Structural analysis of dextran-based hydrogels obtained chemoenzymatically.
This work reports the results of structural analysis in novel dextran-acrylate (dexT70-VA) hydrogels generated chemoenzymatically. Porous structure as well as hydrogel surface and interior morphologies were evaluated by mercury intrusion porosimetry (MIP), nitrogen adsorption (NA), and scanning electron microscopy (SEM) analyses, as a function of the degree of substitution (DS), and initial water content used in the preparation of the hydrogel. MIP analysis showed that the overall networks were clearly macroporous with pore sizes ranging from 0.065 to 10 microm. As expected, the average pore size decreased as DS increased and as initial water content decreased. Moreover, the porosity values ranged from 75 up 90%, which shows that these hydrogels present an interconnected pore structure. Nitrogen adsorption analyses showed that the specific surface area of dexT70-VA hydrogels increased either by increasing the DS or by decreasing the initial water content of the hydrogel. SEM results revealed that the surface of hydrogels with lower DS presented either a porous structure or a polymeric "skin" covering the pores, whereas hydrogels with higher DS were totally porous. Furthermore, the interior morphology varied according to the DS and the initial water content of the hydrogels. Finally, the average pore size was also determined from the swelling of hydrogel using a theoretical model developed by Flory-Rehner. The comparison of the SEM and MIP results with the ones obtained by the equilibrium swelling theory of Flory-Rehner shows that this approach highly underestimates the average pore size.


An evaluation of in-plane shields during thoracic CT.
The object of this study was to compare organ dose and image quality effects of using bismuth and barium vinyl in-plane shields with standard and low tube current thoracic CT protocols. A RANDO phantom was scanned using a 64-slice CT scanner and three different thoracic protocols. Thermoluminescent dosemeters were positioned in six locations to record surface and absorbed breast and lung doses. Image quality was assessed quantitatively using region of interest measurements. Scanning was repeated using bismuth and barium vinyl in-plane shields to cover the breasts and the results were compared with standard and reduced dose protocols. Dose reductions were most evident in the breast, skin and anterior lung when shielding was used, with mean reductions of 34, 33 and 10 % for bismuth and 23, 18 and 11 % for barium, respectively. Bismuth was associated with significant increases in both noise and CT attenuation values for all the three protocols, especially anteriorly and centrally. Barium shielding had a reduced impact on image quality. Reducing the overall tube current reduced doses in all the locations by 20-27 % with similar increases in noise as shielding, without impacting on attenuation values. Reducing the overall tube current best optimises dose with minimal image quality impact. In-plane shields increase noise and attenuation values, while reducing anterior organ doses primarily. Shielding remains a useful optimisation tool in CT and barium is an effective alternative to bismuth especially when image quality is of concern.


Xanthine oxidase is hyper-active in Duchenne muscular dystrophy.
Generation of superoxide by xanthine oxidase can be stimulated under ischemic and aberrant calcium homeostasis. Because patients and mice with Duchenne muscular dystrophy (DMD) suffer from ischemia and excessive calcium influx, we tested the hypothesis that xanthine oxidase activity is elevated and contributes to disease pathology. Xanthine oxidase activity was measured by urinary isoxanthopterin in DMD patients at rest and in response to exercise. Urinary isoxanthopterin/creatinine was elevated compared to age-matched controls and Becker muscular dystrophy (BMD) patients. Concentrations were also increased after a six minute walk test in ambulatory patients. We also measured urinary isoxanthopterin in wildtype mice and a number of dystrophic mouse models; the DMD mouse model (mdx), mdx mice overexpressing a variety of transgenic miniaturized and chimeric skeletal muscle-specific dystrophins and utrophin and the β-sarcoglycan deficient (Scgb-/-) mouse which represents type 2E human limb-girdle muscular dystrophy. Mdx and Scgb-/-mice had greater urinary isoxanthopterin/creatinine than wildtype mice while mdx mice expressing dystrophin or utrophin linking the extracellular matrix to the actin cytoskeleton were not different than wildtype. We also measured higher levels of urinary ortho-tyrosine in humans and mice deficient for dystrophin to confirm elevated oxidative stress. Surprisingly, mdx had lower xanthine oxidase protein levels and higher mRNA in gastrocnemius muscle compared to wildtype mice, however, the enzymatic activity of skeletal muscle xanthine oxidase was elevated above wildtype and a transgenic rescued mdx mouse (DysΔMTB-mdx). Downhill treadmill running also caused significant increases in mdx urinary isoxanthopterin that was prevented with the xanthine oxidase inhibitor allopurinol. Similarly, in vitro eccentric contraction-induced force drop of mdx muscle was attenuated by the allopurinol metabolite, oxypurinol. Together, our data suggests hyper-activity of xanthine oxidase in DMD, identifies xanthine oxidase activity as a contributing factor in eccentric contraction-induced force drop of dystrophin-deficient skeletal muscle and highlights the potential of isoxanthopterin as a noninvasive biomarker in DMD.


Nutrient sufficiency in beef cows grazing on a dwarf bamboo-dominated forestland pasture in Japan.
The nutritional status of cows grazing on a 120-ha public alpine forestland pasture dominated by the dwarf bamboo Sasa senanensis located in central Japan was evaluated over the course of 2 years. Data were collected during grazing seasons in three periods: early (June), mid- (August) and late (late September-early October) periods. During these periods, the number of experimental Japanese Black cows varied between three and six. With the exception of the dry matter (DM) intake in 2005 and the crude protein (CP) digestibility in 2006, the DM and CP intake and digestibility were lower in the mid- and late periods than in the early period for both years (P < 0.05). Metabolizable energy intake was slightly insufficient for the requirement of the cows in the late period of 2005; in the mid- and late periods of 2006, the metabolizable energy intake was 0.4 to 0.5 times the requirement. These results suggest that the energy intake of cows grazing on forestland pasture dominated by S. senanensis would not satisfy their requirements starting in the mid-period (August) grazing, even though the pasture had abundant herbage resources during these periods.


Prevalence of factor V R2 (H1299R) polymorphism in the Lebanese population.
A recently identified polymorphism in factor V gene (His1299Arg; also named HR2) has been reported to be a possible risk factor for the development of venous thromboembolism (VTE), with a high prevalence of 9.5-15.2% in patients of different ethnic groups in different parts of the world. The aim of this study is to assess the prevalence of HR2 haplotype in Lebanon. We randomly selected 125 samples from unrelated donors logged into our HLA registry; these represent healthy Lebanese individuals originating from different provinces and religious communities of the country. Their DNA was extracted using the Pel-Freez extraction kit and stored at -80 degrees C for later use. The CVD StripAssay was used for PCR and reverse hybridisation. It screens for several gene mutations including factor V H1299R. A total of 125 controls were studied: 72 males and 53 females with a median age 42 years. Thirteen (10.4%) had the HR2 haplotype; 11 (8.8%) were heterozygous (R1/R2), and two (1.6%) were homozygous (R2/R2), with an allelic frequency of 0.06. Our study is the first report from Lebanon that describes the prevalence of HR2 haplotype and the frequency of its alleles. We are reporting a high prevalence of the HR2 in our population (10.4%). The hypothesis that A4070G polymorphism might contribute to the expression of a thrombotic phenotype deserves to be tested in our population through larger studies.


A continuum description of the buckling of a line of spheres in a transverse harmonic confining potential.
A line of contacting hard spheres, placed in a transverse confining potential, buckles under compression or when tilted away from the horizontal, once a critical tilt angle is exceeded. This interesting nonlinear problem is enriched by the combined application of both compression and tilt. In a continuous formulation, the profile of transverse sphere displacement is well described by numerical solutions of a second-order differential equation (provided that buckling is not of large amplitude). Here we provide a detailed discussion of these solutions, which are approximated by analytic expressions in terms of Jacobi, Whittaker and Airy functions. The analysis in terms of Whittaker functions yields an exact result for the critical tilt for buckling without compression.


Gene expression and mutation assessment provide clues of genetic and epigenetic mechanisms in liver tumors of oxazepam-exposed mice.
Liver tumors from a previous National Toxicology Program study were examined using global gene expression and mutation analysis to define the mechanisms of carcinogenesis in mice exposed to oxazepam. Five hepatocellular adenomas and 5 hepatocellular carcinomas from male B6C3F1 mice exposed to 5000 ppm oxazepam and 6 histologically normal liver samples from control animals were examined. One of the major findings in the study was upregulation of the Wnt/β-catenin signaling pathway. Genes that activate β-catenin, such as Sox4, were upregulated, whereas genes that inhibit Wnt signaling, such as APC and Crebbp, were downregulated. In addition, liver tumors from oxazepam-exposed mice displayed β-catenin mutations and increased protein expression of glutamine synthetase, a downstream target in the Wnt signaling pathway. Another important finding in this study was the altered expression of oxidative stress-related genes, specifically increased expression of cytochrome p450 genes, including Cyp1a2 and Cyp2b10, and decreased expression of genes that protect against oxidative stress, such as Sod2 and Cat. Increased oxidative stress was confirmed by measuring isoprostane expression using mass spectrometry. Furthermore, global gene expression identified altered expression of genes that are associated with epigenetic mechanisms of cancer. There was decreased expression of genes that are hypermethylated in human liver cancer, including tumor suppressors APC and Pten. Oxazepam-induced tumors also exhibited decreased expression of genes involved in DNA methylation (Crebbp, Dnmt3b) and histone modification (Sirt1). These data suggest that formation of hepatocellular adenomas and carcinomas in oxazepam-exposed mice involves alteration of the Wnt signaling pathway, oxidative stress, and potential epigenetic alterations.


Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior.
We investigated the possible association between DLKI gene promoter region methylation and the increased invasion capacity of non-small cell lung cancer (NSCLC). Lung cancer cell line H1299, as well as the gene transfection and RNA interference technology were used to build DLK gene overexpression and knockdown cells. An in vitro invasion assay was performed to observe the changes in the invasion ability of lung cancer cells. Western blot analysis was used to verify Notchl and matrix metalloproteinase-9 (MMP-9) expression levels and a sulfurous acid sequencing technique was used to test the DNA methylation level in the promoter region. Our results showed that the invasion ability of cells in the overexpression group was significantly enhanced. This ability was considerably reduced in the knockdown group. The Notchl and MMP-9 expression level increased significantly in the overexpression group, while it was reduced considerably in the knockdown group. We detected significantly lower levels of DNA methylation in the promoter region in the overexpression group. It was concluded that methylation of the DLK1 gene promoter region increased the invasion ability of NSCLC. Furthermore, it is possible that this process is related to the Notch signaling pathway.


Downregulation of microRNA-130a contributes to endothelial progenitor cell dysfunction in diabetic patients via its target Runx3.
Dysfunction of endothelial progenitor cells (EPCs) contributes to diabetic vascular disease. MicroRNAs (miRs) have emerged as key regulators of diverse cellular processes including angiogenesis. We recently reported that miR-126, miR-130a, miR-21, miR-27a, and miR-27b were downregulated in EPCs from type II diabetes mellitus (DM) patients, and downregulation of miR-126 impairs EPC function. The present study further explored whether dysregulated miR-130a were also related to EPC dysfunction. EPCs were cultured from peripheral blood mononuclear cells of diabetic patients and healthy controls. Assays on EPC function (proliferation, migration, differentiation, apoptosis, and colony and tubule formation) were performed. Bioinformatics analyses were used to identify the potential targets of miR-130a in EPCs. Gene expression of miR-103a and Runx3 was measured by real-time PCR, and protein expression of Runx3, extracellular signal-regulated kinase (ERK), vascular endothelial growth factor (VEGF) and Akt was measured by Western blotting. Runx3 promoter activity was measured by luciferase reporter assay. A miR-130a inhibitor or mimic and lentiviral vectors expressing miR-130a, or Runx3, or a short hairpin RNA targeting Runx3 were transfected into EPCs to manipulate miR-130a and Runx3 levels. MiR-130a was decreased in EPCs from DM patients. Anti-miR-130a inhibited whereas miR-130a overexpression promoted EPC function. miR-130a negatively regulated Runx3 (mRNA, protein and promoter activity) in EPCs. Knockdown of Runx3 expression enhanced EPC function. MiR-130a also upregulated protein expression of ERK/VEGF and Akt in EPCs. In conclusion, miR-130a plays an important role in maintaining normal EPC function, and decreased miR-130a in EPCs from DM contributes to impaired EPC function, likely via its target Runx3 and through ERK/VEGF and Akt pathways.


Endothelial dysfunction in rheumatic autoimmune diseases.
Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities and differences in vascular disease patterns underlying different rheumatic autoimmune diseases.


Dual alpha(2)-adrenergic agonist and alpha(1)-adrenergic antagonist actions of dexmedetomidine on human isolated endothelium-denuded gastroepiploic arteries.
The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(2)-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K(+) contractions. Interestingly, larger concentrations (>10(-7) mol/L) of both alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone. Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10(-7) mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to alpha(1)-adrenoceptor agonists.


The Pennsylvania Infant and Family Development Project, II: The development of reciprocal interaction in the mother-infant dyad.
In order to assess stability and change in mother-infant interaction, 74 mother-infant dyads were observed at home under naturalistic conditions when infants were 1, 3, and 9 months. Both conceptually and empirically guided data-reduction procedures indicated that 4 summary constructs underlie 15 behavioral categories coded: reciprocal interaction, noninvolvement, distress, and basic care. Mean levels of reciprocal interaction remained unchanged over time, with individual differences being stable. Mean levels of noninvolvement increased from 1 to 3 months only, and remained stable across all time periods, while mean levels of distress and basic care declined linearly across the 9-month periods, with individual dyads displaying little stability. A final analysis assessed stability and change in the 9 component variables comprising the reciprocal interaction construct. Significant change was discerned with respect to several of these components, as well as a good deal of instability. These findings led to the conclusion that, in the face of sameness in mother-infant interaction across the first 9 months, there is also much change.


Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.
The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.


Inhibition of RhoA/MRTF-A signaling alleviates nucleus pulposus fibrosis induced by mechanical stress overload.
: Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, and clinically useful drugs for IDD are unavailable. Mechanical stress overload-induced fibrosis plays a critical role in IDD. RhoA/MRTF-A signaling is known to regulate tissue fibrosis; however, the effect of RhoA/MRTF-A on the development of IDD is unclear. : The expression of aggrecan, collagen I, collagen II, MMP-12, CTGF, and MRTF-A in nucleus pulposus (NP) samples from IDD patients and controls was detected by immunohistochemical staining. Primary nucleus pulposus cells (NPCs) were isolated and cultured to establish an overload strain model treated with or without CCG-1423. The protein levels of RhoA, ROCK2, MRTF-A, CTGF, and MMP-12 as well as fibrosis-associated proteins were detected by western blotting and immunofluorescence. : Collagen I, MMP-12, and CTGF were significantly upregulated, and aggrecan and collagen II were significantly downregulated in the IDD samples. The cellular localization of MRTF-A was associated with intervertebral disc (IVD) degeneration. Overloaded strain enhanced the nuclear translocation of MRTF-A and changed the NPC morphology from spindle-shaped to long strips. Additional experiments showed that RhoA, ROCK2, MRTF-A, SRF, MMP-12, and CTGF were upregulated; however, aggrecan and collagen II were downregulated in NPCs under overload strain. CCG-1423, a RhoA/MRTF-A pathway inhibitor, reversed strain-induced fibrosis. : Mechanical stress activates RhoA/MRTF-A signaling to promote extracellular matrix (ECM) degeneration in the NP, which is associated with the development of IDD. Our findings suggest that the RhoA/MRTF-A inhibitor CCG-1423 can alleviate NPC degeneration caused by overload stress and has potential as a therapeutic agent for IDD.


Early and late behavioral changes in sciatic nerve injury may be modulated by nerve growth factor and substance P in rats: a chronic constriction injury long-term evaluation.
Chronic constriction injury (CCI) simulates the symptoms of chronic nerve compression, which is characterized by allodynia and hyperalgesia. Nerve growth factor (NGF) is released after nerve injury by immune and Schwann cells and transported in retrograde fashion to the dorsal root ganglion (DRG), resulting in increased synthesis of Substance P (SP) and the triggering of neuropathic pain. Here we performed long-term evaluation of allodynia and hyperalgesia in a CCI model, and evaluated the effects of NGF and SP on the peripheral and central nervous systems. Most previous studies have shown deficits and molecular changes 14 days after surgery, however, the long-term effects have not been evaluated. We performed Randall-Selitto, Von Frey, Hargreaves and acetone tests for the entire 56 days post-surgery. Several of these deficits increased 14 to 56 days after CCI and we measured a constant increase in NGF levels in the DRG and spinal cord over the course of the experiment. In contrast, SP optical density maintained enhanced expression in DRG tissue from 14 to 56 days after CCI, whereas it was significantly increased only 56 days post-surgery in spinal cord. We perform long-term evaluation of symptoms associated with CCI and measure associated molecular changes. Moreover, by characterizing the behavioral signatures of this model, our work supports future studies.


The Associations Between Substance Use, Sexual Behaviors, Bullying, Deviant Behaviors, Health, and Cyber Dating Abuse Perpetration.
Dating violence is an important public health concern and is considered to be a form of school violence. While digital technologies have enabled perpetrators of dating violence to target their victims online (cyber dating abuse), little is known about how this form of perpetration relates to specific adolescent risk behaviors. This brief research report focuses on the associations between substance use, sexual behaviors, deviant behaviors, self-reported health, and cyber dating abuse perpetration. Participants included 705 ethnically diverse adolescents ( n = 408; 57.9% female) in Southeast Texas. Having had sexual intercourse or using alcohol or drugs before having sex was significantly linked with cyber dating abuse perpetration, as was poor physical health, and substance use. Consistent with limited research, we found a link between cyber dating abuse and engagement in bullying behaviors. The discussion section includes suggestions for school nurse practice and further research.


Postoperative myocardial infarction and cardiac arrest following primary total knee and hip arthroplasty: rates, risk factors, and time of occurrence.
Cardiac complications are a major cause of postoperative morbidity. The purpose of this study was to determine the rates, risk factors, and time of occurrence for cardiac complications within thirty days after primary unilateral total knee arthroplasty and total hip arthroplasty. The American College of Surgeons National Surgical Quality Improvement Program data set from 2006 to 2011 was used to identify all total knee arthroplasties and total hip arthroplasties. Cardiac complications occurring within thirty days after surgery were the primary outcome measure. Patients were designated as having a history of cardiac disease if they had a new diagnosis or exacerbation of chronic congestive heart failure or a history of angina within thirty days before surgery, a history of myocardial infarction within six months, and/or any percutaneous cardiac intervention or other major cardiac surgery at any time. An analysis of the occurrence of all major cardiac complications and deaths within the thirty-day postoperative time frame was performed. For the 46,322 patients managed with total knee arthroplasty or total hip arthroplasty, the cardiac complication rate was 0.33% (n = 153) at thirty days postoperatively. In both the total knee arthroplasty and total hip arthroplasty groups, an age of eighty years or more (odds ratios [ORs] = 27.95 and 3.72), hypertension requiring medication (ORs = 4.74 and 2.59), and a history of cardiac disease (ORs = 4.46 and 2.80) were the three most significant predictors for the development of postoperative cardiac complications. Of the patients with a cardiac complication, the time of occurrence was within seven days after surgery for 79% (129 of the 164 patients for whom the time of occurrence could be determined). An age of eighty years or more, a history of cardiac disease, and hypertension requiring medication are significant risk factors for developing postoperative cardiac complications following primary unilateral total knee arthroplasty and total hip arthroplasty. Consideration should be given to a preoperative cardiology evaluation and co-management in the perioperative period for individuals with these risk factors.


Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.
Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.


Ferric-coprogen receptor FhuE of Escherichia coli: processing and sequence common to all TonB-dependent outer membrane receptor proteins.
Iron transport via siderophores requires outer membrane receptor proteins and the TonB protein. The FhuE protein of Escherichia coli functions as the receptor for ferric coprogen and ferric-rhodotorulic acid. A chromosomal DNA fragment bearing the fhuE gene was cloned into pACYC184. The gene was localized by insertion mutagenesis by using the transposon Tn1000. Expression in minicells revealed a FhuE precursor with an apparent molecular weight of 82,000 and a FhuE protein with a molecular weight of 76,000. The transcription polarity of the fhuE gene was deduced from the size of truncated polypeptides derived from Tn1000 insertions, which were mapped by restriction analysis. The processing of truncated precursors that were synthesized by insertion mutants was strongly reduced even when the insertion site was close to the carboxy terminus of the FhuE protein. It is concluded that either the efficient insertion of proFhuE into the cytoplasmic membrane or the rate of cleavage of the signal peptide requires a particular conformation of the proFhuE protein, which is only formed by the complete primary structure. The amino-terminal amino acid sequence deduced from the nucleotide sequence was confirmed by gas-phase sequencing of the precursor and the mature form, which were separated by electrophoresis on polyacrylamide gels. The precursor contained an unusually long signal peptide of 36 amino acids. The amino-terminal end of the mature form contained the sequence Glu-Thr-Val Ile-Val. A pentapeptide starting with either Glu or Asp, followed by Thr, and two uncharged residues ending with Val were found in all outer membrane receptor proteins that were constituents of TonB-dependent transport systems.


Deep Hypothermic Circulatory Arrest vs. Antegrade Cerebral Perfusion in Cerebral Protection during the Surgical Treatment of Chronic Dissection of the Ascending and Arch Aorta.
Circulatory arrest during aortic surgery presents a risk of neurological complications. The present study aimed to investigate the effectiveness of deep hypothermic circulatory arrest (DHCA) vs. antegrade cerebral perfusion (ACP) in cerebral protection during the surgical treatment of chronic dissection of the ascending and arch aorta and to assess the quality-of-life (QoL) in the long-term postoperative period with respect to the used cerebral protection method. In a prospective, randomized study, 58 patients with chronic type I aortic dissection who underwent ascending aorta and aortic arch replacement surgery were included. Patients were allocated in two groups: 29 patients who underwent surgery under moderate hypothermia (24°C) combined with ACP and 29 patients who underwent surgery under DHCA (18°C) with craniocerebral hypothermia. The regional hemoglobin oxygen saturation (rSO2, %) were compared during surgery, neurological complications were analyzed during the early postoperative period, QoL was compared in the long-term postoperative period (1-year follow-up). During the early postoperative period, 37.9% of patients in the DHCA group exhibited neurological complications, compared with 13.8% of those in the ACP group (p < .05). The risk of neurological complications in the early postoperative period was dependent on the extent of rSO2 decrease during circulatory arrest. In the ACP group, rSO2 decreased by ≤17% from baseline during circulatory arrest. In the DHCA group, a more profound decrease in rSO2 (>30%) was recorded (p < .05). QoL in the long-term period after surgery improved, but it was not dependent on the cerebral protection method used during surgery. ACP during aortic replacement demonstrated the most advanced properties of cerebral protection that can be evidenced by a lesser degree of neurological complications, compared with patients who underwent surgery under conditions of DHCA. QoL after surgery was not dependent on the cerebral protection method used during surgery.


Control of immune escaped human papilloma virus is regained after therapeutic vaccination.
High-risk human papillomaviruses infect the basal cells of human epithelia. There it deploys several mechanisms to suppress pathogen receptor recognition signalling, impeding the immune system to control viral infection. Furthermore, infected cells become more resistant to type I and II interferon, tumour necrosis factor-α and CD40 activation, via interference with downstream programs halting viral replication or regulating the proliferation and cell death. Consequently, some infected individuals fail to raise early protein-specific T-cell responses that are strong enough to protect against virus-induced premalignant disease and ultimately cancer. Therapeutic vaccines triggering a strong T-cell response against the early proteins can successfully be used to treat patients at the premalignant stage but combinations of different treatment modalities are required for cancer therapy.


Effects of contact with individuals with disabilities: positive attitudes and majoring in education.
Attitudes toward and contact with individuals with disabilities have been topics of research for years. The major purpose of the present study was to determine the effects of contact with individuals with disabilities on attitudes and choosing to major in education. Participants were 211 undergraduate students who completed a survey of attitudes and contact with individuals with physical, developmental, and behavioral disabilities. Results demonstrated that lower misconceptions about disabilities mediated the relation between increased contact with individuals with behavioral disabilities and being an education major. The results of this study (a) can be used to determine how future teachers should be trained and (b) highlight the need for future teachers to engage in certain field experiences.


Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications.
Leaves of Ginkgo biloba, a "living fossil," have been used as traditional herbal medicine for hundreds of years in China. Currently, its application in vascular protection is garnering much attention. In this manuscript, preclinical studies were reviewed to discuss various mechanisms underlying the vascular protection by Ginkgo biloba extract (GBE). Additionally, we reviewed clinical studies to present the application of GBE in the ischaemic disease. GBE, a commonly used dietary supplement, has been shown to act as an antioxidant and freeradical scavenger, a membrane stabilizer, an inhibitor of the platelet-activating factor, a vasodilator, and a regulator of metabolism. Currently, there exist a growing number of clinical studies about GBE in the application of cardiovascular disease, peripheral vascular disease (PVD) and diabetic vascular complications. GBE, a promising therapeutic agent for cardiovascular and ischaemic diseases, exerts vascular- protection function by a comprehensive mechanisms.


Probing charge traps at the 2D semiconductor/dielectric interface.
The family of 2-dimensional (2D) semiconductors is a subject of intensive scientific research due to their potential in next-generation electronics. While offering many unique properties like atomic thickness and chemically inert surfaces, the integration of 2D semiconductors with conventional dielectric materials is challenging. The charge traps at the semiconductor/dielectric interface are among many issues to be addressed before these materials can be of industrial relevance. Conventional electrical characterization methods remain inadequate to quantify the traps at the 2D semiconductor/dielectric interface since the estimations of the density of interface traps, Dit, by different techniques may yield more than an order-of-magnitude discrepancy, even when extracted from the same device. Therefore, the challenge to quantify Dit at the 2D semiconductor/dielectric interface is about finding an accurate and reliable measurement method. In this review, we discuss characterization techniques which have been used to study the 2D semiconductor/dielectric interface. Specifically, we discuss the methods based on small-signal AC measurements, subthreshold slope measurements and low-frequency noise measurements. While these approaches were developed for silicon-based technology, 2D semiconductor devices possess a set of unique challenges requiring a careful re-evaluation when using these characterization techniques. We examine the conventional methods based on their efficacy and accuracy in differentiating various types of trap states and provide guidance to find an appropriate method for charge trap analysis and estimation of Dit at 2D semiconductor/dielectric interfaces.


Development of a screening tool for sleep disordered breathing in children using the phone Oximeter™.
Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory. To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone. Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG. We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value <0.01). PRV analysis reflected a significant augmentation of sympathetic activity provoked by intermittent hypoxia in SDB children. A linear classifier was trained with the most discriminating features to identify children with SDB. The classifier was validated with internal and external cross-validation, providing a high negative predictive value (92.6%) and a good balance between sensitivity (88.4%) and specificity (83.6%). Combining SpO2 and PRV analysis improved the classification performance, providing an area under the receiver operating characteristic curve of 88%, beyond the 82% achieved using SpO2 analysis alone. These results demonstrate that the implementation of this algorithm in the Phone Oximeter will provide an improved portable, at-home screening tool, with the capability of monitoring patients over multiple nights.


Lumbar spine surgery in the elderly. Complications and surgical results.
Diagnosis, postoperative complications, and surgical results in patients over 70 years old who underwent surgery for lumbar nerve root compression of a degenerative origin were evaluated in a prospective, consecutive study. Of the 50 patients investigated, 43 suffered from central spinal stenosis, four from disc herniation, and three from lateral spinal stenosis. All patients were investigated preoperatively and at 4, 12, and 24 months postoperatively. A number of subjective and objective variables were investigated and registered in a computer-coded protocol. Data gathered included intraoperative and postoperative complications, relevant diagnosis, and surgical results. Surgical procedures consisted of decompression with a facet-preserving technique in spinal stenosis and conventional open disc excision for disc herniation. Complications were classified as general (anesthetic, cardiopulmonary, and thromboembolic) and surgical. Patients' opinions on pain relief were assessed with a 4-grade scale. No anesthetic, cardiopulmonary, or thromboembolic complications were seen. Three surgical complications occurred: 1) a patient with spondylitis, 2) a patient with dural leakage with spontaneous recovery, and 3) a patient with postoperative cauda equina syndrome that resulted from peridural hematoma. During follow-up, two patients died from unrelated diseases and cerebrovascular lesions developed in two patients. Among the remaining 46 patients, 37 had improved by the 2-year follow-up and nine were unchanged. No patient deteriorated after the operation. Degenerative disorders of the lumbar spine in patients over 70 year old can be treated with no anesthetic complications and with 2-year results on par with those of decompressive surgery in younger patients.


A comparison of four methods for detecting rotavirus in faeces of bovine calves.
The purpose of the study was to compare the efficacy of four techniques to detect rotavirus in faeces from bovine calves with diarrhoea. The techniques used were an agar gel precipitation test (AGPT), discontinuous counter-immunoelectrophoresis (DCIE), an enzyme-linked immunosorbent assay (ELISA) and polyacrylamide gel electrophoresis with silver staining (PAGE-SS). Faecal samples, 20 each from cow and buffalo calves with diarrhoea from the government cattle farms and the farm of the Agricultural University of Haryana state, India, were tested. PAGE-SS and ELISA were found to be similar in their ability to detect rotavirus antigen, but both methods were found to be significantly superior to DCIE and AGPT (p less than 0.01).


Colistin Resistance in KPC-2- and SHV-5-Producing Klebsiella pneumoniae Clinical Isolates in Bulgaria.
Colistin resistance is increasingly recognized among carbapenemase-producing Klebsiella pneumoniae isolates in several European regions. The current study documents the appearance of colistin resistance among KPC-2 and SHV-5-produning K. pneumoniae strains in Bulgaria. Four colistin-resistant K. pneumoniae isolates were recovered from 2 patients hospitalized in the anesthesiology and resuscitation clinic of a tertiary care university hospital in Sofia, Bulgaria. Microbial identification and antimicrobial susceptibility testing was performed by Vitek 2 (Biomerieux, France). β-Lactamase genes were amplified using a panel of primers for detection of all MBL-types, KPCs, plasmid-mediated AmpCs in single PCR reactions, OXA-type carbapenemases, extended-spectrum β-lactamases (ESBLs) and TEM enzymes. The colistin-resistant mcr-1 gene was also investigated using previously described primers and conditions. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to investigate clonality. The 4 K. pneumoniae isolates exhibited colistin MICs >16 mg/L and showed multidrug-resistant phenotypes, remaining intermediately susceptible only to gentamicin. They were clustered into a single PFGE clonal type and MLST assigned them to sequence type 258. All isolates possessed KPC-2 carbapenemase and SHV-5 ESBL. They were negative for the plasmid-mediated colistin-resistant mcr-1 gene, possibly implying an intrinsic mechanism of resistance. Although colistin use in Bulgaria only started moderately during 2014, the findings of the current study notify the appearance of colistin resistance among carbapenemase-producing Klebsiella species in another European region.


Attenuated Salmonella enterica serovar typhi live vector with inducible chromosomal expression of the T7 RNA polymerase and its evaluation with reporter genes.
Attenuated Salmonella strains with defined gene deletions have been extensively evaluated as suitable live carriers of passenger antigens. A number of strategies for antigen delivery by these strains have been attempted, ranging from plasmid-based to chromosomal integration systems. We report here the chromosomal integration of the T7 RNA polymerase gene (T7pol) in the attenuated strain Salmonella enterica serovar Typhi (Salmonella typhi) CVD908 (aroC(-), aroD(-)). The T7pol gene was amplified by PCR from Escherichia coli BL21(DE3) and cloned in the pNir3 plasmid under the control of the anaerobically inducible nirB promoter. Then it was subcloned in a pKTN701 derivative, suicide plasmid with the R6K ori, and flanked by the aroC gene. After evaluation of its functionality in E. coli SY327, the aroC-T7pol-aroC cassette was integrated into the aroC locus of S. typhi CVD908 by homologous recombination. The resulting strain, S. typhi CVD908-T7pol, was able to transcomplement two plasmids bearing the luc or the lacZ reporter genes controlled by the T7 promoter and produce luciferase and beta-galactosidase under anaerobic culture conditions. Therefore, an inducible system for recombinant antigen production in attenuated S. typhi was achieved.


Improvements in hippocampal-dependent learning and decremental attention in 5-HT(3) receptor overexpressing mice.
The 5-HT3 receptor for serotonin is expressed within limbic structures and is known to modulate neurotransmitter release, suggesting that this receptor may influence learning and memory. Perturbations in serotonergic neurotransmission lead to changes in the ability to attend, learn, and remember. To examine the role of 5-HT3 receptors in learning, memory, and attention, 5-HT3 receptor overexpressing (5-HT3-OE) transgenic mice and their wild-type littermates (WT) were tested in Pavlovian contextual and cued fear conditioning, fear extinction, and latent inhibition (LI) paradigms. Prepulse inhibition (PPI) was assessed to reveal changes in sensorimotor gating. Additionally, anxious behaviors, shock sensitivity, and reactions to novel stimuli were evaluated. 5-HT3-OE mice displayed enhanced contextual conditioning, whereas cued conditioning remained the same as that of WT mice. 5-HT3-OE mice did not differ from WT in extinction rates to either the context or cue. LI was enhanced for 5-HT3-OE mice compared to WT. PPI remained unchanged. No differences in sensitivity to footshock or startle were found. However, 5-HT3-OE mice demonstrated heightened exploratory behavior in response to novel environmental stimuli and decreased anxiety as measured in the elevated plus-maze. Results indicate that overexpression of the 5-HT3 receptor in mouse forebrain results in enhanced hippocampal-dependent learning and attention. Enhanced inspective behavior in response to novelty may contribute to the observed improvements in learning, memory, and attention due to 5-HT3 receptor overexpression.


CD8+ Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma.
Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35-80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.


Development of a Novel Metagenomic Biomarker for Prediction of Upper Gastrointestinal Tract Involvement in Patients With Crohn's Disease.
The human gut microbiota is an important component in the pathogenesis of Crohn's disease (CD), promoting host-microbe imbalances and disturbing intestinal and immune homeostasis. We aimed to assess the potential clinical usefulness of the colonic tissue microbiome for obtaining biomarkers for upper gastrointestinal (UGI) tract involvement in CD. We analyzed colonic tissue samples from 26 CD patients (13 with and 13 without UGI involvement at diagnosis) from the Inflammatory Bowel Disease Multi-Omics Database. QIIME1, DiTaxa, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods were used to examine microbial dysbiosis. Linear support vector machine (SVM) and random forest classifier (RF) algorithms were used to identify the UGI tract involvement-associated biomarkers. There were no statistically significant differences in community richness, phylogenetic diversity, and phylogenetic distance between the two groups of CD patients. DiTaxa analysis predicted significant association of the species Ruminococcus torques with UGI involvement, which was confirmed by the LEfSe analysis (P = 0.025). For the feature ranking method in both linear SVM and RF models, the species R. torques and age at diagnosis contributed to the combined models. The L-methionine biosynthesis III (P = 0.038) and palmitate biosynthesis II (P = 0.050) were under-represented in CD with UGI involvement. These findings suggest that R. torques might serve as a novel potential biomarker for UGI involvement in CD and its correlations, in addition to a range of bacterial species. The mechanisms of interaction between hosts and R. torques should be further investigated.


Characteristic expression of Lewis-antigenic glycolipids in human ovarian carcinoma-derived cells with anticancer drug-resistance.
By comparing ovarian carcinoma-derived KF28 cells with the corresponding anticancer drug-resistant cells, the taxol- and cisplatin-resistant properties were found to be closely related with MDR1 and BSEP, and MRP2 transporters, respectively. In addition to the transporters expression, the amounts of glycolipids, particularly their longer carbohydrate structures, in the resistant cells increased to 3-4-fold of those in the sensitive cells due to enhanced transcription of the respective glycosyltransferases. The major glycolipids in the sensitive and resistant cells were GlcCer and Gb(3)Cer, respectively, and extension of the carbohydrate structure into Lewis antigen characteristically occurred in the resistant cells. Le(b), which was not detected in the cisplatin-resistant cells, was present in the taxol-resistant cells, while Le(x) was present in the cisplatin-resistant cells at a higher concentration than in the taxol-resistant cells. 2-Hydroxy fatty acids were significantly abundant in glycolipids of the resistant cells, but they were not detected in free ceramides or sphingomyelin, indicating that the enhanced synthesis of glycolipids in the resistant cells was not linked with the removal pathway for virulent ceramides derived from sphingomyelin. The resistant cells with abundant glycolipids exhibited lower membrane fluidity than the KF28 cells, and this property might be involved in the anticancer drug-resistance.


Visualization of a Specific Genome Locus by the lacO/LacI-GFP System.
Observing the dynamics of a specific chromosome locus in living cells can provide important information as to the molecular mechanisms underlying events such as chromosome segregation, homologous chromosome pairing, chromosome arrangement, and gene expression. The lacO/LacI-GFP system provides a simple and useful method in which a chromosome locus is visualized by inserting lacO repeat arrays and then expressing an LacI-GFP fusion that specifically binds to the lacO sequence. This system has been adapted for use in Schizosaccharomyces pombe by expressing the LacI-GFP under a promoter of the dis1+ gene. Furthermore, a two-step integration method has been developed that ensures high-efficiency integration of lacO arrays to a desired target position.


Cytoprotective effects of nicotinamide derivatives in endothelial cells.
Following discovery of NAD(+)-dependent reactions that control gene expression, cytoprotection, and longevity, there has been a renewed therapeutic interest in precursors, such as nicotinamide and its derivatives. We tested 20 analogues of nicotinamide for their ability to protect endothelial cells from peroxynitrite stress and their effect on poly (ADP-ribose) polymerase (PARP) activity. Several nicotinamide derivatives protected endothelial cells from peroxynitrite-induced depletion of cellular NAD(+) and ATP concentrations, but only some of these compounds inhibited PARP. We conclude that some nicotinamide derivatives provide protection of endothelial cells against peroxynitrite-induced injury independent of inhibition of PARP activity. Preservation of the NAD(+) pool was a common effect of these compounds.


Raman spectra and structure of yeast phenylalanine transfer RNA in the crystalline state and in solution.
Laser Raman spectra of yeast phenylalanine transfer RNA have been obtained in solution and in orthorhombic and hexagonal crystals. So far as one can tell from the spectra, which are identical in the two crystal forms, the molecular structure of the tRNA is not altered by differences in molecular packing in these two unit cells. In addition, the spectra of the two crystal forms show the same characteristic Raman frequencies and intensities as those of the tRNA in aqueous solution. Thus the structure of the tRNA molecule appears to be the same in the crystals and in aqueous solution. From the spectroscopic changes that result when Mg2+ ions are removed from the native tRNA, it is concluded that the removal of Mg2+ produces a partial disordering of the ribophosphate backbone of the molecule and a lowering of its melting temperature. The melting is shown to be a complex process in that the vibrations specific for adenine indicate a slightly lower melting temperature and those specific for guanine a slightly higher melting temperature than that of the ribophosphate backbone.


Mechanisms of the negative potential associated with Leão's spreading depolarization: A history of brain electrogenesis.
Spreading depolarization (SD) is a self-propagated wave that provokes transient disorder of numerous cell and tissue functions, and that may kill neurons in metabolically compromised tissue. We examined the mechanisms underlying the main hallmark of SD, a giant extracellular potential (ΔVo) for which multiple electromotive forces have been proposed. The end-point is that neurons and not glia, dendritic channels and not spatial currents, and increased sodium conductance rather than potassium gradients, appear to be the main actors in the generation of the negative ΔVo. Neuronal currents are established by two mechanisms, a voltage independent dendritic current, and the differential polarization along the neuron membranes. Notably, despite of a marked drop of ion gradients, these evolve significantly during SD, and yet the membrane potential remains clamped at zero no matter how much inward current is present. There may be substantial inward current or none in function of the evolving portion of the neuron dendrites with SD-activated channels. We propose that the ΔVo promotes swelling-induced dendritic damage. Understanding SD electrogenesis requires all elements relevant for membrane potential, action currents, field potentials and volume conduction to be jointly considered, and it has already encouraged the search for new targets to limit SD-related pathology.


Circadian changes in the temperature of human beings.
Temperature in man measured or recorded by different means, is not constant but varies in a predictable and rhythmic fashion. Circadian (about 24-hour) rhythms have been demonstrated and studied in healthy men and women as well as in patients under a wide variety of experimental conditions and diseases. With the help of special computer programs (Halberg's cosinor) inferential statistical analyses can be performed. There validate and characterize a biological rhythm (i.e., core temperature) by several parameters: the period (tau) the acrophase (phi) (timing of the peak), the amplitude (A) and the rhythm-adjusted mean (M). Each one of these parameters is given with its confidence limits when the studied rhythm is detectable (p less than 0.05). The human temperature (oral, rectal and skin) circadian rhythm has been validated and quantified in healthy newborns, in healthy adults on various diets (including near-fasting conditions: 220 cal/24h, casein) and various type of activities. Food intake does not appear to influence the temperature circadian rhythm. The rhythm persists with a change of period and/or acrophase during isolation underground, without time dues or clues. Its acrophase can be shifted by manipulating synchronizing factors (i.e., shift-working, transmeridian flight). Alteration of circadian temperature rhythm may result from the timed administration of certain drugs (i.e. reserpine) and from certain chronic diseases (without overt fever). A first attempt to use both thermography and chronobiological method has been made independantly by Gautherie et al [40] and Smolensky [41] in the prediction of therapeutic value of a given modality during the course of breast cancer treatment.


Hybrid dysgenesis in Drosophila melanogaster: evidence from sterility and southern hybridization tests that P cytotype is not maintained in the absence of chromosomal P factors.
A two-generation crossing program was used to replace the entire chromosome complement of P strains by M strain chromosomes, the maternal contribution being from the P strain. The cytotype of chromosomally substituted females was indistinguishable from M strain cytotype, judged by the sterility of offspring from the cross of such females to P strain males. In addition, following replacement of the chromosomes, the level of DNA homologous to the P factor was sufficiently low to be explicable by low levels of P factor transposition. These results are consistent with immediate chromosomal control for the switching from P to M cytotype. However, the reverse chromosome substitution, replacing all chromosomes of an M strain with P chromosomes, did not usually lead to immediate change of cytotype properties, showing that there is a true maternal effect in the M to P direction. The absence of true maternal inheritance for P cytotype argues against models of P factor repression which depend on autonomous replication of a nonchromosomal element. The repression could still be explained by nonchromosomal copies of the P factor, provided that these are replenished from chromosomal P factors. A model is put forward in which P cytotype is due to the presence of circular P factors carrying a P factor target sequence, leading to preferential transposition of chromosomal P factors to nonchromosomal target sites.


Modelling the impact of vaccination on infectious diseases dynamics.
This paper investigates consequences of vaccine implementation strategies for infectious diseases by a mathematical model. For an infectious disease, the degree of infection may vary widely among the individuals. Reports show that individuals belonging to certain groups possess considerably higher risk to infection. Incorporating this phenomenon into vaccination strategies, the host is categorized into different groups to measure the outcome of the vaccination. A mathematical model is proposed and analysed to evaluate this measure. Our results suggest that vaccinating a group with certain priority may lead to elimination of the disease effectively. The strategy is cost-effective as well.


Two families of monoclonal antibodies to alpha(1----6)dextran, VH19.1.2 and VH9.14.7, show distinct patterns of J kappa and JH minigene usage and amino acid substitutions in CDR3.
Nine groove-type mAb to alpha(1----6)dextran were cloned and sequenced. Together with previous reports from this laboratory, the VH and VL of 34 mAb have been sequenced, in which 10 VH19.1.2 and 11 VH9.14.7 combined with the V kappa-Ox1 gene to form two major families of anti-alpha(1----6)dextrans. The same D minigene (DFL16) was used by all VH19.1.2 and VH9.14.7 mAb; however, the patterns of JH and J kappa usage are quite different. VH19.1.2 mAb used only JH3 and J kappa 2, whereas VH9.14.7 mAb used three JH (JH1, JH2, and JH3) and all four active J kappa (J kappa 1, J kappa 2, J kappa 4, and J kappa 5). Relative uniformity in the lengths of VH CDR3 and the junctional sequences is seen in both families. Some mAb from different mouse strains share common structural features. The differences in idiotypic specificities and in the amino acid sequences suggest that VH19.1.2 and VH9.14.7 may differ in the conformation of CDR1 and CDR2. Combining with V kappa-Ox1 gene to generate groove-type combining sites to the single site-filling epitope of alpha(1----6)dextran, the two VH chains may require certain conformations of CDR3. Whether such conformational requirements influence the choice of J minigenes, the selection of the length of VH CDR3 and the sequences at junctions, are discussed.


Problems and challenges in the historical study of the neurosciences.
The paper focuses on historiographical questions relevant to the historical study of the neurosciences. I attempt to illuminate these questions by looking at them from the perspective of general historiography of science. In the first section, I consider the disciplinary structure of the modern neurosciences and discuss some of the historiographical problems that are involved in the historical description of a highly multidisciplinary field. For example, how far back in time can one trace brain research as part of the construction that we call the neurosciences? The main part of the paper deals with recent trends in contextualist historiography in relation to the neurosciences. I suggest that one important source for the trend, as it emerged in the 1970s, was a renewed interest in the history of phrenology and its reception in Britain. By looking at the historiography of phrenology, some of the rival positions in modern historiography of science can be illuminated. In the last part of the paper, I comment on the advantages and disadvantages of contextualist historiography of science, including its relation to the producers of science, the scientists.


American College of Sports Medicine position stand. The Female Athlete Triad.
The Female Athlete Triad is a syndrome occurring in physically active girls and women. Its interrelated components are disordered eating, amenorrhea, and osteoporosis. Pressure placed on young women to achieve or maintain unrealistically low body weight underlies development of the Triad. Adolescents and women training in sports in which low body weight is emphasized for athletic activity or appearance are at greatest risk. Girls and women with one component of the Triad should be screened for the others. Alone or in combination, Female Athlete Triad disorders can decrease physical performance and cause morbidity and mortality. More research is needed on its causes, prevalence, treatment, and consequences. All individuals working with physically active girls and women should be educated about the Female Athlete Triad and develop plans to prevent, recognize, treat, and reduce its risks.


[Characterization of pacemaking currents in cultured interstitial cells of Cajal from mice small intestine].
Gastrointestinal motility is initiated by the periodic generation of slow waves. Interstitial cells of Cajal (ICC) are pacemaker cells that generate slow waves and drive spontaneous mechanical contractions of the gastrointestinal smooth muscle. Slow waves generate the periodic activation of spontaneous inward currents (pacemaker currents). The aim of this study was to investigate the characterization of pacemaker currents of ICC. The ICC in mice small intestine were cultured with stem cell factor for 2 days, and then we recorded pacemaker currents and slow waves using a whole-cell patch clamp technique. Under voltage clamp at -80 mV of holding potential, ICC generated pacemaker currents. Tetrodotoxin and nifedipine did not affect on the pacemaker currents. In addition, tetraethylammonium, 4-aminopyridine and glibenclamide did not affect on the pacemaker currents. The reduction of external Na+ concentrations inhibited pacemaker currents. Moreover, these currents were completely abolished in the external Ca2+-free condition. Gadolinium and flufenamic acid, inhibitors of non-selective cationic currents, inhibited pacemaker currents. Thapsigargin and cyclopiazoic acid, inhibitors of Ca2+-ATPase in endoplasmic reticulum, abolished pacemaker currents. Carbachol depolarized membrane potential and increased inward currents. These results suggest that pacemaker currents are mediated by the activation of non-selective cation channel and become a target of neurotransmitters in regulation of intestinal motility.


Unusual Association of Inverse Retinitis Pigmentosa, Scleromalacia, and Neovascular Glaucoma.
A 31-year-old woman with inverse retinitis pigmentosa presented with severe ocular pain and ingrained visual loss. Biomicroscopy revealed a large scleromalacia area above the superior limbus, minimal Descemet's membrane folds, aqueous flare, rubeosis iridis, and mature cataract. Intraocular pressure was 39 mmHg, and the clinical picture was consistent with neovascular glaucoma. After immediate medication to reduce ocular discomfort, an anterior chamber bevacizumab injection was performed. At 1 week post-injection, the rubeosis iridis had largely regressed and intraocular pressure was 21 mmHg. At post-injection 1 month, antiglaucomatous medication was discontinued because intraocular pressure was stable. Clear cornea, normal anterior chamber depth, and mature cataract were seen via biomicroscopy, and increased axial length with no significant change in posterior segment echogenicity were observed on ultrasonography. Three years after the single dose of bevacizumab, neovascularization was not seen in either the anterior chamber angle or on the iris surface, and intraocular pressure remained within normal range. The most important aspect of this case report is that it is the first to show an unusual association between neovascular glaucoma, scleromalacia, and inverse retinitis pigmentosa.


Appraisal of EUS-guided needle-based confocal laser endomicroscopy in the diagnosis of pancreatic lesions: A single Chinese center experience.
In the recent years, EUS is one of the routine procedures in the diagnosis of pancreatic diseases. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel minimally invasive imaging technique in diagnosis of pancreatic diseases. The pilot researches provided us some preliminary findings and conclusions with small samples, low rate of pathological correspondence. The aim of this current study was to evaluate the diagnostic efficacy of EUS-guided nCLE in solid pancreatic lesions (SPLs) and pancreatic cystic lesions (PCLs) based on large samples. The date was obtained on nCLE imaging findings and high rate of correlation with pathology. Patients enrolled in the study were underwent EUS-nCLE to achieve the nCLE images and diagnosis. Comparing with the final diagnosis, including surgical histopathological results or cyto-/histopathology through FNA, the efficacy and accuracy of nCLE in diagnosis in solid and cystic pancreatic lesions were evaluated. In other cases, clinical diagnoses were achieved based on the combination with clinical history, image findings and fluid analysis and cytology, by 3 independent committee members strongly agreed with a concordant diagnosis. Totally 172 patients were enrolled into the study. The overall rate of final diagnosis was about 65% while 50% in cystic lesion. The mean sensitivity, specificity, negative predictive value, positive predictive value and accuracy of the nCLE in diagnosis of PDAC is 90.3%, 89.5%, 93.3%, 85.0% and 90.0% respectively. The efficacy and accuracy of pancreatic cystic lesions were very satisfying and some additional nCLE signs were found, including "black aggregates of cells, forming as gland-like structure, surrounding by fibro and vessels" in neuroendocrine tumors (NETs); "black columnar protrusions near vascular area" in the pseudopapillary solid tumor (SPT); macrophage in tuberculosis (TB) and small aggregate of black regular cells maybe corresponds to ovarian-like stroma in mucinous cystadenoma (MCN). In the study, 20 (11.6%) patients suffered complications, including symptomatic (5.2%) and asymptomatic (6.4%). nCLE observation could improve characterization of indeterminate cysts, or confirm the EUS impression, when cytological confirmation is missing. The technique may deliver information to better guide our clinical decisions.


Pros and cons of using systemic acitretin in the paediatric population.
Acitretin, a synthetic analogue of vitamin A is widely used in dermatology. It has an important role in the treatment of psoriasis and keratinization disorders. In adults its safety and efficacy has been proven in many studies, but there are some concerns regarding the use of acitretin in paediatric population, especially in high doses and as a long-term therapy. In this article we present the main indications of acitretin in children as well as the positive and negative aspects of acitretin treatment in this age population.


[The lactate-pyruvate quotient in the framework of modern thyroid diagnosis].
In literature a big number of central and peripheral parameters for the diagnosis and control of therapeutical measures in diseases of human thyroid gland is described. That means, that none of the methods used has a sufficient weight. The enzymatic estimation of pyruvate and lactate reflect the peripheral effect of the hormones of thyroid gland. The pyruvate and lactate levels differ in the several groups of patients with euthyreosis, hypothyreosis, hyperthyreosis and euthyreotic goitre. Between these all groups the lactate/pyruvate ratio showed highly significant differences. The comparison of the lactate/pyruvate ratio and the T3-values showed highly significant correlation between both parameters. This good conformity is underlined by the behaviour of the parameters in courses of therapy, with additional support by farther functional tests--ETR-, T3- and T4-test. Our results confirmed the suggestion, also in agreement with literature, that the lactate/pyruvate ratio represent a possible enrichment in the laboratory programme for diagnosis and control of therapy in patients with thyroid diseases.


Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post-transfer refinement.
When microbes acquire new abilities through horizontal gene transfer, the genes and pathways must function under conditions with which they did not coevolve. If newly-acquired genes burden the host, their utility will depend on further evolutionary refinement of the recombinant strain. We used laboratory evolution to recapitulate this process of transfer and refinement, demonstrating that effective use of an introduced dichloromethane degradation pathway required one of several mutations to the bacterial host that are predicted to increase chloride efflux. We then used this knowledge to identify parallel, beneficial mutations that independently evolved in two natural dichloromethane-degrading strains. Finally, we constructed a synthetic mobile genetic element carrying both the degradation pathway and a chloride exporter, which preempted the adaptive process and directly enabled effective dichloromethane degradation across diverse Methylobacterium environmental isolates. Our results demonstrate the importance of post-transfer refinement in horizontal gene transfer, with potential applications in bioremediation and synthetic biology.


Quantifying and Improving the Performance of Speech Recognition Systems on Dysphonic Speech.
This study seeks to quantify how current speech recognition systems perform on dysphonic input and if they can be improved. Experimental machine learning methods based on a retrospective database. Single academic voice center. A database of dysphonic speech recordings was created and tested against 3 speech recognition platforms. Platform performance on dysphonic voice input was compared to platform performance on normal voice input. A custom speech recognition model was trained on voice from patients with spasmodic dysphonia or vocal cord paralysis. Custom model performance was compared to base model performance. All platforms performed well on normal voice, and 2 platforms performed significantly worse on dysphonic speech. Accuracy metrics on dysphonic speech returned values of 84.55%, 88.57%, and 93.56% for International Business Machines (IBM) Watson, Amazon Transcribe, and Microsoft Azure, respectively. The secondary analysis demonstrated that the lower performance of IBM Watson and Amazon Transcribe was driven by performance on spasmodic dysphonia and vocal fold paralysis. Thus, a custom model was built to increase the accuracy of these pathologies on the Microsoft platform. Overall, the performance of the custom model on dysphonic voices was 96.43% and on normal voices was 97.62%. Current speech recognition systems generally perform worse on dysphonic speech than on normal speech. We theorize that poor performance is a consequence of a lack of dysphonic voices in each platform's original training dataset. We address this limitation with transfer learning used to increase the performance of these systems on all dysphonic speech.


Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis.
Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation covaried with markers of bone resorption in the total population.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and reactivity of dimethyl gold complexes supported on MgO: characterization by infrared and X-ray absorption spectroscopies.
Dimethyl gold complexes bonded to partially dehydroxylated MgO powder calcined at 673 K were synthesized by adsorption of Au(CH3)2(acac) (acac is C5H7O2) from n-pentane solution. The synthesis and subsequent decomposition of the complexes by treatment in He or H2 were characterized with diffuse reflectance Fourier transform infrared (DRIFT), X-ray absorption near edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) spectroscopies. The XANES results identify Au(III) in the supported complexes, and the EXAFS and DRIFTS data indicate mononuclear dimethyl gold complexes as the predominant surface gold species, consistent with the lack of Au-Au contributions in the EXAFS spectrum and the presence of nu(as)(CH3) and nu(s)(CH3) bands in the IR spectrum. EXAFS data show that each complex is bonded to two oxygen atoms of the MgO surface at an Au-O distance of 2.16 angstroms. The DRIFT spectra show that reaction of Au(CH3)2(acac) with MgO at room temperature also formed Mg(acac)2 and H(acac) species on the support. Treatment of the dimethyl gold complexes in He or H2 at increasing temperatures varying from 373 to 573 K removed CH3 ligands and caused aggregation forming zerovalent gold nanoclusters of increasing size, ultimately with an average diameter of about 30 angstroms. Analysis of the gas-phase products during the genesis of the gold clusters indicated formation of CH4 (consistent with removal of CH3 groups) and CO2 at 473-573 K, associated with decomposition of the organic ligands derived from acac species. O2 and CO2 were also formed in the decomposition of ubiquitous carbonates present on the surface of the MgO support.


Gene expression profiles reveal key pathways and genes associated with neuropathic pain in patients with spinal cord injury.
Previous gene expression profiling studies of neuropathic pain (NP) following spinal cord injury (SCI) have predominantly been performed in animal models. The present study aimed to investigate gene alterations in patients with spinal cord injury and to further examine the mechanisms underlying NP following SCI. The GSE69901 gene expression profile was downloaded from the public Gene Expression Omnibus database. Samples of peripheral blood mononuclear cells (PBMCs) derived from 12 patients with intractable NP and 13 control patients without pain were analyzed to identify the differentially expressed genes (DEGs), followed by functional enrichment analysis and protein‑protein interaction (PPI) network construction. In addition, a transcriptional regulation network was constructed and functional gene clustering was performed. A total of 70 upregulated and 61 downregulated DEGs were identified in the PBMC samples from patients with NP. The upregulated and downregulated genes were significantly involved in different Gene Ontology terms and pathways, including focal adhesion, T cell receptor signaling pathway and mitochondrial function. Glycogen synthase kinase 3 β (GSK3B) was identified as a hub protein in the PPI network. In addition, ornithine decarboxylase 1 (ODC1) and ornithine aminotransferase (OAT) were regulated by additional transcription factors in the regulation network. GSK3B, OAT and ODC1 were significantly enriched in two functional gene clusters, the function of mitochondrial membrane and DNA binding. Focal adhesion and the T cell receptor signaling pathway may be significantly linked with NP, and GSK3B, OAT and ODC1 may be potential targets for the treatment of NP.


[Long-term outcome and health-related quality of life in survivors of severe acute pancreatitis].
To evaluate the health-related quality of life and postdischarge long-term outcome after severe acute pancreatitis. The hospital records of patients with SAP discharged healthy from January 2003 to December 2003 were reviewed. The Rand 36-item Health Survey with accessory question was mailed to each patient. The means and deviations for each of eight scales scores of SF-36 were calculated, the study population scores were compared with general Chinese population; Univariate analysis was applied to determining the effects of variables such as age, sex, causes of disease, mode of treatment, frequency of surgery, financial burden, length of stay, chronic complications. Accessory questions were analyzed separately. The means and deviations for each of eight scales (PF, RP, RE, BP, VT, MH, SF, GH) scores of SF-36 in SAP patients were 83 +/- 15, 62 +/- 42, 69 +/- 36, 80 +/- 15, 69 +/- 19, 72 +/- 15, 75 +/- 18, 65 +/- 18, compared with general people. Except RP and SF, the others were similar. In the ANOVA of Physical Component Summary, the three variables mode of treatment, financial burden and length of stay were included (P < 0.05), while in that of Mental Component Summary, the two variables of gender and financial burden were included (P < 0.05). The health-related quality of life in SAP patients is similar to that of general people. Greater attention should be given to mode of treatment, length of stay and financial burden to improve quality of life.


[Primary suture of older and contaminated wounds. A prospective clinical study].
In a prospective study of 50 consecutive patients primary wound closure was examined on cases with contaminated wounds. In 42 patients the period from the injury to the attendance of the ambulance ranged from 12 to 72 hours. Eight wounds were butcher's knife lesions in professionally exposed persons. Bacterial contamination could be demonstrated in 84% of the microbiologic smears. The principles of therapy were related to the wound care directions of Kirschner 1941 including a careful debridement. Routine administration of antibiotics was not necessary. Primary wound healing was achieved in 48 cases. Sutures were removed after 10.8 days, the time off work was 6.8 days. Wound infection occurred in 2 patients. After removing sutures undisturbed healing was observed in both cases. Due to these results we no longer see a contraindication in the primary closure of contaminated wounds. With careful debridement and conscientious wound control during the first 72 hours, primary suture is of low risk, comfortable to the patients and cost saving.


Elemental sulfur as electron donor and/or acceptor: Mechanisms, applications and perspectives for biological water and wastewater treatment.
Biochemical oxidation and reduction are the principle of biological water and wastewater treatment, in which electron donor and/or acceptor shall be provided. Elemental sulfur (S0) as a non-toxic and easily available material with low price, possesses both reductive and oxidative characteristics, suggesting that it is a suitable material for water and wastewater treatment. Recent advanced understanding of S0-respiring microorganisms and their metabolism further stimulated the development of S0-based technologies. As such, S0-based biotechnologies have emerged as cost-effective and attractive alternatives to conventional biological methods for water and wastewater treatment. For instance, S0-driven autotrophic denitrification substantially lower the operational cost for nitrogen removal from water and wastewater, compared to the conventional process with exogenous carbon source supplementation. The introduction of S0 can also avoid secondary pollution commonly caused by overdose of organic carbon. S0 reduction processes cost-effectively mineralize organic matter with low sludge production. Biological sulfide production using S0 as electron acceptor is also an attractive technology for metal-laden wastewater treatment, e.g. acid mine drainage. This paper outlines an overview of the fundamentals, characteristics and advances of the S0-based biotechnologies and highlights the functional S0-related microorganisms. In particular, the mechanisms of microorganisms accessing insoluble S0 and feasibility to improve S0 bio-utilization efficiency are critically discussed. Additionally, the research knowledge gaps, current process limitations, and required further developments are identified and discussed.


A difficult diagnosis: right unilateral cardiogenic pulmonary edema. Usefulness of biochemical markers of heart failure for the correct diagnosis.
We describe a case of unilateral pulmonary edema occurring in a young woman affected by hypertrophic cardiomyopathy complicated by acute worsening of mitral regurgitation. The relevant role of biochemical markers of heart failure, such as brain natriuretic peptide and carbohydrate antigen 125, in clarifying the final diagnosis of cardiogenic pulmonary edema and modifying treatment accordingly is emphasized.


[An analysis of changes in the background electrical activity of the dog neocortex during elaboration of food-getting conditioned reflexes].
Background electrical activity of different areas of the neocortex was studied at interstimuli periods during elaboration of food-procuring (instrumental) conditioned reflexes in dogs. By using the complex of EEG parameters obtained after a correlation-spectral analysis, it was possible to provide differentiated EEG characteristics of such externally similar conditions as rest in a situation of food-procuring and in an indifferent situation. Further, it has been found that the background activity parameters significantly differ in one and the same situation of food-procuring, depending on the functional state (passive rest and activation of attention). The data obtained point to the informative nature of background electrical activity of the neocortex, whose parameters reflect the peculiarities of specific functional conditions.


Impact of universal hepatitis B vaccination on antenatal hepatitis B prevalence in the Midlands region of the North Island, New Zealand.
Universal hepatitis B vaccination has now been in place in New Zealand for 22 years. A retrospective laboratory data study has been carried out to give objective evidence of the impact that this is having on hepatitis B prevalence in the antenatal population. A retrospective data search was performed of all antenatal hepatitis B surface antigen (HepBsAg) tests carried out at Pathlab Laboratories between 1997 and 2009. When the change in prevalence with time is examined, there is a clear downwards trend in antenatal hepatitis B prevalence rates from 1997 to 2009. Dividing the antenatal population into different age groups, the downward trend is most marked for those aged =20 years. The prevalence of hepatitis B infection in the antenatal population in the Midlands region of New Zealand is now declining and is likely to be as a result of the introduction of the hepatitis B vaccine onto the universal schedule throughout New Zealand in 1988. This would also explain why the decrease is most marked in antenatal women below the age of 20.


[Dipyridamole in the treatment and prevention of cerebral venous thrombosis in women using hormonal contraceptives].
The review covers the topic of cerebral venous thrombosis (CVT) in women taking hormonal contraceptives. The paper gives the definition of CVT, the history and analysis of epidemiological data. It was shown that the increased risk of CVT occurs due to the influence of hormonal contraceptives on the system of hemostasis and severity of the risk depends on the preparation formula, the way and duration of its administration. The authors show the role of combination of hormonal contraceptives with other risk factors and predisposing conditions for the development of thrombosis. The rules for choosing the method of contraception in accordance with generally accepted recommendations are suggested. The description of pathogenic mechanisms of CVT, clinical picture and disease as well as neuroimaging criteria and the rules for choosing a diagnostic method are presented. The authors provide the description of complex therapy in the acute period of the disease, the rules for secondary prevention. Particular attention is paid to the possibility of using dipyridamole, which has a pleiotropic effect, influencing all the components of the Virchov triad, as a part of a complex therapy and secondary prevention.


Fine sediment retention in storage chambers: an assessment of time-dependent effects.
The optimisation of the design of a storage chamber is generally based upon some measure of the chamber's sedimentation efficiency. In the UK, chambers that minimise the deposition of fine sediments are preferred. Previous laboratory and CFD-based studies to measure efficiency have focused on steady flow conditions. However, both the flow hydraulics within a storage chamber and the pollutant loading in the incoming sewage vary markedly during storm events. This paper outlines a CFD-based approach for determining "overall" chamber efficiency. The approach employs an unsteady volume-of-fluid multiphase model and stochastic particle tracking. Preliminary results from a simplified two-dimensional model are presented.


Adherence stages measured by patient-reported outcome instruments in adults with asthma: a scoping review.
Objective: Individuals who are adherent to their asthma inhaled maintenance medication: (1) initiate their treatment (take the first dose); (2) implement it (take it as per prescribed dosing regimen); and persist with it (take it for the entire prescribing period). To avoid unnecessary hospitalizations and costs, patient adherence should be routinely assessed. To this end, we aimed to identify patient-reported outcome instruments (PROs) used for measurement of patient adherence to inhaled maintenance medication in asthmatic adults and to report on the adherence stage that these instruments measured. Data sources: We conducted a scoping review of six databases. Study selection: We searched for studies in which PROs were used to measure patient adherence to inhaled maintenance medication in asthmatic participants aged ≥18 years. We extracted and synthesized data in order to list the available PROs and to report the adherence stages that these instruments measured. Results: We included 186 studies (87 PROs). Among all 87 instruments, none were found to measure all three adherence stages. We found that 1 measured initiation, 2 evaluated initiation and implementation, 74 assessed implementation, 7 measured implementation and persistence. The most used instrument (n = 41 studies or 22%) was the Self-Reported Medication-Taking Scale, which was found to assess implementation only. Conclusion: Our results suggest that no single PRO exists to measure initiation, implementation and persistence with asthma inhaled maintenance medication. Results from this review could therefore guide the development or refinement of PROs that would aim to measure all three adherence stages.


The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles.
Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite.


Terrorist bombings. Lessons learned from Belfast to Beirut.
Experience in the management of mass casualties following a disaster is relatively sparse. The terrorist bombing serves as a timely and effective model for the analysis of patterns of injury and mortality and the determination of the factors influencing casualty survival in the wake of certain forms of disaster. For this purpose, a review of the published experience with terrorist bombings was carried out, providing a study population of 3357 casualties from 220 incidents worldwide. There were 2934 immediate survivors of these incidents (87%), of whom 881 (30%) were hospitalized. Forty deaths ultimately occurred among these survivors (1.4%), 39 of whom were among those hospitalized (4.4%). Injury severity was determined from available data for 1339 surviving casualties, 251 of whom were critically injured (18.7%). Of this population evaluable for injury severity, there were 31 late deaths, all of which occurred among those critically injured, accounting for an overall "critical mortality" rate of 12.4%. Overall triage efficiency was characterized by a mean overtriage rate (noncritically injured among those hospitalized or evacuated) of 59%, and a mean undertriage rate (critically injured among those not hospitalized or evacuated) of .05%. Multiple linear regression analysis of all major bombing incidents demonstrated a direct linear relationship between overtriage and critical mortality (r2 = .845), and an inversely proportional relationship between triage discrimination and critical mortality (r2 = 0.855). Although head injuries predominated in both immediate (71%) and late (52%) fatalities, injury to the abdomen carried the highest specific mortality rate (19%) of any single body system injury among immediate survivors. These data clearly document the importance of accurate triage as a survival determinant for critically injured casualties of these disasters. Furthermore, the data suggest that explosive force, time interval from injury to treatment, and anatomic site of injury are all factors that correlated with the ultimate outcome of terrorist bombing victims. Critical analysis of past disasters should allow for sufficient preparation so as to minimize casualty mortality in the future.


A novel, testis-specific member of the cellular lipophilic transport protein superfamily, deduced from a complimentary deoxyribonucleic acid clone.
A novel member of the cellular lipophilic transport protein superfamily was identified after an antiserum raised against cellular retinoic acid-binding protein (CRABP) was found also to contain antibodies against another 15-kDa protein present in the cytosol of pubertal and adult rat testis. These antibodies were used to screen a rat testis cDNA expression library and isolate a 561-bp clone containing a full open reading frame from which the sequence of a novel 132 amino acid protein was deduced. The protein has 58% amino acid sequence identity to bovine myelin P2, 58% identity to murine adipocyte lipid-binding protein, and 40% identity to rat CRABP. Although the endogenous ligand has not yet been identified, conservation of residues involved in the binding of carboxylate groups suggests that the ligand is a fatty acid or an acidic retinoid. Tissue-specific expression was examined by Northern analysis and immunolocalization and appears to be restricted to late germ cells within the testis and epididymis. Immunostaining was first detectable in mid-pachytene spermatocytes and increased in intensity as these cells progressed to elongated spermatids, suggesting that this testis lipid-binding protein has a specific role in sperm development.


[Investigation of Verification Methods of Field Matching Using Polymer Gel Dosimeter in Proton Therapy].
In our proton beam therapy center, we use imaging plates (IP) for dose verification of field matching in irradiation (called patch-field technique). In this study, a polymer gel dosimeter, which can perform three- dimensional dose distribution measurement, was used as a new tool for the verification of the patch field irradiation method corresponding to the rectangular irradiation. The results of measurements of the PAGAT gel dosimeter to irradiate to two rectangular fields called as patch irradiation fields, which were created using the treatment planning system, were evaluated and compared to the results of IP and plan in profiles near the boundary of two fields. In the case of no gap between the two fields, the relative dose using the gel dosimeter was 10.1% higher compared to that measured with the IP in the midpoint of two fields. In case of overlap (called hot region), the result of gels was 6.3% higher than that of IP. In the case of space (called cold region), the result of gels was 14.9% higher than that of IP. The results of the difference between gel and plan in the midpoint of two fields were 14.2% (no gap), -5.0% (hot), and 10.5% (cold). We found that the gel dosimeter was a 3-D dosimetric tool and possibility method for dose verification of patch fields. In this study, the results were preliminary and included several error factors. In the future, it is necessary to develop a dosimeter with improved and more precise measurements.