a case where the electrochemical reaction drives a thermodynamically unfavorable reversible reaction. Such thermodynamically unfavorable reactions include most of the oxidations catalyzed by dehydrogenases. Yeast alcohol dehydrogenase (E.C. 18.104.22.168) was chosen as a model enzyme because the oxidation of ethanol is thermodynamically very unfavorable and because its kinetics are well known. The electrochemical reaction was the oxidation of NADH which is particularly attractive as a method of cofactor regeneration. Both the electrochemical and enzymatic reactions occur in the same batch reactor in such a way that electrical energy is the only external driving force. Two cases were experimentally and theoretically developed with the enzyme either in solution or immobilized onto the electrode's surface. In both cases, the electrochemical reaction could drive the enzymatic reaction by NADH consumption in solution or directly in the enzyme's microenvironment. However even for a high efficiency of NADH consumption, the rate of enzymatic catalysis was limited by product (acetaldedehyde) inhibition. Extending this observation to the subject of organic synthesis catalyzed by dehydrogenases, we concluded that thermodynamically unfavorable reaction and can only be used in a process if efficient NAD regeneration and product elimination are simultaneously carried out within the reactor.


Increased periostin gene expression in degenerative intervertebral disc cells.
Disc degeneration is a multifactorial disease that may cause clinical symptoms such as chronic back pain or radiculopathy in the extremities. Periostin, an extracellular matrix protein involved in the process of fibrosis, expressed in tissues subjected to mechanical stress such as intervertebral disc. However, the expression of periostin during disc degeneration has not yet been studied. The aim of this study is to elucidate the difference in gene expression profiles between degenerative and nondegenerative intervertebral discs for a better understanding of disc degeneration. Degenerative and nondegenerative nucleus pulposus cells were isolated from elderly patients with degenerative disc disease and younger patients with adolescent idiopathic scoliosis, respectively. Affymetrix GeneChip Human arrays were used to derive gene expression profiles for disc degeneration, and gene expressions of periostin and other degeneration-related markers were confirmed by reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR, and western blot analysis. Immunohistochemical analysis of periostin and Gomori trichrome stain was performed to show the relationship of periostin, fibrosis, and disc degeneration. The mechanical stress experiment was designed to demonstrate the relationship of periostin, stress, and disc degeneration. Fourteen genes were identified to express at significantly different levels between degenerative and nondegenerative groups. An increase of periostin gene expression was observed in human degenerative nucleus pulposus cells for the messenger RNA and protein levels. Histological examination demonstrated an increased positive staining of periostin in degenerative discs from human tissues and rat needle-punctured tails and more fibrosis with architectural disorder and fragmentation in human degenerative disc as compared with nondegenerative discs. The expression of periostin was significantly induced by stress in human degenerative nucleus pulposus cells but not in nondegenerative cells. This study demonstrates for the first time an upregulation of periostin in addition to the expression levels of Type I collagen and matrix metalloproteinase-2 in human disc degeneration. It suggests that periostin may be a candidate gene that shows promise as a new prognostic marker and a therapeutic target that is worth further study to expand our knowledge of its role in disc degeneration.


Post-traumatic erosive dermatosis of the scalp: A hypergranulated variant.
Erosive pustular dermatosis of the scalp is a slowly progressive chronic inflammatory disease that predominantly affects elderly male patients with marked actinic damage. The clinical evolution consists firstly of keratotic and erosive plaques surmounted by yellow-brown crusts and non-follicular pustules; later, the active crusting lesions regress in number and the scarring process causes diffuse cutaneous thinning and loss of hair follicles. However, manifestations may be atypical, leading to frequent misdiagnosis. We present a case series of post-traumatic erosive pustular dermatosis on the scalp of 4 elderly patients. The characterising feature was the presence of erosion consisting of abundant hypergranulation tissue, with an almost total lack of crusts and pustules. Dermoscopy showed a unique pattern of stretched and dilated linear, telangiectatic and polymorphous on-focus vessels, milky-red areas and white scarring areas. This clinical entity is rarely reported in the literature. The majority of reported cases were located on the legs.