Evaluation of the anatomic sinus after transcatheter aortic valve replacement.
Following transcatheter aortic valve replacement (TAVI), the newly formed 'anatomic sinus'. may contribute to the formation of subclinical leaflet thrombosis (SLT).The evaluation of root geometry after TAVI is generally performed using multi-detector computed tomography (MDCT), and the role of transthoracic echocardiography (2D TTE) requires further validation. Thus, we aimed to test the reproducibility of 2D TTE assessment of the anatomic sinus with MDCT as a reference and its association with SLT. 2D TTE was performed in 90 patients, and the echocardiograms were analyzed offline. Both sinus of Valsalva (SOV) and prosthesis diameters were assessed in the long- and short-axis parasternal views (PLAX/PSAX), and the anatomic sinus area was calculated. Inter- and intra-observer reproducibility were assessed using the interclass correlation coefficient (ICC). MDCT was performed in 50 individuals to evaluate concordance with 2D TTE and to detect SLT. There was excellent correlation regarding the diameter of the SOV and the prosthesis in PLAX (ICC: 0.93 (95% CI: 0.76,0.97); ICC: 0.80 (95% CI: 0.63,0.96)) and PSAX view (ICC: 0.90 (95% CI: 0.68,0.97); ICC: 0.88 (95% CI: 0.63,0.96)). Bland-Altman analysis of 2D TTE and MDCT anatomic sinus areas indicated a high level of agreement. SLT was detected in 8 individuals (16%); 3 patients had severe SLT at the level of 1 cusp. 2D TTE might play a role in the evaluation of the anatomic sinus after TAVI. The importance of this space and its effects on the SLT remain uncertain.


[Splenic abscess: a case report and review of the literature].
A patients with multiple splenic abscesses of fungal origin ist presented. It is a unusual pathology that generally, only by postmortem ist diagnosed. The etiology, clinical features, diagnostic methods and therapeutic measures are discussed, and the necessity of early and accurate diagnostic and treatment. The prognosis of the splenic abscess is still associated with a high mortality.


Iodine deficiency: a probable cause of neural tube defect.
Iodine deficiency is the most devastating event in developing brain in the fetus and neonate. Iodine is absolutely necessary on the myelination, neuronal differentiation, and formation of neural processes, synaptogenesis, and neuronal migration by thyroidal hormones throughout pregnancy and shortly after birth. Neural tube defects (NTD) form after third and fourth gestational weeks and their etiologies are multifactorial. We herein present a male newborn with iodine deficiency and thoracic neuroenteric cyst bound to a myelomeningocele via a pedinculi. We hypothesize that iodine deficiency may be a cause of NTD, and iodine supplementation in preconception and pregnancy may prevent NTD.


Roles and responsibilities of the nursing scholar.
Scholarship is an important facet of the nursing profession. There are many components, virtues, and roles and responsibilities of a nursing scholar practicing in today's ever-changing health care environment. Scholarship was redefined by Boyer to include scholarly activities in addition to research. Boyer's Model of Scholarship includes four interrelated and overlapping domains of discovery, integration, application, and teaching. Each domain is explained with examples for the pediatric nurse scholar, which includes roles in academia as well as in the practice setting. Pediatric nurses are key to scholarship in nursing because they work to improve the care of children.


Doping in cyclism: results of unannounced controls in Flanders (1987-1994).
Unannounced doping control in cyclism, the most favourite sport in Flanders, resulted in 7.8% positive cases in 4374 analysed samples during the period 1987-1994. Ephedrines, amphetamine and nandrolone were frequently misused and polydrug abuse including ephedrines and amphetamine seemed to be very popular. The abuse of methamphetamine, methylphenidate and pemoline, formerly favourite drugs in cyclists is decreasing while prolintane, codeine and the anabolic steroids nandrolone and testosterone were more frequently detected. The misuse of forbidden substances by athletes competing in the official Belgian Cyclist Federation and in amateur federations was 5.8% and 8.9%, respectively. Several cyclists however attempted to circumvent doping control.


Magneto-Plasmonics and Resonant Interaction of Light with Dynamic Magnetisation in Metallic and All-Magneto-Dielectric Nanostructures.
A significant interest in combining plasmonics and magnetism at the nanoscale gains momentum in both photonics and magnetism sectors that are concerned with the resonant enhancement of light-magnetic-matter interaction in nanostructures. These efforts result in a considerable amount of literature, which is difficult to collect and digest in limited time. Furthermore, there is insufficient exchange of results between the two research sectors. Consequently, the goal of this review paper is to bridge this gap by presenting an overview of recent progress in the field of magneto-plasmonics from two different points of view: magneto-plasmonics, and magnonics and magnetisation dynamics. It is expected that this presentation style will make this review paper of particular interest to both general physical audience and specialists conducting research on photonics, plasmonics, Brillouin light scattering spectroscopy of magnetic nanostructures and magneto-optical Kerr effect magnetometry, as well as ultrafast all-optical and THz-wave excitation of spin waves. Moreover, readers interested in a new, rapidly emerging field of all-dielectric nanophotonics will find a section about all-magneto-dielectric nanostructures.


A transcriptional regulatory network of Rsv3-mediated extreme resistance against Soybean mosaic virus.
Resistance genes are an effective means for disease control in plants. They predominantly function by inducing a hypersensitive reaction, which results in localized cell death restricting pathogen spread. Some resistance genes elicit an atypical response, termed extreme resistance, where resistance is not associated with a hypersensitive reaction and its standard defense responses. Unlike hypersensitive reaction, the molecular regulatory mechanism(s) underlying extreme resistance is largely unexplored. One of the few known, naturally occurring, instances of extreme resistance is resistance derived from the soybean Rsv3 gene, which confers resistance against the most virulent Soybean mosaic virus strains. To discern the regulatory mechanism underlying Rsv3-mediated extreme resistance, we generated a gene regulatory network using transcriptomic data from time course comparisons of Soybean mosaic virus-G7-inoculated resistant (L29, Rsv3-genotype) and susceptible (Williams82, rsv3-genotype) soybean cultivars. Our results show Rsv3 begins mounting a defense by 6 hpi via a complex phytohormone network, where abscisic acid, cytokinin, jasmonic acid, and salicylic acid pathways are suppressed. We identified putative regulatory interactions between transcription factors and genes in phytohormone regulatory pathways, which is consistent with the demonstrated involvement of these pathways in Rsv3-mediated resistance. One such transcription factor identified as a putative transcriptional regulator was MYC2 encoded by Glyma.07G051500. Known as a master regulator of abscisic acid and jasmonic acid signaling, MYC2 specifically recognizes the G-box motif ("CACGTG"), which was significantly enriched in our data among differentially expressed genes implicated in abscisic acid- and jasmonic acid-related activities. This suggests an important role for Glyma.07G051500 in abscisic acid- and jasmonic acid-derived defense signaling in Rsv3. Resultantly, the findings from our network offer insights into genes and biological pathways underlying the molecular defense mechanism of Rsv3-mediated extreme resistance against Soybean mosaic virus. The computational pipeline used to reconstruct the gene regulatory network in this study is freely available at https://github.com/LiLabAtVT/rsv3-network.


Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium.
Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a "silent" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 µM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.


Intracranial electroencephalography with subdural grid electrodes: techniques, complications, and outcomes.
Intracranial subdural grid monitoring is a useful diagnostic technique for surgical localization in patients with intractable partial epilepsy. The rationale for the present study was to assess the morbidity of intracranial recordings and the surgical outcomes. We retrospectively reviewed the clinical data for 189 unique patients undergoing 198 intracranial subdural grid monitoring sessions between 1996 and 2004 at a tertiary epilepsy center. The mean age of patients undergoing monitoring was 28 +/- 14 years. An average of 63 +/- 23 electrodes were inserted. The mean duration of monitoring was 8 +/- 4 days. Localization of an epileptogenic zone occurred in 156 sessions (79%) resulting in 136 resections (69%). There were 13 major complications (6.6%), including five infections and six hematomas. Three patients (1.5%) developed permanent deficits related to implantation. Sixty-two (47%) of 136 patients undergoing resection were seizure-free after resection. An additional 38 patients (28%) had a significant reduction in seizures. The mean follow-up was 51 +/- 30 months. The duration of monitoring, bone flap replacement, number of electrodes, and perioperative corticosteroids were not associated with infection or complication. Subdural grid monitoring for identification an epileptogenic focus is high yield, revealing a focus in 79% of monitoring sessions. Complications rarely result in permanent morbidity (1.5%). Surgical outcome indicated that 74% of patients experienced a favorable reduction in seizure tendency.


An automated electrokinetic continuous sample introduction system for microfluidic chip-based capillary electrophoresis.
An automated and continuous sample introduction system for microfluidic chip-based capillary electrophoresis (CE) was developed in this work. An efficient world-to-chip interface for chip-based CE separation was produced by horizontally connecting a Z-shaped fused silica capillary sampling probe to the sample loading channel of a crossed-channel chip. The sample presentation system was composed of an array of bottom-slotted sample vials filled alternately with samples and working electrolyte, horizontally positioned on a programmable linearly moving platform. On moving the array from one vial to the next, and scanning the probe, which was fixed with a platinum electrode on its tip, through the slots of the vials, a series of samples, each followed by a flow of working electrolyte was continuously introduced electrokinetically from the off-chip vials into the sample loading channel of the chip. The performance of the system was demonstrated in the separation and determination of FITC-labeled arginine and phenylalanine with LIF detection, by continuously introducing a train of different samples. Employing 4.5 kV sampling voltage (1000 V cm(-1) field strength) for 30 s and 1.8 kV separation voltage (400 V cm(-1) field strength) for 70 s, throughputs of 36 h(-1) were achieved with <1.0% carryover and 4.6, 3.2 and 4.0% RSD for arginine, FITC and phenylalanine, respectively (n = 11). Net sample consumption was only 240 nL for each sample.


Diabetes mellitus associated with bilateral granulosa cell tumors in a mare.
Both ovaries in a 10-year-old American Saddle Horse mare were determined to be larger than normal. The mare had problems with infertility during the preceding 3 years. Clinical evaluation revealed that the mare was polyuric, polydypsic, hyperinsulinemic, and hyperglycemic, and had reduced tolerance to exogenous glucose. Bilateral granulosa cell tumors were identified on histologic examination of the ovaries. The precise mechanism for the secondary diabetes mellitus was not determined; however, the cause was suspected to be a result of the synthesis and release of a hormonal substance by the tumor that affected carbohydrate metabolism and resulted in decreased peripheral sensitivity to insulin.


Factors affecting medical students' interests in working in rural areas in North India-A qualitative inquiry.
The shortage of doctors, especially in rural areas, is a major concern in India, which in turn affects the effective delivery of health care services. To support new policies able to address this issue, a study was conducted to determine the discouraging and encouraging factors affecting medical students' interests towards working in rural areas. This cross-sectional, descriptive qualitative study has been conducted in three states of North India. It comprised six focus group discussions, each consisting of 10-20 medical students of six government medical colleges. The verbatim and thematic codes have been transcribed by using a 'categorical aggregation approach'. The discussions were thematically analyzed. Ninety medical students participated in the study. The discouraging factors were grouped under two broad themes namely unchallenging professional environment (poor accommodation facilities and lack of necessary infrastructure; lack of drug and equipment supplies; inadequate human resource support; lesser travel and research opportunities) and gap between financial rewards and social disadvantages (lower salary and incentives, social isolation, political interference, lack of security). Similarly, the encouraging factors were congregated under three main themes namely willingness to give back to disadvantaged communities (desire to serve poor, underprivileged and home community), broader clinical exposure (preferential admission in post-graduation after working more than 2-3 years in rural areas) and higher status and respect (achieving higher social status). This qualitative study highlights key factors affecting medical students' interest to work in rural areas. A substantial similarity was noted between the factors which emerge from the current study and those documented in other countries. These findings will help policymakers and medical educators to design and implement a comprehensive human resource strategy that shall target specific factors to encourage medical students to choose job positions in rural areas.


Update on the distribution of the co-invasive Schyzocotyle acheilognathi (= Bothriocephalus acheilognathi), the Asian fish tapeworm, in freshwater fishes of Mexico.
The Asian fish tapeworm, Schyzocotyle acheilognathi (syn. Bothriocephalus acheilognathi) represents a threat to freshwater fish, mainly cyprinids, across the globe. This tapeworm possesses an extraordinary ability to adapt to different environmental conditions and, because of that, from its natural geographical origin in mainland Asia, it has colonized every continent except Antarctica. It is thought that this pathogenic tapeworm was first co-introduced into Mexico in 1965 from China, with the grass carp Ctenopharyngodon idella, although the first formal record of its presence was published in 1981. Over the past 35 years, the Asian fish tapeworm has invaded about 22% of the freshwater fish in Mexico. Because fish communities in Mexico are characterized by high species richness and levels of endemism, S. acheilognathi is considered as a co-introduced and co-invasive species. In this review, we update the geographic distribution and host spectrum of the Asian fish tapeworm in Mexico. Up until December 2016, the tapeworm had been recorded in 110 freshwater fish species (96 native and 14 introduced), included in 51 genera, 11 families and 4 orders; it was also widely distributed in all types of aquatic environments, and has been found in 214 localities. We present novel data from a survey aimed at establishing the distribution pattern of the tapeworm in native freshwater fishes of two rivers in north-central Mexico, and the genetic variation among individuals of this co-invasive species collected from different host species and localities. We discuss briefly the factors that have determined the remarkable invasive success of this parasite in freshwater systems in Mexico.


Induction of cell cycle arrest at G1 and S phases and cAMP-dependent differentiation in C6 glioma by low concentration of cycloheximide.
Differentiation therapy has been shown effective in treatment of several types of cancer cells and may prove to be effective in treatment of glioblastoma multiforme, the most common and most aggressive primary brain tumor. Although extensively used as a reagent to inhibit protein synthesis in mammalian cells, whether cycloheximide treatment leads to glioma cell differentiation has not been reported. C6 glioma cell was treated with or without cycloheximide at low concentrations (0.5-1 μg/ml) for 1, 2 and 3 days. Cell proliferation rate was assessed by direct cell counting and colony formation assays. Apoptosis was assessed by Hoechst 33258 staining and FACS analysis. Changes in several cell cycle regulators such as Cyclins D1 and E, PCNA and Ki67, and several apoptosis-related regulators such as p53, p-JNK, p-AKT, and PARP were determined by Western blot analysis. C6 glioma differentiation was determined by morphological characterization, immunostaining and Western blot analysis on upregulation of GFAP and o p-STAT3 expression, and upregulation of intracellular cAMP. Treatment of C6 cell with low concentration of cycloheximide inhibited cell proliferation and depleted cells at both G2 and M phases, suggesting blockade at G1 and S phases. While no cell death was observed, cells underwent profound morphological transformation that indicated cell differentiation. Western blotting and immunostaining analyses further indicated that changes in expression of several cell cycle regulators and the differentiation marker GFAP were accompanied with cycloheximide-induced cell cycle arrest and cell differentiation. Increase in intracellular cAMP, a known promoter for C6 cell differentiation, was found to be elevated and required for cycloheximide-promoted C6 cell differentiation. Our results suggest that partial inhibition of protein synthesis in C6 glioma by low concentration of cycloheximide induces cell cycle arrest at G1 and M phases and cAMP-dependent cell differentiation.


Covalent attachment of ferrocene to soybean peroxidase glycans: electron transfer mediation to redox enzymes.
The electrochemical properties of native soybean peroxidase (SBP) and of SBP modified with covalently attached ferrocene electron-transfer mediators within microcavities etched at the tip of 25 mum radius platinum microelectrodes are reported. The microcavities incorporate approximately 50 fmol of SBP. In the microcavity, native SBP undergoes a relatively fast reduction but a very slow oxidation. Ferrocene mediators have been attached to the SBP glycans (Fc-SBP) (approximately 1.5 ferrocene mediators per SBP molecule). Cyclic voltammetry reveals that these centers are capable of mediating the reduction of oxidized SBP and increase the rate of heterogeneous electron transfer between the enzyme and the electrode by >10-fold. Micromolar concentrations of H2O2 chemically oxidize the SBP and Fc-SBP systems leading to an electrocatalytic reduction at approximately -0.1 V. Successive additions of 2.5 micromol of H2O2 at a constant applied potential of -0.1 V gave a steady-state constant current of approximately 60 nA within 20 s. The steady-state current increased linearly with peroxide concentration for 2.5 <or= [H2O2] <or= 42 microM. Ferrocene-modified SBP shows an approximately 3-fold increase in the sensitivity of the steady-state current response to successive additions of hydrogen peroxide compared to the native enzyme. This observation indicates increased turnover of the redox enzyme per unit time in the presence of the covalently attached ferrocene mediators.


[Immunobiology of vesicular mole and choriocarcinoma].
Molar tissue expresses HLA antigens evidenced in the father. These antigens are present on the trophoblastic extravillous tissue, not on the syncytium and cytotrophoblast. These antigens show some characteristics of Qa murine antigens mapped in the HLA system linked to class I antigens. Antibodies anti HLA against the partner antigens and lymphocytotoxic antibodies have been evidenced in the serum of patients with vesicular mole. In vesicular mole the production of antibodies should be determined by the immunogenicity of cells that infiltrate the decidua, expressing paternal HLA antigens. It has been demonstrated that the recognition of "not self" antigens in the mother should stimulate a cellular immune response. We do not know why the tumor grows. Maybe the woman is not able to produce anti HLA antibodies although recognizes them as "not self", or the patients is not antigenically stimulated because there is immunocompatibility between the two partners. The literature shows that the development and progression of the disease are stimulated by histocompatibility, although this factors does not seem fundamental. If the two partners are histocompatible the tumor can be less immunogenic, so the mother shows a lower response and the growth of the tumor appears to be favoured.


A 44-kb deleted-type copy number variation is associated with decreasing complement component activity and calf mortality in Japanese Black cattle.
Calf mortality generally occurs in calves prior to weaning, which is a serious problem in cattle breeding. Several causative variants of monogenic Mendelian disorders in calf mortality have been identified, whereas genetic factors affecting the susceptibility of calves to death are not well known. To identify variants associated with calf mortality in Japanese Black cattle, we evaluated calf mortality as a categorical trait with a threshold model and performed a genome-wide copy number variation (CNV) association study on calf mortality. We identified a 44-kb deleted-type CNV ranging from 103,317,687 to 103,361,802 bp on chromosome 5, which was associated with the mortality of 1-180-day-old calves. The CNV harbored C1RL, a pseudogene, and an IncRNA localized in the C1R and C1S gene cluster, which is a component of the classical complement activation pathway for immune complexes for infectious pathogens. The average complement activity in CNVR_221 homozygotes at postnatal day 7 was significantly lower than that of wild-type animals and heterozygotes. The frequency of the risk allele in dead calves suffering from diarrhea and pneumonia and in healthy cows was 0.35 and 0.28, respectively (odds ratio = 2.2, P = 0.016), suggesting that CNVR_221 was associated with the mortality of Japanese Black calves suffering from an infectious disease. This study identified a deleted-type CNV associated with the mortality of 1-180-day-old calves. The complement activity in CNVR_221 homozygotes was significantly lower than that in heterozygotes and wild type animals. The frequency of the risk allele was higher in dead calves suffering from an infectious disease than in healthy cows. These results suggest that the existence of CNVR_221 in calves could be attributed to a reduction in complement activity, which in turn leads to susceptibility to infections. Thus, the risk allele could serve as a useful marker to reduce the mortality of infected Japanese Black calves.


Interaction of septadian and circadian rhythms in life-threatening ventricular arrhythmias in patients with implantable cardioverter-defibrillators.
Previous studies have shown that life-threatening ventricular arrhythmias display both circadian and septadian (day of the week) periodicity. We hypothesized that assessing the relation between these circadian and septadian rhythms may provide important pathophysiologic information about the mechanism of sudden cardiac death. Using the database from a population of 683 consecutive patients with a third-generation implantable cardioverter-defibrillator (ICD), we examined the time pattern of ICD activations for rapid (prospectively defined as cycle length <280 ms) tachycardias for each day of the week. A total of 5,270 arrhythmic episodes were analyzed. Despite the fact that event distribution was significantly nonuniform (p <0.001) for both circadian and septadian analyses, the circadian pattern was strikingly similar for each day of the week with a relatively broad peak between 9 A.M. and 6 P.M. and a long nadir between 9 P.M. and 6 A.M. We conclude that the trigger factors responsible for the daily circadian distribution of life-threatening ventricular arrhythmias in a population with ICDs are similar throughout the week and may thus be unrelated to the standard work week. These data suggest that the physiologic modulators of circadian and septadian rhythms may be different.


The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway.
Cells with aberrations in chromosomal ploidy are normally removed by apoptosis. However, aneuploid neurons have been shown to remain functional and active both in the cortex and in the retina. Lim1 horizontal progenitor cells in the chicken retina have a heterogenic final cell cycle, producing some cells that enter S-phase without proceeding into M-phase. The cells become heteroploid but do not undergo developmental cell death. This prompted us to investigate if the final cell cycle of these cells is under the regulation of an active DNA damage response. Our results show that the DNA damage response pathway, including γ-H2AX and Rad51 foci, is not triggered during any phase of the different final cell cycles of horizontal progenitor cells. However, chemically inducing DNA adducts or double-strand breaks in Lim1 horizontal progenitor cells activated the DNA damage response pathway, showing that the cells are capable of a functional response to DNA damage. Moreover, manipulation of the DNA damage response pathway during the final cell cycle using inhibitors of ATM/ATR, Chk1/2, and p38MAPK, neither induced apoptosis nor mitosis in the Lim1 horizontal progenitor cells. We conclude that the DNA damage response pathway is functional in the Lim1 horizontal progenitor cells, but that it is not directly involved in the regulation of the final cell cycle that gives rise to the heteroploid horizontal cell population.


Opioid agonist treatment in transition: A cross-country comparison between Austria, Germany and Switzerland.
OAT is a well developed and successful treatment strategy for opioid dependent patients in Europe. It has significantly contributed to the fight against the HIV and HCV pandemics, leading to an increased life expectancy in this population. Building on the OAT experiences in Austria, Germany, and Switzerland and their models of care, the objective of this study is to analyse experiences and changes in patient structures to identify necessary adaptations for the system of care. We analysed national register-based data from patients receiving OAT during the period spanning from 2010 to 2020 in Austria, Germany (cases), and Switzerland. We examined and compared OAT policies and practice at national levels through a review of literature and publicly available policy documents. Across these three countries, the life expectancy of OAT patients increased substantially. The mean age increased from 33.0 in 2010 to 39.1 in 2020 in Austria, from 35.6 years to 41.5 years in Germany (cases), and from 39.6 to 47.1 in Switzerland, respectively. In all three countries, the percentage of patients/cases aged 60 years and older increased more than tenfold between 2010 and 2020. Integrated support models, reliable care structures, internationally comparable high treatment coverage, flexible prescribing practices, and a wide range of available OAT medications are successful strategies. The experiences in these countries indicate that it is possible to address the complex and chronic nature of opioid dependence and its concurrent mental and physical health challenges, resulting in an increasing life expectancy of OAT patients.


Internal resistance in winter oilseed rape inhibits systemic spread of the vascular pathogen Verticillium longisporum.
Verticillium longisporum is a vascular fungal pathogen presently threatening oilseed rape production in Europe. Systemic spread and vascular responses were studied in a susceptible ('Falcon') and a resistant genotype (SEM 05-500256) of Brassica napus. Colonization of both genotypes after dip-inoculation of the roots followed by quantitative polymerase chain reaction revealed similarities only in the initial stages of root penetration and colonization of the hypocotyl, while a substantial invasion of the shoot was only recorded in 'Falcon'. It is concluded that the type of resistance represented in SEM 05-500256 does not prevent the plant base from being invaded as it is internally expressed well after root penetration and colonization of the plant base. The morphological and biochemical nature of barriers induced in the hypocotyl tissue upon infection was studied with histochemical methods accompanied by biochemical analyses. Histochemical studies revealed the build-up of vascular occlusions and the reinforcement of tracheary elements through the deposition of cell wall-bound phenolics and lignin. Furthermore, the accumulation of soluble phenolics was observed. Although these responses were found in vascular tissues of both genotypes, they occurred with a significantly higher intensity in the resistant genotype and corresponded with the disease phenotype. In the resistant genotype phenols were differentially expressed in a time-dependent manner with preformed soluble and cell wall-bound phenolics at earlier time points and de novo formation of lignin and lignin-like polymers at later stages of infection. This is the first study identifying a crucial role of phenol metabolism in internal defense of B. napus against V. longisporum and locating the crucial defense responses in the plant hypocotyl.


The role of evidence reports in evidence-based medicine: a mechanism for linking scientific evidence and practice improvement.
In this article two related questions are considered: (1) Why isn't evidence-based medicine (EBM) more consistently implemented? and (2) Using the EBM paradigm, by what mechanism can we link evidence reports to concrete practice improvement activities? To motivate a systematic analysis, answers to these questions are framed within the context of a general conceptual model for practice improvement, using as an example the application of this general model to the question of improving anticoagulation. The potential role of evidence reports is quite broad and to be most effective, they should (1) be considered as part of a comprehensive strategy for practice improvement and (2) be designed with their customers in mind. A system-based method for using the information from evidence reports involves ultimately suggesting specific practice improvement strategies in which the strategies are defined in terms of (1) a set of functional specifications and (2) a toolbox of implementation options. Such an approach brings to bear the specialized expertise and generalized fund of scientific knowledge used to produce the evidence report, but does so in a way that facilitates local tailoring. That is, while information synthesis should be global, implementation must be local.


A risk score to predict in-hospital mortality in patients with acute coronary syndrome at early medical contact: results from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.
A number of models have been built to evaluate risk in patients with acute coronary syndrome (ACS). However, accurate prediction of mortality at early medical contact is difficult. This study sought to develop and validate a risk score to predict in-hospital mortality among patients with ACS using variables available at early medical contact. A total of 62,546 unselected ACS patients from 150 tertiary hospitals who were admitted between 2014 and 2017 and enrolled in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, were randomly assigned (at a ratio of 7:3) to a training dataset (n=43,774) and a validation dataset (n=18,772). Based on the identified predictors which were available prior to any blood test, a new point-based risk score for in-hospital death, CCC-ACS score, was derived and validated. The CCC-ACS score was then compared with Global Registry of Acute Coronary Events (GRACE) risk score. The in-hospital mortality rate was 1.9% in both the training and validation datasets. The CCC-ACS score, a new point-based risk score, was developed to predict in-hospital mortality using 7 variables that were available before any blood test including age, systolic blood pressure, cardiac arrest, insulin-treated diabetes mellitus, history of heart failure, severe clinical conditions (acute heart failure or cardiogenic shock), and electrocardiographic ST-segment deviation. This new risk score had an area under the curve (AUC) of 0.84 (P=0.10 for Hosmer-Lemeshow goodness-of-fit test) in the training dataset and 0.85 (P=0.13 for Hosmer-Lemeshow goodness-of-fit test) in the validation dataset. The CCC-ACS score was comparable to the Global Registry of Acute Coronary Events (GRACE) score in the prediction of in-hospital death in the validation dataset. The newly developed CCC-ACS score, which utilizes factors that are acquirable at early medical contact, may be able to stratify the risk of in-hospital death in patients with ACS. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.


A Central Line Care Maintenance Bundle for the Prevention of Central Line-Associated Bloodstream Infection in Non-Intensive Care Unit Settings.
OBJECTIVE To evaluate a central line care maintenance bundle to reduce central line-associated bloodstream infection (CLABSI) in non-intensive care unit settings. DESIGN Before-after trial with 12-month follow-up period. SETTING A 1,250-bed teaching hospital. PARTICIPANTS Patients with central lines on 8 general medicine wards. Four wards received the intervention and 4 served as controls. INTERVENTION A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance. RESULTS Data were collected for 25,542 catheter-days including 43 CLABSI (rate, 1.68 per 1,000 catheter-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors but this was not statistically significant (95% CI, -5.3% to 0.4%). On control floors, there was a smaller but marginally significant decrease in CLABSI incidence during the study (change in monthly rate, -1.1%; 95% CI, -2.1% to -0.1%). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance before intervention vs 87.9% during intervention/follow-up; P<.001) but improvement was also observed on control wards (84.9% compliance before intervention vs 90.9% during intervention/follow-up; P=.001). CONCLUSIONS A multifaceted program to improve catheter care was associated with improvement in catheter dressing care but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non-intensive care unit patients. Infect Control Hosp Epidemiol 2016;37:692-698.


Transesophageal atrial pacing complications in patients suspected of tachy-brady syndrome.
The clinical effects of transesophageal atrial pacing (TAP) were assessed in 308 patients. Indications for TAP included evaluation for pacemaker implantation in patients suspected of sinus node dysfunction and determination of the suitable type of pacemaker. Most patients underwent program stimulation including rapid as well as burst stimulation. In one patient, following the study, cerebral arterial embolism occurred, most likely secondary to an induced arrhythmia. That was the only single case of permanent consequences following TAP. Additionally, one patient was accidentally stimulated in the ventricle using low voltage electric current that induced ventricular fibrillation. This was promptly reversed with defibrillation. Twenty-six patients in whom an arrhythmia was previously induced, required medical therapy, two of whom required cardioversion, and 24 required drug therapy, subsequent to clinical intolerance of the arrhythmia. No lethal complications occurred.


[Percutaneous electrical nerve stimulation of peripheral nerve for the intractable occipital neuralgia].
Occipital neuralgia is characterized by pain paroxysm occurring within distribution of the greater or lesser occipital nerves. The pain may radiates from the rear head toward the ipso-lateral frontal or retro-orbital regions of head. Though known causes include head injuries, direct occipital nerve trauma, neuroma formation or upper cervical root compression, most people have no demonstrable lesion. A sample of 8 patients (5 females, 3 males) aging 63,5 years on the average with occipital neuralgia has been recruited. The occipital neuralgic pain had presented since 4, 6 years and they had been treated by pharmacological therapy without benefit. Some result has been obtained by blocking of the grand occipital nerve so that the patients seemed to be suitable for subcutaneous peripheral neurostimulation. The pain was evaluated by VAS and SVR scales before treatment (TO) and after three and twelve months (T1, T2). During the follow up period 7 patients have been monitored for a whole year while one patient was followed only for 3 months in that some complications have presented. In the other 7 patients pain paroxysms have interrupted and trigger point disappeared with a VAS and SVR reduction of about 71% and 60%, respectively. Our experience demonstrates a sound efficacy of such a technique for patients having occipital neuralgia resistant to pharmacological therapies even if action mechanisms have not yet clearly explained. Some hypothesis exist and we think it might negatively affect the neurogenic inflammation that surely acts in pain maintaining.


[Karyotype of Nicotiana tabacum L. artificial haploids].
Twenty-five platelets obtained by culturing anthers of Nicotiana tabacum L. var. "Wisconsin 38" are haploids (22) or mixoploids (3). Numerous aneuhaploid cells were observed in 15 haploid plants (n = 18, 20, 22, 23, 25, 26, 28). Such a chromosomic variability careful caryological studies of haploid plants before these are used in genetic work.


Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue.
In this study, epididymal adipose tissue from male annexin 1 (ANXA1)-null and wild-type control mice were used to explore the potential role of ANXA1 in adipocyte biology. ANXA1 was detected by Western blot analysis in wild-type tissue and localized predominantly to the stromal-vascular compartment. Epididymal fat pad mass was reduced by ANXA1 gene deletion, but adipocyte size was unchanged, suggesting that ANXA1 is required for the maintenance of adipocyte and/or preadipocyte cell number. Epididymal tissue from wild-type mice responded in vitro to noradrenaline and isoprenaline with increased glycerol release, reduced IL-6 release, and increased cAMP accumulation. Qualitatively similar but significantly attenuated responses to the catecholamines were observed in tissue from ANXA1-null mice, an effect that was not associated with changes in beta-adrenoceptor mRNA expression. Lipopolysaccharide (LPS) also stimulated lipolysis in vitro, but its effects were muted by ANXA1 gene deletion. By contrast, LPS failed to influence IL-6 release from wild-type tissue but stimulated the release of the cytokine from tissue from ANXA1-null mice. ANXA1 gene deletion did not affect glucocorticoid receptor expression or the ability of dexamethasone to suppress catecholamine-induced lipolysis. It did, however, augment IL-6 expression and modify the inhibitory effects of glucocorticoids on IL-6 release. Collectively, these studies suggest that ANXA1 supports aspects of adipose tissue mass and alters the sensitivity of epididymal adipose tissue to catecholamines, glucocorticoids, and LPS, thereby modulating lipolysis and IL-6 release.


Patient activation and adherence to physical therapy in persons undergoing spine surgery.
Prospective longitudinal study. To determine the association between baseline patient activation and participation in postoperative physical therapy in a cohort of individuals after lumbar spine surgery. The Patient Activation Measure is a recently developed tool to assess patient activation. Patient activation is defined as an individual's propensity to engage in adaptive health behavior that may, in turn, lead to improved patient outcomes. It has not previously been used in spine research. We assessed baseline patient activation levels in individuals presenting for surgery of the lumbar spine via the Patient Activation Measure. Differences in patient characteristics across patient-activation quartiles were assessed using analysis of variance. After surgery, we assessed attendance (self-reported weekly) and engagement in physical therapy (at the last visit, using the Hopkins Rehabilitation Engagement Rating Scale) and determined the ratio of sessions attended to sessions prescribed. The influence of baseline patient activation, in the setting of other patient characteristics, to predict attendance and engagement with physical therapy was examined using linear regression methods. Scores on the Patient Activation Measure were positively correlated with participation (r = 0.53) and engagement (r = 0.75) in physical therapy. Individuals with low activation were more likely to report low self-efficacy for physical therapy, low hope, and external locus of control compared with those with high activation. Increased patient activation is associated with improved adherence with physical therapy as reflected in attendance and engagement.


CPD Aligned to Competency Standards to Support Quality Practice.
As medication experts, pharmacists are key members of the patient's healthcare team. Pharmacists must maintain their competence to practice to remain responsive to the increasingly complex healthcare sector. This paper seeks to determine how competence training for pharmacists may enhance quality in their professional development. Results of two separately administered surveys (2012 and 2013) were compared to examine the reported continued professional development (CPD) practices of Australian pharmacists. Examination of results from both studies enabled a focus on how the competency standards inform CPD practice.In the survey administered in 2012, 91% (n = 253/278) pharmacists reported that they knew their current registration requirements. However, in the survey administered in 2013, only 43% (n = 46/107) reported utilization of the National Competency Standards Framework for Pharmacists in Australia (NCS) to self-asses their practice as part of their annual re-registration requirements. Fewer, 23% (n = 25/107), used the NCS to plan their CPD. This may be symptomatic of poor familiarity with the NCS, uncertainty around undertaking self-directed learning as part of a structured learning plan and/or misunderstandings around what CPD should include. This is supported by thematic analysis of pharmacists' social media comments. Initial and ongoing competence training to support meaningful CPD requires urgent attention in Australia. The competence (knowledge, skills and attributes) required to engage in meaningful CPD practice should be introduced and developed prior to entry into practice; other countries may find they are in a similar position.


Diffusing alpha-emitters radiation therapy in combination with temozolomide or bevacizumab in human glioblastoma multiforme xenografts.
Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ doubled the cytotoxic effect of each of the treatments alone in U87 cultured cells. A colony formation assay demonstrated that the surviving fraction of U87 cells treated by TMZ in combination with alpha irradiation was lower than was achieved by alpha- or x-ray irradiation as monotherapies, or by x-ray combined with TMZ. The treatment of U87-bearing mice with DaRT and TMZ delayed tumor development more than the monotherapies. Unlike other radiation types, alpha radiation did not increase VEGF secretion from U87 cells in culture. BEV treatment introduced several days after DaRT implantation improved tumor control, compared to BEV or DaRT as monotherapies. The combination was also shown to be superior when starting BEV administration prior to DaRT implantation in large tumors relative to the seed size. BEV induced a decrease in CD31 staining under DaRT treatment, increased the diffusive spread of 224Ra progeny atoms in the tumor tissue, and decreased their clearance from the tumor through the blood. Taken together, the combinations of DaRT with standard-of-care chemotherapy or antiangiogenic therapy are promising approaches, which may improve the treatment of GBM patients.


Clinical significance of SPOCK2 expression signature for high-grade serous ovarian cancer patients.
Background: SPOCK2 is a member of the SPOCK family, a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. The purpose of this study was to explore expression profile of SPOCK2, and evaluate prognostic potential and its correlation with immune infiltration in high-grade serous ovarian cancer (HGSOC). Methods: Expression of SPOCK2 mRNA and protein between normal and tumor tissues were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Receiver operating characteristic (ROC) curve was used to evaluate diagnostic performance of SPOCK2. Kaplan-Meier method and Cox regression analysis were conducted to assess the effect of SPOCK2 on survival. Nomogram was used to predict the impact of SPOCK2 on prognosis. LinkedOmics were used to find correlated genes and perform functional enrichment analyses. The relationships between SPOCK2 and tumor infiltrating lymphocytes (TILs) were determined by tumor-immune system interaction database (TISIDB) and GSVA package (V1.34.0). Results: SPOCK2 was highly expressed in HGSOC tissue compared to normal tissue at both mRNA (p < 0.001) and protein (p = 0.03) levels. The area under the curve (AUC) is 0.894 (CI: 0.865-0.923). Kaplan-Meier analysis showed that HGSOC patients with high-level SPOCK2 mRNA expression had a worse overall survival (OS) than those with a low expression (HR = 1.45, p = 0.005). Univariate logistic regression analysis found that age, primary therapy outcome, tumor status, tumor residual, and SPOCK2 expression level were significantly associated with OS (p < 0.05). The nomogram model indicated an effective predictive performance of SPOCK2. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) term analyses showed that SPOCK2 were mainly involved in regulating extracellular matrix. Immune infiltration analysis showed that SPOCK2 may correlate with abundance of TILs. Conclusion: SPOCK2 has potentials to estimate diagnosis and prognosis for HGSOC and is involved in regulating extracellular matrix and immune cell infiltration.


[Endocrinopathies Associated with Immune Checkpoint Inhibitors].
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years, these drugs have been increasingly used in the treatment of many neoplasms in advanced stages. However, the change in the regulation of the immune system induced by these drugs has the potential adverse effect of inducing autoimmunity in practically all organ systems. Endocrinopathies are one of the most common autoimmune adverse eventsof these drugs. Non-systematic review of endocrinopathies reported in the context of treatment with ICIs. A search was carried out on PubMed until January 31st, 2020, and articles were selected based on their relevance and excluded in case of redundant content. The following search terms were used: "immune checkpoint inhibitor" and "endocrinopathy" / "endocrine system diseases" / "pituitary" / "thyroid" / "diabetes" / "adrenal" / "parathyroid". Endocrinopathies with all classes of ICIs (anti-CTLA-4, anti-PD-1, anti-PD-L1) have been reported. Thyroid dysfunction is the most frequently reported endocrinopathy, mainly with anti-PD-1 and anti-PD-L1. Hypophysitis is the most prevalent with anti-CTLA-4. The incidence of autoimmune diabetes in this context is increasing, mainly with anti-PD-1 and anti-PD-L1. Rare cases of primary adrenal insufficiency, Graves' disease and primary hypoparathyroidism have also been reported. Knowing the spectrum of endocrinopathies triggered by ICI, as well as their clinical features, diagnosis and treatment criteria is essential, given its high prevalence and the increasing number of cancer patients treated with these new drugs.


A new method for determination of postmortem interval: citrate content of bone.
Few accurate methods exist currently to determine the time since death (postmortem interval, PMI) of skeletonized human remains found at crime scenes. Citrate is present as a constituent of living human and animal cortical bone at very uniform initial concentration (2.0 ± 0.1 wt %). In skeletal remains found in open landscape settings (whether buried or not), the concentration of citrate remains constant for a period of about 4 weeks, after which it decreases linearly as a function of log(time). The upper limit of the dating range is about 100 years. The precision of determination decreases slightly with age. The rate of decrease appears to be independent of temperature or rainfall but drops to zero for storage temperature <0°C.


Cephalometric evaluation of the airway space and head posture in children with normal and atypical deglutition: correlations study.
Head posture has been related to pharyngeal space, especially in the syndrome of obstructive sleep apnea (OSA) in adults. However no studies were found that evaluated the possible correlation between head posture and pharyngeal airway space measured in children with atypical swallowing. The purpose of this study was to evaluate the possible correction between head posture and the measurement of pharyngeal space on radiographs of children who were in the period of mixed dentition who demonstrated atypical swallowing and in children with normal deglutition. A retrospective clinical study, using cephalometric analysis of lateral radiographs to obtain measures of the antero-posterior dimension of the pharyngeal airway space (PAS) and the angle formed between the base of the skull and the odontoid process (CC1) between two groups: the 55 radiographs experimental group (with atypical swallowing) and 55 radiographs of the control group (normal swallowing). The Spearman Coefficient of Correlation was used to evaluate the possible relationship between PAS and CC1 was used. Results indicated a positive correlation between measures of CC1 and PAS (r = 0357) only in the control group (normal swallowing). There is positive correlation between head posture and measure pharyngeal airway space (PAS) in the group of normal swallowing. This correlation was not observed in the experimental group (atypical swallowing).


Terrestrial mesopredators did not increase after top-predator removal in a large-scale experimental test of mesopredator release theory.
Removal or loss of top-predators has been predicted to cause cascading negative effects for ecosystems, including mesopredator release. However, reliable evidence for these processes in terrestrial systems has been mixed and equivocal due, in large part, to the systemic and continued use of low-inference study designs to investigate this issue. Even previous large-scale manipulative experiments of strong inferential value have been limited by experimental design features (i.e. failure to prevent migration between treatments) that constrain possible inferences about the presence or absence of mesopredator release effects. Here, we build on these previous strong-inference experiments and report the outcomes of additional large-scale manipulative experiments to eradicate Australian dingoes from two fenced areas where dingo migration was restricted and where theory would predict an increase in extant European red foxes, feral cats and goannas. We demonstrate the removal and suppression of dingoes to undetectable levels over 4-5 years with no corresponding increases in mesopredator relative abundances, which remained low and stable throughout the experiment at both sites. We further demonstrate widespread absence of negative relationships between predators, indicating that the mechanism underpinning predicted mesopredator releases was not present. Our results are consistent with all previous large-scale manipulative experiments and long-term mensurative studies which collectively demonstrate that (1) dingoes do not suppress red foxes, feral cats or goannas at the population level, (2) repeated, temporary suppression of dingoes in open systems does not create mesopredator release effects, and (3) removal and sustained suppression of dingoes to undetectable levels in closed systems does not create mesopredator release effects either. Our experiments add to similar reports from North America, Asia, Europe and southern Africa which indicate that not only is there a widespread absence of reliable evidence for these processes, but there is also a large and continually growing body of experimental evidence of absence for these processes in many terrestrial systems. We conclude that although sympatric predators may interact negatively with each other on smaller spatiotemporal scales, that these negative interactions do not always scale-up to the population level, nor are they always strong enough to create mesopredator suppression or release effects.


Concatameric cloning of porcine microRNA molecules after assembly PCR.
While the number of human or murine microRNAs (miRNAs) increases continuously, there are limited data available from other species. We report a novel identification method of small RNAs such as miRNAs, which allows simultaneous cloning of five RNA molecules within the same insert. First, RNA molecules <40nt were polyadenylated and five concatamerising 5' DNA adaptors were ligated to the molecules in independent reactions. Reverse transcription was carried out using oligo d(T)(18) primers with concatamerising 5' overhangs. The introduced complementary termini in the different reactions enabled the subsequent coupling of five purified antisense strands to one molecule by means of an assembly PCR. After cloning, small RNAs were identified by DNA sequencing. By means of this cloning approach, we identified 10 novel and one known porcine miRNAs. Furthermore, the endogenous expression of the cloned miRNAs was quantified in various tissues using a qRT-PCR approach.


Rapid cycling bipolar disorders in primary and tertiary care treated patients.
Rapid cycling (RC) affects 13-30% of bipolar patients. Most of the data regarding RC have been obtained in tertiary care research centers. Generalizability of these findings to primary care populations is thus questionable. We examined clinical and demographic factors associated with RC in both primary and tertiary care treated populations. Clinical data were obtained by interview from 240 bipolar I disorder (BDI) or bipolar II disorder (BDII) community-treated patients and by chart reviews from 119 bipolar patients treated at an outpatient clinic of a teaching hospital. Lifetime history of rapid cycling was present in 33.3% and 26.9% of patients from the primary and tertiary care samples, respectively. Among community-treated patients, lifetime history of RC was significantly associated with history of suicidal behavior and higher body mass index. There was a trend for association between RC and BDII, psychiatric comorbidity, diabetes mellitus, as well as lower age of onset of mania/hypomania. In the tertiary care treated sample there was a trend for association between lifetime history of RC and suicidal behavior. Tertiary versus primary care treated subjects with lifetime history of RC demonstrated markedly lower response to mood stabilizers. Lifetime history of RC is highly prevalent in both primary and tertiary settings. Even primary care treated subjects with lifetime history of RC seem to suffer from a more complicated and less treatment-responsive variant of bipolar disorder. Our findings further suggest relatively good generalizability of data from tertiary to primary care settings.


Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats.
This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24-27 months) Sprague-Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3-5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N-Methyl-d-Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network.


Immunochemical characterization of Amaranthus retroflexus pollen extract: extensive cross-reactive allergenic components among the four species of Amaranthaceae/Chenopodiaceae.
The importance of Amaranthus retroflexus pollen in causing respiratory allergy has been well ascertained in many countries including Iran with a high positive rate (69%) among Iranian allergic patients. The aim of the present study is to identify the allergenic properties of A. retroflexus pollen. Sixteen patients with allergy to A. retroflexus pollen were selected for the study. The antigenic and allergenic profiles of the A. retroflexus pollen extract as well as pollen extracts from other species of the Amaranthaceae/Chenopodiaceae family, including Chenopodium album, Kochia scoparia, and Salsola kali, were evaluated by ELISA, immunoblotting, and immunoblot inhibition assays. The resolved protein fractions on SDS-PAGE ranged from 10-85 kDa. Several allergenic components (MW 85, 45, 39, 18, 15, and 10 kDa) of the A. retroflexus pollen extract were recognized by using patients' sera by specific antibody of IgE class using ELISA and immunoblot assays. The IgE reactivity of the A. retroflexus pollen extract was partially inhibited by all three pollen extracts tested. The inhibition by the S. kali pollen extract was more than those by other pollen extracts. Moreover, the wheal diameters by the A. retroflexus pollen extract were highly correlated with those by C. album, K. scoparia and S. kali pollen extracts. In conclusion, three proteins with apparent MWs of 39, 45, and 66 kDa are suggested as the common allergenic components among the four pollens from the Amaranthaceae/Chenopodiaceae family. It appears that there are some common (similar) epitopes among the four common allergenic pollens.


Selection mechanisms underlying high impact biomedical research--a qualitative analysis and causal model.
Although scientific innovation has been a long-standing topic of interest for historians, philosophers and cognitive scientists, few studies in biomedical research have examined from researchers' perspectives how high impact publications are developed and why they are consistently produced by a small group of researchers. Our objective was therefore to interview a group of researchers with a track record of high impact publications to explore what mechanism they believe contribute to the generation of high impact publications. Researchers were located in universities all over the globe and interviews were conducted by phone. All interviews were transcribed using standard qualitative methods. A Grounded Theory approach was used to code each transcript, later aggregating concept and categories into overarching explanation model. The model was then translated into a System Dynamics mathematical model to represent its structure and behavior. Five emerging themes were found in our study. First, researchers used heuristics or rules of thumb that came naturally to them. Second, these heuristics were reinforced by positive feedback from their peers and mentors. Third, good communication skills allowed researchers to provide feedback to their peers, thus closing a positive feedback loop. Fourth, researchers exhibited a number of psychological attributes such as curiosity or open-mindedness that constantly motivated them, even when faced with discouraging situations. Fifth, the system is dominated by randomness and serendipity and is far from a linear and predictable environment. Some researchers, however, took advantage of this randomness by incorporating mechanisms that would allow them to benefit from random findings. The aggregation of these themes into a policy model represented the overall expected behavior of publications and their impact achieved by high impact researchers. The proposed selection mechanism provides insights that can be translated into research coaching programs as well as research policy models to optimize the introduction of high impact research at a broad scale among institutional and governmental agencies.


Pulmonary alveolar proteinosis in children: a case series.
Pulmonary alveolar proteinosis, (PAP) is a rare disease of unknown etiology, characterized by accumulation of intraalveolar proteinaceous material which is rich in lipid and positive on periodic acid-Schiff stain. Two clinically different pediatric types have been defined as congenital PAP which is fulminant and fatal, and a late-onset PAP which is similar to the adult form and less severe. Eight children with late-onset PAP were hospitalized from 1998 to 2005 in Mofid Children Hospital. Characteristics of these patients and the methods of diagnosis and treatment are presented in this case series.


The approach to heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize multimolecular complexes of platelet factor 4 (PF4) bound to heparin. HIT is an intense hypercoagulability state (increased thrombin generation in vivo) that is complicated more often by venous thromboembolism (deep vein thrombosis, pulmonary embolism) than by arterial thrombosis. HIT is a risk factor for coumarin-induced microthrombosis, particularly affecting acral regions of limbs with deep vein thrombosis (venous limb gangrene). Coumarins (e.g., warfarin) are therefore contraindicated during the acute (thrombocytopenic) phase of HIT. Venous thromboembolism can occur early during an episode of HIT, sometimes even before HIT-associated platelet count declines become clear. Recognition of HIT may be facilitated through the use of a clinical scoring system, the 4Ts ( Thrombocytopenia, Thrombosis, Timing, and o Ther explanations). Anti-PF4/polyanion enzyme-immunoassays (EIAs) and washed platelet activation assays readily detect HIT antibodies, and thus have high diagnostic sensitivity; however, only the platelet activation assays have high diagnostic specificity, suggesting that HIT is likely to be overdiagnosed in settings where EIAs are used exclusively for diagnosis. Treatment of HIT emphasizes substitution of heparin with an alternative nonheparin anticoagulant, such as a direct thrombin inhibitor (lepirudin, argatroban), or an indirect (antithrombin-mediated) inhibitor of factor Xa (danaparoid, fondaparinux?).


Sexual ornamentation reflects antibacterial activity of ejaculates in mallards.
Bacteria present in ejaculates can impair sperm function and reduce male reproductive success. Thus, selection should favour the evolution of antimicrobial defences to limit the detrimental effects of sperm-associated bacteria. Additionally, current hypotheses suggest that ornamental traits may signal information about the infection status of an individual or the ability of an individual to resist bacterial-induced sperm damage. However, despite the evolutionary implications of ejaculate antimicrobials, and the putative importance of pathogens for the evolution of male ornamentation, tests of these hypotheses are lacking. We examined the antibacterial activity of semen from mallard ducks (Anas platyrhynchos) and tested whether the bactericidal capacity of semen was associated with bill coloration, a sexually selected trait. We show that mallard semen exhibits significant antibacterial activity, as measured by the in vitro capacity to kill Escherichia coli and Staphylococcus aureus. Furthermore, we demonstrate that males with more colourful bills have semen with superior bacterial-killing ability. These results suggest that females could use male phenotypic traits to avoid sexually transmitted pathogens and acquire partners whose sperm suffer less bacteria-induced damage.


[Amputation as a treatment for complications on a traumatic dislocations of the knee. Case report].
Vascular lesion associated with knee dislocation represents a common and potentially devastating complication. A delay in revascularization that exceeds 8 hours can lead to amputation of the extremity. Therefore it is mandatory to do an immediate examination and an effective diagnosis to rule out this complication. A 19-year-old male was struck by a motor vehicle and caused traumatic dislocation of the left knee as observed on X-rays. The knee was reduced immediately. At 12 hours, the patient presented edema on the extremity and was then stabilized with external fixators. On the third day the patient developed a compartmental syndrome and artery obstruction, and required fasciotomies and revascularization of the popliteal artery. Twenty four hours later, again the artery was obstructed, conducing to supracondylar amputation. The purpose of this article is to show that a knee dislocation, with vascular complications, may lead to extremity amputation as a drastic treatment. It is important to emphasize that vigilance of vascular permeability has to be followed every 2-3 hours, for at least 72 hours after the injury, and assisted with Doppler study. And if needed, at the moment when a pulse abnormality is detected an arteriography study must be realized.


Reelin restricts dendritic growth of interneurons in the neocortex.
Reelin is a large secreted glycoprotein that regulates neuronal migration, lamination and establishment of dendritic architecture in the embryonic brain. Reelin expression switches postnatally from Cajal-Retzius cells to interneurons. However, reelin function in interneuron development is still poorly understood. Here, we have investigated the role of reelin in interneuron development in the postnatal neocortex. To preclude early cortical migration defects caused by reelin deficiency, we employed a conditional reelin knockout (RelncKO) mouse to induce postnatal reelin deficiency. Induced reelin deficiency caused dendritic hypertrophy in distal dendritic segments of neuropeptide Y-positive (NPY+) and calretinin-positive (Calr+) interneurons, and in proximal dendritic segments of parvalbumin-positive (Parv+) interneurons. Chronic recombinant Reelin treatment rescued dendritic hypertrophy in Relncko interneurons. Moreover, we provide evidence that RelncKO interneuron hypertrophy is due to presynaptic GABABR dysfunction. Thus, GABABRs in RelncKO interneurons were unable to block N-type (Cav2.2) Ca2+ channels that control neurotransmitter release. Consequently, the excessive Ca2+ influx through AMPA receptors, but not NMDA receptors, caused interneuron dendritic hypertrophy. These findings suggest that reelin acts as a 'stop-growth-signal' for postnatal interneuron maturation.


Diversity and population-genetic properties of copy number variations and multicopy genes in cattle.
The diversity and population genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analysed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, and Romagnola), sequenced to 11-fold coverage to identify 1,853 non-redundant CNV regions. Supported by high validation rates in array comparative genomic hybridization (CGH) and qPCR experiments, these CNV regions accounted for 3.1% (87.5 Mb) of the cattle reference genome, representing a significant increase over previous estimates of the area of the genome that is copy number variable (∼2%). Further population genetics and evolutionary genomics analyses based on these CNVs revealed the population structures of the cattle taurine and indicine breeds and uncovered potential diversely selected CNVs near important functional genes, including AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1 Additionally, 121 CNV gene regions were found to be either breed specific or differentially variable across breeds, such as RICTOR in dairy breeds and PNPLA3 in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, suggesting that subfunctionalization, neofunctionalization, or overdominance play roles in diversifying those fertility-related genes. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds and a basis for correlating structural variation with complex traits in the future.


Increased "default mode" activity in adolescents prenatally exposed to cocaine.
Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting-state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation.


Assessment of the photosensitive patient.
Photosensitivity is an abnormal cutaneous response to photosensitizing substances and sunlight or artificial light. Proper assessment of the photosensitive patient is important in defining photosensitive diseases and reactions.


Moderate alcohol consumption in pregnancy and subsequent left-handedness.
Alcohol in high doses is neurotoxic to the developing brain but it is not yet settled whether small doses give rise to more subtle effects. The aim of the study was to establish whether a moderate intake of alcohol in pregnancy would increase the frequency of left-handedness in the offspring. Such an association could indicate a possible subtle prenatal neurotoxic effect. This was a follow-up study of a group of pregnant women who took part in a community trial in 1984 to 1987. Data on alcohol consumption were reported by consecutively sampled pregnant women in the 36th week of gestation. Hand preference for their offspring was reported by the mothers in a self-administered questionnaire when their children were 5 to 9 years old. Ninety-one percent participated in the follow-up study. The study showed that 9.1% of the children were left-handed, with a higher prevalence among boys (11.8%). Results showed a slightly higher frequency of being left-handed among children exposed to alcohol in fetal life, but the findings were not statistically significant at a 0.05 level.


Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer.
Sox9 is a high-mobility-group domain-containing transcription factor required for chondrocyte differentiation and cartilage formation. We used a yeast two-hybrid method based on Son of Sevenless (SOS) recruitment to screen a chondrocyte cDNA library and found that the catalytic subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA-Calpha) interacted specifically with SOX9. Next we found that two consensus PKA phosphorylation sites within SOX9 could be phosphorylated by PKA in vitro and that SOX9 could be phosphorylated by PKA-Calpha in vivo. In COS-7 cells cotransfected with PKA-Calpha and SOX9 expression plasmids, PKA enhanced the phosphorylation of wild-type SOX9 but did not affect phosphorylation of a SOX9 protein in which the two PKA phosphorylation sites (S(64) and S(211)) were mutated. Using a phosphospecific antibody that specifically recognized SOX9 phosphorylated at serine 211, one of the two PKA phosphorylation sites, we demonstrated that addition of cAMP to chondrocytes strongly increased the phosphorylation of endogenous Sox9. In addition, immunohistochemistry of mouse embryo hind legs showed that Sox9 phosphorylated at serine 211 was principally localized in the prehypertrophic zone of the growth plate, corresponding to the major site of expression of the parathyroid hormone-related peptide (PTHrP) receptor. Since cAMP has previously been shown to effectively increase the mRNA levels of Col2a1 and other specific markers of chondrocyte differentiation in culture, we then asked whether PKA phosphorylation could modulate the activity of SOX9. Addition of 8-bromo-cAMP to chondrocytes in culture increased the activity of a transiently transfected SOX9-dependent 48-bp Col2a1 chondrocyte-specific enhancer; similarly, cotransfection of PKA-Calpha increased the activity of this enhancer. Mutations of the two PKA phosphorylation consensus sites of SOX9 markedly decreased the PKA-Calpha activation of this enhancer by SOX9. PKA phosphorylation and the mutations in the consensus PKA phosphorylation sites of SOX9 did not alter its nuclear localization. In vitro phosphorylation of SOX9 by PKA resulted in more efficient DNA binding. We conclude that SOX9 is a target of cAMP signaling and that phosphorylation of SOX9 by PKA enhances its transcriptional and DNA-binding activity. Because PTHrP signaling is mediated by cAMP, our results support the hypothesis that Sox9 is a target of PTHrP signaling in the growth plate and that the increased activity of Sox9 might mediate the effect of PTHrP in maintaining the cells as nonhypertrophic chondrocytes.


Suicidal attempts and stressful life events among women in a homeless situation in Madrid (Spain).
The objective of this article is to analyze the relationship between suffering from stressful life events (SLE) and subsequent suicidal behavior among women in a homeless situation, examining the differences in the number and characteristics of SLE experienced by attempters and nonattempters. The study was carried out based on the data obtained from a sample of women living homeless in Madrid (Spain; n = 138). The information was gathered using a structured interview. The results show that 46% of these women living homeless in Madrid had attempted suicide, and 32% of them had done so for the first time when they were homeless. We observed a high level of SLE among the women in a homeless situation, with a substantial increase in the number and severity of the stressors suffered by the interviewees who had attempted suicide, both during their childhood and adolescence and in their later lives. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Multiple pathways for repair of DNA double-strand breaks in mammalian chromosomes.
To study repair of DNA double-strand breaks (DSBs) in mammalian chromosomes, we designed DNA substrates containing a thymidine kinase (TK) gene disrupted by the 18-bp recognition site for yeast endonuclease I-SceI. Some substrates also contained a second defective TK gene sequence to serve as a genetic donor in recombinational repair. A genomic DSB was induced by introducing endonuclease I-SceI into cells containing a stably integrated DNA substrate. DSB repair was monitored by selection for TK-positive segregants. We observed that intrachromosomal DSB repair is accomplished with nearly equal efficiencies in either the presence or absence of a homologous donor sequence. DSB repair is achieved by nonhomologous end-joining or homologous recombination, but rarely by nonconservative single-strand annealing. Repair of a chromosomal DSB by homologous recombination occurs mainly by gene conversion and appears to require a donor sequence greater than a few hundred base pairs in length. Nonhomologous end-joining events typically involve loss of very few nucleotides, and some events are associated with gene amplification at the repaired locus. Additional studies revealed that precise religation of DNA ends with no other concomitant sequence alteration is a viable mode for repair of DSBs in a mammalian genome.


Evidence of lateral transmission of aggressive features between different types of breast cancer cells.
Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral heterogeneity and tumor cell plasticity importantly contribute to disease progression and treatment failure. However, the dynamic interactions between different tumor clones, as well as their contribution to tumor aggressiveness are still poorly understood. In this study, we provide evidence of a lateral transmission of aggressive features between aggressive and non-aggressive tumor cells, consisting of gain of expression of cancer stem cell markers, increased expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in response to CXCL12, which correlated with high levels of secretion of pro-inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2 by the aggressive cells. Noteworthy, we found no evidence of a TGF-β participation in the inducible-invasive phenotype. Altogether, our results provide evidence of communication between tumor cells with different potentials for aggressiveness, which could influence intra-tumoral population dynamics promoting the emergence of clones with novel functions. Understanding these interactions will provide better targets for diagnosis, prognosis and therapeutic strategies.


Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease.
Mitochondrial dysfunction has been implicated in multiple neurodegenerative diseases but remains largely unexplored in Creutzfeldt-Jakob disease. Here, we characterize the mitochondrial respiratory chain at the individual neuron level in the MM1 and VV2 common molecular subtypes of sporadic Creutzfeldt-Jakob disease. Moreover, we investigate the associations between the mitochondrial respiratory chain and neuropathological markers of the disease.Brain tissue from individuals with sporadic Creutzfeldt-Jakob disease and age-matched controls were obtained from the brain collection of the Austrian Creutzfeldt-Jakob Surveillance. The mitochondrial respiratory chain was studied through a dichotomous approach of immunoreactivities in the temporal cortex and the hippocampal subregions of CA4 and CA3.We show that profound deficiency of all mitochondrial respiratory complexes (I-V) occurs in neurons of the severely affected temporal cortex of patients with Creutzfeldt-Jakob disease. This deficiency correlates strongly with the severity of neuropathological changes, including vacuolation of the neuropil, gliosis and disease associated prion protein load. Respiratory chain deficiency is less pronounced in hippocampal CA4 and CA3 regions compared to the temporal cortex. In both areas respiratory chain deficiency shows a predilection for the MM1 molecular subtype of Creutzfeldt-Jakob disease.Our findings indicate that aberrant mitochondrial respiration could be involved early in the pathogenesis of sporadic Creutzfeldt-Jakob disease and contributes to neuronal death, most likely via ATP depletion. Based on these results, we propose that the restricted MRI diffusion profile seen in the brain of patients with sporadic Creutzfeldt-Jakob disease might reflect cytotoxic changes due to neuronal respiratory chain failure and ATP loss.


Studing cranial vault modifications in ancient Mesoamerica.
The artificial modification of infant cranial vaults through massages or by means of constriction and compression devices constitutes a readily visible, permanent body modification that has been employed cross-culturally to express identity, ethnicity, beauty, status and gender. For those ancient societies that staged head shaping, these cultural correlates may be ascertained by examining cranial shapes together with other data sets from the archaeological record. Studies of skulls modified for cultural reasons also provide important clues for understanding principles in neural growth and physiopathological variation in cranial expansion. This paper focuses on head shaping techniques in Mesoamerica, where the practice was deeply rooted and widespread before the European conquest. It provides a comprehensive review of the Mesoamericanistic research on shaping techniques, implements and taxonomies. An up-dated, interdisciplinary examination of the physiological implications and the cultural meanings of artificially produced head shapes in different times and culture areas within Mesoamerica leads to a discussion of the scope, caveats, and future directions involved in this kind of research in the region and beyond.


Clinical observations on 76 cluster headache cases.
76 cases of cluster headache are reviewed. Besides confirming established notions, the present study calls attention to the following points: (a) the peculiar behaviour of patients during the attacks does not appear explainable in simple terms of reaction to pain; (b) the occurrence of ECG abnormalities during the attacks in addition to bradycardia; (c) the well-known tendency of cluster headache attacks to recur at the same time of day, has in our cases a very high peak at 3 p.m., and (d) when the attacks occur in sleep hours, the time relationship with REM sleep stage is confirmed in our cases which have been recorded at night.


Service development of a nurse-led community-based PICC insertion service.
Patients receiving intravenous therapy require reliable venous access. Typically patients with poor peripheral access or requiring long-term treatment from an outpatient antibiotic therapy (OPAT) service need to receive secondary care input for safe central line placement, and radiological confirmation of the correct line tip placement where necessary, if treatment is to proceed as planned. Technological developments that enable accurate ultrasound-guided vein selection and electrocardiograph (ECG)-guided central line tip placement have eliminated the need for radiological or fluoroscopic confirmation of correct tip placement for peripherally placed central catheters (PICCs). This article outlines the development of an out-of-hospital nurse-led PICC insertion service using the Sherlock 3CG® Tip Confirmation System (C.R Bard) to meet the needs of patients requiring long-term intravenous treatment from an OPAT service, and its impact on reducing treatment delays and the need for secondary care intervention.


Effects of handedness & saccadic bilateral eye movements on the specificity of past autobiographical memory & episodic future thinking.
The present research investigated the effects of personal handedness and saccadic eye movements on the specificity of past autobiographical memory and episodic future thinking. Handedness and saccadic eye movements have been hypothesised to share a common functional basis in that both influence cognition through hemispheric interaction. The technique used to elicit autobiographical memory and episodic future thought involved a cued sentence completion procedure that allowed for the production of memories spanning the highly specific to the very general. Experiment 1 found that mixed-handed (vs. right handed) individuals generated more specific past autobiographical memories, but equivalent numbers of specific future predictions. Experiment 2 demonstrated that following 30s of bilateral (horizontal) saccades, more specific cognitions about both the past and future were generated. These findings extend previous research by showing that more distinct and episodic-like information pertaining to the self can be elicited by either mixed-handedness or eye movements. The results are discussed in relation to hemispheric interaction and top-down influences in the control of memory retrieval.


Occupational brain cancer risks in Umbria (Italy), with a particular focus on steel foundry workers.
As a part of the Occupational Cancer Monitoring (OCCAM) project, a routine analysis based on Umbria region cancer registry (RTUP) database in 2002-2008 was performed. Among other results, the incidental finding of brain cancer increased risk in steel foundry workers in Terni province (Italy), lead us to deepen the analysis, focusing on this specific industrial sector. A monitoring study, based on Umbria Regional Cancer Registry data, was recently carried out. Brain cancer cases and controls identified within this preliminary study were selected. Therefore, we considered all incident cases (in Umbria region 2002-2008) of brain cancer occurred among workers occupied for at least one year in private companies since 1974 and controls randomly sampled from the same population. Afterwards, taking in to account results from steel foundry in Terni province, we further deepened our analysis, focusing on this productive sector. Odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple logistic regression models, adjusted by age at diagnosis or sampling, sex and province of residence, when appropriate. Statistical analyses were carried out on 14913 subjects, 56 cases and 14857 controls. Significantly increased ORs were observed for garment, mechanical manufacturing and chemical industries. Moreover, the risk estimates were strongly correlated with exposures in iron and steel foundries and a cluster of 14 cases in the same foundry in Terni was observed (OR 9.59, 90% CI 2.76-33.34). Results of this explorative study showed increased ORs of brain cancer in some productive branches, involving possible exposures to chemical compounds and/or solvents. Moreover, our results pointed out a significantly increased risk in Terni foundry workers, determining an interesting brain cancer cluster (14 cases). Further studies on this industrial sector are needed with improved definitions of tasks and exposures.


Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer.
Cancer genomic DNA sequences enable identification of all mutations and suggest targets for precision medicine. The identities and patterns of the mutations themselves also provide critical information for deducing the originating DNA damaging agents, causal molecular mechanisms, and thus additional therapeutic targets. A classic example is ultraviolet light, which crosslinks adjacent pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine deaminase APOBEC3B, which was identified recently as a source of DNA damage and mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser extents additional cancer types. This enzyme is normally an effector protein in the innate immune response to virus infection but upregulation in these cancer types causes elevated levels of genomic C-to-U deamination events, which manifest as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide contexts (preferentially 5'-TCA and 5'-TCG). Genomic C-to-U deamination events within the same trinucleotide contexts also lead to cytosine mutation clusters (kataegis), and may precipitate visible chromosomal aberrations such as translocations. Clinical studies indicate that APOBEC3B upregulation correlates with poorer outcomes for estrogen receptor-positive breast cancer patients, including shorter durations of disease-free survival and overall survival after surgery. APOBEC3B may therefore have both diagnostic and prognostic potential. APOBEC3B may also be a candidate for therapeutic targeting because inhibition of this non-essential enzyme is predicted to decrease tumor mutation rates and diminish the likelihood of undesirable mutation-dependent outcomes such as recurrence, metastasis, and the development of therapy resistant tumors.


A short history of data banking in the United States from 1974 to 2003.
There have been 4 major longitudinal data banking efforts within the United States: ARAMIS, the Western Consortium, and the individual data banks of Drs. Ted Pincus and Fred Wolfe. ARAMIS began in the 1970s, and helped to develop the language and methodology of rheumatology data banks using biannual surveys. The National Data Bank for Rheumatic Diseases used the ARAMIS model beginning in the late 1990s to form a very large contemporary rheumatology data bank. Hybrid models using both survey data and clinical data were put into practice by Pincus and Wolfe, and by Paulus at the Western Consortium.


Superficial zone protein affects boundary lubrication on the surface of mandibular condylar cartilage.
We examined the localization and boundary lubricating function of superficial zone protein (SZP) on the surface of mandibular condylar cartilage. Chondrocytes were separated from the surface layer of mandibular condylar cartilage of 6- to 9-month-old female pigs. A cyclic tensile strain of 7% or 21% cell elongation was applied to the cultured chondrocytes. Gene expression levels of cartilage matrix proteins and secretory phospholipase A(2) (sPLA(2)) were quantified by real-time polymerase chain reaction analysis. The friction coefficient of the mandibular condylar surface was measured by a friction tester before and after treatment with 0.1 U/ml sPLA(2). Significantly higher mRNA levels of SZP and type I collagen were found in chondrocytes from the superficial layer than in those in the other layers. The SZP mRNA level was up-regulated by cyclic tensile strain of 7% and 21% cell elongation. Cyclic tensile strain of 21% cell elongation up-regulated the sPLA(2) mRNA level. The friction coefficient of the condylar surface was increased significantly by treatment with sPLA(2). The removal of SZP from the surface layer of mandibular condylar cartilage by sPLA(2) resulted in a significant increase in the friction coefficient on the surface of articular cartilage.


Disparities in digital reporting of illness: A demographic and socioeconomic assessment.
Although digital reports of disease are currently used by public health officials for disease surveillance and decision making, little is known about environmental factors and compositional characteristics that may influence reporting patterns. The objective of this study is to quantify the association between climate, demographic and socio-economic factors on digital reporting of disease at the US county level. We reference approximately 1.5 million foodservice business reviews between 2004 and 2014, and use census data, machine learning methods and regression models to assess whether digital reporting of disease is associated with climate, socio-economic and demographic factors. The results show that reviews of foodservice businesses and digital reports of foodborne illness follow a clear seasonal pattern with higher reporting observed in the summer, when most foodborne outbreaks are reported and to a lesser extent in the winter months. Additionally, factors typically associated with affluence (such as, higher median income and fraction of the population with a bachelor's degrees) were positively correlated with foodborne illness reports. However, restaurants per capita and education were the most significant predictors of illness reporting at the US county level. These results suggest that well-known health disparities might also be reflected in the online environment. Although this is an observational study, it is an important step in understanding disparities in the online public health environment.


Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosis.
Survivin, an inhibitor of apoptosis, is over-expressed in foetal tissues and human cancers, but it is almost undetectable in normal tissues. Here we have assessed the level of the survivin protein in some benign tumors of the nervous system: meningioma, schwannoma, low-grade ependymoma, pilocytic astrocytoma and pituitary adenoma. Using immuno-blot analysis we present evidence that these low-grade tumors are positive for survivin expression. In agreement, flow cytometrical analysis showed that both spontaneous and radiation-induced apoptosis levels are very low in these neoplasms. Using host cell reactivation assay we have also shown that these tumor cells are proficient in the repair of gamma-ray-induced DNA damage. However, they are deficient in the removal of ultraviolet (UV) light-induced DNA photolesions, especially the shwannoma- and the pituitary adenoma-derived cells. These results suggest that survivin overexpression may be an early event in the stepwise tumoregenesis and hence could be responsible for the onset as well as the growth advantage during tumoregenic progression of malignant as well as benign neoplasms.