Growth and development of children prenatally exposed to telbivudine administered for the treatment of chronic hepatitis B in their mothers.
We studied the growth and development of children prenatally exposed to telbivudine used to treat chronic hepatitis B virus (HBV) infection in their mothers. Maternal abnormalities during pregnancy and delivery and infant congenital anomalies, physical development status, developmental quotient (DQ), HBV vertical transmission status, and HBV vaccination outcomes of 54 infants were evaluated (2010-2013). No fetal abnormalities were observed during pregnancy or delivery. Postpartum, three infants (5.56%) had abnormalities: ankyloglossia, cutaneous hemangioma, and vaginal canal leak. Height and weight were within the normal range at birth and at 6 weeks, but were higher than the reference at 12 months (p<0.05). Body mass index increased gradually with age (p<0.05). DQ scores were normal (84.81%, 229/270) in 37 children (68.52%), abnormal or suspicious for a developmental delay (15.19%, 41/270) in 17 children (31.48%), and indicated a developmental delay (4.07%, 11/270) in seven children (12.96%). There were no significant differences in developmental delay between children prenatally exposed to telbivudine and controls (p>0.05). HBV vertical transmission was successfully blocked in all infants. The effective HBV vaccination rate was 98.15% (53/54). The growth and development of children prenatally exposed to telbivudine was normal, indicating that telbivudine treatment during pregnancy is safe and effective.


Nutrition profile of very low birth weight infants with extrauterine growth restriction in NICU.
Extrauterine growth restriction (EUGR) is associated with long-term complications such as neurodevelopmental dysplasia, increased mortality, and chronic metabolic disease. The incidence of EUGR in very low birth weight infants (VLBWIs) is generally high. This study's objectives were to (1) evaluate the nutritional support of VLBWIs with EUGR in our hospital NICU in the past 2 y and (2) provide guidance for improving clinical practice. Preterm infants (birth weight < 1500 g) admitted to our hospital from February 2017 to July 2019 were enrolled in the study. Nutrient intakes were recorded daily, and growth parameters were regularly measured. Based on whether the infants reached the 10th percentile of the 2013 Fenton growth curve at discharge, the infants were divided into a EUGR group (n = 134) and a non-EUGR group (n = 34) and their nutrition support were compared with current ESPGHAN guidelines. A total of 138 VLBWIs were enrolled in the study. Growth restriction was 18.1% at birth and 75.4% at discharge for weight. Enteral nutrition (EN) was initiated late compared with the guidelines. The cumulative EN interruption time was long, especially in the EUGR group. Insufficient energy and amino acid intakes were prevalent, and cumulative energy and amino acid deficits failed to be compensated at discharge. Lower Z-score at birth (OR = 0.055, 95% CI = 0.018-0.172, p < 0.001) and long cumulative interruption time (OR = 1.058, 95% CI = 1.001-1.119, p = 0.046) were risk factors for EUGR incidence. In general, the nutritional support for VLBWIs was inadequate, conservative enteral feeding was the main reason.


Canadian guidelines for the management of plaque psoriasis: overview.
New clinical treatment guidelines for plaque psoriasis, written by a panel of 16 Canadian dermatologists, were recently published online. These Canadian Guidelines for the Management of Plaque Psoriasis are evidence based and free of any influence from corporate sponsors and have been endorsed by the Canadian Dermatology Association (CDA). The Guidelines offer treatment recommendations for mild and moderate to severe body psoriasis, as well as for psoriasis affecting specific areas of the skin, such as the facial, flexural, and genital areas; nails; scalp; and palms and soles. The present overview describes the genesis and contents of the Guidelines, which are available in full through the CDA at <http://www.dermatology.ca/guidelines/cdnpsoriasisguidelines.pdf> (English) or <http://www.dermatology.ca/french/psoriasisguidelines.html> (French).


Estimating left ventricular work by gated blood pool ventriculogram.
Utilizing simplifying assumptions and a formula for ventricular radioactivity versus time, a method is presented for the estimation of systolic ventricular work. This value in MKS units is calculated from data available from the radionuclide blood pool ventriculogram.


Neurosurgical applications of MRI guided laser interstitial thermal therapy (LITT).
MRI-guided laser interstitial thermal therapy (LITT) is the selective ablation of a lesion or a tissue using heat emitted from a laser device. LITT is considered a less invasive technique compared to open surgery that provides a nonsurgical solution for patients who cannot tolerate surgery. Although laser ablation has been used to treat brain lesions for decades, recent advances in MRI have improved lesion targeting and enabled real-time accurate monitoring of the thermal ablation process. These advances have led to a plethora of research involving the technique, safety, and potential applications of LITT.LITT is a minimally invasive treatment modality that shows promising results and is associated with decreased morbidity. It has various applications, such as treatment of glioma, brain metastases, radiation necrosis, and epilepsy. It can provide a safer alternative treatment option for patients in whom the lesion is not accessible by surgery, who are not surgical candidates, or in whom other standard treatment options have failed. Our aim is to review the current literature on LITT and provide a descriptive review of the technique, imaging findings, and clinical applications for neurosurgery.


An Outbreak Investigation of Salmonella Typhimurium Illnesses in the United States Linked to Packaged Leafy Greens Produced at a Controlled Environment Agriculture Indoor Hydroponic Operation - 2021.
In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state partners investigated a multistate outbreak of Salmonella Typhimurium illnesses linked to packaged leafy greens from a controlled environment agriculture (CEA) operation in Illinois. Thirty-one illnesses and four hospitalizations were reported in four states, with a significant epidemiologic signal for packaged leafy greens from Farm A. A traceback investigation for leafy greens included seven points of service (POS) with food exposure data from eight ill people. Each POS was supplied leafy greens by Farm A. FDA investigators observed operations at Farm A and noted that 1) the firm did not consider their indoor hydroponic pond water as agricultural water, 2) condensate dripping from the chiller water supply line inside the building, and 3) unprotected outdoor storage of packaged soilless growth media and pallets used for finished product. FDA collected 25 product, water, and environmental samples from Farm A. The outbreak strain was recovered from a water sample collected from a stormwater drainage basin located on the property adjacent to Farm A. In addition, an isolate of Salmonella Liverpool was recovered from two indoor growing ponds within the same growing house, but no illnesses were linked to the isolate. Farm A voluntarily recalled all implicated products and provided their root cause analysis (RCA) and return-to-market plan to FDA. While the source and route of the contamination were not determined by the RCA, epidemiologic and traceback evidence confirmed the packaged salads consumed by ill persons were produced by Farm A. This was the first investigation of a multistate foodborne illness outbreak associated with leafy greens grown in a CEA operation. This outbreak demonstrated the need for growers using hydroponic methods to review their practices for potential sources and routes of contamination and to reduce food safety risks when identified.


Microplanning verification and 2017/2018 measles vaccination campaign in Nigeria: Lessons learnt.
The measles supplemental immunisation activity is an effective strategy that improves vaccination coverage and reduces measles-related morbidity and mortality. However, the lack of compliance with microplanning processes, contributes to improper estimation of resources needed for a good SIA in Nigeria. We described the microplanning verification process for 2017/2018 measles vaccination campaign and highlighted the contribution of selected variables to the output of the microplan. We conducted microplanning verification in 2 phases. In Phase 1, we verified at least 30% of randomly selected microplans to assess compliance with the steps and processes of developing good microplans. In Phase 2 we conducted desk review of the entire states micoplans and verified some selected variables at the ward level to corroborate the findings of the microplans. We collected data using open data kit and verification checklist. We conducted data analysis using SPSS and Microsoft Excel version 2016. All states in Nigeria verified their wards' microplans, 21 states (57%) verified more than 30% ,16 states (43%) verified less than 30%, Kebbi State verified the lowest (5.3%). Over 90% of microplans verified complied with the microplanning processes. We observed that overall, there was no significant difference in the number of target population, vaccination teams and qualified vaccinators after the verification process. The microplans for 2017/2018 measles vaccination campaign were developed according to the required procesesses, the target population, vaccination teams and qualified vaccinators were physically and realistically estimated. Adherence to microplanning processes is critical to the success of immunization programs.


Hyperglycemia management in hospitalized patients with COVID-19.
It has been well established that patients with diabetes who have COVID-19 have a more severe disease course and higher mortality. Providing adequate care for these patients has required hospitals to adapt protocols for monitoring blood glucose and administering therapy to protect both patient and caregiver safety. Inpatient use of continuous glucose monitoring systems or home-use glucose monitoring systems has provided options for reduced contact glucose monitoring. For therapy, protocols for managing hyperglycemia and diabetes ketoacidosis have been designed with less frequent monitoring and medication administration. Finally, telemedicine has allowed for consultative care in a manner not requiring physical proximity.


Double-sided battle: The role of ethylene during Monilinia spp. infection in peach at different phenological stages.
Controversy exists on whether ethylene is involved in determining fruit resistance or susceptibility against biotic stress. In this work, the hypothesis that ethylene biosynthesis in peaches at different phenological stages may be modulated by Monilinia spp. was tested. To achieve this, at 49 and 126 d after full bloom (DAFB), ethylene biosynthesis of healthy and infected 'Merryl O'Henry' peaches with three strains of Monilinia spp. (M. fructicola (CPMC6) and M. laxa (CPML11 and ML8L) that differ in terms of aggressiveness) was analysed at the biochemical and molecular level along the course of infection in fruit stored at 20 °C. At 49 DAFB, results evidenced that infected fruit showed inhibition of ethylene production in comparison with non-inoculated fruit, suggesting that the three Monilinia strains were somehow suppressing ethylene biosynthesis to modify fruit defences to successfully infect the host. On the contrary, at 126 DAFB ethylene production increased concomitantly with brown rot spread, and values for non-inoculated fruit were almost undetectable throughout storage at 20 °C. The expression of several target genes involved in the ethylene biosynthetic pathway confirmed that they were differentially expressed upon Monilinia infection, pointing to a strain-dependent regulation. Notably, Prunus persica 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) (PpACS) family was the most over-expressed over time, demonstrating a positive ethylene regulation, especially at 126 DAFB. At this phenological stage it was demonstrated the ability of Monilinia spp. to alter ethylene biosynthesis through PpACS1 and benefit from the consequences of an ethylene burst likely on cell wall softening. Overall, our results put forward that infection not only among different strains but also at each stage is achieved by different mechanisms, with ethylene being a key factor in determining peach resistance or susceptibility to brown rot.


Matrix attachment regions as targets for retroviral integration.
The randomness of retroviral integration has been debated for many years. Recent evidence indicates that integration site selection is not random, and that it is influenced by both viral and cellular factors. To study the role of DNA structure in site selection, retroviral integration near matrix attachment regions (MARs) was analyzed for three different groups of retroviruses. The objective was to assess whether integration near MARs may be a factor for integration site selection. Results indicated that MLV, SL3-3 MuLV, HIV-1 and HTLV-1 integrate preferentially near MARs, specifically within 2-kilobases (kb). In addition, a preferential position and orientation relative to the adjacent MAR was observed for each virus. Further analysis of SL3-3 MuLV insertions in common integration sites (CISs) demonstrated a higher frequency of integration near MARs and an orientation preference that was not observed for integrations outside CISs. These findings contribute to a growing body of evidence indicating that retroviral integration is not random, that MARs influence integration site selection for some retroviruses, and that integration near MARs may have a role in the insertional activation of oncogenes by gammaretroviruses.


New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines.
Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant, cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1α and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the α-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.


Reduced communication between frontal and temporal lobes during talking in schizophrenia.
Communication between the frontal lobes, where speech and verbal thoughts are generated, and the temporal lobes, where they are perceived, may occur through the action of a corollary discharge. Its dysfunction may underlie failure to recognize inner speech as self-generated and account for auditory hallucinations in schizophrenia. Electroencephalogram was recorded from 10 healthy adults and 12 patients with schizophrenia (DSM-IV) in two conditions: talking aloud and listening to their own played-back speech. Event-related electroencephalogram coherence to acoustic stimuli presented during both conditions was calculated between frontal and temporal pairs, for delta, theta, alpha, beta, and gamma frequency bands. Talking produced greater coherence than listening between frontal-temporal regions in all frequency bands; however, in the lower frequencies (delta and theta), there were significant interactions of group and condition. This finding revealed that patients failed to show an increase in coherence during talking, especially over the speech production and speech reception areas of the left hemisphere, and especially in patients prone to hallucinate. Reduced fronto-temporal functional connectivity may contribute to the misattribution of inner thoughts to external voices in schizophrenia.


Radiation dosimetry analyses of radiographic imaging systems used for orthodontic treatment: comparison among child, adolescent, and adult patients.
The aim of this study was to compare the effective doses of orthodontic radiographs in children, adolescents, and adults. We exposed a child, an adolescent (simulated by an adult female phantom), and adult male phantoms using common scanning protocols for panoramic radiography, cephalography, and cone-beam computed tomography (CBCT). Glass dosimeters were placed in the organs of the phantom to measure the absorbed doses. The effective doses were deduced using tissue weighting factors as defined in the ICRP Publication 103. For panoramic imaging, the parotid gland had the highest absorbed dose in the child and the submandibular glands had the highest absorbed dose in both the adolescent and adult phantoms. For cephalography, the organs and tissues located closest to the X-ray tube had the highest absorbed dose values. For CBCT, the lenses of the eyes received the highest absorbed dose. Effective doses with CBCT were the greatest in the adolescent phantom, followed by in the adult and child phantoms. Dental practitioners should be aware of patient age, as younger patients will incur greater risks from radiation.


Making space for criminalistics: Hans Gross and fin-de-siècle CSI.
This article explores the articulation of a novel forensic object-the 'crime scene'-and its corresponding expert-the investigating officer. Through a detailed engagement with the work of the late nineteenth-century Austrian jurist and criminalist Hans Gross, it analyses the dynamic and reflexive nature of this model of 'CSI', emphasising the material, physical, psychological and instrumental means through which the crime scene as a delineated space, and its investigator as a disciplined agent operating within it, jointly came into being. It has a further, historiographic, aim: to move away from the commonplace emphasis in histories of forensics on fin-de-siècle criminology and toward its comparatively under-explored contemporary, criminalistics. In so doing, it opens up new ways of thinking about the crime scene as a defining feature of our present-day forensic culture that recognise its historical contingency and the complex processes at work in its creation and development.


Serum ICAM-1 level and ICAM-1 gene 1462A>G (K469E) polimorphism on microalbuminuria in nondiabetic, nonhypertensive and normolipidemic obese patients: Genetical background of microalbuminuria in obesity.
A growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts. Microalbuminuria is the early marker of renal involvement. Although most of obese patients carries multiple risk factors for microalbuminuria, some obese individuals without risk factor may progress to microalbuminuria. The present study was performed to examine the role of ICAM-1 gene 1462A>G (K469E) polymorphism on microalbuminuria in obese subjects without diabetes mellitus, hypertension, hiperlipidemia and older age. Ninety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study. Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay (ELISA) method. ICAM-1 gene 1462A>G (K469E) polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Nepholometric method was used to examine urinary albumin loss, and microalbuminuria was measured by albumin to creatinine ratio. Obese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects (p: 0.043 and p: 0.011; respectively). GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers (p: 0.042). Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria (p: 0.002 and p: 0.03; respectively). Logistic regression analysis indicated a 7.39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A>G (K469E) polymorphism. GG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor.


Immune response in human visceral leishmaniasis: analysis of the correlation between innate immunity cytokine profile and disease outcome.
We investigated the cytokine profile of cells of the innate immune response and its association with active (ACT), asymptomatic (AS) and cured (CUR) human visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency of cytokine-producing cells was determined after short-term in vitro incubation of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we observed an increase of IL-4+ neutrophils, IL-10+ eosinophils besides a decrease of tumour necrosis factor (TNF)-alpha+ eosinophils/monocytes. Yet in ACT, we observed an increase of IL-4+ neutrophils and natural killer (NK) cells and IL-10+ monocytes, a reduced frequency of IL-12+ and IFN-gamma+ eosinophils and lower levels of TNF-alpha+ and IL-12+ monocytes. AS presented a mixed profile, characterized by an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, of IL-12+ eosinophils/monocytes, as well as increase of IL-4+ neutrophils and NK cells and IL-10+ eosinophils/monocytes. In contrast, CUR was characterized by a type 1 response with an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, associated with an increase in IL-12+ monocytes. In conclusion, we show a correlation between innate immune cytokine patterns and clinical status of VL, suggesting that these cells, in addition to other factors, may contribute to the cytokine microenvironment in which Leishmania-specific T cells are primed and to disease outcome.


Diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 more strongly than aryl morpholino triazenes.
Several diaryl triazene derivatives were synthesized and tested for their ability to inhibit cytochrome P450 1A1 and 1B1 as a potential means to prevent and treat cancer. These compounds are more planar than their conformational flexible aryl morpholino triazene counterparts that were previously shown to inhibit the above enzymes. As a result, the diaryl triazenes are more likely to exhibit increased binding to the enzyme active sites and inhibit these enzymes more strongly than the aryl morpholino triazenes. The data indicates that the diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 one to two orders of magnitude more strongly than the aryl morpholino triazenes. Furthermore, compounds 8-10 strongly inhibited cytochrome P450 1B1 with IC50 values of 51 nM, 740 nM, and 590 nM respectively. Thus, diaryl triazenes should be further investigated as a potential chemopreventive agent.


Association of fibroblast growth factor 21 with alcohol consumption and alcohol liver cirrhosis.
Fibroblast growth factor 21 (FGF21) is produced in the liver and binds to different complex receptor/coreceptor systems. Besides many other processes, FGF21 regulates the intake of simple sugars and alcohol. Increased levels of FGF21 decrease harmful alcohol intake in mice. To increase our understanding on the relationship between FGF21 and alcohol intake in humans, we aimed to measure FGF21 levels in patients with alcoholic liver cirrhosis (ALC) in comparison to patients with nonalcoholic liver cirrhosis (NALC) and healthy persons based on their present alcohol consumption. Alcohol intake was verified by urinary ethyl glucuronide (uETG) levels, eating and drinking behaviour by a Food Frequency Questionnaire and FGF 21 plasma levels were determined by ELISA in 96 persons (ALC n = 41; NALC n = 34; healthy n = 21). Both ALC and NALC patients with elevated ETG levels (≥0.5 μg/ml; indicating alcohol consumption in the last 12-72 h) showed significantly higher FGF21 plasma levels in comparison to patients with negative ETG levels. Eating behaviour did not have an impact on FGF21 plasma levels. Increased FGF21 levels in patients with recent alcohol consumption (verified by ETG) confirmed the first part of the liver-brain endocrine axis: alcohol consumption was associated with increased FGF21 levels. We could not confirm that elevated FGF21 levels were associated with reduced alcohol intake as a result. That points towards a pathology in this pathway, which might be caused by a malfunction of β‑Klotho or FGF receptors according to other studies and chronic alcohol dependency. Further research is required to clarify these pathologies, which may open new pharmacological treatment for patients with alcohol use disorder and alcohol dependence.


Preparation and influencing factors of sirolimus liposome by supercritical fluid.
We prepared the sirolimus liposome by rapid expansion of supercritical solution (RESS) technology of supercritical fluid, and studied the effects of temperature, pressure, and equilibrium time on the average particle size and envelop rate of liposome. The conditions of the minimal average particle size of liposome were 328K of temperature (35MPa), 35MPa of pressure (333K), and 50 minutes of equilibrium (343K) time, respectively. The conditions of the maximal envelop rate of liposome were 333K of temperature (30MPa), 35MPa of pressure (343K), and 50 minutes of equilibrium (323K) time, respectively.


vB_EfaS-DELF1, a novel Siphoviridae bacteriophage with highly effective lytic activity against vancomycin-resistant Enterococcus faecalis.
Enterococcus faecalis is an environmental agent of bovine mastitis in cows and has many cytopathic effects on the urinary tract in both humans and animals. In this study, a novel lytic bacteriophage, vB_EfaS-DELF1, was isolated against 21 E. faecalis isolated from bovine mastitis, including vancomycin-resistant E. faecalis (VRE). vB_EfaS-DELF1 bacteriophage was specific for E. faecalis and showed no lytic effects against other tested Enterococcus spp., Gram-negative, or Gram-positive bacteria. Moreover, no activity was observed against yogurt starters. The phage suspension was stable in a wide range of pH, salinity, and temperature. It retained its activity in 3.5 % fat milk. vB_EfaS-DELF1 has the common phenotypic features of Siphoviridae with a double-strand DNA of 40,248 bp in length and a G + C content of 34.9 %. The genome encodes 62 putative ORFs and no tRNA. No undesirable genes such as lysogenic mediators, antibiotic resistance, or virulence factor genes were detected in the genome. The comparative genomic analysis demonstrated similarity to the other available phage genomes. The highest similarity was observed with two other phages (50 % coverage and 82.38 % identities with IME-EFm1; 35 % coverage and 86.22 % identities with IME-EFm5) that were placed in the same clade. The differences with the other aligned phages were high and were placed in distant clusters. Regarding the specificity of this new bacteriophage against all of the tested E. faecalis isolates and, in particular, against the vancomycin-resistant ones, and also the absence of antibiotic resistance or virulence genes in its genome, vB_EfaS-DELF1 is suggested as a potential candidate for biocontrol of E. faecalis infections.


What might COVID-19 have taught us about the delivery of Nurse Education, in a post-COVID-19 world?
For Nurse Education in the UK, pre-existing challenges already included the need to develop curricula to align with new Nursing and Midwifery Council (NMC) educational standards; and increased numbers entering pre-registration Nurse Education programmes in order to address workforce deficits. Further disruption due to COVID-19, forced Nurse Educators overnight to rapidly adopt and to innovatively use current and emerging technologies to maintain engagement with, and to continue delivering education to, students during the pandemic. Although the full extent of these enforced changes is unknown at this time, this paper argues that online delivery is a necessary and inevitable transition, addressing some of these pre-existing challenges, and that the pandemic has hastened this. It is therefore crucial that Nurse Educators lead the way in navigating this period of uncertainty, viewing the pandemic as an opportunity to plan for the future, to establish how online teaching and learning can continue to benefit Nurse Education in a post-COVID-19 world, not just in the UK, but across the globe.


The reliability and validity of the Life Satisfaction Index-A with survivors of traumatic brain injury.
To investigate the internal consistency, long-term stability and validity of the Life Satisfaction Index-A (LSI-A) in a sample of survivors of traumatic brain injury (TBI). Cohort study. LSI-A was administered to survivors of TBI at 12, 24, 48 and 60 months post-injury during telephone interviews. Participants rated their quality of life, independence and participation in activities as well as health status at 24 months. Internal consistency was evaluated with Coefficient alpha. Pearson's r was used to investigate score stability. Test validity was explored with Pearson's r and Analysis of Covariance with age and sex as covariates. None. Coefficient alphas ranged from 0.85-0.92. Test-re-test coefficients ranged from 0.42-0.77. The LSI-A was positively correlated with self-reported quality of life, independence, activity level and health status. The LSI-A is a reliable and valid measure of the construct of life satisfaction among survivors of TBI.


Shielding effects of Selectron applicator and pellets on isodose distributions.
The Selectron is a mobile remote afterloading device which was developed specifically to reduce the radiation exposure to hospital personnel during intracavitary brachytherapy. Applicators for these devices contain source trains of 48 spherical pellets per channel, composed of both active and inactive pellets which have an external diameter of 2.5 mm. The configuration of pellets is chosen to optimize the dose distribution in accordance with the patient's geometry. A new dose calculation model has been proposed based on the separation of radiation into primary and secondary components. This model takes into account the attenuation of the primary radiation by the pellets. Isodose distributions around a Selectron standard applicator containing a typical patient loading of active pellets were measured and compared with those calculated by program SEEDS of the Atomic Energy of Canada Ltd. (AECL) Theraplan computer planning system. The shielding effects of the stainless steel applicator tubes, the ovoids, screws, inactive and active pellets will be considered. The effects of scatter and attenuation by the pellets will be illustrated by measured isodose distributions around a single applicator tube.


An electrogenic NA+/K+ pump in the choroid plexus.
Intracellular electrical potential and potassium activity was measured by means of microelectrodes in the epithelial cells of choroid plexus from bullfrogs (Rana catesbeiana). Ouabain applied from the ventricular side caused an abrupt depolarisation of 10 mV but only a gradual loss of potassium from the cells. Readministration of potassium to the ventricular solution of plexuses which were previously depleted of potassium, caused a hyperpolarisation of about 4 mV. These two experiments are consistent with the notion of an electrogenic Na+/K+ pump situated at the ventricular membrane and which pumps potassium into the cell and sodium into the ventricle. The numerical values obtained suggest that 3 sodium ions are pumped for 2 potassium ions. The permeability coefficient for potassium exit from the cell is calculated to be 1.24 . 10(-5) cm-1 . s-1 expressed per cm2 of flat epithelium.


The basic antioxidant structure for flavonoid derivatives.
An antioxidant structure-activity study is carried out in this work with ten flavonoid compounds using quantum chemistry calculations with the functional of density theory method. According to the geometry obtained by using the B3LYP/6-31G(d) method, the HOMO, ionization potential, stabilization energies, and spin density distribution showed that the flavonol is the more antioxidant nucleus. The spin density contribution is determinant for the stability of the free radical. The number of resonance structures is related to the π-type electron system. 3-hydroxyflavone is the basic antioxidant structure for the simplified flavonoids studied here. The electron abstraction is more favored in the molecules where ether group and 3-hydroxyl are present, nonetheless 2,3-double bond and carbonyl moiety are facultative.


Structural and functional characterization of NDBP-4 family antimicrobial peptides from the scorpion Mesomexovis variegatus.
Six peptides, belonging to the NDBP-4 family of scorpion antimicrobial peptides were structurally and functionally characterized. The sequence of the mature peptides VpCT1, VpCT2, VpCT3 and VpCT4 was inferred by transcriptomic analysis of the venom gland of the scorpion Mesomexovis variegatus. Analysis of their amino acid sequences revealed patterns that are also present in previously reported peptides that show differences in their hemolytic and antimicrobial activities in vitro. Two other variants, VpCT3W and VpCTConsensus were designed to evaluate the effect of sequence changes of interest on their structure and activity. The synthesized peptides were evaluated by circular dichroism to confirm their α-helical conformation in a folding promoting medium. The peptides were assayed on two Gram-positive and three Gram-negative bacterial strains, and on two yeast strains. They preferentially inhibited the growth of Staphylococcus aureus, were mostly ineffective on Pseudomonas aeruginosa, and moderately inhibited the growth of Candida yeasts. All six peptides exhibited hemolytic activity on human erythrocytes in the range of 4.8-83.7 μM. VpCT3W displayed increased hemolytic and anti-yeast activities, but showed no change in antibacterial activity, relative to its parental peptide, suggesting that Trp6 may potentiate the interaction of VpCT3 with eukaryotic cell membranes. VpCTConsensus showed broader and enhanced antimicrobial activity relative to several of the natural peptides. The results presented here contribute new information on the structure and function of NDBP-4 antimicrobial peptides and provides clues for the design of less hemolytic and more effective antimicrobial peptides.


Psychological (co)morbidity in patients with psoriasis: the impact of pruritus and anogenital involvement on symptoms of depression and anxiety and on body dysmorphic concerns - a cross-sectional study.
While stress plays a paramount role on the onset/exacerbation of psoriasis, via overactivation of the hypothalamic-pituitary-adrenal axis and increased release of pro-inflammatory cytokines, cutaneous inflammatory response induces, in turn, anxiety/depression symptoms, via body disfigurement and stigmatisation. The intensity of pruritus and anogenital involvement are additional risk factors for psychological comorbidity.Aims were to (1) examine the effects of intensity of pruritus and anogenital psoriasis on disease burden and psychological comorbidity and (2) identify the variables associated with the presence of clinically significant depression, anxiety, and dysmorphic concerns. Cross-sectional study. Conducted at the University Medical Center Hamburg-Eppendorf (UKE). 107 patients with psoriasis (mean age = 46.3, SD = 14.6 years; 53.3% male): 64 with none/mild pruritus; 43 with moderate/severe pruritus; 31 with anogenital psoriasis; 76 not affected in the anogenital area. Disease severity was assessed with Psoriasis Area and Severity Index and intensity of pruritus was rated by patients. Patient-reported outcomes included the Dermatology Life Quality Index, ItchyQoL, Patient Benefit Index, Perceived Stigmatisation Questionnaire, and Relationship and Sexuality Scale. Psychological morbidity was assessed with the Patient Health Questionnaire, Generalised Anxiety Disorder, and Dysmorphic Concern Questionnaire. Patients with moderate/severe pruritus reported more quality of life impairments, depression, anxiety and dysmorphic concerns, and less treatment benefits than those with none/mild pruritus. Moderate/severe pruritus had a deleterious effect on depression and stigmatisation for patients without anogenital involvement. Less patient benefits were associated with a higher likelihood of clinically significant depression/anxiety. Pruritus induces significant burden and psychological morbidity, particularly for patients without anogenital involvement. However, coping strategies used by patients with anogenital psoriasis might be dysfunctional for overall psychosocial adaptation. Patient-centred healthcare might be the best way to prevent psychological comorbidity. Ethics Committee of the Medical Association of Hamburg (process number PV6083, 28 May 2019).


An injectable heparin-conjugated hyaluronan scaffold for local delivery of transforming growth factor β1 promotes successful chondrogenesis.
Cartilage lacks basic repair mechanisms and thus surgical interventions are necessary to treat lesions. Minimally-invasive arthroscopic procedures require the development of injectable biomaterials to support chondrogenesis of implanted cells. However, most cartilage tissue engineering approaches rely on pre-culture of scaffolds in media containing growth factors (GFs) such as transforming growth factor (TGF)-β1, which are crucial for cartilage formation and homeostasis. GFs media-supplementation is incompatible with injectable approaches and has led to a knowledge gap about optimal dose of GFs and release profiles needed to achieve chondrogenesis. This study aims to determine the optimal loading and release kinetics of TGF-β1 bound to an engineered GAG hydrogel to promote optimal cartilaginous matrix production in absence of TGF-β1 media-supplementation. We show that heparin, a GAG known to bind a wide range of GFs, covalently conjugated to a hyaluronan hydrogel, leads to a sustained release of TGF-β1. Using this heparin-conjugated hyaluronan hydrogel, 0.25 to 50 ng TGF-β1 per scaffold was loaded and cell viability, proliferation and cartilaginous matrix deposition of the encapsulated chondroprogenitor cells were measured. Excellent chondrogenesis was found when 5 ng TGF-β1 per scaffold and higher were used. We also demonstrate the necessity of a sustained release of TGF-β1, as no matrix deposition is observed upon a burst release. In conclusion, our biomaterial loaded with an optimal initial dose of 5 ng/scaffold TGF-β1 is a promising injectable material for cartilage repair, with potentially increased safety due to the low, locally administered GF dose. STATEMENT OF SIGNIFICANCE: Cartilage cell-based products are dependent on exogenous growth factor supplementation in order for proper tissue maturation. However, for a one-step repair of defects without need for expensive tissue maturation, an injectable, growth factor loaded formulation is required. Here we show development of an injectable hyaluronan hydrogel, which achieves a sustained release of TGF-β1 due to covalent conjugation of heparin. These grafts matured into cartilaginous tissue in the absence of growth factor supplementation. Additionally, this system allowed us to screen TGF-β1 concentrations to determine the mimimum amount of growth factor required for chondrogenesis. This study represents a critical step towards development of a minimally-invasive, arthroscopic treatment for cartilage lesions.


Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.
Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.


Expression of syncytin in leukemia and lymphoma cells.
Syncytin is a placenta-specific protein and generally believed to play a pivotal role in syncytiotrophoblast morphogenesis. In this study, transcripts of this gene were quantified by real-time RT-PCR and the translated products were measured by an indirect immunofluorescence assay. Results showed that syncytin was found to be expressed in all nine leukemia and lymphoma cell lines studied albeit at different levels and in 43 peripheral blood samples of 57 leukemia or lymphoma patients. Neither the transcripts nor the translated syncytin was detected in blood samples of normal individuals. In conclusion, peripheral blood syncytin may serve as a marker for leukemia and lymphoma.


[Holistic school development in the implementation of educational technologies in times of digital transformation-a case study on the self-evaluation tool SELFIE].
The digital transformation is increasingly shaping the education system and school development. In this context, the implementation of educational technologies in schools and classrooms plays a critical role. In systemic terms, this is a school development task that involves sustainable and continuous changes at all levels of school and poses (new) challenges for the groups of school stakeholders. In addition to the development of organizational, teaching and personnel dimensions, this also requires changes in the technology and cooperation mechanisms specific to the needs of individual schools. By means of a case study, this study analyzes the implementation and execution of the self-evaluation tool SELFIE at a school using a multimethodological approach. The results of the self-evaluation (n = 265) as well as findings from multi-episodic interviews (n = 11) with various school actors are presented and interpreted in consideration of the school development dimensions. In the discussion, SELFIE is first critically reflected as an eligible digital tool for self-evaluation in relation to the implementation of educational technologies. Second, its effects on the school development dimensions are discussed. Finally, an outlook on the potentials as well as critical challenges of SELFIE with regard to school development for research and practice is given.


Relationship between peripheral blood flow in extremities and choroidal circulation.
The aim of this study was to explore the relationship between subjectively estimated and objectively measured finger temperature on the one, and choroidal blood flow on the other side. We measured submacular choroidal blood flow (CBF) in 73 healthy subjects. Based on the history of cold hands and feet, they were divided in three groups, reporting "never", "sometimes" and "always" having cold extremities. As an objective measure of finger temperature, it was recorded at the fingertips with an infrared thermometer (IRT). Analysis of variance for CBF based on the group selection and with blood and intraocular pressures as covariates was performed, as well as the correlation between CBF and IRT. There were 37 subjects in the group with "never" cold extremities, 20 in the group with "sometimes", and 16 subjects in the group with "always" cold extremities. Average age was 44.2 ± 12.9 years. CBF was 11.5 ± 7.3 AU (arbitrary units), 13.6 ± 6.1 AU and 14.3 ± 4.6 AU in the three groups, respectively. The ANOVA p-value was 0.04. Pearson's R for correlation between CBF and IRT was - 0.51, p < 0.001. Subjectively and objectively, colder extremities are associated with higher CBF, possibly due to the redistribution of blood flow.


Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk.
Apolipoprotein E (APOE) ε4-carrier status or ε4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE ε2 or heterogeneous effect of ε2, ε3, and ε4 haplotypes. We leveraged results from an autopsy-confirmed AD study to generate a weighted risk score for APOE (APOE-npscore). We regressed cerebrospinal fluid (CSF) amyloid and tau biomarkers on APOE variables from the Wisconsin Registry for Alzheimer's Prevention (WRAP), Wisconsin Alzheimer's Disease Research Center (WADRC), and Alzheimer's Disease Neuroimaging Initiative (ADNI). The APOE-npscore explained more variance and provided a better model fit for all three CSF measures than APOE ε4-carrier status and ε4 allele count. These findings were replicated in ADNI and observed in subsets of cognitively unimpaired (CU) participants. The APOE-npscore reflects the genetic effect on neuropathology and provides an improved method to account for APOE in AD-related analyses.


Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine-1-phosphate.
Sphingosine-1-phosphate (SPP) has attracted much attention as a possible second messenger controlling cell proliferation and motility and as an intracellular Ca(2+)-releasing agent. Here, we present evidence that SPP activates a G protein-coupled receptor in the plasma membrane of various cells, leading to increase in cytoplasmic Ca2+ concentration ([Ca2+]i), inhibition of adenylyl cyclase, and opening of G protein-regulated potassium channels. In human enbryonic kidney (HEK) cells, SPP potently (EC50, 2 nM) and rapidly increased [Ca2+]i in a pertussis toxin-sensitive manner. Pertussis toxin-sensitive increase in [Ca2+]i was also observed with sphingosylphosphorylcholine (EC50, 460 nM), whereas other sphingolipids, including ceramide-1-phosphate, N-palmitoyl-sphingosine, psychosine, and D-erythro-sphingosine at micromolar concentrations did not or only marginally increased [Ca2+]i. Furthermore, SPP inhibited forskolin-stimulated cAMP accumulation in HEK cells and increased binding of guanosine 5'3-O-(thio) triphosphate to HEK cell membranes. Rapid [Ca2+]i responses were also observed in human transitional bladder carcinoma (J82) cells, monkey COS-1 cells, mouse NIH 3T3 cells, Chinese hamster ovary (CHO-K1) cells, and rat C6 glioma cells, whereas human HL-60 leukemia cells and human erythroleukemia cells failed to respond to SPP. In guinea pig atrial myocytes, SPP activated Gi protein-regulated inwardly rectifying potassium channels. Activation of these channels occurred strictly when SPP was applied at the extracellular face of atrial myocyte plasma membrane as measured in cell-attached and inside-out patch clamp current recordings. We conclude that SPP, in addition to its proposed direct action on intracellular Ca2+ stores, interacts with a high affinity Gi protein-coupled receptor in the plasma membrane of apparently many different cell types.


Biomanipulation as a strategy for minimizing ecological risks in river supplied with reclaimed water.
Reclaimed water is an effective method for addressing water pollution and shortages. However, its use may contribute to the collapse of receiving water (algal blooms and eutrophication) owing to its unique characteristics. A three-year biomanipulation project was conducted in Beijing to investigate the structural changes, stability, and potential risks to aquatic ecosystems associated with the reuse of reclaimed water in rivers. During the biomanipulation, the proportion of Cyanophyta in the community structure of phytoplankton density in river supplied with reclaimed water decreased, and the community composition shifted from Cyanophyta and Chlorophyta to Chlorophyta and Bacillariophyta. The biomanipulation project increased the number of zoobenthos and fish species and significantly increased fish density. Despite the significant difference in aquatic organisms community structure, diversity index and community stability of aquatic organisms remained stable during the biomanipulation. Our study provides a strategy for minimizing the hazards of reclaimed water through biomanipulation by reconstructing the community structure of reclaimed water, thereby making it safe for large-scale reuse in rivers.


The Fc binding regions in protein A are not responsible for the polyclonal B cell activating property of protein A.
To test whether the polyclonal B cell activating property of protein A is due to its ability to bind to the Fc part of immunoglobulins, experiments were carried out with purified monomeric or dimeric Fc-binding fragments of protein A. Neither monomeric nor dimeric fragments induced polyclonal antibody synthesis in vitro, whereas intact protein A was a strong activator. It is concluded that the Fc binding part of protein A is not responsible for activation of polyclonal antibody synthesis.


Translation and adaptation to Spanish of Aberdeen varicose veins questionnaire.
The purpose of the study is to translate the Aberdeen Varicose Vein Questionnaire (AVVQ) into Spanish and evaluate the feasibility and reliability of the Spanish-translated AVVQ in patients with chronic venous disease. Reliability was assessed by test and retest of the Spanish translated AVVQ in a sample of 77 patients. The questionnaires were answered within a 2-week interval. There was a 100% test and retest response. The AVVQ showed 6.5% of missing responses. Cronbach's alpha was 0.71 indicating an adequate level of internal consistency. Spearman's rho showed a significant strong association between test and retest scores (rho = 0.84, p < 0.0001). The Spanish-translated AVVQ is a reliable tool in our daily clinical practice in order to measure the impact of venous disease in the quality of life.


Effects of high hoses of estrogen on prolactin-binding activity and growth of carcinogen-induced mammary cancers in rats.
Specific binding sites for prolactin (PRL) were present in membrane preparations from 7,12-dimethylbenz(a)-anthracene-induced rat mammary tumors. The specific binding of PRL was time and temperature dependent. A significant negative correlation was noted between administered doses of estrogen and the subsequent binding of PRL to tumor cell membranes. Injections of 10 or 25 mug estradiol benzoate daily for 10 days effectively inhibited mammary tumor growth and significantly reduced specific PRL binding to mammary tumor cell membranes.


Improved detection of acute parvovirus B19 infection by immunoglobulin M EIA in combination with a novel antigen EIA.
Although parvovirus B19 is a significant blood product contaminant, few methods other than polymerase chain reaction (PCR) have been developed to detect the presence of the virus. A B19 antigen enzyme immunoassay (EIA) has been developed and the sensitivity of detection is ascertained using dilutions of the B19 capsid protein VP2 and 10-fold dilutions of B19 viraemic serum. Once the assay cut-off was established, a panel of viraemic donations (n = 70) was screened by the antigen EIA. The B19 immunoglobulin M (IgM) and IgG status of these specimens was also determined. During screening of blood donor units by quantitative PCR, 70 individuals were identified with levels of B19 DNA greater than 10(6) IU/ml at the time of blood donation. The sensitivity of the B19 antigen EIA was estimated to be equivalent to between 10(8) and 10(9) IU/ml B19 DNA or 1-10 pg/ml of recombinant capsid protein. B19 detection was significantly enhanced when viraemic specimens were pretreated with a low pH proprietary reagent. Unlike other virus-detection assays, detection of the B19 antigen was not affected by the presence of B19 IgM or IgG antibodies. In addition, the assay was capable of detecting all three genotypes of human erythrovirus. Combined specimen analysis by the B19 antigen assay and a B19 IgM assay facilitated the detection of 91% of acute B19 infections in the test population. In combination with B19 IgM detection, application of the B19 antigen EIA is a flexible and efficient method of detecting recent B19 infection and can be used as an alternative to PCR.


MR imaging in hydatid disease of the liver.
We describe the appearance on MR of hydatid disease of the liver in 2 patients. The lesions were well demonstrated using spin-echo pulse sequences, and could be easily seen with either T1 or T2 weighting; however, maximum information was obtained using both. In these 2 cases, a thin, low signal boundary was noted around the cysts; this finding may prove useful in differential diagnosis.


Pathogenic T cell cytokines in multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system that is believed to have an autoimmune etiology. As MS is the most common nontraumatic disease that causes disability in young adults, extensive research has been devoted to identifying therapeutic targets. In this review, we discuss the current understanding derived from studies of patients with MS and animal models of how specific cytokines produced by autoreactive CD4 T cells contribute to the pathogenesis of MS. Defining the roles of these cytokines will lead to a better understanding of the potential of cytokine-based therapies for patients with MS.


Improving the resistance of Anammox granules to extreme pH shock: The effects of denitrification sludge EPS enhanced by a fluctuating C/N ratio cultivation on granules.
This study investigated the effects of denitrification sludge EPS enhanced (DS-EPSCN) by a fluctuating carbon and nitrogen ratio (C/N) cultivation strategy on the properties of Anammox granules under extreme acid or alkaline shock. The results showed that the DS-EPSCN significantly improved the nitrogen removal performance of low-density Anammox granular sludge (Granules-L) and high-density Anammox granular sludge (Granules-H) under extreme acid shock (pH 5.0). The contents of high-molecular-weight substances (such as aromatic proteins and polysaccharides) in the DS-EPSCN rose markedly, contributing to a substantial increase in the flocculation efficiency under acidic conditions and increasing the granule stability. In addition, abundant amounts of N-butyryl-dl-homoserine lactone (C4-HSL) and N-hexanoyl-dl-homoserine lactone (C6-HSL) in the DS-EPSCN promoted the granule activity. However, under extreme alkaline shock (pH 10.5), the flocculation efficiency of the DS-EPSCN was poor, and the addition of DS-EPSCN had no influence on the stability of the granules but improved the activity of the Granules-H. The reason was that the release mechanism of the endogenous acyl-homoserine lactone (AHL) signals in the Granules-H was activated by the exogenous C4-HSL and C6-HSL in the DS-EPSCN under alkaline conditions, leading to increased Granules-H activity. This research provides a novel approach to enhance the resistance of Anammox granular sludge to extreme pH shock.


Homocysteine induces connective tissue growth factor expression in vascular smooth muscle cells.
Increased homocysteine levels in blood might be an important risk factor for the development of cardiovascular diseases. Connective tissue growth factor (CTGF) was found to be involved in atherosclerotic plaque progression. So far, the possible connection between homocysteine and CTGF has not been studied. This study was designed to test whether homocysteine could induce CTGF expression in vascular smooth muscle cells (VSMC). Hyperhomocysteinemia was induced in Sprague-Dawley rats after 4 weeks of a high-methionine diet. CTGF mRNA and protein expression was detected in the aortas isolated from hyperhomocysteinemic rats, but not in the controls. The underlying mechanism of homocysteine-induced CTGF expression was investigated in cultured human umbilical vein smooth muscle cells (HUVSMC). CTGF mRNA expression was induced after treatment with dl-homocysteine (50 micromol L(-1)) for 1 h, which remained at the elevated level for up to 8 h. CTGF protein level increased after homocysteine treatment for 8 h, and the elevated status was maintained for up to 48 h. Several intracellular signals elicited by homocysteine are involved in CTGF synthesis, including protein kinase C (PKC) activation and reactive oxygen species (ROS). Transfection HUVSMCs with a CTGF small interference RNA (siRNA) plasmid, which specifically inhibited the expression of CTGF, decreased extracellular matrix (ECM) accumulation caused by homocysteine. Our results demonstrate that homocysteine could increase the expression of CTGF in VSMC both in vivo and in vitro. The novel findings suggest that homocysteine might contribute to accelerated progression of atherosclerotic lesions by inducing CTGF expression.


Do readmissions and reoperations adversely affect patient-reported outcomes following complex adult spinal deformity surgery at a minimum 2 years postoperative?
Unplanned readmissions and reoperations are known to be associated with undesirable costs and potentially inferior outcomes in complex adult spinal deformity (ASD) surgery. A paucity of literature exists on the impact of readmissions/reoperations on patient-reported outcomes (PRO) in this population. Consecutively treated adult patients who underwent complex ASD surgery at a single institution from 2015-2018 and minimum 2-year follow-up were studied. Demographics/comorbidities, operative factors, inpatient complications, and postoperative clinical and patient-reported outcomes (SRS-22r, ODI) were assessed for those with and without readmission/reoperation. 175 patients (72% female, mean age 52.6 ± 16.4) were included. Mean total instrumented/fused levels was 13.3 ± 4.1, range 6-25. The readmission and reoperation rates were 16.6% and 12%, respectively. The two most common causes of reoperation were pseudarthrosis (5.1%) and PJK (4.0%). Predictors for readmission within 2 years following surgery included pulmonary, cardiac, depression and gastrointestinal comorbidities, along with performance of a VCR, and TLIF. At 2 years postoperatively, those who required a readmission/reoperation had significant increases in SRS and reductions in ODI compared to 1-year and preoperative values. Inpatient complications did not negatively impact 2-year PRO's. The 2-year MCID in PROs was not significantly different between those with and without readmission/reoperation. Complex ASD surgery carries risk, but the vast majority can achieve MCID (SRS-86.4%, ODI-68.2%) in PROs by 2 years. Importantly, even those with inpatient complications and those who required unplanned readmission/reoperation can improve PROs by 2-year follow-up compared to preoperative baseline and 1-year follow-up and achieve similar improvements compared to those who did not require a readmission. III.


Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder.
Lower urinary tract symptoms (LUTS) are frequent in motor neuron disease (MND) patients, but clinical factors related to them are unknown. We describe differences in LUTS among MND phenotypes and their relationship with other clinical characteristics, including prognosis. For this study, we collected clinical data of a previously published cohort of patients diagnosed with classical amyotrophic lateral sclerosis (cALS), progressive muscular atrophy (PMA) or primary lateral sclerosis (PLS) with and without LUTS. Familial history was recorded and the C9ORF72 expansion was analysed in the entire cohort. Patients were followed-up for survival until August 2016. Fifty-five ALS patients (37 cALS, 10 PMA and 8 PLS) were recruited. Twenty-four reported LUTS and neurogenic bladder (NB) could be demonstrated in nine of them. LUTS were not influenced by age, phenotype, disability, cognitive or behavioural impairment, or disease progression, but female sex appeared to be a protective factor (OR=0.39, p=0.06). Neither family history nor the C9ORF72 expansion was linked to LUTS or NB. In the multivariate analysis, patients reporting LUTS early in the disease course tended to show poorer survival. In this study, LUTS appear to be more frequent in male MND patients, but are not related to age, clinical or genetic characteristics. When reported early, LUTS could be a sign of rapid disease spread and poor prognosis. Further prospective longitudinal and neuroimaging studies are warranted to confirm this hypothesis.


Food-processing approaches to altering allergenic potential of milk-based formula.
All the major cow milk proteins in their native states are potential allergens in infants with milk allergy. Heat treatment can reduce the antigenicity of whey proteins considerably, but it has virtually no effect on the antigenicity of casein. Infants allergic to milk still react to heat-denatured whey proteins. Therefore heat denaturation alone cannot produce a formula with low allergenicity. Enzyme hydrolysis reduces the antigenicity and allergenicity of protein. Partial hydrolysis produces hydrolysate consisting mainly of large peptides, whereas extensive hydrolysis produces hydrolysate containing a mixture of large and small peptides and free amino acids. Enzyme hydrolysis often produces bitter peptides and destroys the physical functionality of protein. When hydrolysate formula is made, casein or whey protein hydrolysate is ultrafiltered to remove large residual peptides. Certain amino acids are fortified to provide a balanced amino acid profile. The final formulation must comply with the recommendations of the Codex Alimentarius Commission (FAO/WHO) and the U.S. Infant Formula Act to provide adequate infant nutrition. Protein hydrolysate-based formula can be improved by further reducing the residual allergenicity, increasing the small peptide content, and improving the taste.


Lowered superoxide dismutase in highly metastatic B16 melanoma cells.
Superoxide dismutases (SOD), which are enzymes scavenging the superoxide radical, were studied in two variant lines of the B16 melanoma: B16F1 with low metastatic potential and B16F10 with high metastatic potential. SOD activity was measured by a method utilizing reduction in the chemiluminescence of luminol. Using cell free extracts it was shown that the highly metastatic B16F10 cell line has a SOD activity lower (20.70 +/- 3.07) units/mg protein, n = 8, than that of the less metastatic B16F1 cell line (81.38 +/- 6.78) units/mg protein, n = 8. Acrylamide gel electrophoresis suggested that Mn-SOD activity is higher in B16F1 cells.


Long-range J(CH) heteronuclear coupling constants in cyclopentane derivatives.
Detailed measurements of long-range heteronuclear spin-spin coupling constants, especially (2, 3)J(CH) spin-spin couplings for various cyclopentane derivatives, are reported. The measurements are based on a 2D heteronuclear correlation experiment named G-BIRD(R, X)-CPMG-HSQMBC.


MicroRNA-708 prevents ethanol-induced hepatic lipid accumulation and inflammatory reaction via direct targeting ZEB1.
Alcoholic liver disease (ALD) was a global liver disease which divided into liver inflammation, fatty liver, alcoholic hepatitis or cirrhosis. Abnormal expression levels of some microRNAs (miRNA) family members often lead to ALD and other liver diseases. MicroRNA-708 (miR-708) was known to suppress the proliferation and metastasis of hepatocellular carcinoma (HCC), but its role in the progression of ALD was not clear. In this study, the expression level of miR-708 was down-regulated in ethanol-induced L0-2 cells. ZEB1 could decrease the PPAR-α expression while increase the SREBP-1 expression. Meanwhile, the expression levels of TNF-α and IL-6 were up-regulated by ZEB1. Of note, ZEB1 aggravated the apoptotic rate of L0-2 cells induced by ethanol via inhibiting p-AKT and p-mTOR of AKT/mTOR signaling pathway. What's more, it was demonstrated that miR-708 family members particularly target ZEB1 3'-UTR regions and can down-regulate the expression level of ZEB1 in L0-2 cells. Sum up, these results indicated that miR-708 might inhibit the liver inflammation and lipid accumulation by targeting ZEB1 via regulating AKT/mTOR signaling pathway.


An electrochemical assay for DNA methylation, methyltransferase activity and inhibitor screening based on methyl binding domain protein.
DNA methylation is one of important epigenetics events, and responsible to transcription, genomic imprinting and cellular differentiation. Aberrant DNA methylation is always contacted with various diseases. Methyl binding domain (MBD) proteins can specifically bind to the methylated CpG dinucleotides. Conventional assay for DNA methylation normally need bisulfide treatment, methylated nucleotide labeling or PCR amplification. Here, we fabricated a novel electrochemical biosensor for detection of DNA methylation, assay of DNA methyltransferase (MTase) activity and screening of MTase inhibitor based on MBD protein and coomassie brilliant blue G250 (CBB-G250), where the electrochemical signal of CBB-G250 was used to monitor the methylation event. After the hybrids of DNA S1 and DNA S2 were treated with M. SssI MTase in the presence of S-adenosylmethionine, the MBD proteins were specifically conjugated to the methylation site of CpG dinucleotides, and then, the MBD proteins were stained with CBB-G250. The electrochemical signal of CBB-G250 increased linearly with increasing M. SssI MTase concentration in the range from 0.1 to 40 unit/mL. Furthermore, the inhibition investigation demonstrates that fisetin and chlorogenic acid can inhibit the M. SssI MTase activity with the IC(50) value of 153.12 and 137.07 μM, respectively. Therefore, we think that this study may provide a sensitive platform for screening of DNA MTase inhibitors.


Probing spatial spin correlations of ultracold gases by quantum noise spectroscopy.
Spin noise spectroscopy with a single laser beam is demonstrated theoretically to provide a direct probe of the spatial correlations of cold fermionic gases. We show how the generic many-body phenomena of antibunching, pairing, antiferromagnetic, and algebraic spin liquid correlations can be revealed by measuring the spin noise as a function of laser width, temperature, and frequency.


Comparison of the Ca2+ binding properties of the gamma-carboxyglutamic acid-containing module of protein Z in the intact protein and in N-terminal fragments.
Protein Z is a vitamin K-dependent plasma protein of unknown function. Its modular structure is identical with those of factors VII, IX, X, and protein C. These proteins have an N-terminal gamma-carboxyglutamic acid (Gla)-containing module which binds six to ten Ca2+. In factors IX, X, and protein C, the adjacent epidermal growth factor (EGF)-like module binds one Ca2+ whereas the EGF-like module in protein Z does not. We have compared the Ca2+ binding properties of a fragment of protein Z comprising the Gla and N-terminal EGF-like modules (pZ-GlaEGFN) with those of intact protein Z and the isolated Gla module by measuring the Ca(2+)-induced quenching of the intrinsic protein fluorescence. The similar Ca2+ affinities of pZ-GlaEGFN and protein Z indicate that pZ-GlaEGFN has a native conformation and normal Ca2+ binding properties. A comparison of the Ca2+ binding to pZ-GlaEGFN with those to the corresponding fragments of factors IX, X, and protein C indicate that Ca2+ binding to the N-terminal EGF-like modules in the latter proteins does not influence the folding and Ca2+ binding properties of their Gla modules. Furthermore, the Ca(2+)-induced fluorescence enhancements of GlaEGF fragments from factors IX, X, and protein C appear to be caused by Ca2+ binding to the site in the EGF-like modules since it is not observed for pZ-GlaEGFN.


Cholinergic neurotransmission in the basolateral amygdala during cued fear extinction.
Cholinergic neuromodulation plays an important role in numerous cognitive functions including regulating arousal and attention, as well as associative learning and extinction processes. Further, studies demonstrate that cholinergic inputs from the basal forebrain cholinergic system influence physiological responses in the basolateral amygdala (BLA) as well as fear extinction processes. Since rodent models display individual differences in conditioned fear and extinction responses, this study investigated if cholinergic transmission in the BLA during fear extinction could contribute to differences between extinction resistant and extinction competent phenotypes in outbred Long-Evans male rats. Experiment 1 used in vivo microdialysis to test the hypothesis that acetylcholine (ACH) efflux in the BLA would increase with presentation of an auditory conditioned stimulus (CS+) during extinction learning. Acetylcholine efflux was compared in rats exposed to the CS+, a CS- (the tone never paired with a footshock), or to a context shift alone (without CS+ tone presentation). Consistent with acetylcholine's role in attention and arousal, ACH efflux in the BLA was increased in all three groups (CS+, CS-, Shift Alone) by the initial context shift into the extinction learning chamber, but returned more rapidly to baseline levels in the Shift Alone group (no CS+). In contrast, in the group exposed to the CS+, ACH efflux in the BLA remained elevated during continued presentation of conditioned cues and returned to baseline more slowly, leading to an overall increase in ACH efflux compared with the Shift Alone group. Based on the very dense staining in the BLA for acetylcholinesterase (ACHE), Experiment 2 examined if individual differences in fear extinction were associated with differences in cholinesterase enzyme activity (CHE) in the BLA and/or plasma with a separate cohort of animals. Cholinesterase activity (post-testing) in both the BLA and plasma was higher in extinction competent rats versus rats resistant to extinction learning. There was also a significant negative correlation between BLA CHE activity and freezing during extinction learning. Taken together, our results support a role for ACH efflux in the BLA during cued fear extinction that may be modulated by individual differences in ACHE activity, and are associated with behavioral responses during fear extinction. These findings implicate individual differences in cholinergic regulation in the susceptibility to disorders with dysregulation of extinction learning, such post-traumatic stress disorder (PTSD) in humans.


Infection control in public health: a new perspective.
As public health continues to meet the challenges of old and new health risks, the practice of infection control will be an integral part of its services. The public health infection control program should include effective policies and procedures, in-service programs and implementation, and systems of surveillance specific to each department. Public health personnel must place emphasis on the practice of infection control in the community setting. The ICP who accepts this challenge will be in the forefront of infection control in public health. Infection control is a respected part of the hospital setting and now is the time for the ICP to tailor this program to the public health delivery system.


Treatment of depression in patients with congestive heart failure.
Heart failure is common, and depression is common in heart failure patients, adding substantially to the burden of the disease. There is some evidence for the safe and at least modestly effective use of psychotherapy and antidepressants to treat depression in heart failure patients. Cognitive behavioral psychotherapy and selective serotonin reuptake inhibitors are first line treatments. The efficacy of depression treatment in altering cardiac outcomes in heart failure patients has yet to be established.


Impact of unplanned events on early postoperative results of minimally invasive esophagectomy.
Minimally invasive esophagectomy (MIE) is increasingly performed worldwide. Unplanned events during thoracoscopy or laparoscopy can jeopardize the procedure, sometimes necessitating conversion to open surgery. The aim of this study was to evaluate the impact of unplanned events on early postoperative outcomes after MIE. A consecutive group of 303 patients who underwent MIE between January 2011 and December 2015 were reviewed. The patients were allocated to two groups comprising those with (G-UPE, 85 patients) and without unplanned events (G-Regular, 218 patients). Unplanned events, defined as events that clearly changed or prolonged the procedure included intraoperative bleeding, chest and/or peritoneal adhesions, tumor invasion (sT4a + T4b), non-radical resection (R2 resection), and conversion for any reason. Differences in postoperative complications between the groups were analyzed. The most common unplanned events were pleural and/or peritoneal adhesions (28/89, 31.5%), followed by intraoperative discovery of tumor invasion (sT4a + T4b, 25/89, 28.1%). There were significant differences in the incidence of respiratory (57.6% vs. 8.3%) and nervous system complications (10.6% vs. 2.7%), postoperative infection (32.9% vs. 5.0%), and chylothorax (8.2% vs. 0.9%) between the G-UPE and G-Regular groups, respectively (P < 0.05). The most common reasons for conversion to open procedures were pleural and/or peritoneal adhesions (9/38, 23.8%) and intraoperative bleeding (7/38, 18.4%). The main reasons for R2 resection were tumor invasion of the trachea or bronchus (7/21, 33.2%) and of the aorta (5/21, 23.8%). Unplanned events during MIE increase the incidence of postoperative complications. Improved clinical staging and more careful surgery minimize unplanned events.


A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients.
Recent research in systemic lupus erythematosus (SLE) yielded new antigens and antibodies in SLE patients. We describe the various autoantibodies that can be detected in patients with SLE. A literature review, using the terms "autoantibody" and "systemic lupus erythematosus", was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity and other clinical manifestations. One hundred and eighty autoantibodies were so far described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of an autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 180 autoantibodies. SLE is so far the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of a polyclonal B cell activation, impaired apoptotic pathways, or the outcome of an idiotypic network dysregulation.


Antigenic and immunogenic evaluation of Helicobacter pylori FlaA epitopes.
Helicobacter pylori are among most common human pathogens affecting at least half of the world's population. Mobility is one of the important primary factors in bacterial colonization and invasion. The purpose of this research is cloning, expression, and purification of FlaA protein specific epitopes in order to evaluate their antigenicity and immunogenicity. The antigenic region of the flaA gene was bioinformatically predicted using Epitope mapping software's and the predicted epitopes were expressed in a prokaryotic expression vector. The antigen was injected into the animal model (mice BALB/c) and some indicators including IgG1, IgG2a, IgA, IFN-γ, and IL 5 were measured. The immunogenicity studies in animal models by measuring serum antibodies (IgG1, IgG2a, and IgA) and cytokines (IFN-γ and IL5) revealed that the rFlaA induces a proper immune response in animal models. The recombinant FlaA protein is antigenic and immunogenic. Therefore, it might be used in order to design of specific diagnostic kits and recombinant vaccines against H. pylori.


Reductions in midbrain GABAergic and dopamine neuron markers are linked in schizophrenia.
Reductions in the GABAergic neurotransmitter system exist across multiple brain regions in schizophrenia and encompass both pre- and postsynaptic components. While reduced midbrain GABAergic inhibitory neurotransmission may contribute to the hyperdopaminergia thought to underpin psychosis in schizophrenia, molecular changes consistent with this have not been reported. We hypothesised that reduced GABA-related molecular markers would be found in the midbrain of people with schizophrenia and that these would correlate with dopaminergic molecular changes. We hypothesised that downregulation of inhibitory neuron markers would be exacerbated in schizophrenia cases with high levels of neuroinflammation. Eight GABAergic-related transcripts were measured with quantitative PCR, and glutamate decarboxylase (GAD) 65/67 and GABAA alpha 3 (α3) (GABRA3) protein were measured with immunoblotting, in post-mortem midbrain (28/28 and 28/26 control/schizophrenia cases for mRNA and protein, respectively), and analysed by both diagnosis and inflammatory subgroups (as previously defined by higher levels of four pro-inflammatory cytokine transcripts). We found reductions (21 - 44%) in mRNA encoding both presynaptic and postsynaptic proteins, vesicular GABA transporter (VGAT), GAD1, and parvalbumin (PV) mRNAs and four alpha subunits (α1, α2, α3, α5) of the GABAA receptor in people with schizophrenia compared to controls (p < 0.05). Gene expression of somatostatin (SST) was unchanged (p = 0.485). We confirmed the reduction in GAD at the protein level (34%, p < 0.05). When stratifying by inflammation, only GABRA3 mRNA exhibited more pronounced changes in high compared to low inflammatory subgroups in schizophrenia. GABRA3 protein was expressed by 98% of tyrosine hydroxylase-positive neurons and was 23% lower in schizophrenia, though this did not reach statistical significance (p > 0.05). Expression of transcripts for GABAA receptor alpha subunits 2 and 3 (GABRA2, GABRA3) were positively correlated with tyrosine hydroxylase (TH) and dopamine transporter (DAT) transcripts in schizophrenia cases (GABRA2; r > 0.630, GABRA3; r > 0.762, all p < 0.001) but not controls (GABRA2; r < - 0.200, GABRA3; r < 0.310, all p > 0.05). Taken together, our results support a profound disruption to inhibitory neurotransmission in the substantia nigra regardless of inflammatory status, which provides a potential mechanism for disinhibition of nigrostriatal dopamine neurotransmission.


German version of the Multidimensional Body-Self Relations Questionnaire - Appearance Scales (MBSRQ-AS): confirmatory factor analysis and validation.
The Multidimensional Body-Self Relations Questionnaire (MBSRQ) is a widely used questionnaire that measures body image as a multidimensional construct. The Appearance Scales (AS) of the MBSRQ (Appearance Evaluation, Appearance Orientation, Body Areas Satisfaction, Overweight Preoccupation and Self-Classified Weight) are subscales which facilitate a parsimonious assessment of appearance-related aspects of body image. The current study tested the psychometric properties and factor structure of a German translation of the MBSRQ-AS. Participants were n=230 female patients with the SCID diagnosis of an eating disorder and n=293 female healthy controls. In a confirmatory factor analysis, convincing goodness-of-fit indices emerged. The subscales of the questionnaire yielded good reliability and convergent and discriminant validity coefficients, with most items showing excellent characteristics. Like the English version, the German adaptation of the questionnaire can be recommended for a multidimensional assessment of appearance-related aspects of body image in both research and clinical practice.


Synchrotron Microbeam Radiation Therapy for the Treatment of Lung Carcinoma: A Preclinical Study.
In the past 3 decades, synchrotron microbeam radiation therapy (S-MRT) has been shown to achieve both good tumor control and normal tissue sparing in a range of preclinical animal models. However, the use of S-MRT for the treatment of lung tumors has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model. Lewis Lung carcinoma-bearing mice were irradiated with 2 cross-fired arrays of S-MRT or synchrotron broad-beam (S-BB) radiation therapy. S-MRT consisted of 17 microbeams with a width of 50 µm and center-to-center spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy whereas S-BB delivered a homogeneous entrance dose of 5.16 Gy (corresponding to the S-MRT valley dose). Both treatments prolonged the survival of mice relative to the untreated controls. However, mice in the S-MRT group developed severe pulmonary edema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent postmortem examination of tumor size revealed that the mice in the S-MRT group had notably smaller tumor volume compared with the S-BB group, despite the presence of edema. Mice that were sham-implanted did not display any decline in health after S-MRT, experiencing only mild and transient edema between 4 days and 3 months postirradiation which disappeared after 4 months. Finally, a parallel study investigating the lungs of healthy mice showed the complete absence of radiation-induced pulmonary fibrosis 6 months after S-MRT. S-MRT is a promising tool for the treatment of lung carcinoma, reducing tumor size compared with mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimizing S-MRT parameters to minimize pulmonary edema and maximize the therapeutic ratio.


Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones near a source of lead emissions.
The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones were identified by a multivariate statistical analysis. Within each zone, the total dietary intake of lead was estimated for adults and children as a percentage of the provisional tolerably weekly intake (PTWI), and as a result recommendation on restrictions in use of locally grown fruit and vegetables were given to the public. The pattern of lead deposition in the area during the period 1981-1988 was monitored and the amount of lead ingested via vegetables was toxically evaluated. Lead emission reduction measures introduced in the factory and in the traffic during the period produced significant reductions in lead deposition.


Recognition of fasting or overall hyperglycaemia when starting insulin treatment in patients with type 2 diabetes in general practice.
The efficacy of various regimens of initial insulin treatment in poorly controlled type 2 diabetes was compared with regard to diurnal glucose variation. Randomized controlled trial. Setting. Insulin therapy initiated on hospital wards, follow-up as outpatients for 12 months. Fifty-two type 2 diabetic patients (HbA1c >7.5%, mean 9.8%) on maximal oral therapy. Interventions. Insulin only (IO), bedtime insulin with sulphonylurea (glipizide) (IS), or bedtime insulin with metformin (IM). HbA1c and body weight. HbA1c decreased on average by 1.8, 1.0 and 1.5 percentage points in the IO, IS, and IM groups, respectively (p always <0.025). Body weight increased, most in the IO patients (+6.2 kg), least in the IM patients (+3.4 kg). Analysing all treatment groups combined, a similar HbA1c reduction was observed in patients with overall hyperglycaemia (low fasting plasma glucose/HbA1c ratio) and in patients with fasting hyperglycaemia (high fasting plasma glucose/HbA1c ratio). Within the overall hyperglycaemia group, the IS and IM patients had smaller decreases in HbA1c (-1.5 and -1.3 percentage points, respectively) than the IO patients (-2.7 percentage points). On the other hand, within the fasting hyperglycaemia group HbA1c reductions were -1.2, -0.8 and -1.5 percentage points, in the IO, IS, and IM groups, respectively. Not all poorly controlled type 2 diabetic patients should automatically be treated with an oral agent and bedtime insulin. Two daily insulin injections is a valid choice, particularly if the patient has overall hyperglycaemia.


Quantitative proteomics identify novel miR-155 target proteins.
MicroRNAs are 22 nucleotides long non-coding RNAs and exert their function either by transcriptional or translational inhibition. Although many microRNA profiles in different tissues and disease states have already been discovered, only little is known about their target proteins. The microRNA miR-155 is deregulated in many diseases, including cancer, where it might function as an oncoMir. We employed a proteomics technique called "stable isotope labelling by amino acids in cell culture" (SILAC) allowing relative quantification to reliably identify target proteins of miR-155. Using SILAC, we identified 46 putative miR-155 target proteins, some of which were previously reported. With luciferase reporter assays, CKAP5 was confirmed as a new target of miR-155. Functional annotation of miR-155 target proteins pointed to a role in cell cycle regulation. To the best of our knowledge we have investigated for the first time miR-155 target proteins in the HEK293T cell line in large scale. In addition, by comparing our results to previously identified miR-155 target proteins in other cell lines, we provided further evidence for the cell line specificity of microRNAs.


Identification of Key Genes and Pathways in Osteoarthritis via Bioinformatic Tools: An Updated Analysis.
Osteoarthritis (OA) is a severe and common degenerative disease; however, the exact pathology of OA is undefined. Our study is designed to investigate the underlying molecular mechanism of OA with bioinformatic tools. Three updated GEO datasets: GSE55235, GSE55457, and GSE82107 were selected for data analyzing. R software was utilized to screen and confirm the candidate differentially expressed genes in the development of OA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway were performed to identify the enriched GO terms and signaling pathways. Protein and protein interaction (PPI) models were built to observe the connected relationship among each potential protein. A total of 113 upregulated genes and 161 downregulated genes were found by integrating 3 datasets. GO enrichment indicated that cell differentiation, cellular response to starvation, and negative regulation of phosphorylation were important biological processes. KEGG enrichment indicated that FoxO, IL-17 signaling pathways, and osteoclast differentiation mainly participated in the progression of OA. Combining the molecular function and PPI results, ubiquitylation was identified as a pivotal bioactive reaction involved in OA. Our study provided updated candidate genes and pathways of OA, which may benefit further research and treatment for OA.


Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.
Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.


Site-Specific Effects of Online rTMS during a Working Memory Task in Healthy Older Adults.
The process of manipulating information within working memory is central to many cognitive functions, but also declines rapidly in old age. Improving this process could markedly enhance the health-span in older adults. The current pre-registered, randomized and placebo-controlled study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) applied at 5 Hz over the left lateral parietal cortex to enhance working memory manipulation in healthy elderly adults. rTMS was applied, while participants performed a delayed-response alphabetization task with two individually titrated levels of difficulty. Coil placement and stimulation amplitude were calculated from fMRI activation maps combined with electric field modeling on an individual-subject basis in order to standardize dosing at the targeted cortical location. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. When compared to the results from our previous study, in which rTMS was applied over the left prefrontal cortex, we found equivalent effect sizes but opposite directionality suggesting a site-specific effect of rTMS. These results demonstrate engagement of cortical working memory processing using a novel TMS targeting approach, while also providing prescriptions for future studies seeking to enhance memory through rTMS.


Supercomputing with toys: harnessing the power of NVIDIA 8800GTX and playstation 3 for bioinformatics problem.
Modern video cards and game consoles typically have much better performance to price ratios than that of general purpose CPUs. The parallel processing capabilities of game hardware are well-suited for high throughput biomedical data analysis. Our initial results suggest that game hardware is a cost-effective platform for some computationally demanding bioinformatics problems.


Profiles of patients with cocaine and alcohol use disorder based on cognitive domains and their relationship with relapse.
Relapse in drug use constitutes a research topic on addiction that is relevant for understanding both the addictive process and its clinical implications. The objective of this study was to explore if it is possible to identify patient profiles according to their performance on cognitive tasks whilst examining the relationship between such profiles and relapse. The sample consisted of 222 patients with dependence on cocaine and / or alcohol, of which 86 % were men. Cognitive domains related to salience, decision- making, and emotional processing were measured. Latent class analysis revealed three patient profiles that differ in terms of performance on cognitive tasks. Two of these profiles are clearly differentiated in terms of their execution of the impulsive decision-making task. The third patient profile, unlike the latter two, is composed of patients with severe alterations in the three domains evaluated. Analysis revealed that patients in Profile 3 are those with the highest rates of relapse in cocaine (Profile 1 = 40.3 %; Profile 2 = 35.6 %; Profile 3 = 69.2 %; Chi2 = 9.169; p < .05) and cocaine and alcohol use (Profile 1 = 55.1 %; Profile 2 = 54.1 %; Profile 3 = 80 %; Chi2 = 6.698; p < .05). The results support the postulates of the I-RISA model. From a clinical perspective, these findings highlight the need for a comprehensive evaluation of the cognitive domains involved in addiction.


Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum.
The effects of purified Ca2+, phospholipid-dependent protein kinase (C-kinase) were studied on adenylate cyclase activity from rat brain striatum. C-kinase treatment of the membranes stimulated adenylate cyclase activity, the maximal stimulation between 50-80% was observed at 3.5 U/ml, whereas the catalytic subunit of cAMP dependent protein kinase did not show any effect on enzyme activity. The inclusion of Ca2+ and phosphatidyl serine did not augment the percent stimulation of adenylate cyclase by C-kinase, however EGTA inhibited the stimulatory effect of C-kinase on enzyme activity. Furthermore, the known inhibitors of C-kinase such as polymyxin-B and 1-(5-Isoquinoline sulfonyl)-2-methylpiperazine dihydrochloride (H-7) also inhibited the stimulatory effect of C-kinase on adenylate cyclase activity. In addition, in the presence of GTP the stimulatory effects of C-kinase on basal and N-Ethylcarboxamide adenosine- (NECA-), dopamine-(DA) and forskolin- (FSK) sensitive adenylate cyclase activities were augmented. On the other hand, the inhibitory effect of high concentrations of GTP on enzyme activity was attenuated by C-kinase treatment. In addition, oxotremorine inhibited adenylate cyclase activity in a concentration dependent manner, with an apparent Ki of about 10 microM and C-kinase treatment almost completely abolished this inhibition. These data suggest that C-kinase may play an important role in the regulation of adenylate cyclase activity possibly by interacting with a guanine nucleotide regulatory protein.


Dynamics between insight and medication adherence in first-episode psychosis: Study of 3-year trajectories.
While specialized early intervention programs represent the gold standard in terms of optimal management of first-episode psychosis (FEP), poor medication adherence remains a predominant unmet need in the treatment of psychosis. In this regard, an interaction between insight and adherence in FEP patients has been hypothesized but has been challenged by multiple pitfalls. Latent profile analysis and trajectory modeling techniques were used to evaluate insight and adherence of 331 FEP patients engaged at the beginning, middle, and end of a 3-year specialized early psychosis program. A Bayesian model comparison approach was used to compare scores of clinical, functional, and socioeconomic outcomes at the end point of the study. Nearly one-third of the patients maintain a high level of insight and adherence during the entire program. At the end of the 3-year follow-up, more than three-quarters of patients are considered adherent to their medication. Patients with low levels of insight and adherence at the beginning of the program improve first in terms of adherence and then of insight. Furthermore, patients with high levels of insight and adherence are most likely to reach functional recovery and to experience an increase in environmental quality of life. Latent FEP subpopulations can be identified based on insight and adherence. Medication adherence was the first variable to improve, but a gain in insight possibly plays a role in the reinforcement of adherence.