Severe intraprosthetic regurgitation by immobile leaflet after trans-catheter aortic valve implantation.
Aortic regurgitation mainly in the form of paravalvular leaks is a frequent complication of trans-catheter aortic valve implantation (TAVI). We describe a case of an 86-year-old woman with severe aortic stenosis, who underwent trans-apical TAVI with a 23-mm Edwards-SAPIEN valve. Immediately post-implantation, severe intravalvular leak was observed on trans-esophageal echocardiogram (TEE) due to an immobile cusp associated with left-ventricular distension and cardiovascular collapse. Despite successfully treating the leak with the implantation of a second valve of the same diameter within the first one, the hemodynamic status remained unstable. Peripheral extracorporeal membrane oxygenation (ECMO) was established but resulted in a fatal outcome due to intractable heart failure.


A stomaplasty for total laryngectomy with a previous tracheostomy.
Stomaplasties were widely used to prevent or revise stomal stenosis, however, a previous tracheostomy can limit the choice of some techniques. This study aims to deal with this condition through a novel and simple technique called "Collar stomaplasty". This study involved 43 patients submitted for laryngectomy between 2017 and 2020. A tracheostomy 6-31 days prior to laryngectomy was performed in all cases. The collar stomaplasty, shaping the previous tracheostomy and surrounding skin, included 17 cases and the traditional X-shaped stomaplasty included 26 cases. Fisher's exact test was applied in an intergroup comparison of complications. One out of the collar stomaplasty group demonstrated perioperative stomal infection and avascular necrosis (5.9%). Another developed stomal stenosis (5.9%). In the X-shaped stomaplasty group, necrosis at the tip of the tracheal flap occurred in 14 cases (53.8%), and stomal stenosis occurred in 5 cases (19.2%). A statistically significance occurred in stomal necrosis (p<0.05) while no statistically difference is observed in stomal stenosis (p>0.05) between these two groups. The collar stomaplasty technique creates a laryngectomy tracheostoma by remodeling a previous tracheostomy. A wide and stable stoma, which facilitates stomal care, can be accomplished by this simple technique.


A scoping review establishes need for consensus guidance on reporting health equity in observational studies.
To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension. We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity. We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators". Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies.


The effects of an occlusive zinc medicated dressing on the bacterial flora in excised wounds in the rat.
The effects of three different dressings - two occlusive and one non-occlusive - on the bacterial flora of excised wounds in rats were studied. The number of colony forming units per gram of granulation tissue were significantly lower 4, 8 and 12 days postoperatively in wounds treated with a zinc medicated occlusive dressing compared with wounds treated with non-zinc medicated occlusive hydrocolloid dressing or wet-to-dry non-occlusive gauze dressing. The minimum inhibitory concentration (MIC) of zinc sulphate was determined on different strains of bacteria isolated from the wounds of rats and on strains isolated from humans. The most susceptible species isolated from both rat wounds and humans were Streptococcus sp., STaphylococcus aureus and Escherichia coli; whereas, Proteus and Enterococcus sp. had higher MIC-values. In vitro, the hydrocolloid dressing disclosed no antibacterial effects. If the practitioner prefers an occlusive dressing we believe, due to our animal and in vitro experiments, that the zinc medicated occlusive dressing will reduce the risk of wound infection in man.


Management of a Persistent Cystic Duct Stump Leak Following Cholecystectomy With Percutaneous Transabdominal Cystic Duct Stump Embolization.
Cystic duct stump leak remains a difficult clinical problem despite advancements in endoscopic techniques. When these minimally invasive strategies fail, patients are often subject to high morbidity and mortality associated with open surgical exploration. We report the successful treatment of persistent biliary leak from the cystic duct stump following cholecystectomy using percutaneous transabdominal access of the cystic duct and coil embolization.


Managing Chronic Pain in Special Populations with Emphasis on Pediatric, Geriatric, and Drug Abuser Populations.
In the adult population chronic pain can lead to loss of productivity and earning potential, and decreased quality of life. There are distinct groups with increased vulnerability for the emergence of chronic pain. These groups may be defined by developmental status and/or life circumstances. Within the pediatric, geriatric, and drug abuser populations, chronic pain represents a significant health issue. This article focuses on known anatomic, physiologic, and genetic mechanisms underlying chronic pain in these populations, and highlights the need for a multimodal approach from multiple health care professionals for management of chronic pain in those with the most risk.


Dorsal Preservation Rhinoplasty: Method and Outcomes of the Modified Subdorsal Strip Method.
There has been particular recent interest in dorsal preservation rhinoplasty techniques because of claims of superior functional and aesthetic results relative to conventional hump reductions. The septum in dorsal preservation rhinoplasty is managed in a variety of ways with differences largely based on the location of septal excision (subdorsal resection, midseptal resection, and inferior septal resection). The technical considerations of a modified subdorsal strip method using a structural preservation technique are described. This technique maintains a subdorsal and caudal strut of cartilage. Patient-reported measures demonstrate significantly improved functional and aesthetic outcomes postoperatively with this procedure.


LncRNA landscape and associated ceRNA network in placental villus of unexplained recurrent spontaneous abortion.
Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions frustrates women of childbearing age profoundly. The gene expression patterns and biological characteristics of placental villus in patients with URSA remain largely unknown. The aim of our study was to identify potential lncRNAs as well as their action mechanisms in URSA. The ceRNA microarray was used to identify the mRNA and lncRNA expression profiles of URSA patients and normal pregnancy. Functional enrichment analyses for differentially expressed mRNAs in URSA were performed. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. Subsequently, the co-dysregulated ceRNA network of URSA was established, and the enrichment analyses for the mRNAs in the ceRNA network was implemented. qRT-PCR was performed to validated the expression of key ENST00000429019 and mRNAs in URSA. We found that URSA placental villus have distinct mRNA and lncRNA expression profiles through ceRNA microarray, with a total of 347 mRNAs and 361 lncRNAs differentially expressed compared with controls. The functional enrichment analysis revealed that ncRNA processing, DNA replication, cell cycle, apoptosis, cytokine-mediated signaling pathway, ECM-receptor interaction were the potentially disrupted pathways in URSA patients. Then we constructed a co-dysregulated ceRNA network and found differentially expressed mRNAs were regulated by a small fraction of hub lncRNAs. Finally, we found a key network of ENST00000429019 and three cell proliferation or apoptosis related key mRNAs (CDCA3, KIFC1, NCAPH), and validated their expression and regulation in tissue and cellular levels. This study identified a key ceRNA network, which might take part in URSA and correlate with cell proliferation and apoptosis. Optimistically, this study may deepen our apprehensions about the underlying molecular and biological causes of URSA and provide an important theoretical basis for future therapeutic strategies for patients with URSA.


Response of young cattle to anthelmintic treatment during autumn in a mediterranean-type climatic environment.
A worm control programme in which heifers were treated with anthelmintic on three occasions during autumn, was tested in Mediterranean-type climatic environment of south-west Western Australia. The experiment aimed to determine if the treatments would prevent the heifers contaminating their pastures with worm eggs during autumn, thereby improving their growth performances the following winter. An attempt was made to measure the availability of infective larvae of abomasal worms on the heifers' pastures during early winter by counting the worms in steers, previously of low worm status, that grazed with the heifers from late autumn until the start of mating in mid-winter. The anthelmintic treatments reduced the contamination of pasture for most of the autumn. The treated heifers that grazed these pastures grew faster, and by the start of mating two months after the last treatment were about 22 kg heavier, than untreated heifers grazing contaminated pasture. At the end of mating six weeks later the difference was 45 kg in favour of the treated heifers. At this time the heifers grew faster than those left untreated, but by late November they had not attained the weight of the heifers grazing uncontaminated pasture. The heifers that grazed uncontaminated pasture produced more calves the following autumn than did those grazing contaminated pasture. The abomasal worm counts of the steers, with a mean of about 46,000 worms, failed to reveal any difference between treatments in the availability of larvae of abomasal worms on pasture. However, it was concluded that the treatments probably exerted their effect on growth rates by reducing the number of infective larvae ingested by heifers grazing the uncontaminated pasture during winter.


Baseline and on-statin treatment lipoprotein(a) levels for predicting cardiovascular events in patients with familial hypercholesterolemia.
Lipoprotein(a) [Lp(a)] has been considered as a causal risk factor for cardiovascular disease (CVD) in the general population and levels vary in different ethnicities. However, no systemic analysis is currently available regarding the relation of plasma Lp(a) levels to cardiovascular events (CVEs) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). Three hundred and ninety-three patients with HeFH undergoing Lp(a) measurement at baseline were consecutively enrolled and followed prospectively for an average of 36.5 months. Lp(a) levels were determined using an immunoturbidimetry assay. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the prognostic value of Lp(a) on CVEs. Thirty-five events occurred during follow-up. Lp(a) was significantly higher in patients with CVEs (53.3 mg/dL versus 31.7 mg/dL, p < 0.001). In Kaplan-Meier analysis, patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.004). After adjusting for confounding risk factors, per log unit increase in baseline Lp(a) was independently associated with CVEs [HR: 2.03(1.28-3.21), p = 0.002]. HRs remained unchanged after accounting for hard endpoints and did not vary too much in several relevant subgroups. Adding Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification and integrated discrimination. Moreover, HR for upper versus lower tertile of change in Lp(a) was 2.68 (1.11-6.48) for CVEs after one year. Both baseline and on-statin treatment Lp(a) levels were associated with an increased risk of CVEs in patients with HeFH, suggesting that Lp(a) measurement might clinically help further risk stratification of FH patients.


Effects of fatty liver on the size and composition of high-density lipoprotein cholesterol subpopulations in adolescents with type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) is an emerging disease in the pediatric population. The association between T2DM and non-alcoholic fatty liver disease (NAFLD) has been described. Recent evidence suggests that sizes and composition of high-density lipoprotein (HDL) may be more important that HDL-C levels in predicting coronary heart disease. There is not data regarding the HDL subclasses distribution and composition in T2DM youths with NAFLD. This cross-sectional study included 47 adolescents with T2DM and 23 non-diabetic controls of both sexes aged 10 to 18 years. The presence of NAFLD was determined estimated proton density fat fraction (PDFF) by magnetic resonance by spectroscopy. We compared the HDL subclasses distribution (HDL2b, HDL2a, HDL3a HDL3b and HDL3c) and the HDL chemical composition (total protein, triglyceride, phospholipid, cholesteryl esters, and free cholesterol) between the groups of adolescents with T2DM and the control group. Patients with T2DM and NAFLD had a significantly lower proportion HDL2b (P = .040) and a higher proportion of HDL3c (P = .035); higher proportion of TG (P = .032) and a lower CE (P = .002) and FC (P < .001). A negative association was observed between PDFF and the percentages of HDL2b (r2 = -0.341, P = .004) and the average particle size (r2 = -0.327, P = .05), and a positive association with HDL3c subpopulations (r2 = 0.327, P = .015); about composition inside HDL particle, a positive association with PDFF and the TG (r2 = 0.299, P = .013) and negative with CE (r2 = -0.265, P = .030). In adolescents diagnosed with T2DM, the presence of NAFLD is associated with abnormalities in the distribution of HDL subpopulations and the lipid composition of HDL particles.


Potential inhibitors of microglial activation from the roots of Wikstroemia lichiangensis W. W. Sm.
Research on natural inhibitors of microglial overactivation derived from members of the Wikstroemia genus revealed that the extract of W. lichiangensis W. W. Sm. Has a remarkable inhibitory effect on nitric oxide production in overactivated microglia. In the present study, thirty-four compounds, including five undescribed sesquiterpenoids [wiksdauctins A-B (1-2) and wikscarotins A-C (3-5)] and one undescribed lignan [wikstroeminasin A (8)], were isolated from a 95% EtOH extract of W. lichiangensis roots using bio-guided phytochemical research. The structures of the isolated compounds were elucidated using comprehensive spectroscopic analyses. Furthermore, their anti-neuroinflammatory effects were evaluated in lipopolysaccharide-stimulated BV-2 microglia. Seventeen isolated compounds exhibited stronger inhibitory effects than positive control minocycline (IC50 values of 67.08 ± 1.95 μM), with IC50 values ranging from 7.35 ± 2.51 to 64.49 ± 3.38 μM. The findings of this study imply that the isolated compounds might serve as potential therapeutic agents for neurodegenerative diseases.


Invited Review: Factors associated with atypical brain development in preterm infants: insights from magnetic resonance imaging.
Preterm birth (PTB) is a leading cause of neurodevelopmental and neurocognitive impairment in childhood and is closely associated with psychiatric disease. The biological and environmental factors that confer risk and resilience for healthy brain development and long-term outcome after PTB are uncertain, which presents challenges for risk stratification and for the discovery and evaluation of neuroprotective strategies. Neonatal magnetic resonance imaging reveals a signature of PTB that includes dysconnectivity of neural networks and atypical development of cortical and deep grey matter structures. Here we provide a brief review of perinatal factors that are associated with the MRI signature of PTB. We consider maternal and foetal factors including chorioamnionitis, foetal growth restriction, socioeconomic deprivation and prenatal alcohol, drug and stress exposures; and neonatal factors including co-morbidities of PTB, nutrition, pain and medication during neonatal intensive care and variation conferred by the genome/epigenome. Association studies offer the first insights into pathways to adversity and resilience after PTB. Future challenges are to analyse quantitative brain MRI data with collateral biological and environmental data in study designs that support causal inference, and ultimately to use the output of such analyses to stratify infants for clinical trials of therapies designed to improve outcome.


T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct.
BscCD19xCD3 is a bispecific single-chain antibody construct with exceptional cytotoxic potency in vitro and in vivo. Here, we have investigated the biological activity of bscCD19xCD3 in chimpanzee, the only animal species identified in which bscCD19xCD3 showed bispecific binding, redirected B-cell lysis and cytokine production comparable to human cells. Pharmacokinetic analysis following 2-h intravenous infusion of 0.06, 0.1 or 0.12 mug/kg of bscCD19xCD3 as part of a dose escalation study in a single female chimpanzee revealed a half-life of approximately 2 h and elimination of the bispecific antibody from circulation within approximately 8 h after the end of infusion. This short exposure to bscCD19xCD3 elicited a transient increase in serum levels of IFNgamma, IL-6, IL-2, soluble CD25, and transiently upregulated expression of CD69 and MHC class II on CD8-positive cells. Cytokine release and upregulation of T-cell activation markers were not observed with vehicle controls. A multiple-dose study using 5 weekly doses of 0.1 mug/kg in two animals also showed transient cytokine release and an activation of peripheral T cells with a first-dose effect, accompanied by a transient lymphopenia. While oscillations of T-cell counts were relatively even during repeated treatments, the amplitudes of peripheral B cells declined with every infusion, which was not observed in a vehicle control animal. Our data show that bscCD19xCD3 can be safely administered to chimpanzees at dose levels that cause fully reversible T-cell activation and, despite a very short exposure time, cumulative loss of peripheral B lymphocytes. A clinical trial testing prolonged administration of bscCD19xCD3 (MT103) for improving efficacy is currently ongoing.


Structure Identification and Functional Mechanism of Natural Active Components: A Special Issue.
The natural active components derived from plants have attracted widespread attention due to their abundant species and source advantages [...].


Antitumor activity of HER-2 inhibitors.
Activation of intracellular mitogenic signal transduction pathways driven by the ErbB family of receptor tyrosine kinases has been implicated in a variety of cancers. Amongst these, the tumorigenic roles of the Epidermal Growth Factor receptor (EGFR) and HER-2 have been most extensively studied. Therapeutic antibodies and small molecule kinase inhibitors targeting EGFR have recently received regulatory agency approval for the treatment of colon and lung cancer, respectively. In this review, I briefly describe these agents and their potential use in inhibiting the growth of tumors that overexpress HER-2. I also discuss other therapeutics currently available or being developed specifically to target HER-2 dependent tumors.


Practical Issues and Future Perspectives for Inflammation in Areas of Interstitial Fibrosis and Tubular Atrophy in Chronic Active T cell-Mediated Rejection: Three Case Reports with Commentary.
The 2017 Banff meeting provided specific criteria for the diagnosis of tubulointerstitial changes in chronic active T cell-mediated rejection (CATCR), with an emphasis on inflammation in areas of interstitial fibrosis and tubular atrophy, which was thought to reflect an ongoing T cell-mediated alloimmunity. CATCR is considered to occur as a consequence of persistent or recurrent acute T cell-mediated rejection. Acute T cell-mediated rejection is an acute cytotoxic T-cell reaction to HLA antigens on the donor kidneys and causes tubulitis, interstitial inflammation, and intimal arteries. However, unlike early T-cell transplant damage, CATCR can sometimes be difficult to diagnose because the subsequent chronic T-cell damage can become more complex from the accumulation of previous immune and nonimmune injuries. Furthermore, scoring inflammation in areas of interstitial fibrosis and tubular atrophy has potential problems because other diseases and not even native kidneys can have scattered inflammatory cells. Therefore, detailed insights on the pathogenesis of CATCR are indispensable for appropriate diagnosis and further treatment. In this study, the pathologic characteristics and possible factors involved in the interstitial lesions in both typical and complex cases of CATCR are discussed.


Identification of a phospholipase C beta subtype in rat taste cells.
From rat circumvallate papillae a novel phospholipase C (PLC) subtype has been cloned and identified as most closely related to human PLC beta2. The corresponding mRNA was only detected in sensory lingual tissue but not in non-taste lingual tissue or any other tissues examined by Northern blot analysis. In situ hybridization revealed that a subset of taste receptor cells of circumvallate papillae was specifically labeled. A functional involvement of this PLC beta subtype in taste signal transduction emerged from biochemical analysis monitoring the second messenger response in circumvallate preparations induced by denatonium benzoate. This bitter agent elicited a rapid and transient increase of the inositol 1,4,5-trisphosphate level; this response was blocked by U73122, a potent inhibitor of PLC, and by PLC beta2-specific antibodies. These data indicate that a phospholipase C beta2 isoform mediates a denatonium benzoate-induced second messenger response of taste sensory cells in the circumvallate papillae.


Comparative transcriptome and microbiota analyses provide new insights into the adverse effects of industrial trans fatty acids on the small intestine of C57BL/6 mice.
To reveal the mechanism that links industrial trans fatty acids (iTFAs) to various chronic diseases, we examined the impact of iTFAs on the local microenvironment of the small intestine (duodenum, jejunum and ileum). Forty male 8-week-old mice were fed diets containing one of the following: (1) low soybean oil (LS); (2) high soybean oil (HS); (3) low partially hydrogenated oil (LH), and (4) high partially hydrogenated oil (HH). The analysis of microbiota from small intestinal content was performed by real-time qPCR. The fatty acid composition of small intestine mucosa was measured by GC/MS, and comparative transcriptome of the small intestinal mucosa was analyzed by RNA-sequencing. The intake of iTFAs changed the fatty acid spectrum of the small intestine mucosa, especially the excessive accumulation of iTFA (mainly elaidic acid). For microbiota, the relative abundance of δ- and γ-proteobacteria, Lactobacillus, Desulfovibrio, Peptostreptococcus and Turicibacter were significantly different in the iTFA diet groups compared to the control group. Based on the identification of differently expressed genes(DEGs) and pathway annotation, comparative transcriptome analysis of the small intestine mucosa revealed obvious overexpression of genes involved in the extracellular matrix (ECM)-receptor interaction and the peroxisome proliferator-activated receptor signaling pathway, which suggests that ECM remodeling and abnormal lipid metabolism may have occurred with iTFA ingestion. Our research demonstrated multiple adverse effects of iTFA that may have originated from the small intestine. This finding could be to facilitate the development of new strategies to suppress iTFA-related diseases by reversing the adverse effects of iTFA on intestinal health.


Experimental evidence for a non-renin mediated pathway during TAME-esterase induced contractions in rat aorta in vitro.
Possible pharmacological effects of N-alpha-tosyl L-arginine methyl ester [TAME] were studied on rat aorta strips in vitro. Results showed that [TAME]-esterase was an endothelium dependent component that involved a nitric oxide cyclic-GMP mediated pathway. Furthermore, during activation of Kinin-Kallikrein system, TAME-esterase induced contractions involve degradation of kinins by kininases.


Selective staining of a subset of Purkinje cells in the human cerebellum with monoclonal antibody mabQ113.
MabQ113 is a monoclonal antibody raised against rat cerebellum which selectively strains Purkinje cells. Likewise, in mabQ113-immunoperoxidase stained sections of human cerebellum, deposits of reaction product are found only in the Purkinje cells. The dendritic arborizations, cell body, and axonal processes are immunoreactive. In rat, mabQ113 reveals a series of parasagittal antigenic bands which run throughout the cerebellar cortex. The staining distribution in human cerebellar cortex likewise reveals heterogenous staining but the pattern is a complex one and seems to be unlike the parasagittal banding found in the rat. In a number of human diseases Purkinje cell degeneration is not uniform throughout the vermis and cerebellar hemispheres. It is possible that mabQ113+ and mabQ113- subsets of Purkinje cells may respond differentially to various pathological conditions.


An indigenous, inexpensive operating microscope.
A method of assembling an inexpensive operating microscope from resources indigenous to a developing country is described.


Prediction of micro-hardness in thread rolling of St37 by convolutional neural networks and transfer learning.
This study introduces a non-destructive method by applying convolutional neural networks (CNN) to predict the micro-hardness of the thread-rolled steel. Material microstructure images were collected for our research, and micro-hardness tests were conducted to label the extracted microstructure images. In recent years, researchers have used machine learning (ML) and deep learning (DL) models to predict material properties for forming, machining, additive manufacturing, and other processes. However, they encountered industrial limitations primarily because of the absence of historical information on new and unknown materials, which are necessary to predict material properties by DL models. These problems can be solved by employing CNN models. In our work, we used a CNN model with two convolutional layers and visual geometry group (VGG19) as transfer learning (TL). We predicted four classes of micro-hardness of the St37 rolled threads. The prediction results of the micro-hardness test images by our proposed CNN model and pre-trained VGG19 model are comparable. Our proposed model has produced the same precision and recall scores as VGG19 for class B and class C hardness. VGG19 performed slightly better than our model for precision in class A and recall in class D. We observed that the training time of our proposed model using the CPU (central processing unit) was approximately nine times faster than the VGG19 model. Our proposed CNN and VGG19 have direct applications in advanced manufacturing (AM). They can automatically predict the micro-hardness in the thread rolling of St37. Our proposed model requires less memory and computational power and can be deployed more efficiently than the VGG19 model. The online version contains supplementary material available at 10.1007/s00170-022-10355-4.


Sequence of interleukin-2 isolated from human placental poly A+ RNA: possible role in maintenance of fetal allograft.
There are several cell types within the placenta that produce cytokines which can contribute to the regulatory mechanisms that ensure normal pregnancy. The immunological milieu at the maternofetal interface is considered to be crucial for survival of the fetus. Interleukin-2 (IL-2) is expressed by the syncytiotrophoblast, the cell layer between the mother and the fetus. IL-2 appears to be a key factor in maintenance of pregnancy. Therefore, it was important to determine the sequence of human placental interleukin-2. Direct sequencing of human placental IL-2 cDNA was determined for the coding region. Subclone sequencing was carried out for the 5'- and 3'-untranslated regions (5'-UTR and 3'-UTR). The 5'-UTR for human placental IL-2 cDNA is 294 bp, which is 247 nucleotides longer than that reported for cDNA IL-2 derived from T cells. The sequence of the coding region is identical to that reported for T cell IL-2, while sequence analysis of the polymerase chain reaction (PCR) product showed that the cDNA from the 3' end was the same as that reported for cDNA from T cells. Human placental IL-2 cDNA is 1,028 base pairs (excluding the poly A tail), which is 247 bp longer at the 5' end than that reported for IL-2 T cell cDNA. Therefore, the extended 5'-UTR of the placental IL-2 cDNA may be a consequence of alternative promoter utilization in the placenta.


Early experience of laparoscopic complete en bloc excision for choledochal cysts in adults.
For choledochal cyst, the treatment of choice is total excision of the cyst because there is a risk of biliary cancer including the gallbladder. The current report describes the authors' early experiences using their technique of laparoscopic en bloc excision of choledochal cysts with Roux-en-Y biliary reconstruction. Between September 2009 and July 2011, laparoscopic excision for choledochal cyst was attempted for 20 patients at the Division of Hepatobiliary and Pancreatic Surgery, Asan Medical Center. Clinical, radiologic, and surgical data were analyzed retrospectively. The mean age of the patients was 37.8 ± 11.1 years (range, 18-65 years), and the male-to-female ratio was 1:4.0 (4:16). According to Todani's classification, there were four type 1a cases, seven type 1c cases, and nine type 4a cases. The mean operation time was 395.8 ± 58.7 min. No perioperative transfusions were required. The average body mass index was 23.5 ± 4.04 kg/m(2). Conversion to laparotomy was required for seven patients (35 %) due to bleeding (n = 1), Roux loop venous congestion (n = 1), abdominal obesity (n = 2), and severe fibrosis and inflammation around the cyst (n = 3). No malignancies were identified. Of the 13 patients who underwent laparoscopy, the jejunojejunostomy was created extracorporeally for the first 2 patients and intracorporeally for the subsequent 11 patients. All hepaticojejunostomies were performed intracorporeally. Oral feeding was resumed on postoperative day 3. The mean postoperative hospital stay was 9.3 days (range, 8-36 days). No major complications or mortalities occurred. The morbidity and mortality rates for the authors' method are comparable with previously reported results. Although the conversion rate, mean operation time, and hospital stay were greater than reported in some studies, this probably reflected the authors' learning curve for this technically challenging procedure. They believe laparoscopic approaches will eventually become an advantageous treatment option for laparotomy offered to selected choledochal cyst patients.


Novel Function of a Transcription Factor WT1 in Regulating Decidualization in Human Endometrial Stromal Cells and Its Molecular Mechanism.
The Wilms tumor suppressor gene (WT1) encodes an essential transcription factor regulating mammalian urogenital development. However, the function of WT1 in human endometrium is still unclear. The current study examined the involvement of WT1 in the regulation of IGF-binding protein-1 (IGFBP-1) and prolactin (PRL), which are specific markers of decidualization, in human endometrial stromal cells (ESCs) undergoing decidualization. ESCs isolated from proliferative-phase endometrium were incubated with cyclic adenosine monophosphate (cAMP) to induce decidualization. cAMP increased WT1 expression with the induction of IGFBP-1 and PRL. Knockdown of WT1 by small interfering RNA inhibited cAMP-induced expression of IGFBP-1 and PRL. cAMP also induced the recruitment of WT1 to the IGFBP-1 and PRL promoters. To investigate the mechanism by which WT1 is upregulated by cAMP, we focused on C/EBPβ, a gene that regulates the expression of many genes during decidualization. Knockdown of C/EBPβ decreased cAMP-increased WT1 expression. cAMP increased the recruitment of C/EBPβ to the WT1 enhancer that is located approximately 14,000 bp downstream from the transcription start site. To test the endogenous function of the WT1 enhancer region on WT1 expression, the endogenous WT1 enhancer region was deleted by CRISPR/Cas9 system in HEK293 cells. The increase of WT1 expression by cAMP was not observed in the enhancer-deleted clones. Chromatin immunoprecipitation assay revealed that this enhancer region has high levels of H3K27ac and H3K4me1, which are active enhancer marks. These results show the role of WT1 in regulating decidualization in human ESCs. C/EBPβ is an upstream gene that regulates WT1 expression by binding to the novel enhancer region.


Clinical effects of infusing anti-Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes into patients with severe chronic active EBV infection.
Immune cell therapy with autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) or lymphokine-activated killer (LAK) cells was performed in 2 adults with severe chronic active EBV infection (SCAEBV). The patient in case 1, who had complications of pancytopenia, high fever, and massive splenomegaly, was treated with 13 doses of LAK cell infusion followed by 4 doses of autologous CTL infusion. The patient in case 2, who had liver dysfunction due to natural killer cell-type infection, was treated with 4 doses of autologous CTL infusion. In case 1, the LAK cell infusions were effective in lowering the viral load and improving several biochemical parameters (lactate dehydrogenase, soluble interleukin 2 receptor) and resulted in complete amelioration of the high fever. Subsequent infusions of autologous CTLs reduced the viral load only temporarily and were accompanied by an increase in frequency of EBV-specific T-cells in the blood. However, the patient's main problem of pancytopenia was not resolved. In case 2, infusion of autologous CTLs did not improve the patient's hepatic dysfunction or viral load but caused a significant increase in autoantibody levels. Thus the effect of auto-CTL treatment was limited or deteriorative in SCAEBV patients.


Case study: flame arresters and exploding gasoline containers.
This paper describes the case study of a portable plastic gasoline container explosion and fire. While working at home on a science project to determine the burn rates of different types of wood fuel, a 14-year-old boy was severely burned after flames traveled back up into the portable gasoline container and exploded. A witness heard the explosion and reports that the flames went perhaps 10 ft in the air. It is shown by experimentation that a flame arrester installed in the pour opening of the portable gasoline container would have prevented an explosion inside the gasoline container.


Impact of aging on innate immunity.
Immune responses in higher organisms are triggered by the recognition of a limited diversity of microbiological products by cells of the innate or "natural" immune system. As a result, in addition to the direct protective effect of natural immunity, antigen-presenting cells, particularly dendritic cells, are activated to process and present an enormous number of peptide antigens to the T lymphocytes of the adaptive immune system. These, together with the B lymphocytes, then mediate specific immune responses and maintain acquired immunological memory. The aging immune system is less well able to cope with infectious disease than the youthful immune system; this review will briefly consider what is known of the age-associated alterations in innate immunity, and how these may also impact on adaptive immunity.


Purification and properties of rabbit liver acid-lipase (4-methylumbelliferyl oleate hydrolase).
An acid lipase was purified from rabbit liver lysosomes by, in sequence, osmotic treatment of the lysosomal fraction, Sephadex LH-20, DEAE-Sephadex A-50, Bio-Gel A-5m, hydroxyapatite and, finally, Sephadex G-200 column chromatography. The substrate was 4-methylumbelliferyl oleate. The enzyme was solubilized by Sephadex LH-20 column chromatography instead of detergents and organic solvents, to obtain an intrinsic macromolecule. 4-Methylumbelliferyl oleate hydrolase, osmotically released from lysosomal particles, had a very high molecular weight (greater than 800 000) which was reduced by gel filtration on a Sephadex LH-20 column; the final molecular weight of the purified enzyme was 58 000. The specific activity of 4-methylumbelliferyl oleate hydrolase increased at almost the same rate as acid cholesterol esterase and triacylglycerol lipase after Sephadex LH-20 column chromatography; the thermal stability of the activity of the three enzymes was almost identical. We also discuss the properties of the enzyme molecule and the interaction between the enzyme and the lysosomal membrane.


The ecological basis of parasite control: ticks and flies.
Tick and fly control programmes have undergone radical review in recent years. Insecticidal control measures are now often seen as a means of reducing target populations to a level sufficiently low for final eradication by biological or ecological techniques, the sterile male method (SIRM) being particularly favoured. As a preliminary, the new range of insecticidal application techniques includes insecticidal tags, bands, blouses, implants and pheromone baits. The final eradication programme could then involve the use of sterile flies or sterile hybrid ticks, for example. Immunization of cattle against ticks, the use of tick-resistant crossbreeds of cattle, tick-repellent grasses and dung burying beetles are among the additional techniques now being actively investigated.


The degradation of municipal solid waste incineration leachate by UV/persulfate and UV/H2O2 processes: The different selectivity of SO4•- and •OH.
In this work, the different selectivity of SO4•- and •OH towards municipal solid waste incineration leachates (MSWILs) was studied by a comparative study of UV/persulfate (PS) and UV/H2O2. Results showed SO4•- preferentially mineralized carbon atoms of higher average oxidation state, while •OH showed a two-stage mechanism of partial oxidation and mineralization successively. Electron spin resonance (ESR) analysis showed SO4•- had superior selectivity towards MSWILs than •OH, and Fe(II) would significantly affect the selectivity via forming Fe-MSWILs complex. As the consequence, Fe(II) showed slightly negative effect on UV/PS, but greatly enhanced the performance of UV/H2O2/Fe(II). High concentration of Cl- affected the degradation of non-fluorescent substances by UV/PS, while SO42- and NO3- showed no effect. In contrast, anions showed no effect on UV/H2O2. In addition, •OH preferentially attacked large molecules, but SO4•- showed no selectivity. This study further revealed the selectivity of SO4•- and •OH in the treatment of hypersaline wastewater, and provided theoretical support for the development of targeted technology.


Test-retest reliability of stability outcome measures during treadmill walking in patients with balance problems and healthy controls.
Improvement of balance control is an important rehabilitation goal for patients with motor and sensory impairments. To quantify balance control during walking, various stability outcome measures have described differences between healthy controls and patient groups with balance problems. To be useful for the evaluation of interventions or monitoring of individual patients, stability outcome measures need to be reliable. What is the test-retest reliability of six stability outcome measures during gait? Patients with balance problems (n = 45) and healthy controls (n = 20) performed two times a two-minute walk test (2MWT). The intraclass correlation coefficient (ICC) and Bland-Altman analysis (coefficient of repeatability; CR) were used to evaluate the test-retest reliability of six stability outcome measures: dynamic stability margin (DSM), margin of stability (MoS), distance between the extrapolated centre of mass (XCoM) and centre of pressure (CoP) in anterior-posterior (XCoM-CoPAP) and medial-lateral (XCoM-CoPML) direction, and inclination angle between centre of mass (CoM) and CoP in anterior-posterior (CoM-CoPAP-angle) and medial-lateral (CoM-CoPML-angle) direction. A two way mixed ANOVA was performed to reveal measurement- and group-effects. The ICCs of all stability outcome measures ranged between 0.51 and 0.97. Significant differences between the measurements were found for the DSM (p = 0.017), XCoM-CoPAP (p = 0.008) and CoM-CoPAP-angle (p = 0.001). Significant differences between controls and patients were found for all stability outcome measures (p < 0.01) except for the MoS (p = 0.32). For the XCoM-CoP distances and CoM-CoP angles, the CRs were smaller than the difference between patients and controls. Based on the ICCs, the reliability of all stability outcome measures was moderate to excellent. Since the XCoM-CoPML and CoM-CoPML-angle showed no differences between the measurements and smaller CRs than the differences between patients and controls, the XCoM-CoPML and CoM-CoPML-angle seem the most promising stability outcome measures to evaluate interventions and monitor individual patients.


"Creative Solutions": selling cigarettes in a smoke-free world.
To analyse the development and execution of the "Creative Solutions" Benson & Hedges advertising campaign to understand its social, political, and commercial implications. Searches of the Philip Morris documents and Legacy Tobacco Documents websites for relevant materials; Lexis/Nexis searches of major news and business publications; and denotative and connotative analyses of the advertising imagery. Philip Morris developed the Creative Solutions campaign in an effort to directly confront the successes of the tobacco control movement in establishing new laws and norms that promoted clean indoor air. The campaign's imagery attempted to help smokers and potential smokers overcome the physical and social downsides of smoking cigarettes by managing risk and resolving internal conflict. The slogans suggested a variety of ways for smokers to respond to restrictions on their habit. The campaign also featured information about the Accommodation Program, Philip Morris's attempt to organise opposition to clean indoor air laws. The campaign was a commercial failure, with little impact on sales of the brand. Philip Morris got some exposure for the Accommodation Program and its anti-regulatory position. The lack of commercial response to the ads suggests that they were unable to successfully resolve the contradictions that smokers were increasingly experiencing and confirms the power of changing social norms to counter tobacco industry tactics.


Single-dose pharmacokinetics and anticonvulsant efficacy of primidone in mice.
The pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single-dose administration in mice. The half-life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy. The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half-life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short-term oral PRM administration in mice is from derived PB.


Fine structure of muscle insertions on the larval shell and operculum of the nudibranch Phestilla sibogae (Mollusca: Gastropoda) before and during metamorphosis.
In Phestilla, the attachment of the larval body to shell and operculum occurs at muscle insertion sites. Attachment zones are specialized areas of squamous epithelium wherein the cells contain structures considered to be cytoplasmic anchors. The anchors are intracellular organelles consisting of apical and basal hemidesmosomal plaques connected by bundles of tonofilaments which traverse the cells. Muscle-to-epithelium and epithelium-to-shell adhesion is probably due to an extracellular cement. At metamorphosis, both shell and operculum are lost. Electron microscopic investigation of shell and opercular attachment sites during metamorphosis has demonstrated that apical hemidesmosomes lose their integrity and tonofilament bundles pull away from the apical plasmalemma of the epithelial cells as the cells lose contact with the shell or operculum.


Promoting the electrocatalytic properties of nickel aerogel by gold decoration for efficient electrocatalytic oxygen evolution in alkali.
Decorating Au onto Ni aerogel via a one-step spontaneous gelation preserved the highly porous structure of Ni aerogel, and contributed to more active sites and enhanced intrinsic activity for water oxidation with low overpotential of 377 mV for the current density of 100 mA cm-2.


Special delivery from mitochondria to peroxisomes.
Inter-organellar communication and interactions are necessary and accepted consequences of the segregation of biochemical functions into subcellular organelles. Recently, Heidi McBride and her collaborators found a novel link between mitochondria and peroxisomes in their discovery of mitochondria-derived vesicles (MDVs), which appear to fuse with a fraction of pre-existing peroxisomes in mammalian cells. We discuss the potential role of this vesicle population in the context of pathways for the exchange of metabolites and/or macromolecules between these compartments.


A labile sulfur in trisulfide affects cytochrome P-450 dependent lipid peroxidation in rat liver microsomes.
The effects of trisulfide derivatives were studied on cytochrome P-450-dependent lipid peroxidation using rat liver microsomal systems. Cytochrome P-450-dependent lipid peroxidation was induced by carbon tetrachloride or tert-butylhydroperoxide and was evident by an increase in thiobarbituric acid-reactive substances (TBA-RS) and oxygen consumption. In these cytochrome P-450-dependent lipid peroxidation systems, pretreatment of microsome with trisulfide derivatives (cystine trisulfide and thiocyclam) significantly inhibited TBA-RS formation and oxygen consumption compared with disulfide or thiol analogs (cystine, nereistoxin, or cysteine). The labile sulfur contained in trisulfide disappeared during incubation with liver microsomes. In the CCl4-induced lipid peroxidation system, the cytochrome P-450 level and NAD(P)H-cytochrome P-450 reductase activity were significantly decreased by the addition of trisulfide derivatives. Therefore, in cytochrome P-450-dependent lipid peroxidation system, the potential effects of trisulfide appear to be mediated via enzyme inhibition. These results suggest that pretreatment of the trisulfide derivatives may affect the toxic function of exogenous xenobiotics or drugs, which are reduced by the liver enzyme cytochrome P-450 to radical species.


Cervical multisegmental motor responses in healthy subjects.
Experimental design. This descriptive design study presents multisegmental motor responses in the upper extremities after stimulation of cervical spinal vertebrae. Neuro Lab of Texas Woman's University, School of Physical Therapy, Texas, USA. In trial 1, C7 spinal segment was electrically stimulated in 13 healthy subjects using surface electrodes while recording responses from abductor digiti minimi (ADM), abductor pollicis brevis (APB), flexor carpi radialis (FCR) and biceps brachii (BB) in the right upper extremity. In trial 2, C7 stimulation was carried out while recording responses from the APB and BB bilaterally. In trial 3, C7 stimulation was carried out while recording responses from the flexor hallucis brevis (FHB), soleus, vastus medialis (VMO) and gluteus medius (GM) in the right lower extremity. The amplitude of the signal and the deflection latency were the measured parameters. Descriptive statistics were completed on the data. Results showed response amplitudes in all muscles of the upper extremities ranging from 328 to 1239 μV, with the largest recorded from the APB and ADM, then the FCR and BB. Muscular responses were recorded simultaneously in bilateral muscles. Response latency was comparable, in bilateral similar muscles, and was varied from 6 to 16.5 msec, being longer in the ADM and APB, shorter in FCR and shortest in the BB. No lower limb muscles responded to C7 spinal stimulation, using current setup/method. These responses appear to be caused by stimulating the dorsal roots or motor nuclei of the cervical region and could be useful in testing patients with cervical spinal disorders.


Carbohydrate epitopes on Haemonchus contortus antigens.
Extracts of infective larvae and adults of the trichostrongylid Haemonchus contortus were studied for the presence of carbohydrate moieties. Several different lectin-binding sites were demonstrated in both stages using a panel of nine lectins. The carbohydrate specificity of the lectins used strongly suggests that alpha-D-mannose, alpha-D-glucose, and D-N-acetylglucosamine are the most important carbohydrate epitopes present on H. contortus proteins. Thus, N-linked oligosaccharides form the major part of the carbohydrate moieties on these glycoproteins. Treatment with sodium periodate was performed to investigate the immunoreactivity towards the carbohydrate moieties. This treatment resulted in a reduction in the immunoreactivity of these antigens as demonstrated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting, suggesting that a substantial part of the host immune response against H. contortus is directed against the carbohydrate epitopes on the parasite antigens.


Human-Animal Relationships and Social Work: Opportunities Beyond the Veterinary Environment.
A species-spanning approach that incorporates clients' relationships with their companion animals into family genograms, schools of social work curricula, continuing education, interviews, assessments, and interventions offers increased career opportunities, professional and personal growth and development, and a more comprehensive resolution of clients' issues, social justice concerns, and the prevention of family violence. This article identifies six reasons why social workers should be cognizant of human-animal relationships and introduces nine ways, with action steps, in which social workers can include these relationships into training and practice outside the more developed field of veterinary social work. These venues include: agencies working in child protection and child sexual abuse; children's advocacy centers and courthouse facility dogs; animal shelters; domestic violence shelters; public policy advocacy; clinical practice; agencies working with older and disabled populations; veterinary sentinels for intimate partner violence; and pet support services for homeless populations. Such attention to the human-animal bond can utilize social workers' problem-solving skills to improve delivery of services, identify clients' risk and resiliency factors, enhance social and environmental justice, expand academic inquiry, and increase attention to all of the vulnerable members of families and communities.


Self-care in Iranian patients with diabetes: A systematic review and meta-analysis.
Self-care is a major factor in managing diabetes. This study aimed to determine the self-care status of Iranian patients with diabetes and to estimate the percentage of self-care in these individuals through a systematic review and meta-analysis. In this systematic review and meta-analysis 53 domestic articles published in Farsi and English were evaluated. We conducted database searches in domestic and foreign databases of Scientific Information Database (SID), MagIran, Google Scholar, Web of Science, Pub Med, and Scopus with no time limit. Data analysis was performed in Stata version 12 using meta-analysis method and the random effects model. A total of 50 articles (53 groups) with a sample size of 9565 were systematically reviewed. The percentage of self-care in patients with diabetes was reported to be 48.86 (95% confidence interval [CI]: 43.79-53.94). According to the results, the percentage of self-care score was higher in patients with type I diabetes (55.53) when compared with patients with type II diabetes (49.26). Since patients with diabetes obtained only half of the self-care score and given the importance of self-care in controlling and treating diabetes, it is necessary to perform actions to improve self-care such as benefiting from health facilities, and social and family support.


[Prophylaxis of cytomegalovirus infection in heart transplantation].
Cytomegalovirus (CMV) is a common complication after heart transplantation, affecting almost half of all recipients. The clinical spectrum of this infection includes, in order of greater to lesser severity, latent infection, asymptomatic viremia, CMV syndrome and CMV disease. CMV is associated with rejection and vascular graft disease and is a major cause of morbidity and mortality. The factors most frequently involved in susceptibility to this infection and its severity are donor and recipient CMV serological status, the intensity of immunosuppression and the type of immunosuppressive agents used. The management strategies of this infection include universal or targeted prophylaxis, preemptive therapy and treatment of established disease. The use of preventive measures significantly reduces the incidence of symtomatic infection or CMV disease, which has been reported to be less than 3% in some recent series.


Barriers and facilitators to primary care for people with mental health and/or substance use issues: a qualitative study.
Mental health and/or substance use issues are associated with significant disparities in morbidity and mortality. The aim of this study was to identify the mechanisms underlying poor primary care access for this population. This was a community-based participatory action qualitative study, in which 85 adults who self-identified as having a serious mental health and/or substance use issue and 17 service providers from various disciplines who worked with this population participated in a semi-structured interview. Client, service provider and health system barriers to access were identified. Client factors, including socioeconomic and psychological barriers, make it difficult for clients to access primary care, keep appointments, and/or prioritize their own health care. Provider factors, including knowledge and personal values related to mental health and substance use, determine the extent to which clients report their specific needs are met in the primary care setting. Health system factors, such as models of primary care delivery, determine the context within which both client and service provider factors operate. This study helps elucidate the mechanisms behind poor primary health care access among people with substance use and/or mental health issues. The results suggest that interdisciplinary, collaborative models of primary healthcare may improve accessibility and quality of care for this population, and that more education about mental health and substance use issues may be needed to support service providers in providing adequate care for their clients.


[Prophylaxis of venous thromboembolism in orthopedic surgery. Role of the new anticoagulants].
Patients undergoing a total hip or total knee arthroplasty are at high risk of thromboembolism in the postoperative period and after hospital discharge; consequently, clinical guidelines recommended thromboprophylaxis for 10-35 days. Although improved surgical techniques and widespread use of anticoagulants have substantially reduced the incidence of thromboembolic events, venous thromboembolic disease is still a dangerous complication and, in these patients, pulmonary embolism remains the main cause of death. Low molecular weight heparins have long been the mainstay of prevention. However, parenteral administration is inconvenient for many patients, which can sometimes cause poor treatment adherence. In recent years, a new class of oral, fixed-dose anticoagulants, with different mechanisms of action, few interactions and a predictable effect, has been developed. At present, a thrombin inhibitor (dabigatran) and two FXa inhibitors (rivaroxaban and apixaban) are available for prophylaxis in patients after total knee or total hip arthroplasty. In several phase III clinical trials, these drugs have been shown to have equal or superior efficacy and a similar degree of safety to conventional therapy with enoxaparin. These new drugs can significantly improve long-term prevention, particularly in the community setting.


Anthropogenic and naturally occurring polybrominated phenolic compounds in the blood of cetaceans stranded along Japanese coastal waters.
We determined the residue levels and patterns of hydroxylated polybrominated diphenyl ethers (OH-PBDEs), and related compounds, such as PBDEs, methoxylated PBDEs (MeO-PBDEs), and bromophenols (BPhs) in the blood of eleven cetacean species stranded along the Japanese coasts. The dominant OH- and MeO-PBDE isomers found in all cetaceans were 6OH-BDE47 and 6MeO-BDE47. Additionally, 2,4,6-triBPh was dominant isomer in all cetaceans. In contrast, specific differences in the distribution of para- and meta- OH-PBDE isomers and some BPhs (potential PBDEs metabolites) were found among the cetaceans. Residue levels of ΣMeO-PBDEs and 6OH-BDE47 + 2'OH-BDE68, and 2,4,6-triBPh and 6OH-BDE47 + 2'OH-BDE68 showed a significant positive correlation. These results may suggest that the large percentages of OH-PBDEs, MeO-PBDEs and 2,4,6-triBPh might share common source (i.e. biosynthesis by marine organisms), or metabolic pathway in cetacean species. Significant correlations were found between the concentrations of BDE99 and 2,4,5-triBPh. This result suggested that 2,4,5-triBPh in cetaceans could be a metabolite of BDE99.


Realizing tight-binding Hamiltonians using site-controlled coupled cavity arrays.
Analog quantum simulators rely on programmable and scalable quantum devices to emulate Hamiltonians describing various physical phenomenon. Photonic coupled cavity arrays are a promising alternative platform for realizing such simulators, due to their potential for scalability, small size, and high-temperature operability. However, programmability and nonlinearity in photonic cavities remain outstanding challenges. Here, using a silicon photonic coupled cavity array made up of [Formula: see text] high quality factor ([Formula: see text] up to[Formula: see text]) resonators and equipped with specially designed thermo-optic island heaters for independent control of cavities, we demonstrate a programmable photonic cavity array in the telecom regime, implementing tight-binding Hamiltonians with access to the full eigenenergy spectrum. We report a [Formula: see text] reduction in the thermal crosstalk between neighboring sites of the cavity array compared to traditional heaters, and then present a control scheme to program the cavity array to a given tight-binding Hamiltonian. The ability to independently program high-Q photonic cavities, along with the compatibility of silicon photonics to high volume manufacturing opens new opportunities for scalable quantum simulation using telecom regime infrared photons.


Studies with antisera against peripheral nervous system myelin and myelin basic proteins. I. Effects of antiserum upon living cultures of nervous tissue.
We studied the effects of antiserum against rat peripheral nervous system (PNS) myelin, rat or chicken central nervous system myelin basic protein (BP), or rabbit P2 protein from PNS myelin on myelinated cultures containing only rat dorsal root ganglion neurons and Schwann cells. While anti-PNS myelin serum consistently produced segmental PNS demyelination, anti-BP serum and anti-P2 serum did not. The culture results suggest that the myelin PNS proteins P1 (identical to basic protein from central nervous system myelin) and P2 are not exposed on the extracellular surfaces of myelin-related Schwann cells in tissue culture.


Management Options for Linear Scleroderma ("En Coup de Sabre").
En coup de sabre (ECDS) is a form of linear-scleroderma, primarily affecting the face. Despite effectiveness of pharmacological interventions in the management of lesions, sequelae of cutaneous deformities are common. Review the existing surgical tools for the correction of "en coup de sabre" ECDS lesions and facial deformities. The authors conducted a literature search for reports on surgical interventions for ECDS deformations, in the electronic databases of PubMed, Scopus, and Cochrane Library Databases. Twenty-six publications reporting 39 patients were found in the literature. The average age of patients was 25 ± 4.7 years. Thirty-one of the patients were females. Six methods were found in the literature for surgical correction of ECDS. Fat grafting was performed in 41% of patients, surgical reconstruction in 18%, injectable fillers in 15%, implants in 10%, botulinum toxin injections in 8%, and bone/cartilage grafts in 8%. Imaging studies of the skull and face were performed in 36% of patients. Bony defects were found in 64.3% of them. Different surgical and minimally invasive options exist in the armamentarium of clinicians correcting ECDS deformities. Tailoring the method of correction to patient's needs and expectation is crucial in ensuring patient satisfaction.


Gastrointestinal and Hepatic Manifestations of COVID-19: Evolving Recognition and Need for Increased Understanding in Vulnerable Populations.
The novel coronavirus, SARS-CoV-2, has caused a global pandemic with high morbidity and mortality. It was first observed to cause a severe acute respiratory syndrome. However, gastrointestinal and hepatic manifestations have been increasingly recognized. Gastrointestinal symptoms include diarrhea, epigastric pain, nausea, and vomiting. Diarrhea is the most common GI manifestation of SARS-CoV-2 and can present without or without respiratory symptoms. Patients with GI symptoms have been associated with longer duration of illness and may be associated with more severe illness. Mechanism of diarrhea is thought to be related to direct viral cytotoxicity occurring when the SARS-CoV-3 enters GI cells via the ACE-2 receptor. Inflammatory response and cytokine release likely contributes to symptoms. SARS-CoV-2 can cause hepatic injury. Studies have shown mild to moderate elevation of liver enzymes. The pattern of liver abnormalities can be hepatocellular, cholestatic or mixed. Patients with severe infection have significantly higher rates of liver injury and worse outcomes. Proposed mechanisms for injury include immune mediated systemic inflammatory response, direct cytotoxicity from viral replication and hypoxia-reperfusion dysfunction. Recent data suggests that GI and hepatic injury may be under-recognized manifestation of SARS-CoV-2 infection. Patients with diarrhea and liver disease may have a worse prognosis. The rapidly evolving literature continues to reveal a growing body of information which enables updated guidance for management. More investigation is needed which focuses on vulnerable patients, including the elderly, those with underlying illness, as well as, racial and ethnic minorities.


Dysphagia Caused by Diffuse Idiopathic Skeletal Hyperostosis.
Diffuse idiopathic skeletal hyperostosis, or Forestier disease, is a relatively common disease in the elderly population. Although reported in the orthopedic and rheumatology literature, it has not, to date, been reported in the maxillofacial or dental literature. It is a disease entity that often presents with head and neck symptoms that might go unrecognized by the consultant oral and maxillofacial surgeon.


Calcific thrombi of the inferior vena cava in infants and children.
Calcified caval thrombus should be considered in any infant or child where calcifications are noted in the high right retroperitoneal area on plain x-rays of the abdomen. Although typically bullet-shaped in configuration, the calcium distribution in the neonate may be atypical or incompletely developed, suggesting neuroblastoma. Definitive diagnosis can be made by inferior vena cavagram. As no deaths or complications have been attributed to the lesion in the cases thus far reported, no specific treatment is recommended.


Radiation-induced contrast enhancement following proton radiotherapy for low-grade glioma depends on tumor characteristics and is rarer in children than adults.
Proton beam radiotherapy (PRT) is used in the treatment of low-grade glioma (LGG) to mitigate long-term sequelae. Following PRT, increased rates of radiation-induced contrast enhancements (RICE) are suspected but poorly understood. We analyzed consecutive 227 patients (42 children and 185 adults) treated with PRT (54 Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. Tumors were graded WHO 1 in a minority (n = 22, 12%) of adults, but a majority of children (n = 29, 69%). In contrast, tumors were graded WHO 2 in the majority (n = 160, 87%) of adults and a minority of children (n = 10, 24%). Five-year overall survival following PRT was 81% in adults and 91% in children. The risk of RICE was 5-fold more frequent in adults (25%) vs. children (5%; p = 0.0043). In children and adults, RICE were symptomatic in 50% and 55% (n = 1 and 26) of cases with CTCAE grade 0 in 47% (n = 23), grade 1 in 25% (n = 12), 0% grade 2 (n = 0) and 29% grade 3 (n = 14), respectively. In adults, RICE risk was associated to WHO grading (8% in WHO grade 1 vs. 24% in WHO grade 2, p = 0.026), independent of age (p = 0.44) and irradiation dose (p = 0.005), but not independent of IDH mutational status. These data demonstrate effectiveness of PRT for LGG in both children and adults. The RICE risk is lower in children which are a main target group for PRT and differs with WHO grading.


NIHSS score and arteriographic findings in acute ischemic stroke.
To test the hypothesis that the National Institutes of Health Stroke Scale (NIHSS) score is associated with the findings of arteriography performed within the first hours after ischemic stroke. We analyzed NIHSS scores on hospital admission and clinical and arteriographic findings of 226 consecutive patients (94 women, 132 men; mean age 62+/-12 years) who underwent arteriography within 6 hours of symptom onset in carotid stroke and within 12 hours in vertebrobasilar stroke. From stroke onset to hospital admission, 155+/-97 minutes elapsed, and from stroke onset to arteriography 245+/-100 minutes elapsed. Median NIHSS was 14 (range 3 to 38), and scores differed depending on the arteriographic findings (P<0.001). NIHSS scores in basilar, internal carotid, and middle cerebral artery M1 and M2 segment occlusions (central occlusions) were higher than in more peripherally located, nonvisible, or absent occlusions. Patients with NIHSS scores > or =10 had positive predictive values (PPVs) to show arterial occlusions in 97% of carotid and 96% of vertebrobasilar strokes. With an NIHSS score of > or =12, PPV to find a central occlusion was 91%. In a multivariate analysis, NIHSS subitems such as "level of consciousness questions," "gaze," "motor leg," and "neglect" were predictors of central occlusions. There is a significant association of NIHSS scores and the presence and location of a vessel occlusion. With an NIHSS score > or =10, a vessel occlusion will likely be seen on arteriography, and with a score > or =12, its location will probably be central.


Surgical Adhesives in Facial Plastic Surgery.
In facial plastic surgery, attaining hemostasis may require adjuncts to traditional surgical techniques. Fibrin tissue adhesives have broad applications in surgery and are particularly useful when addressing the soft tissue encountered in facial plastic surgery. Beyond hemostasis, tissue adhesion and enhanced wound healing are reported benefits associated with a decrease in operating time, necessity for drains and pressure dressings, and incidence of wound healing complications. These products are clinically accessible to most physicians who perform facial plastic surgery, including skin grafts, flaps, rhytidectomy, and endoscopic forehead lift.


The FASILA Score: A Novel Bio-Clinical Score to Predict Massive Blood Transfusion in Patients with Abdominal Trauma.
Early identification of patients who may need massive blood transfusion remains a major challenge in trauma care. This study proposed a novel and easy-to-calculate prediction score using clinical and point of care laboratory findings in patients with abdominal trauma (AT). Patients with AT admitted to a trauma center in Qatar between 2014 and 2017 were retrospectively analyzed. The FASILA score was proposed and calculated using focused assessment with sonography in trauma (0 = negative, 1 = positive), Shock Index (SI) (0 = 0.50-0.69, 1 = 0.70-0.79, 2 = 0.80-0.89, and 3 ≥ 0.90), and initial serum lactate (0 ≤ 2.0, 1 = 2.0-4.0, and 2 ≥ 4.0 mmol/l). Outcome variables included mortality, laparotomy, and massive blood transfusion (MT). FASILA was compared to other prediction scores using receiver operating characteristics and areas under the curves. Bootstrap procedure was employed for internal validation. In 1199 patients with a mean age of 31 ± 13.5 years, MT, MT protocol (MTP) activation, exploratory laparotomy (ExLap), and hospital mortality were related linearly with the FASILA score, Injury Severity Score, and total length of hospital stay. Initial hemoglobin, Revised Trauma Score (RTS), and Trauma Injury Severity Score (TRISS) were inversely proportional. FASILA scores correlated significantly with the Assessment of Blood Consumption (ABC) (r = 0.65), Revised Assessment of Bleeding and Transfusion (RABT) (r = 0.63), SI (r = 0.72), RTS (r = - 0.34), and Glasgow Coma Scale (r = - 0.32) and outperformed other predictive systems (RABT, ABC, and SI) in predicting MT, MTP, ExLap, and mortality. The novel FASILA score performs well in patients with abdominal trauma and offers advantages over other scores.


Bibliometric analysis of pharmacist's research on antimicrobial stewardship in Japan: an interrupted time series analysis on the implementation of the certification system for infection control pharmacists.
Pharmacist plays an integral role in promoting antimicrobial stewardship (AS) strategies by committing to the evidence-based activities in this field. The present study aims to document trends in actual achievements through bibliometric analysis and identify the future direction of pharmacists with expertise in AS by describing the characteristics of articles on AS written by Japanese pharmacists. The study searched for articles written in Japanese and English on Ichushi-Web and MEDLINE, respectively, until December 2020 for published articles relevant to AS. The articles were classified into the seven groups according to content. Interrupted time series analysis (ITSA) was performed to identify the effect of the certification system for infection control pharmacy specialists (ICPSs) on the number of articles in Japanese. The study retrieved 476 and 145 titles from Ichushi-Web and MEDLINE, respectively, out of which 383 and 123 articles written in Japanese and English, respectively, were considered relevant to AS. A continued publication was found for Japanese articles written by pharmacists assigned to large-sized hospitals since 1998, whereas few articles in English were published until 2017. The most frequent content of articles in both languages was intervention (56.7 and 59.0%, respectively). ITSA indicated that the number of publication slightly increased before [β1 = 1.33, 95% confidence interval (CI): - 0.62-3.28; P = 0.169] the implementation of the system. Moreover, the level (β2 = 11.41, 95%CI: - 0.23-23.05; P = 0.054) increased after the implementation of the system, whereas the slope decreased (β3 = - 2.07, 95%CI: - 4.16-0.03; P = 0.053). However, the changes were not statistically significant. The study identified the contribution of pharmacists by documenting trends in AS practice and by conducting bibliometric analysis. The implementation of the ICPS certification system positively influenced the trend of publications. Therefore, the study recommends that policymakers and stakeholders should promote and support the evidence-based activities for AS for pharmacists in small- to medium-sized hospitals.


Determination of picomolar levels of platinum in estuarine waters: a comparison of cathodic stripping voltammetry and isotope dilution-inductively coupled plasma mass spectrometry.
A comparative study to determine picomolar concentrations of platinum in natural waters was performed using two different analytical techniques. Results obtained by cathodic stripping voltammetry (CSV) were compared with those obtained by isotope dilution-inductively coupled plasma mass spectrometry (ID-ICPMS) combined with anion exchange resin column extraction method. Using successive UV irradiations with low-pressure mercury (L-Hg) lamp for 4h prior to CSV analysis, the results of both methods were comparable. Without adequate photolytic decomposition, the results obtained using CSV were generally lower than those obtained using ID-ICPMS in the estuarine waters around Tokyo Bay. This difference implies the presence of organically complexed Pt species in the estuarine waters. The Pt enrichment in the middle of the Tokyo Bay estuaries probably reflects the anthropogenic release of Pt from highly populated areas in Tokyo.


Gastrin secretion by ovine antral mucosa in vitro.
The effect on gastrin and somatostatin release in sheep of stimulatory and inhibitory peptides and pharmacological agents was investigated using an in vitro preparation of ovine antral mucosa. Carbachol stimulated gastrin release in a dose-dependent manner but had no effect on somatostatin release. As atropine blocked the effect of carbachol, cholinergic agonists appear to stimulate gastrin secretion directly through muscarinic receptors on the G-cell and not by inhibition of somatostatin secretion. Both vasoactive-intestinal peptide (VIP) and gastric-inhibitory peptide (GIP) increased somatostatin release but did not inhibit basal gastrin secretion, although VIP was effective in reducing the gastrin response to Gastrin-releasing peptide (GRP). Porcine and human GRP were stimulatory to gastrin secretion in high doses but bombesin was without effect. The relative insensitivity to GRP (not of ovine origin) previously reported from intact sheep may be caused either by a high basal release of somatostatin or by the ovine GRP receptor or peptide differing from those of other mammalian species.


Explaining the success of karmic religions.
One of the central claims of Norenzayan et al.'s article is that supernatural monitoring and intergroup competition have facilitated the rise of large-scale prosocial religions. Although the authors outline in detail how social instincts that govern supernatural monitoring are honed by cultural evolution and have given rise to Big Gods, they do not provide a clear explanation for the success of karmic religions. Therefore, to test the real scope of their model, Norenzayan et al. need to seriously engage with questions concerning the evolution of karmic prosocial religions.


[Diagnosis and Treatment of Spondylodiscitis/Spondylitis in Clinical Practice].
The clinical presentation of spondylsodiscitis/spondylitis are manifold. This commonly leads to a period of several months from initial symptoms to final diagnosis. A standardised treatment is difficult. The purpose of this study is to investigate the treatment carried out for patients with spondylodiscitis or spondylitis to develop an individualised standard care for better treatment. Data of 90 patients were retrospective analysed. In particular documented data of the initial examination and the following treatments concerning identification of causes and systematically control of pathogens were examined. In 91 % of patients a diagnostically conclusive MRI was conducted. The degree of spondylidiscitis/spondylitis was mainly ASA criteria I or II (86 %). In 96 % of patients different diagnostic methods for identification of pathogens were conducted and documented. RESULTS confirmed the most common pathogens mentioned in the literature. 75 % of patients were treated by surgery. In 93 % of patients an antibiotic treatment was documented. 50 patients (81 %) were successfully healed. It is important to identify and treat spondylodiscitis/spondylitis as early as possible. Diagnosis by means of blood culture and MRI and treatment of the infection with antibiotics and possibly surgical interventions seem be very suitable, but need to be individualised to each and every patient.


α-MSH is partially involved in the immunomodulation of Nile tilapia (Oreochromis niloticus) antibacterial immunity.
α-Melanocyte-stimulating hormone (α-MSH) is a well-studied neuropeptide controlling skin and hair color. Besides, numerous immunomodulation roles of α-MSH were recorded in humans and mice. However, the regulatory effects of α-MSH in teleost immunity haven't been well elucidated. In this study, several precursor molecules of α-MSH (POMCs) and its receptors (MCRs) in Nile tilapia (Oreochromis niloticus) were characterized, and their expression characteristics and specific functions on antibacterial immunity were determined. Overall, POMCs and MCRs were principally detected in the brain, skin, and liver, and were remarkably promoted post Streptococcus agalactiae infection. However, tiny POMCs and MCRs were observed in tilapia immune organs (head kidney and spleen) or lymphocytes, and no evident immunomodulation effect was detected in vitro. Moreover, the in vivo challenge experiments revealed that α-MSH protects tilapia from bacterial infection by regulating responses in the brain and intestine. This study lays theoretical data for a deeper comprehension of the immunomodulation mechanisms of teleost α-MSH and the evolutional process of the vertebrate melanocortin system.


Hyperostotic paraganglioma of occipitotemporal bone.
A 25-year-old male presented with off-and-on vertigo of 10-year duration. He had left-sided cerebellar signs, left vocal cord paresis, and minimal left-sided hearing impairment. Computed tomography of the head revealed significant hyperostosis of squamous occipital, mastoid, and petrous temporal bone with no adjacent soft tissue mass. On excision, it turned out to be paraganglioma. Paraganglioma as a pure bony mass is not reported in the literature. The site of origin of such a tumor could not be ascertained, even on generous screening. The tumor remained nonsecretory on clinical and biochemical investigations.


Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2.
We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein-protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.


Four-dimensional processing of deformable cardiac PET data.
A four-dimensional deformable motion algorithm is described for use in the motion compensation of gated cardiac positron emission tomography. The algorithm makes use of temporal continuity and a non-uniform elastic material model to provide improved estimates of heart motion between time frames. Temporal continuity is utilized in two ways. First, incremental motion fields between adjacent time frames are calculated to improve estimation of long-range motion between distant time frames. Second, a consistency criterion is used to insure that the image match between distant time frames is consistent with the deformations used to match adjacent time frames. The consistency requirement augments the algorithm's ability to estimate motion between noisy time frames, and the concatenated incremental motion fields improve estimation for large deformations. The estimated motion fields are used to establish a voxel correspondence between volumes and to produce a motion-compensated composite volume.


Conditional chromosome splitting in Saccharomyces cerevisiae using the homing endonuclease PI-SceI.
A novel chromosome engineering technology is described which enables conditional splitting of natural chromosomes in haploid cells of the yeast Saccharomyces cerevisiae. The technology consists of introduction of a recognition sequence for the homing endonuclease PI-SceI into the S. cerevisiae genome and conditional expression of the gene encoding the PI-SceI enzyme under the control of the MET3 promoter. To test the technology, we split chromosome V upstream of GLC7 by use of the autonomously replicating sequence (ARS)-added polymerase-chain-reaction-mediated chromosome-splitting (ARS-PCS) method that we recently developed. A recognition sequence for PI-SceI was subsequently introduced downstream of the GLC7 locus. Splitting was analyzed following induction of the PI-SceI-encoding gene. Approximately 50% of the clones tested had the expected minichromosome harboring only the GLC7 gene, suggesting that any desired chromosomal region may be converted into a new chromosome by use of this method. Because this technology allows initial construction of a strain harboring multiple constructs prior to subsequent induction of random chromosome loss events under specific selective conditions, we propose that this technology may be applicable to reconstructing the S. cerevisiae genome by means of combinatorial loss of minichromosomes.


Benign paroxysmal positional vertigo as the cause of dizziness in patients after severe traumatic brain injury: diagnosis and treatment.
To identify patients with benign paroxysmal positional vertigo (BPPV) among patients with severe traumatic brain injury (TBI) and to evaluate the effectiveness of the Particle Repositioning Maneouvre (PRM). Eighteen months prospective study of 150 consecutive patients with severe TBI referred to an in-patients rehabilitation department. A structured interview emphasizing the possible presence of vertigo followed by a detailed neuro-otological examination. Patients diagnosed with BPPV were immediately treated with the PRM. BPPV diagnosis was based on a positive Dix-Hallpike positional test. PRM efficacy was determined by repeating the positional test 1 or 2 weeks after treatment. Twenty out of 150 (13.3%) patients complained about positional vertigo. The diagnosis of BPPV was confirmed in 10 patients. Signs and symptoms were completely relieved in six patients after a single PRM, while the other four patients needed repeated treatment for complete resolution of BPPV. About half of the patients with severe TBI who complain about positional vertigo suffer from BPPV. These patients can be efficiently treated by physical maneouvres improving the rehabilitation outcome.


Present status of tumor immunology in clinical gynecology.
The function of the immune system is to protect the body from damage caused by invading microorganisms, that is, bacteria, viruses, fungi, and parasites. The humoral mechanism functions through plasma cells producing antibodies that control bacterial infections. Viruses, fungi and parasites are controlled through the thymus dependent T lymphocytes. It is now clear that cancers also invoke immunologic reactions in their hosts. Cancer cells, like bacteria and viruses have their own characteristic antigens. An antigen is defined as a substance, usually a protein or polysaccharide, that the body recognizes as foreign, and to whose presence it reacts by forming antibodies. Antigenic differences represent the first known qualitative distinction between cancer cells and their normal counterparts. These qualitative differences between normal and cancer cells had escaped other methods of investigation, but were revealed by immunological techniques that take advantage of the extraordinary power of discrimination of the immune defense mechanism itself. This mechanism is capable of distinguishing even minute differences between protein molecules, probably one different amino acid in a chain of several thousand. Burnet's clonal selection theory has become the central dogma of immunology. It can be summarized by saying that lymphocytes have been destined from time immemorial to identify a specific antigen. When the lymphocyte encounters that antigen it becomes a sensitized lymphocyte, and on contact with similar antigens again produces an immune response including the production of very potent pharmacologic agents called lymphokines. Immunodeficiency diseases are identified by increased frequency of infections in patients. The impaired immunity decreases the patient's protection against developing a malignancy. Autoimmunity is the reaction of the immune system against the body's own tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


A meta-analysis of public compliance to boil water advisories.
Water utilities that generally provide continuous and reliable service to their customers may sometimes issue an advisory notification when service is interrupted or water quality is compromised. When the contamination is biological, utilities or the local public health agencies issue a 'boil water advisory' (BWA). The public health effectiveness of a BWA depends strongly on an implicit public understanding and compliance. In this study, a meta-analysis of 11 articles that investigated public compliance to BWA notifications was conducted. Awareness of BWA was moderately high, except in situations involving extreme weather. Reported rates of compliance were generally high, but when rate of awareness and non-compliant behavior such as brushing teeth were factored in, the median effective compliance rate was found to be around 68 percent. This does not include situations where people forgot to boil water for some part of the duration, or ingested contaminated water after the BWA was issued but before they became aware of the notification. The two-thirds compliance rate is thus an over-estimate. Results further suggest that timeliness of receipt, content of the advisory, and number of sources reporting the advisory have a significant impact on public response and compliance. This analysis points to improvements in the phrasing and content of BWA notices that could result in greater compliance, and recommends the use of a standard protocol to limit recall bias and capture the public response accurately.


Interferon protects neurons in culture infected with vesicular stomatitis and herpes simplex viruses.
The protective effect of crude rat interferon against infection by vesicular stomatitis virus (VSV) and herpes simplex virus (HSV) was assessed in two culture systems: the PC12 cell line and dissociated rat neurons derived from the superior cervical ganglion (SCG). Interferon was induced in rat embryo cells by inactivated Newcastle disease virus, and its effect was assessed by reduction of viral yields and prevention of viral cytopathology. Interferon protected PC12 cells, both in the presence and absence of nerve growth factor (NGF), against infection by both viruses, although at differing concentrations: protection against VSV was noted at approximately a 10-fold lower interferon concentration than that required to inhibit HSV infection. Dissociated SCG neurons were also protected, but higher interferon concentrations were required. These results demonstrate that the antiviral state can be established in neurons in response to interferon.


Factors affecting nucleosome disassembly by protamines in vitro. Histone hyperacetylation and chromatin structure, time dependence, and the size of the sperm nuclear proteins.
Histone displaced in vitro from nuclei by protamine competition display a higher degree of hyperacetylation than the residual histones. In addition, hyperacetylated core particle pools are disassembled in vitro with a higher efficiency than control or nonacetylated core particles and when analyzed by electron microscopy display an elongated shape (length/width ratio = 1.52 +/- 0.19) instead of the round compact shape of control nucleosomes (length/width ratio = 1.06 +/- 0.06). In the absence of histone hyperacetylation, the fish protamines, salmine and iridine (32-33 residues), are relatively inefficient in disassembling nucleosomal core particles in vitro as compared to the large (65-70 residues), tyrosine-containing protamines from rooster (galline), squid, and cuttlefish which disassemble nucleosomes in a range of protamine concentrations close to physiological. The fact that an artificially cross-linked salmine dimer acquires the ability of the large protamines from rooster, squid, and cuttlefish to disassemble core particles in vitro and also binds more tightly to the DNA, suggests that the size of the sperm nuclear protamines is a critical factor in this process. Even when the core histones of spermatid chromatin are hyperacetylated in the trout testis, the replacement process by iridine or salmine is slow and time-dependent in vitro. However, since spermiogenesis in trout occurs over several weeks, the slow in vitro nucleosome disassembly process by salmine is sufficient to allow complete displacement, thus supporting the hypothesis that a protamine-mediated displacement of the histones from DNA in vivo may take place in the salmonid fishes by a mechanism similar to that in the rooster, squid, and cuttlefish.


Stability analysis of the antibiotic cocktail used by Treviso Tissue Bank Foundation for tissues decontamination.
Although careful donor selection reduces tissue contamination, close microbiological control of harvested allografts remains a key task of tissue banks. To guarantee the safety of human tissues for allograft transplantation, a decontamination regimen must be adopted which, as recommended by European guidelines, is active against the majority of microorganisms isolated in tissues. Antibiotic decontamination methods differ from one tissue bank to another in terms of antimicrobial agents, temperature and length of exposure. After identifying the most effective antibiotics against the bacterial strains most commonly isolated in allografts, Treviso Tissue Bank Foundation demonstrated the efficacy of an antibiotic cocktail for tissue decontamination containing Gentamicin, Vancomycin and Meropenem. The aim of this study was to analyse the degradation kinetics of the three antibiotics according to preparation method and use. The results show that only Meropenem is unstable at + 4 °C, while Gentamicin and Vancomycin are valid for over 10 days. We thus established to add Meropenem before the start of the tissue decontamination phase.


Auditory brainstem responses in neonatally sound deprived CBA/J mice.
Auditory brainstem responses (ABR) from ten normal (3 males, 7 females) and ten environmentally sound deprived CBA/J mice (6 males, 4 females) were elicited by 30 dB HL click stimuli delivered via specially constructed, matched insert earphones. The mice were tested at 44-49 days of age under chloral hydrate sedation using an electrode montage of vertex/linked bilateral bullae/presacrum. The deprived mice were killed immediately after testing and serial transverse sections were prepared from their brains. Examination of globular cells of the ventromedial ventral cochlear nuclei revealed significantly smaller cross-sectional areas of these cells than in previously studied normal mice. Although monaural thresholds did not differ between the two groups, significantly shorter mean latencies were observed in the ABRs of the sound deprived group in wave I as well as in the interpeak latencies of the later ABR components (I-IV, I-V, and III-V). These electrophysiologic alterations in brainstem conduction presumably reflect the anatomical changes demonstrated in neonatally sound deprived mice.


Poly(ADP-ribose) polymerase 2 contributes to neuroinflammation and neurological dysfunction in mouse experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by entry of activated T cells and antigen presenting cells into the central nervous system and subsequent autoimmune destruction of nerve myelin. Previous studies revealed that non-selective inhibition of poly(ADP-ribose) polymerases (PARPs) 1 and 2 protect against neuroinflammation and motor dysfunction associated with EAE, but the role of the PARP-2 isoform has not yet been investigated selectively. EAE was induced in mice lacking PARP-2, and neurological EAE signs, blood-spine barrier (BSB) permeability, demyelination and inflammatory infiltration were monitored for 35 days after immunization. Mice lacking PARP-2 exhibited significantly reduced overall disease burden and peak neurological dysfunction. PARP-2 deletion also significantly delayed EAE onset and reduced BSB permeability, demyelination and central nervous system (CNS) markers of proinflammatory Th1 and Th17 T helper lymphocytes. This study represents the first description of a significant role for PARP-2 in neuroinflammation and neurological dysfunction in EAE.


Conscious Augmentation of Creative State Enhances "Real" Creativity in Open-Ended Analogical Reasoning.
Humans have an impressive ability to augment their creative state (i.e., to consciously try and succeed at thinking more creatively). Though this "thinking cap" phenomenon is commonly experienced, the range of its potential has not been fully explored by creativity research, which has often focused instead on creativity as a trait. A key question concerns the extent to which conscious augmentation of state creativity can improve creative reasoning. Although artistic creativity is also of great interest, it is creative reasoning that frequently leads to innovative advances in science and industry. Here, we studied state creativity in analogical reasoning, a form of relational reasoning that spans the conceptual divide between intelligence and creativity and is a core mechanism for creative innovation. Participants performed a novel Analogy Finding Task paradigm in which they sought valid analogical connections in a matrix of word-pairs. An explicit creativity cue elicited formation of substantially more creative analogical connections (measured via latent semantic analysis). Critically, the increase in creative analogy formation was not due to a generally more liberal criterion for analogy formation (that is, it appeared to reflect "real" creativity rather than divergence at the expense of appropriateness). The use of an online sample provided evidence that state creativity augmentation can be successfully elicited by remote cuing in an online environment. Analysis of an intelligence measure provided preliminary indication that the influential "threshold hypothesis," which has been proposed to characterize the relationship between intelligence and trait creativity, may be extensible to the new domain of state creativity.


α1-Adrenergic receptors mediate combined signals initiated by mechanical stretch stress and norepinephrine leading to accelerated mouse vein graft atherosclerosis.
The molecular mechanism underlying how hypertension with increased norepinephrine (NE) accelerates vascular remodeling is unknown. The present study examined the hypothesis that the additive effects of mechanical stretch stress (SS) and NE on vascular remodeling are mediated by α1-adrenergic receptors (α1-ARs). In vitro quiescent mouse vascular smooth muscle cells were cultivated on a flexible membrane and treated by mechanical SS (10% elongation) with or without NE (10(-7) mol/L) in the absence or presence of prazosin, a selective antagonist of α1-ARs (Praz; 10(-7) mol/L). In vivo mouse vena cava segments were grafted into carotid arteries, the mice were treated by prazosin (1 mg/kg/d, intraperitoneally) or saline for 2 weeks and 4 weeks, and wall thickness of the vein grafts was quantified. Mechanical SS could induce Gαq translocation; increase expression of α1B-ARs, α1D-ARs, and Ki67; and rapidly activate extracellular signal-regulated kinases (ERKs) compared with negative controls (P < .05). However, the peak levels of ERK activation and Ki67 expression in vascular smooth muscle cells were stimulated by combining SS and NE (ratio of phosphorylated ERK [pERK]/β-actin and Ki67 positive rates, SS+NE [1.07 ± 0.04 and 73% ± 3%]; SS [0.83 ± 0.07 and 53% ± 2%]; NE [0.63 ± 0.11 and 42% ± 2%]), which could be partially inhibited by prazosin (ratio of pERK/β-actin and Ki67 positive rates, SS+NE+Praz [0.83 ± 0.08 and 40% ± 7% vs SS+NE; P < .05], SS+Praz [0.60 ± 0.04 and 26% ± 2% vs SS; P < .05], NE+Praz [0.32 ± 0.12 and 23% ± 2% vs NE; P < .05]) or small interfering RNAs of α1B-ARs and α1D-ARs (P < .05 vs siRNA control). Significantly increased wall thickness was seen in the vein grafts (VG2W, 39.20 ± 3.10 μm; VG4W, 60.35 ± 4.94 μm) compared with control veins (negative controls, 9.90 ± 0.38 μm; P < .05). The effect was partially inhibited by prazosin (VGP2W, 26.22 ± 1.84 μm, and VGP4W, 42.17 ± 1.75 μm vs VG2W and VG4W; P < .05). These results suggest that α1-ARs may partially mediate the intracellular signals induced by mechanical SS with or without NE via Gαq protein/ERKs pathway triggering increased proliferation of vascular smooth muscle cells and leading to accelerated neointima formation of vein grafts.