Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder project.
Up to 70% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) experience sleep problems including difficulties initiating and maintaining sleep. Sleep problems in children with ADHD can result in poorer child functioning, impacting on school attendance, daily functioning and behaviour, as well as parental mental health and work attendance. The Sleeping Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep program in treating sleep problems experienced by children with ADHD. We have demonstrated the feasibility and the acceptability of this treatment program in a pilot study. This randomised controlled trial (RCT) is being conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate to severe sleep problems. Children are recruited from public and private paediatric practices across the state of Victoria, Australia. Upon receiving informed written consent, families are randomised to receive either the behavioural sleep intervention or usual care. The intervention consists of two individual, face-to-face consultations and a follow-up phone call with a trained clinician (trainee consultant paediatrician or psychologist), focusing on the assessment and management of child sleep problems. The primary outcome is parent- and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are child sleep (actigraphy and parent report), behaviour, daily functioning, school attendance and working memory, as well as parent mental health and work attendance. We are also assessing the impact of children's psychiatric comorbidity (measured using a structured diagnostic interview) on treatment outcome. To our knowledge, this is the first RCT of a behavioural intervention aiming to treat sleep problems in children with ADHD. If effective, this program will provide a feasible non-pharmacological and acceptable intervention improving child sleep and ADHD symptoms in this patient group. Current Controlled Trials ISRCTN68819261. ISRCTN: ISRCTN68819261.


The coding and noncoding transcriptome of Neurospora crassa.
Long non protein coding RNAs (lncRNAs) have been identified in many different organisms and cell types. Emerging examples emphasize the biological importance of these RNA species but their regulation and functions remain poorly understood. In the filamentous fungus Neurospora crassa, the annotation and characterization of lncRNAs is incomplete. We have performed a comprehensive transcriptome analysis of Neurospora crassa by using ChIP-seq, RNA-seq and polysome fractionation datasets. We have annotated and characterized 1478 long intergenic noncoding RNAs (lincRNAs) and 1056 natural antisense transcripts, indicating that 20% of the RNA Polymerase II transcripts of Neurospora are not coding for protein. Both classes of lncRNAs accumulate at lower levels than protein-coding mRNAs and they are considerably shorter. Our analysis showed that the vast majority of lincRNAs and antisense transcripts do not contain introns and carry less H3K4me2 modifications than similarly expressed protein coding genes. In contrast, H3K27me3 modifications inversely correlate with transcription of protein coding and lincRNA genes. We show furthermore most lincRNA sequences evolve rapidly, even between phylogenetically close species. Our transcriptome analyses revealed distinct features of Neurospora lincRNAs and antisense transcripts in comparison to mRNAs and showed that the prevalence of noncoding transcripts in this organism is higher than previously anticipated. The study provides a broad repertoire and a resource for further studies of lncRNAs.


Defining the cognitive enhancing properties of video games: Steps Towards Standardization and Translation.
Ever since video games were available to the general public, they have intrigued brain researchers for many reasons. There is an enormous amount of diversity in the video game research, ranging from types of video games used, the amount of time spent playing video games, the definition of video gamer versus non-gamer to the results obtained after playing video games. In this paper, our goal is to provide a critical discussion of these issues, along with some steps towards generalization using the discussion of an article published by Clemenson and Stark (2005) as the starting point. The authors used a distinction between 2D versus 3D video games to compare their effects on the learning and memory in humans. The primary hypothesis of the authors is that the exploration of virtual environments while playing video games is a human correlate of environment enrichment. Authors found that video gamers performed better than the non-video gamers, and if non-gamers are trained on playing video gamers, 3D games provide better environment enrichment compared to 2D video games, as indicated by better memory scores. The end goal of standardization in video games is to be able to translate the field so that the results can be used for greater good.


[Lipid evaluation in cerebral infarction in its early phase and in the 4th month. Practical consequences].
Plasma lipid values studied in 30 subjects with stroke at days 1, 2 and 4 of the early phase indicated a significant decrease in total cholesterol, HDL-cholesterol and apolipoprotein A1 from day 1 to 4. However, there was no significant difference between values at day 1 and during the 4th month of convalescence. Since some patients admitted to hospital are never followed up later in a hospital environment, it would seem advisable, for practical purposes, to perform plasma lipid analysis on the first day of admission.


AFLP: a new technique for DNA fingerprinting.
A novel DNA fingerprinting technique called AFLP is described. The AFLP technique is based on the selective PCR amplification of restriction fragments from a total digest of genomic DNA. The technique involves three steps: (i) restriction of the DNA and ligation of oligonucleotide adapters, (ii) selective amplification of sets of restriction fragments, and (iii) gel analysis of the amplified fragments. PCR amplification of restriction fragments is achieved by using the adapter and restriction site sequence as target sites for primer annealing. The selective amplification is achieved by the use of primers that extend into the restriction fragments, amplifying only those fragments in which the primer extensions match the nucleotides flanking the restriction sites. Using this method, sets of restriction fragments may be visualized by PCR without knowledge of nucleotide sequence. The method allows the specific co-amplification of high numbers of restriction fragments. The number of fragments that can be analyzed simultaneously, however, is dependent on the resolution of the detection system. Typically 50-100 restriction fragments are amplified and detected on denaturing polyacrylamide gels. The AFLP technique provides a novel and very powerful DNA fingerprinting technique for DNAs of any origin or complexity.


Mapping of contextual modulation in the population response of primary visual cortex.
We review the evidence of long-range contextual modulation in V1. Populations of neurons in V1 are activated by a wide variety of stimuli outside of their classical receptive fields (RF), well beyond their surround region. These effects generally involve extra-RF features with an orientation component. The population mapping of orientation preferences to the upper layers of V1 is well understood, as far as the classical RF properties are concerned, and involves organization into pinwheel-like structures. We introduce a novel hypothesis regarding the organization of V1's contextual response. We show that RF and extra-RF orientation preferences are mapped in related ways. Orientation pinwheels are the foci of both types of features. The mapping of contextual features onto the orientation pinwheel has a form that recapitulates the organization of the visual field: an iso-orientation patch within the pinwheel also responds to extra-RF stimuli of the same orientation. We hypothesize that the same form of mapping applies to other stimulus properties that are mapped out in V1, such as colour and contrast selectivity. A specific consequence is that fovea-like properties will be mapped in a systematic way to orientation pinwheels. We review the evidence that cytochrome oxidase blobs comprise the foci of this contextual remapping for colour and low contrasts. Neurodynamics and motion in the visual field are argued to play an important role in the shaping and maintenance of this type of mapping in V1.


Crystalline films of interdigitated structures formed via amidinium-carboxylate interactions at the air-water interface.
Electrostatic interactions between amidinium and carboxylates were used for the construction of interdigitated architectures at the air-solution interface. Spreading the water-insoluble amphiphile p-pentadecylbenzoic acid (A) on an aqueous solution of p-methylbenzamidinium (B) ions results in an intercalation of the water-soluble base between the acidic headgroups of the water-insoluble amphiphile to form an amorphousA-B-A-B monolayer according to grazing incidence X-ray diffraction (GIXD) and X-ray reflectivity measurements. Upon compression the monolayer transforms into a crystalline film composed of three bilayers with interdigitated hydrocarbon chains, and a top layer whose chains are disordered. Water-insoluble p-heptadecylbenzamidinium spread on an aqueous solution of benzoic acid displays a surface pressure-area isotherm similar to that obtained from the above system. A mechanism that accounts for the formation of these films is presented. Deposition of p-heptadecylbenzamidinium and p-pentadecylbenzoic acid amphiphiles in a 1:1 ratio on pure water led to the formation of a crystalline monolayer phase but which is partially disordered. Over an aqueous solution containing a 1:1 mixture of benzamidinium and benzoic acid no measurable binding of these solute molecules to the polar headgroups of the 1:1 mixed monolayer could be detected by X-ray reflectivity or GIXD.


Gene-specific selection against experimental fanconi anemia gene inactivation in human cancer.
The Fanconi anemia (FA) gene family comprises at least 12 genes interacting in a common pathway involved in DNA repair. To gain insight into the role of FA gene inactivation occurring in tumors among the general population, we endogenously targeted in cancer cells four FA genes that act at different stages of the FA pathway. After successful mono-allelic deletion of all genes, the sequential homozygous deletion was achieved only for FANCC and FANCG, acting upstream, but not for BRCA2 or FANCD2, acting downstream in the FA pathway. Targeting of the second allele in in BRCA2 and FANCD2 heterozygote clones resulted in redeletion exclusively of the already defective allele in multiple instances (13x concerning BRCA2, 25x concerning FANCD2), strongly suggesting a detrimental phenotype. Unlike complete FANCD2 disruption, the mere reduction of FANCD2 protein levels had no discernible effect. In addition, we confirmed that human cancer cells harboring the Seckel ATR mutation display impaired FANCD2 monoubiquitination and FANCD2 nuclear focus formation, as well as an increased sensitivity to DNA interstrand-crosslinking agents. Nevertheless, these cells were viable, indicating an ATR-independent function of FANCD2, distinct from its major known functions, to be responsible for the detrimental effects of FANCD2 loss. In conclusion, we established the downstream FA genes FANCD2 and BRCA2 to represent particularly vulnerable parts of the FA pathway, providing direct evidence for the paradoxical assumption that their inactivation could be predominantly selected against in cancer cells. This would explain why certain FA gene defects, despite an apparent selection for FA pathway inactivation in cancer, are rarely observed in tumors among the general population.


The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.
Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity among residents of malaria endemic areas indicate that memory responses to Plasmodium Ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. In contrast, multiple exposures to radiation-attenuated Plasmodium berghei sporozoites (Pb γ-spz) induce long-lasting protective immunity to experimental sporozoite challenge. We previously demonstrated that sterile protection induced by Pb γ-spz is MHC class I-dependent and CD8 T cells are the key effectors. IFN-γ(+) CD8 T cells that arise in Pb γ-spz-immunized B6 mice are found predominantly in the liver and are sensitive to levels of liver-stage Ag depot and they express CD44(hi)CD62L(lo) markers indicative of effector/effector memory phenotype. The developmentally related central memory CD8 T (TCM) cells express elevated levels of CD122 (IL-15Rβ), which suggests that CD8 TCM cells depend on IL-15 for maintenance. Using IL-15-deficient mice, we demonstrate in this study that although protective immunity is inducible in these mice, protection is short-lived, mainly owing to the inability of CD8 TCM cells to survive in the IL-15-deficient milieu. We present a hypothesis consistent with a model whereby intrahepatic CD8 TCM cells, being maintained by IL-15-mediated survival and basal proliferation, are conscripted into the CD8 effector/effector memory T cell pool during subsequent infections.


Outcomes and complications of radiation therapy in patients with familial adenomatous polyposis.
The outcomes, complications, and rates of secondary malignancies from radiation therapy (RT) are not known for patients with familial adenomatous polyposis (FAP). We queried the Hereditary Gastrointestinal Cancer Registry (HGCR) for patients with FAP who received RT. Outcomes assessed included acute and late treatment toxicity and secondary malignancies. We identified 15 patients undergoing 18 treatment courses. Median follow-up was 3.1 years after RT. Treated sites included rectal cancer, desmoid, prostate cancer, breast cancer, melanoma, medulloblastoma, gastric cancer, and glioma. Secondary tumors occurred in two patients: a medulloblastoma was diagnosed in a patient treated for glioma, and a desmoid tumor was diagnosed in a patient treated for rectal cancer. All nine patients treated with intra-abdominal or pelvic RT had prior prophylactic proctocolectomies, yet only one patient experienced grade 3 gastrointestinal toxicity. Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) toxicities were grade 1 in seven treatment courses (39%), grade 2 in five courses (28%), and grade 3 in two courses (11%). In this cohort, RT was well tolerated with adverse effects comparable with non-FAP patients. Secondary in-field tumors occurred in 2 of 15 patients and their increased risk in this cohort was likely due to prior predilection from FAP itself, although an increased role of RT cannot be ruled out.


Graphene-based 2D constructs for enhanced fibroblast support.
Complex skin wounds have always been a significant health and economic problem worldwide due to their elusive and sometimes poor or non-healing conditions. If not well-treated, such wounds may lead to amputation, infections, cancer, or even death. Thus, there is a need to efficiently generate multifunctional skin grafts that address a wide range of skin conditions, including non-healing wounds, and enable the regeneration of new skin tissue. Here, we propose studying pristine graphene and two of its oxygen-functionalized derivatives-high and low-oxygen graphene films-as potential substrates for skin cell proliferation and differentiation. Using BJ cells (human foreskin-derived fibroblasts) to represent basic skin cells, we show that the changes in surface properties of pristine graphene due to oxygen functionalization do not seem to statistically impact the normal proliferation and maturation of skin cells. Our results indicate that the pristine and oxidized graphenes presented relatively low cytotoxicity to BJ fibroblasts and, in fact, support their growth and bioactivity. Therefore, these graphene films could potentially be integrated into more complex skin regenerative systems to support skin regeneration. Because graphene's surface can be relatively easily functionalized with various chemical groups, this finding presents a major opportunity for the development of various composite materials that can act as active components in regenerative applications such as skin regeneration.


[Three hypotonic neonates with hypertrophic cardiomyopathy: Pompe's disease].
Three neonatal patients, one girl and two boys, presented with infantile Pompe's disease. A generalized hypotonia with decreased tendon reflexes and heart failure due to hypertrophic cardiomyopathy dominated the clinical picture in all three; these symptoms are uniformly and characteristically present. This autosomal recessive glycogen storage disease is caused by a deficiency of lysosomal alpha-glucosidase. The diagnosis, suspected on the basis of the characteristic clinical picture and the results of simple laboratory tests, is made by measurement of the enzymatic activity or DNA analysis. Most patients die in their first year of life, no treatment being available.


Postoperative periclavicular radiotherapy in breast cancer patients with 1-3 positive axillary lymph nodes. Outcome and morbidity.
The goal of this work was to examine the possible influence of periclavicular irradiation on outcome of breast cancer patients with 1-3 positive lymph nodes with special emphasis on late toxicity rates. Between 1997 and 2000, 235 breast cancer patients (T1-2, 1-3 involved lymph nodes) were treated at our department following breast conservative surgery: 139 patients (59.1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not (noPCLNI). Patients were re-examined or contacted by phone with regard to treatment-related late effects. After a median follow-up of 78 months (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4 periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group. We could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with or without periclavicular lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation.


Role of the nurse in thrombolytic therapy.
The introduction of thrombolytic therapy has led to significant changes in the management of patients with myocardial infarction. This article reviews the current literature and discusses the role of the nurse and the implications for practice.


Hearing loss as a predictor for hearing protection attenuation among miners.
This study investigated risk factors for poor earplug fit, with a focus on the association between hearing loss and personal attenuation ratings (PARs). Earplug fit was assessed by obtaining PARs using a real ear at attenuation threshold (REAT) system. Hearing loss was assessed using the unoccluded hearing thresholds measured during the REAT testing and the results of a speech-in-noise test. Potential predictors of PARs were modelled using both simple and multiple linear regression. Hearing loss was the primary predictor of interest. Data were collected from 200 workers at ten above-ground mining sites in the Midwestern USA. Workers reported wearing their hearing protection on average 73.9% of the time in a high noise environment (mean 8-hour time-weighted average noise exposure 85.5 dBA, range 65-103 dBA). One-quarter (26.7%) of workers were found to have a hearing loss (hearing threshold ≥25 dB across 1-4 kHz), and 42% reported symptoms of tinnitus. Workers with a hearing loss had a significantly lower PAR than those without a hearing loss (β=-5.1, SE=1.7). The results of the adjusted regression models suggest that workers with hearing loss achieved significantly lower PARs than those without hearing loss. This association between hearing loss and hearing protection devices (HPD) fit brings into focus the potential benefit of fit checks to be included in hearing conservation programmes. Workers found to have hearing loss should be prioritised for fit testing, as their hearing impairment may be associated with poor HPD fit.


MIrExpress: A Database for Gene Coexpression Correlation in Immune Cells Based on Mutual Information and Pearson Correlation.
Most current gene coexpression databases support the analysis for linear correlation of gene pairs, but not nonlinear correlation of them, which hinders precisely evaluating the gene-gene coexpression strengths. Here, we report a new database, MIrExpress, which takes advantage of the information theory, as well as the Pearson linear correlation method, to measure the linear correlation, nonlinear correlation, and their hybrid of cell-specific gene coexpressions in immune cells. For a given gene pair or probe set pair input by web users, both mutual information (MI) and Pearson correlation coefficient (r) are calculated, and several corresponding values are reported to reflect their coexpression correlation nature, including MI and r values, their respective rank orderings, their rank comparison, and their hybrid correlation value. Furthermore, for a given gene, the top 10 most relevant genes to it are displayed with the MI, r, or their hybrid perspective, respectively. Currently, the database totally includes 16 human cell groups, involving 20,283 human genes. The expression data and the calculated correlation results from the database are interactively accessible on the web page and can be implemented for other related applications and researches.


Emergency Department Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Many Patients Have No Identifiable Risk Factor and Discordant Empiric Therapy Is Common.
Community-onset urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, which are resistant to ceftriaxone and usually coresistant to fluoroquinolones, are increasing worldwide. We investigate and describe in detail UTIs caused by ESBL-producing Enterobacteriaceae in our emergency department (ED), and determine the proportion that occurred in patients without health care-associated risk factors and who received discordant initial antibiotic therapy. At an urban public hospital in Northern California, microbiology staff prospectively reviewed ED urine culture results weekly for 1 year and presumptively identified ESBL-producing isolates by ceftriaxone plus ceftazidime resistance. For isolates associated with a clinical UTI, patient demographic and case clinical features were abstracted retrospectively. Health care-associated infections were defined by standard risk factors plus aged 65 years or older, bladder catheter, urologic procedure, functional dependence, or antibiotics in the previous 90 days. Community-associated infections were defined by absence of these. A subset of community-associated ESBL-producing Escherichia coli isolates underwent genotyping. Electronic health record query was used to determine the denominator of ED UTI patients who underwent urine culture during the study period. Between August 2016 and July 2017, there were 1,045 unique ED patients diagnosed with a UTI, whose specimens underwent culture. There were 62 ESBL-producing isolates (5.9%; 95% confidence interval [CI] 4.6% to 7.5%). Selected characteristics of the entire ESBL UTI cohort were median age 50 years, 37 (60%) patients were women, 28 (44%) Hispanic, 11 (18%) had been hospitalized in the previous 3 months, 19 (31%) had pyelonephritis, 49 (79%) of isolates were E coli, 44 (71%) were levofloxacin-resistant, and 24 (23%) nitrofurantoin-resistant. Initial antibiotic choice was discordant with isolate susceptibility in 26 of 56 cases (46%; 95% CI 33% to 60%), and the initial oral antibiotic prescred was discordant in 19 of 41 cases (46%; 95% CI 31% to 63%). Twenty-seven infections (44%; 95% CI 31% to 57%) were categorized as community-associated. Eight patients with community-associated infection were women younger than 50 years, with no comorbidities and no more than 1 UTI in the previous year. Of 12 community-associated E coli isolates tested, all were confirmed to harbor ESBL genes; the CTX-M1 β-lactamase gene was found in 8 (67%); 4 belong to genotype ST131. At this single Northern California ED, greater than 5% of culture-proven UTI were caused by ESBL-producing Enterobacteriaceae, and in nearly half of cases there was no identifiable health care-associated risk factor. Levofloxacin co-resistance and discordant antibiotic therapy were common.


Each degree of glucose intolerance in pregnancy predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum.
Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes mellitus (T2DM) that is proportional to the severity of antepartum dysglycemia (i.e., highest in women with gestational diabetes mellitus [GDM], followed by those with milder dysglycemia). However, the pathophysiologic changes driving this risk are not known. Thus, we evaluated the longitudinal changes in β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum after gestational dysglycemia. A total of 337 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at 3 months, 1 year, and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (GIGT; n = 60); abnormal GCT, followed by normal glucose tolerance (NGT) on the OGTT (abnormal GCT NGT; n = 96); and normal GCT with NGT (n = 76). At each of 3 months, 1 year, and 3 years postpartum, the prevalence of glucose intolerance increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P < 0.001), whereas β-cell function, assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2), and insulin sensitivity (Matsuda index), progressively decreased across the groups (all P < 0.002). Each group predicted distinct trajectories of ISSI-2, Matsuda index, and fasting and 2-h glucose (all P < 0.001). Notably, GDM, GIGT, and abnormal GCT NGT predicted varying rates of declining β-cell function and insulin sensitivity, as well as rising glycemia, compared with normal GCT NGT. Each degree of gestational glucose intolerance predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum that drive their differential risk of future T2DM.


Cutting balloon angioplasty versus standard balloon angioplasty for failing infra-inguinal vein grafts: comparative study of short- and mid-term primary patency rates.
To evaluate the results of a recent change in practice in our institution using cutting balloon angioplasty instead of standard balloon angioplasty as the primary treatment for failing infra-inguinal vein bypass grafts. In this nonrandomized cohort study with a historical control, failing infra-inguinal vein grafts were identified at duplex surveillance or clinical examination. Patients had confirmatory arteriography and balloon angioplasty at the same attendance. Interventions proximal or distal to the graft itself and prosthetic grafts were not included. Patients were entered into a duplex graft surveillance program. Initial assessment of technical success was duplex or improvement 4-6 weeks after the primary angioplasty. Twenty-seven consecutive patients were treated with standard balloon angioplasty, then 11 consecutive patients were treated with cutting balloon angioplasty. Initial technical success was 74% for the standard balloon versus 82% for the cutting balloon. The primary patency rate at 6 months was 16/26 (62%) for standard balloon angioplasty and 8/10 (80%) for cutting balloon angioplasty (p = 0.44). The primary patency rate at 12 months was 9/25 (36%) for standard balloon angioplasty and 5/10 (50%) for cutting balloon angioplasty (p = 0.47). The use of cutting balloons for primary angioplasty of infra-inguinal vein grafts offers no definite advantage over standard balloon angioplasty in this institution or compared with patency rates after standard balloon angioplasty reported elsewhere. Larger multicenter studies would be required to demonstrate whether there was any real difference between the two techniques.


Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis.
To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis. We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to identify putatively causal genes. We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 × 10-8, OR ≥ 2.2), 1 on chromosome 15, harboring only the LRRK1 gene, and 1 on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage disequilibrium. Colocalization signals with expression quantitative trait loci for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding leucine-rich repeat kinase 1, a protein involved in B-cell development, and NR1H3 liver X receptor alpha, a transcription factor whose activation inhibits inflammatory processes. This study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the human leukocyte antigen (HLA) region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.


Dynamical Learning of Dynamics.
The ability of humans and animals to quickly adapt to novel tasks is difficult to reconcile with the standard paradigm of learning by slow synaptic weight modification. Here, we show that fixed-weight neural networks can learn to generate required dynamics by imitation. After appropriate weight pretraining, the networks quickly and dynamically adapt to learn new tasks and thereafter continue to achieve them without further teacher feedback. We explain this ability and illustrate it with a variety of target dynamics, ranging from oscillatory trajectories to driven and chaotic dynamical systems.


The use of simvastatin for the prevention of gallstones in the lithogenic prairie dog model.
Surgery for morbid obesity is rapidly increasing. Patients undergoing bariatric surgery are prone to gallstone development during the rapid weight loss. These patients are often given medications such as ursodeoxycholic acid to prevent gallstone formation; however, these medications are often poorly tolerated by patients, who subsequently discontinue them. We performed a study in a lithogenic animal model to assess the effectiveness of a potential alternate medication for gallstone prevention. 20 male prairie dogs were randomly separated into 2 groups and fed a lithogenic diet for 28 days. The study group animals were given 2.5 mg of the HMG-CoA reductase inhibitor simvastatin. Total cholesterol and triglycerides were measured and an open cholecystectomy was performed on each animal at the conclusion of the study period. The gallbladder was visually inspected for gallstones and microscopic biliary cholesterol crystal formation. There was a decrease of 36% in the total cholesterol of the study animals compared to controls. The animals treated with simvastatin showed gallstone formation in 5/10 (50%) of animals, compared with 6/10 (60%) of control animals. The study animals demonstrated microscopic cholesterol crystal formation in 80%, identical to the number found in the control animals. Despite a reduction in cholesterol, simvastatin prevented neither gallstone formation nor biliary cholesterol crystals in this animal model. Given the rapid increase in the number of bariatric surgical procedures coupled with the poor tolerance of ursodeoxycholic acid, viable alternatives should continue to be sought for these patients.


The Impact of Hemolysis on Cell-Free microRNA Biomarkers.
Cell-free microRNAs in plasma and serum have become a promising source of biomarkers for various diseases. Despite rapid progress in this field, there remains a lack of consensus regarding optimal quantification methods, reference genes, and quality control of samples. Recent studies have shown that hemolysis occurring during blood collection has substantial impact on the microRNA content in plasma/serum. To date, the impact of hemolysis has only been investigated for a limited number of microRNAs, mainly the red blood cell (RBC)-enriched miRs-16 and -451. In contrast, the effect of hemolysis on other microRNAs - in particular those proposed as biomarkers - has not been addressed. In this study we profiled the microRNA content of hemolyzed and non-hemolyzed plasma as well as RBCs to obtain a profile of microRNAs in the circulation affected or unaffected by hemolysis. Profiling by TaqMan Array Microfluidic Cards was used to compare three pairs of hemolyzed and non-hemolyzed plasma (with varying degrees of hemolysis) and one RBC sample. A total of 136 microRNAs were detectable in at least two of the samples, and of those 15 were at least twofold elevated in all three hemolyzed samples. This number increased to 88 microRNAs for the sample with the highest level of hemolysis, with all of these also detected in the RBC profile. Thus these microRNAs represent a large proportion of detectable microRNAs and those most likely to be affected by hemolysis. Several of the hemolysis-susceptible microRNAs (e.g., miRs-21, -106a, -92a, -17, -16) have also been previously proposed as plasma/serum biomarkers of disease, highlighting the importance of rigorous quality control of plasma/serum samples used for measurement of circulating microRNAs. As low-level hemolysis is a frequent occurrence during plasma/serum collection it is critical that this is taken into account in the measurement of any candidate circulating microRNA.


Closed-form inverse kinematics for interventional C-arm X-ray imaging with six degrees of freedom: modeling and application.
For trauma and orthopedic surgery, maneuvering a mobile C-arm fluoroscope into a desired position to acquire an X-ray is a routine surgical task. The precision and ease of use of the C-arm becomes even more important for advanced interventional imaging techniques such as parallax-free X-ray image stitching. Today's standard mobile C-arms have been modeled with only five degrees of freedom (DOF), which definitely restricts their motions in 3-D Cartesian space. In this paper, we present a method to model both the mobile C-arm and patient's table as an integrated kinematic chain having six DOF without constraining table position. The closed-form solutions for the inverse kinematics problem are derived in order to obtain the required values for all C-arm joint and table movements to position the fluoroscope at a desired pose. The modeling method and the closed-form solutions can be applied to general isocentric or nonisocentric mobile C-arms. By achieving this we develop an efficient and intuitive inverse kinematics-based method for parallax-free panoramic X-ray imaging. In addition, we implement a 6-DOF C-arm system from a low-cost mobile fluoroscope to optimally acquire X-ray images based solely on the computation of the required movement for each joint by solving the inverse kinematics on a continuous basis. Through simulation experimentation, we demonstrate that the 6-DOF C-arm model has a larger working space than the 5-DOF model. C-arm repositioning experiments show the practicality and accuracy of our 6-DOF C-arm system. We also evaluate the novel parallax-free X-ray stitching method on phantom and dry bones. Using five trials, results show that parallax-free panoramas generated by our method are of high visual quality and within clinical tolerances for accurate evaluation of long bone geometry (i.e., image and metric measurement errors are less than 1% compared to ground-truth).


Trauma and posttraumatic stress disorder in the community: the 1996 Detroit Area Survey of Trauma.
The study estimates the relative importance of specific types of traumas experienced in the community in terms of their prevalence and risk of leading to posttraumatic stress disorder (PTSD). A representative sample of 2181 persons in the Detroit area aged 18 to 45 years were interviewed by telephone to assess the lifetime history of traumatic events and PTSD, according to DSM-IV. Posttraumatic stress disorder was assessed with respect to a randomly selected trauma from the list of traumas reported by each respondent, using a modified version of the Diagnostic Interview Schedule, Version IV, and the World Health Organization Composite International Diagnostic Interview. The conditional risk of PTSD following exposure to trauma was 9.2%. The highest risk of PTSD was associated with assaultive violence (20.9%). The trauma most often reported as the precipitating event among persons with PTSD (31% of all PTSD cases) was sudden unexpected death of a loved one, an event experienced by 60% of the sample, and with a moderate risk of PTSD (14.3%). Women were at higher risk of PTSD than men, controlling for type of trauma. The risk of PTSD associated with a representative sample of traumas is less than previously estimated. Previous studies have overestimated the conditional risk of PTSD by focusing on the worst events the respondents had ever experienced. Although recent research has focused on combat, rape, and other assaultive violence as causes of PTSD, sudden unexpected death of a loved one is a far more important cause of PTSD in the community, accounting for nearly one third of PTSD cases.


Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.
Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.


Vitamin D and the cardiovascular system.
Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion.


[Catalytic properties of induced L-lysine-alpha-oxidase].
Regulation of biosynthesis of L-lysine-alpha-oxidase from Trichoderma sp using biostimulators was studied. Specific activity of L-lysine-alpha-oxidase was increased 2.7-fold in presence of biostimulators; this occurred due to induction of the enzyme, properties of which were described previously. Catalytic and physico-chemical properties of the enzyme studied were not altered after addition of stimulators into the cultivation medium of the producing strain. Small amounts of L-lysine-alpha-oxidase isozyme were detected in the medium during cultivation; the isozyme was less active and had lower molecular mass as compared with the enzyme studied.


Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone.
Malignant ascites (MA) is associated with poor prognosis and limited palliative therapeutic options. Therefore, quality of life (QoL) assessment is of particular importance to demonstrate new treatment value. Following the demonstration of the superiority of catumaxomab and paracentesis over paracentesis on puncture-free survival, this analysis aimed at comparing deterioration in QoL between both the treatment options. In a randomised, multicentre, phase II/III study of patients with MA due to epithelial cell adhesion molecule (EpCAM) positive cancer, the QoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) questionnaire at screening, 1, 3 and 7 months after treatment and in the case of re-puncture on the day of paracentesis. Time to first deterioration in QoL was defined as a decrease in the QoL score of at least five points and compared between the catumaxomab (n=160) and control (n=85) groups using the log-rank test and Cox proportional hazards models adjusted for baseline score, country and primary tumour type. Deterioration in QoL scores appeared more rapidly in the control than in the catumaxomab group (median 19-26 days versus 47-49 days). The difference in time to deterioration in QoL between the groups was statistically significant for all scores (P<0.01). The hazard ratios ranged from 0.08 to 0.24 (P<0.01). Treatment with catumaxomab delayed deterioration in QoL in patients with MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL for a prolonged survival period.


Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII.
High levels of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) have been found to be effective in providing haemostasis in haemophiliacs and in normal individuals with acquired inhibitors to factor VIII (FVIII) or FIX. However, the mechanism of this therapeutic effect of FVIIa is unclear. Opinion is divided over whether high-dose FVIIa therapy works primarily by a tissue factor (TF)-dependent or -independent mechanism. Our group originally favoured a TF-dependent mechanism; however, we have recently found that, at levels comparable with those attained therapeutically, FVIIa activates enough FX on activated platelets to restore platelet surface thrombin generation. These data now lead us to favour a primarily (although not necessarily exclusively) TF-independent mechanism for the haemostatic effect of high-dose FVIIa. We believe that a platelet surface localization of FVIIa activity explains both its safety and efficacy, as well as its haemostatic effect in patients with thrombocytopenia and platelet function defects. Localization on activated platelets would tend to restrict the activity of FVIIa to sites of injury. Activation of FX on the platelet surface in haemophiliacs would provide FXa in a favourable location to escape inhibition by plasma protease inhibitors and be incorporated into platelet prothrombinase complexes. Activation of FIX and FX on platelet surfaces in thrombocytopenia would result in more thrombin generation per platelet, possibly leading to formation of a stable fibrin network even in the absence of an optimal initial platelet plug.


Cardiovascular health and depression.
Research has shown that depression increases the likelihood that otherwise healthy people will develop ischemic heart disease (IHD) and worsens the prognosis of patients who already have IHD. Moreover, concerns about safety (e.g., cardiac side effects, drug-drug interactions) have caused physicians to be hesitant about using antidepressant agents in patients with IHD. This article is based on a recent roundtable of experts who met to discuss risk, diagnosis, and treatment options for depression in patients with IHD. This article reviews clinical and epidemiological studies that have described a link between depression and the subsequent development of IHD and have examined the role of depression as a predictor of cardiac events in patients with existing IHD. The article addresses the issue of whether depression can be safely and efficaciously treated both in patients with stable IHD and in those with acute coronary syndromes. The authors discuss safety issues related to the potential for interactions between antidepressants and cardiovascular medications, the use of nonpharmacologic treatment options such as psychosocial interventions, and the effect of antidepressant therapy on quality of life in patients with IHD. The article concludes with practical clinical guidance concerning the management of depression in patients who have recently experienced myocardial infarction.


In vitro degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds.
This study investigated the in vitro degradation of porous poly(propylene fumarate) (PPF-based) composites incorporating microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) during a 26-week period in pH 7.4 phosphate-buffered saline at 37 degrees C. Using a fractional factorial design, four formulations of composite scaffolds were fabricated with varying PEG content of the microparticles, microparticle mass fraction of the composite material, and initial leachable porogen content of the scaffold formulations. PPF scaffolds without microparticles were fabricated with varying leachable porogen content for use as controls. The effects of including PLGA/PEG microparticles in PPF scaffolds and the influence of alterations in the composite formulation on scaffold mass, geometry, water absorption, mechanical properties and porosity were examined for cylindrical specimens with lengths of 13 mm and diameters of 6.5 mm. The composite scaffold composition affected the extent of loss of polymer mass, scaffold length, and diameter, with the greatest loss of polymer mass equal to 15+/-5% over 26 weeks. No formulation, however, exhibited any variation in compressive modulus or peak compressive strength over time. Additionally, sample porosity, as determined by both mercury porosimetry and micro-computed tomography did not change during the period of this study. These results demonstrate that microparticle carriers can be incorporated into PPF scaffolds for localized delivery of bioactive molecules without altering scaffold mechanical or structural properties up to 26 weeks in vitro.


Engineering bacteria to solve the Burnt Pancake Problem.
We investigated the possibility of executing DNA-based computation in living cells by engineering Escherichia coli to address a classic mathematical puzzle called the Burnt Pancake Problem (BPP). The BPP is solved by sorting a stack of distinct objects (pancakes) into proper order and orientation using the minimum number of manipulations. Each manipulation reverses the order and orientation of one or more adjacent objects in the stack. We have designed a system that uses site-specific DNA recombination to mediate inversions of genetic elements that represent pancakes within plasmid DNA. Inversions (or "flips") of the DNA fragment pancakes are driven by the Salmonella typhimurium Hin/hix DNA recombinase system that we reconstituted as a collection of modular genetic elements for use in E. coli. Our system sorts DNA segments by inversions to produce different permutations of a promoter and a tetracycline resistance coding region; E. coli cells become antibiotic resistant when the segments are properly sorted. Hin recombinase can mediate all possible inversion operations on adjacent flippable DNA fragments. Mathematical modeling predicts that the system reaches equilibrium after very few flips, where equal numbers of permutations are randomly sorted and unsorted. Semiquantitative PCR analysis of in vivo flipping suggests that inversion products accumulate on a time scale of hours or days rather than minutes. The Hin/hix system is a proof-of-concept demonstration of in vivo computation with the potential to be scaled up to accommodate larger and more challenging problems. Hin/hix may provide a flexible new tool for manipulating transgenic DNA in vivo.


[Estimation of the risk of drug-related problems in nursing home residents : A retrospective analysis of routine data].
Polypharmacy and drug-related problems are major challenges in the care and treatment of nursing home residents. Many interventional studies showed disappointing results, which lead to the question if this could also be due to the selection of the target parameters of these studies. A routine data set from six long-term care facilities was retrospectively analyzed. The question is if the recently validated medication risk score (MERIS) is suitable for carrying out a risk assessment in a population of nursing home residents. Associations between MERIS and the dependent variables hospital admissions and falls over 12 months and a weight loss of ≥ 5% over 3 months were examined. Out of 495 residents 38.6% (n = 191) have a high risk of drug-related problems according to MERIS. A univariate regression analysis showed a significantly increased risk of hospital admissions (OR 2.2; p < 0.001) and weight loss of ≥ 5% (OR 1.95; p = 0.041) with high MERIS, but no significant association with falls. In the multivariate regression the risk of hospitalization was increased by diabetes mellitus (OR 1.88; p = 0.004), falls in the same period (OR 1.91; p = 0.001), positive MERIS (OR 1.75; p = 0.006) and decreased with stable weight (OR 0.88; p = 0.004). The results indicate the potential of the score for future research projects and individual risk assessment; however, due to the limitations of retrospective secondary analyses further studies are required.


Arteriovenous malformations of the lateral ventricle.
Nine cases with arteriovenous malformations (AVM's) predominantly involving the lateral ventricle are presented. All the AVM's were small, but caused intraventricular hemorrhage in eight cases. Only two patients had an intracerebral hemorrhage large enough to warrant evacuation. Eight patients were under the age of 40 years at the onset of their disease. Computerized tomography demonstrated intraventricular hemorrhage in eight patients, and after intravenous administration of contrast medium a small area of enhancement with dilated subependymal draining veins was seen in seven. The lateral ventricles were of normal size in seven cases, and only two patients required a shunting procedure. Angiography demonstrated that the lesion was an AVM in eight patients, and did not visualize the lesion in the ninth. One patient suffered a recurrent intraventricular hemorrhage when the AVM was demonstrated, although repeated angiography had failed to disclose a vascular lesion at his first intraventricular hemorrhage 14 months before. All nine lesions were resected by microsurgical techniques, and the results were excellent in eight patients. Of four caudate lesions, three were resected through a frontal transcortical approach and the other was operated on through an anterior transcallosal approach; the results were excellent in three of these patients. Only one (Case 4) was left with neurological deficits; he had confusion and disorientation following a right frontal transcortical approach. Even in the dominant hemisphere, lesions in the head of the caudate nucleus could be safely resected by an anterior transcallosal approach. Two choroidal lesions located in the temporal horn and trigone on the dominant side were resected through a middle temporal gyrus approach, and three thalamic lesions through a posterior transcallosal approach, all with excellent results. In all cases the brain opening required was about the width of the retractor (maximum 2.0 cm, average 1.5 cm).


An Adhesive Bioink toward Biofabrication under Wet Conditions.
Three-dimensional (3D) bioprinting is driving significant innovations in biomedicine over recent years. Under certain scenarios such as in intraoperative bioprinting, the bioinks used should exhibit not only cyto/biocompatibility but also adhesiveness in wet conditions. Herein, an adhesive bioink composed of gelatin methacryloyl, gelatin, methacrylated hyaluronic acid, and skin secretion of Andrias davidianus is designed. The bioink exhibits favorable cohesion to allow faithful extrusion bioprinting in wet conditions, while simultaneously showing good adhesion to a variety of surfaces of different chemical properties, possibly achieved through the diverse bonds presented in the bioink formulation. As such, this bioink is able to fabricate sophisticated planar and volumetric constructs using extrusion bioprinting, where the dexterity is further enhanced using ergonomic handheld bioprinters to realize in situ bioprinting. In vitro experiments reveal that cells maintain high viability; further in vivo studies demonstrate good integration and immediate injury sealing. The characteristics of the bioink indicate its potential widespread utility in extrusion bioprinting and will likely broaden the applications of bioprinting toward situations such as in situ dressing and minimally invasive tissue regeneration.


Activity of MKT 077, a rhodacyanine dye, against human tumor colony-forming units.
MKT 077 is related to rhodamine 123 dye and demonstrates preferential accumulation in the mitochondria of cancer cells compared to normal cells. This difference in retention between cancer and normal cells led to the finding that MKT 077 selectively inhibits the growth of cancer cells in vitro. To define the preclinical activity profile of MKT 077, the compound was tested in vivo against a large variety of human tumors utilizing the human tumor-cloning assay. MKT 077 was studied using a sequential 2 h exposure separated by 24 h (2-24-2 h) and a 24 h exposure at final concentrations of 0.1, 0.2, 1.0, 2.0, 10.0 and 20.0 microg/ml. MKT 077 was also studied using continuous exposure at final concentrations of 0.1, 1.0 and 10 microg/ml. A decrease in tumor colony formation was considered significant if survival of colonies treated with MKT 077 was 50% or less compared to untreated controls. A total of 149 specimens was treated with MKT 077 with 51, 58 and 34 evaluable specimens with the 2-24-2 h, the 24 h and the continuous exposure, respectively. The results of the present study suggest a positive relationship between concentration and response. No relationship between exposure schedule and activity was observed. Inhibitory effects were obtained against multiple tumor types. High cytotoxic activity was obtained against breast, ovary, endometrial, colon and non-small cell lung cancer with concentrations of 2 microg/ml or above. In conclusion, the broad spectrum of cytotoxicity of MKT 077 in the human tumor-cloning assay and the unique mechanism of action of MKT 077 encourage additional preclinical and clinical studies with this compound and other rhodacyanine dyes.


Molecular characterization of endometrial cancer: a correlative study assessing microsatellite instability, MLH1 hypermethylation, DNA mismatch repair protein expression, and PTEN, PIK3CA, KRAS, and BRAF mutation analysis.
Endometrial cancer is associated with numeric and structural chromosomal abnormalities, microsatellite instability (MSI), and alterations that activate oncogenes and inactivate tumor suppressor genes. The aim of this study was to characterize a set of endometrial cancers using multiple molecular genetic and immunohistochemical techniques. Ninety-six cases were examined for genomic alterations by MSI, MLH1 promoter hypermethylation, p53 and mismatch repair protein expression (MLH1, MSH2, MSH6, PMS2), and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. At least 1 alteration was identified in 48 of 87 (55%) specimens tested for PTEN, making it the most common abnormality in this study. A PIK3CA alteration was observed in 16 (17%) specimens. Twenty-nine of 94 (31%) MSI tested tumors exhibited an MSI-H phenotype. Of the 29 MSI-H cases, 24 (83%) were positive for methylation of the MLH1 promoter region. Twenty-three (82%) of the 28 MSI-H cases with immunohistochemistry results showed loss of expression of MLH1/PMS2 (n=19), MSH2/MSH6 (n=2), or MSH6 only (n=2). Of the 19 MSI-H cases with loss of MLH1/PMS2 on immunohistochemistry, 18 were positive, and 1 was equivocal for MLH1 promoter hypermethylation. Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation. No BRAF V600E mutations were indentified. This study provides a comprehensive molecular genetic analysis of commonly analyzed targets in a large cohort of endometrial cancers.


The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C.
Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after pegylated glycol-interferon plus ribavirin (Peg-IFN/RBV) therapy in patients with chronic hepatitis C, the risk factors for the development of HCC are not fully understood. The aim of this study was to clarify the incidence and the risk factors for the development of HCC after Peg-IFN/RBV therapy in patients with chronic hepatitis C. A total of 474 patients with chronic hepatitis C who received Peg-IFN/RBV therapy between December 2004 and August 2010 were enrolled and followed in a multicenter trial. The patients were assessed for HCC by either ultrasound or computed tomography every 6 months. The incidence and risk factors for the development of HCC were identified. Of the 474 patients, 23 developed HCC during a median follow-up of 4 years and 8 months (range 1-6 years and 3 months) after completion of Peg-IFN/RBV therapy. According to a univariate analysis, higher age, low platelet counts, a low level of serum albumin, a high level of alpha-fetoprotein (AFP) and a sustained viral response (SVR) to Peg-IFN/RBV therapy were independent factors associated with the occurrence of HCC. The multivariate analysis using the Cox proportional hazard model revealed the risk factors for HCC were the platelet count, AFP level and the outcome of Peg-IFN/RBV therapy. To reduce the incidence of HCC in chronic hepatitis C, attainment of a sustained response rate is an essential issue. For patients with low platelet counts and/or a high AFP level, strict surveillance should be continued even after eradication of HCV because the risk of HCC was found to be higher for these patients.


Inducible gene expression mediated by a repressor-operator system isolated from Lactococcus lactis bacteriophage r1t.
A regulatory region of the temperate Lactococcus lactis bacteriophage r1t chromosome has been cloned and characterized. It encompasses the two divergently oriented genes rro, encoding the phage repressor, and tec. Both genes, of which the transcription start sites have been mapped, are preceded by consensus -35 and -10 promoter sequences. The region contains three 21 bp direct repeats with internal dyad symmetry which probably act as operators. Two of these repeats partially overlap the two promoter sequences. The distant third repeat is located within the tec coding sequence. Gel mobility shift assays demonstrated that Rro specifically binds to this sequence. To study possible transcriptional regulation of the region, a lacZ translational fusion with an open reading frame following tec was constructed. Under conditions that favour the lysogenic life cycle of r1t, beta-galactosidase activity was very low. Expression of the lacZ fusion could be induced 70-fold by the addition of mitomycin C at a concentration which promotes the switch of r1t from the lysogenic to the lytic life cycle. In non-induced cells, promoter activity was repressed by Rro, as a frameshift mutation in rro resulted in constitutive expression of the lacZ gene fusion.


Oxidative stress in heart tissue of hyperthyroid and iron supplemented rats.
This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation or cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (CSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters-GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.


The new back-to-school basics: COVID-19 hygiene education for elementary students.
Context: In the midst of the COVID-19 pandemic- with undulating statistics of new cases and deaths and with schools set to reopen in the fall of 2020 after a long hiatus- the objective was to address the needs and methods of preparing children for a safe return to school. Objective: To educate 1st - 5th grade elementary school children about proper health and safety precautions during the COVID-19 pandemic. Study Design and Setting: Three monthly virtual sessions via zoom were implemented with focuses on hygiene, physical activity, and healthy coping mechanisms during a pandemic. The hygiene lecture included interactive demonstrations on handwashing, coughing/sneezing precautions, and appropriate mask-wearing behavior. During the coping mechanisms session, children were asked to use art or free text to answer the question "How has COVID-19 changed my feelings?" The physical activity session discussed safe ways for children to stay active during the pandemic. Both quantitative (pre and post-knowledge assessment quizzes) and qualitative (free text, drawings) data were collected through electronic surveys. Quizzes were designed for the appropriate grade level and used a combination of multiple choice, free text, checkboxes, and pictures to address common themes. Population studied and Intervention: School-aged children (1st-5th grade) at the Raindrop Foundation of San Antonio participated in educational sessions about maintaining proper COVID-19 hygiene. Outcome Measures and Results: Final results show six 1st - 2nd graders and nine 3rd - 5th graders consistently participated in the project. The children involved could identify proper mask-wearing etiquette, safe coughing habits, and when and how to wash their hands. Emotions reported were both positive (ex. happy) and negative (ex. Sad, bored). Reported activities were indoor electronic games and work. Children reported missing friends and going to parks. Conclusions: These educational sessions were organized to teach children safe practices for their return to school, develop coping skills, and also help them adapt to physical activity while maintaining social distancing. Participant 1st - 5th graders answered most questions correctly and displayed the basics of COVID-19 safety knowledge. The children surveyed are experiencing mixed emotions during the pandemic due to feelings of social isolation.


[The adenohypophyseal response and effect of GnRh (Dirigestran inj. Spofa) administration in cows in the postpartum period].
Radioimmunological investigation (RIA) of the level of pituitary FSH in the peripheral blood of cows after parturition demonstrated that this level increased successively. The FSH value of 32.93 +/- 3.71 ng per 1 ml, recorded the fourth to sixth day post partum, increased to as much as 57.78 +/- 40.98 ng per 1 ml 40 days after parturition. The LH level changed only slightly over the same period (from 1.12 +/- 0.21 ng per ml to 1.72 +/- 1.15 ng per ml). The concentration of progesterone in the blood of the cows was about 0.40 ng per ml during the first 15 days after parturition, but from the 25th day post partum it trebled, on an average (1.53 +/- 1.19 - 1.59 +/- 1.25 ng per ml). The response of the adenohypophysis of the cows to the administration of 200 micrograms of synthetic gonadoreline (spec. Dirigestran inj. Spofa) increased with increasing length of time from parturition. FSH concentration increased less markedly during the first 28 days p.p. and this increase was not uniform in time (the average increase was 1.5 to three times); in the later period the highest increase 300-500% was recorded, as a rule, 120 minutes after GnRH administration. The situation was similar in the increase in LH concentration in peripheral blood, but after the 26th day post partum the average increase in LH accounted for 500 to 600%. The concentration of progesterone in peripheral blood increased by more than 300%, on an average, from the 25th day after parturition. This testifies to the first post partum ovulation and to the formation of a new yellow body in the majority of cows under study.(ABSTRACT TRUNCATED AT 250 WORDS)


Automated Non-Invasive Measurement of Single Sperm's Motility and Morphology.
Measuring cell motility and morphology is important for revealing their functional characteristics. This paper presents automation techniques that enable automated, non-invasive measurement of motility and morphology parameters of single sperm. Compared to the status quo of qualitative estimation of single sperm's motility and morphology manually, the automation techniques provide quantitative data for embryologists to select a single sperm for intracytoplasmic sperm injection. An adapted joint probabilistic data association filter was used for multi-sperm tracking and tackled challenges of identifying sperms that intersect or have small spatial distances. Since the standard differential interference contrast (DIC) imaging method has side illumination effect which causes inherent inhomogeneous image intensity and poses difficulties for accurate sperm morphology measurement, we integrated total variation norm into the quadratic cost function method, which together effectively removed inhomogeneous image intensity and retained sperm's subcellular structures after DIC image reconstruction. In order to relocate the same sperm of interest identified under low magnification after switching to high magnification, coordinate transformation was conducted to handle the changes in the field of view caused by magnification switch. The sperm's position after magnification switch was accurately predicted by accounting for the sperm's swimming motion during magnification switch. Experimental results demonstrated an accuracy of 95.6% in sperm motility measurement and an error <10% in morphology measurement.


Prognostic Value of Neurological Status on Hospital Arrival for Short-Term Outcome in Patients With Cardiovascular Shock - Sub-analysis of the Japanese Circulation Society Cardiovascular Shock Registry.
Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA). Methods and Results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1-3 (not fully alert but awake without any stimuli); arousable, JCS 10-30 (arousable with stimulation); and coma JCS 100-300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16-2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76-4.22, P<0.001) (reference: alert) independently predicted 30-day mortality. Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.


[Approach of a person with infected venous ulcers].
People infected with venous wounds need to solve the acute problem (infection), later to treat the underlying cause (venous hypertension). By a proper assessment of the person can establish a comprehensive treatment. In the case above is achieved healing a venous ulcer 12 years of evolution in 11 weeks of treatment, with consequent savings for the health system, improving the quality of life of the person and the environment and cut red tape care.


Retrospective Study of Long-Term Outcome of Phacoemulsification in 22 Feline Eyes with Presumed Congenital/Juvenile Cataracts (2007-2020).
The objective of this study was to determine the complication risk and prevalence after phacoemulsification in cats with presumed congenital/inherited cataracts. Twelve client-owned cats were included in the study. This retrospective study spanned 13 yr and involved 22 eyes. The median age at the time of surgery was 15 mo (range: 4.5-168 mo of age). Recorded complications were 3 eyes developed postoperative ocular hypertension, 1 eye developed glaucoma, 7 eyes developed feline herpes virus-1 signs, and 7 eyes developed postoperative uveitis >2 wk after surgery. No eyes had developed intraocular sarcomas at the time of their last exam. All eyes remained visual at last follow-up (range: 0.5-121 mo). Success was defined as a comfortable and visual eye without intraocular neoplasia, glaucoma, a partial or complete retinal detachment, or uveitis that occurred >2 wk after surgery or persisted longer than 2 wk. Twenty-one out of 22 eyes had a successful outcome. In this study, cats with presumed congenital/juvenile cataracts who underwent phacoemulsification had an excellent outcome.


Advanced reproductive age and fertility: no. 269, November 2011.
To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management,and to review investigations in the assessment of ovarian aging. This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology.


Assemblages of Necrophagous Blow Flies (Diptera: Calliphoridae) in Four Contrasting Ecoregions of Los Angeles County, California, United States.
An ecological study to evaluate necrophagous species richness, abundance, and diversity was conducted in four contrasting ecoregions of Los Angeles County, California, United States: a highly anthropized area, two moderately populated areas, and a sparsely populated area. Our hypothesis states that there will be higher abundance of exotic species in greatly anthropized ecoregions and higher diversity of native calliphorid flies in sparsely populated sites. A total of 2,883 blow flies belonging to 12 species were captured from the four ecoregions. The exotic Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) was the most abundant species, representing 72.84% of all Calliphoridae collected. The highest abundance was in the highly anthropized ecoregion. Differences of the blow fly assemblages across environmentally and anthropically different ecoregions were found, and that the relative abundance of the exotic species increased with anthropization. Our results suggest that both anthropization and elevation alter the structure of blow fly assemblages, modifying the abundance and species richness of Calliphoridae. The results of this study support the hypothesis of biotic homogenization, since we found a higher proportional abundance of exotic species and lower diversity of native blow flies in ecoregions heavily modified by human action. Additionally, the hypothesis of intermediate disturbance was supported as the highest diversity was found in the ecoregion with moderate anthropization mixed with natural elements. This is the first study to conduct an intensive survey of the Calliphoridae assemblages in Los Angeles County, which can be potentially used as a tool in human and veterinary health and forensic sciences.


Hospitalised patients' awareness of their rights: a cross-sectional survey from a tertiary care hospital on the east coast of Peninsular Malaysia.
Optimal patient care varies considerably from place to place and is influenced by scientific as well as social developments. The purpose of this study was to investigate awareness and pertinent issues regarding informed consent among hospitalised patients and to determine lapses, in order to improve the standard of care. A questionnaire-based cross-sectional survey was conducted among inpatients at a tertiary care level hospital. 90 percent of patients were aware of their rights, and 85 percent had enough information regarding their illness and modality of treatment. However, treatment options were discussed with 45 percent of cases only, and 65 percent of patients were informed of their duration of treatment. Most of the patients from the surgical group, haemodialysis unit and those with minor ailments were very satisfied with the doctors (92 percent, 86 percent and 96 percent, respectively), as opposed to only 36 percent of cancer patients and 70 percent of acquired immunodeficiency syndrome (AIDS) patients (p-value is less than 0.0001). Almost all patients (99 percent) said that their religious beliefs were respected by the staff and they had no problems in accessing them in times of need. Informed consent was obtained by the doctor in 98 percent of cases and by the nurse in two percent. 98 percent of the patients mentioned that their treatments/examinations were conducted in an atmosphere of privacy and that their personal information was kept confidential by their doctors. Patients were reasonably informed about their illness. Their privacy and religious beliefs were duly respected. Treatment options and the duration of treatment were not discussed with all patients. Cancer and AIDS patients were less satisfied with the attending staff. The results suggest that there is a need for periodic surveys of patient satisfaction with the quality of care.


Methodology: ssb-MASS: a single seed-based sampling strategy for marker-assisted selection in rice.
Integrated breeding approaches such as combining marker-assisted selection and rapid line fixation through single-seed-descent, can effectively increase the frequency of desirable alleles in a breeding program and increase the rate of genetic gain for quantitative traits by shortening the breeding cycle. However, with most genotyping being outsourced to 3rd party service providers' nowadays, sampling has become the bottleneck for many breeding programs. While seed-chipping as prevailed as an automatable seed sampling protocol in many species, the symmetry of rice seeds makes this solution as laborious and costly as sampling leaf tissue. The aim of this study is to develop, validate and deploy a single seed sampling strategy for marker-assisted selection of fixed lines in rice that is more efficient, cost-effective and convenient compared to leaf-based sampling protocols without compromising the accuracy of the marker-assisted selection results. Evaluations replicated across accessions and markers showed that a single rice seed is sufficient to generate enough DNA (7-8 ng/μL) to run at least ten PCR trait-markers suitable for marker-assisted selection strategies in rice. The DNA quantity and quality extracted from single seeds from fixed lines (F6) with different physical and/or chemical properties were not significantly different. Nor were there significant differences between single seeds collected 15 days after panicle initiation compared to those harvested at maturity. A large-scale comparison between single seed and leaf-based methodologies showed not only high levels of genotypic concordance between both protocols (~ 99%) but also higher SNP call rates in single seed (99.24% vs. 97.5% in leaf). A cost-benefit analysis showed that this single seed sampling strategy decreased the cost of sampling fourfold. An advantage of this approach is that desirable genotypes can be selected before investing in planting activities reducing the cost associated with field operations. This study reports the development of a cost-effective and simple single seed genotyping strategy that facilitates the adoption and deployment of marker-assisted selection strategies in rice. This will allow breeders to increase the frequency of favorable alleles and combine rapid generation advancement techniques much more cost-effectively accelerating the process and efficiency of parental selection and varietal development.


Implanted biofuel cell operating in a living snail.
Implantable biofuel cells have been suggested as sustainable micropower sources operating in living organisms, but such bioelectronic systems are still exotic and very challenging to design. Very few examples of abiotic and enzyme-based biofuel cells operating in animals in vivo have been reported. Implantation of biocatalytic electrodes and extraction of electrical power from small living creatures is even more difficult and has not been achieved to date. Here we report on the first implanted biofuel cell continuously operating in a snail and producing electrical power over a long period of time using physiologically produced glucose as a fuel. The "electrified" snail, being a biotechnological living "device", was able to regenerate glucose consumed by biocatalytic electrodes, upon appropriate feeding and relaxing, and then produce a new "portion" of electrical energy. The snail with the implanted biofuel cell will be able to operate in a natural environment, producing sustainable electrical micropower for activating various bioelectronic devices.


Exact density profile of a stochastic reaction-diffusion process.
We calculate exactly the time dependent density profile of a one-dimensional stochastic reaction-diffusion process of hard-core particles subjected to the reactions AA <--> OO and AO <--> OA. The solution is based on the fundamental property that the evolution operator, defined over an appropriate vector space, transforms vectors with n kinks into vectors with n or n+2 kinks, only. In this space, a basis vector is represented by a string of plus and minus signs and a kink is defined as a pair of opposite signs. The exact time dependent profiles are calculated for the cases of uncorrelated initial states that are translational invariant as well as initial states that are inhomogeneous in space.


Sweat gland carcinoma with lung metastases.
Sweat gland carcinoma is a rare skin tumor. The tumor has propensity to spread to lymph nodes and distant metastases has been reported. Their exact incidence in the Indian setting is not known. Aspects related to treatment are also not clearly defined. Though surgery forms the initial treatment approach, adjuvant treatment has not been properly explored. We report here a case of sweat gland carcinoma with bilateral lung metastases.


Metal ion content of dolichos biflorus lectin and effect of divalent cations on lectin activity.
The metal ion content of the Dolichos biflorus seed lectin has been determined by using atomic absorption spectrophotometry. Ca2+, Mg2+, Mn2+, Zn2+, and Cu2+ were all found in the native lectin and could be removed to different degrees by using a variety of techniques such as high ionic strength, low pH, chelating agent, and combinations of these procedures. By use of affinity electrophoresis, the remaining binding capacity of the lectin could easily be determined, and the D. biflorus lectin showed an absolute requirement for divalent cations to be able to bind N-acetyl-D-galactosamine. The association constant (Ka) of the lectin for N-acetyl-D-galactosamine was determined after remetallization of the lectin with each individual metal ion and a combination of them. The Ka of the lectin for the hapten differed depending on which divalent cation had been used for remetallization. Ca2+ ion alone was equal to a combination of all metal ions in its ability to confer the highest binding activity of the lectin for N-acetyl-D-galactosamine. The other cations, Mg2+, Mn2+, Zn2+, and Cu2+, could not restore the binding activity of the lectin to the same degree as Ca2+ or a combination of all ions. The D. biflorus lectin is, therefore, one of the first lectins that has been shown to require only a single cation to fully retain its binding activity in contrast to most lectins that require a combination of Ca2+, Mn2+, Mg2+, or Zn2+. Furthermore, we have shown that there is a selective process of ion uptake into the lectin since the metal ion ratios in the native lectin compared to the whole seed are quite different.


Subclavian steal syndrome. Part 1: Proximal vertebral to common carotid artery transposition in three patients, and historical review.
Three patients with central nervous system symptoms due to subclavian steal syndrome were treated with proximal vertebral to common carotid artery transposition. Neurological symptoms were relieved or improved in all three, with no decrease in blood pressure or pulse in the ipsilateral upper extremity. The colorful history of this syndrome is reviewed, and the various surgical approaches to its treatment are discussed. Although the literature suggests that the commonly used carotid to subclavian artery bypass graft and other similar extrathoracic procedures are generally safe and effective for relief of symptoms of the steal, there is also evidence that these bypasses may fail to restore antegrade flow in the vertebral artery, and, in fact, may steal from the carotid artery. Thus, the blood flow provided to the brain by these procedure may be hardly more than that provided by vertebral artery ligation, whereas the principal effect is to restore blood flow into the upper extremity. Vertebral artery ligation alone has been used in 20 patients, with neurological improvement in all cases and production of persistent intermittent brachial claudication in only one. These considerations and our patient experience suggest that a relatively simple operation, proximal vertebral to common carotid artery transposition, which emphasizes restoration of flow to the brain rather than to the upper extremity, may be preferable for most patients with neurological symptoms of subclavian steal syndrome.


Thromboprophylaxis in surgical and medical patients.
Venous thromboembolism (VTE) remains the most common preventable cause of death in hospitalized patients. There is much evidence to show the efficacy of prophylactic strategies to prevent VTE in at-risk hospitalized patients. For example, pharmacological prophylaxis reduces the risk of pulmonary embolism by 75% in general surgical patients and by 57% in medical patients. Thus international guidelines strongly recommend effective preventive strategies for all hospitalized patients defined as moderate to high risk for VTE. Effective pharmacological thromboprophylaxis includes low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and warfarin. Mechanical prophylaxis with graduated compression stockings and intermittent pneumatic compression is also recommended as an alternative or in combination with pharmacological prophylaxis. Although the volume of evidence supporting the use of thromboprophylaxis is growing, the number of patients receiving adequate prophylaxis is not. Several studies have shown that nearly half of the patients undergoing major surgery or hospitalized for medical illnesses do not receive appropriate antithrombotic prophylaxis. Reducing the discrepancy between evidence-based recommendations and clinical practice seems to be a cost-effective goal. Developing and promoting local protocols and educational activities to encourage prophylaxis in daily clinical practice may be effective. New oral anticoagulant drugs with potentially favorable pharmacokinetic and pharmacodynamic characteristics have been developed. After the positive results of phase 3 clinical trials, some of these drugs have been approved for clinical use in the prevention of VTE in the high-risk setting of major orthopedic surgery. These agents include the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban.


The use of mathematical models to inform influenza pandemic preparedness and response.
Influenza pandemics have occurred throughout history and were associated with substantial excess mortality and morbidity. Mathematical models of infectious diseases permit quantitative description of epidemic processes based on the underlying biological mechanisms. Mathematical models have been widely used in the past decade to aid pandemic planning by allowing detailed predictions of the speed of spread of an influenza pandemic and the likely effectiveness of alternative control strategies. During the initial waves of the 2009 influenza pandemic, mathematical models were used to track the spread of the virus, predict the time course of the pandemic and assess the likely impact of large-scale vaccination. While mathematical modeling has made substantial contributions to influenza pandemic preparedness, its use as a realtime tool for pandemic control is currently limited by the lack of essential surveillance information such as serological data. Mathematical modeling provided a useful framework for analyzing and interpreting surveillance data during the 2009 influenza pandemic, for highlighting limitations in existing pandemic surveillance systems, and for guiding how these systems should be strengthened in order to cope with future epidemics of influenza or other emerging infectious diseases.


An outcome evaluation of a hospital-based early intervention program.
To determine the effectiveness of the Health Care Intervention Service (HIS), an early intervention program for general hospital patients with alcohol dependence or at risk for alcohol dependence. HIS consists of screening, assessment and assignment to either full or risk-reduction intervention. Full intervention includes a referral to treatment. Outcomes were compared across three groups: those who received a full intervention, those who received a risk-reduction intervention, and a comparison group of similar patients from hospitals with no HIS program. Patients were screened for alcohol involvement and interviewed during their hospitalization (prior to the intervention in HIS hospitals) and again 6 months following the intervention. Full intervention was effective in increasing the probability of abstinence, reducing the number of heavy drinking days, and encouraging patients to accept the referral to treatment. Risk-reduction intervention was effective in reducing alcohol consumption and consequences, but only for those patients who had some signs of dependence at the first interview. HIS has demonstrated its effectiveness in a "real world" bureaucratic and clinical environment.


[Clinico-morphological parameters of heroin abuse and pathology connected with it].
Morphological manifestations of narcomania in heroin users are described. Diseases associated with heroin narcomania and causes of death of heroin users are presented. Morphological manifestations at the site of injections and inflammatory reactions in parenchymatous organs are characterized. The authors pay special attention to the productive inflammation which can serve as one of the signs that confirm narcomania in cases with parenteral injections of crude heroin. The authors refer the granulomas to toxic allergic form of granulomatous hypersensitive inflammation.


Video game addiction test: validity and psychometric characteristics.
The study explores the reliability, validity, and measurement invariance of the Video game Addiction Test (VAT). Game-addiction problems are often linked to Internet enabled online games; the VAT has the unique benefit that it is theoretically and empirically linked to Internet addiction. The study used data (n=2,894) from a large-sample paper-and-pencil questionnaire study, conducted in 2009 on secondary schools in Netherlands. Thus, the main source of data was a large sample of schoolchildren (aged 13-16 years). Measurements included the proposed VAT, the Compulsive Internet Use Scale, weekly hours spent on various game types, and several psychosocial variables. The VAT demonstrated excellent reliability, excellent construct validity, a one-factor model fit, and a high degree of measurement invariance across gender, ethnicity, and learning year, indicating that the scale outcomes can be compared across different subgroups with little bias. In summary, the VAT can be helpful in the further study of video game addiction, and it contributes to the debate on possible inclusion of behavioral addictions in the upcoming DSM-V.


[Prevention of stress-induced and hypoxic heart lesions by means of an antioxidant ionol].
It was shown in experiments on male Wistar rats that activation of peroxidized oxidation of myocardial lipids and accumulation of hydroperoxides in the myocardium comprise the decisive link of the pathogenic chain of stress and hypoxic damages to the heart. Injection of a potent non-toxic antioxidant into the animals before exposure to the stress or hypoxia blocks the activation of peroxidized oxidation and prevents disorder of the contractile function and damage to the heart muscle appraised according to the elimination of enzymes from the myocardial cells.


Factors influencing subjective sleepiness in patients with obstructive sleep apnea syndrome.
The aim of the present paper was to clarify the factors influencing subjective daytime sleepiness in patients with obstructive sleep apnea syndrome (OSAS). Subjects included 230 adult male OSAS patients aged 20-73 years. Single and multiple linear regression analyses were performed to estimate the association between the Epworth Sleepiness Scale (ESS) and the following variables: Minnesota Multiphasic Personality Inventory (MMPI), Self-Rating Depression Scale (SDS), age, body mass index (BMI), sleep duration during the preceding month and apnea-hypopnea index (AHI). Single linear regression analysis showed that age had a negative association with ESS score, while BMI, AHI, SDS, hypochondriasis (Hs), hysteria, psychopathic deviant, psychasthenia, schizophrenia and hypomania on the MMPI had a positive association with ESS score. However, the other remaining parameters such as nocturnal sleep duration during the preceding month, depression, masculinity-femininity, paranoia, social introversion on the MMPI had no statistical association with ESS score. Multiple linear regression analysis with stepwise elimination method was applied to choose the significant factors associated with ESS. It was found that three variables including age, AHI and Hs scores were independent factors influencing ESS score. The R(2) for the model was 0.14, suggesting that these factors account for 14% of possible variance of subjective daytime sleepiness of OSAS patients. These results suggest that subjective daytime sleepiness in patients with OSAS may be influenced not only by the severity of respiratory disorder indices but also by certain personality characteristics affecting Hs score and by age.


Unique CT imaging advantages. Hemorrhage and calcification.
Computed tomography remains the imaging modality of choice in the detection of two processes: acute intracranial hemorrhage and calcification; however, in the subacute and chronic stages of hemorrhage, MR imaging is more sensitive in aging and staging hemorrhage. FLAIR imaging increases the sensitivity of MR imaging in the detection of subarachnoid hemorrhage. The signal characteristics of calcification on MR imaging is variable, especially on T1-weighted images decreasing its detectability. CT is superior to MR imaging in the detection of calcification. A number of factors including slice thickness, as well as window width and level may affect the detectability of calcification on CT.


Chronic Inflammatory Disease in the Pancreas, Kidney and Salivary Glands of English Cocker Spaniels and Dogs of Other Breeds Shows Similar Histological Features to Human IgG4-related Disease.
Chronic pancreatitis (CP) is a common disease in the English cocker spaniel (ECS) and is characterized histologically by duct destruction, interlobular fibrosis and dense periductular and perivenous lymphocytic aggregates. These features are also found in human autoimmune pancreatitis type 1, part of a glucocorticoid-responsive, multiorgan syndrome, newly recognized as IgG4-related disease (IgG4-RD). Human IgG4-RD affects one or several organs, often showing a predominance of IgG4+ plasma cells histologically, with an IgG4+:total IgG+ plasma cell ratio of >40%. This study investigated whether ECSs with CP and/or inflammatory disease in several organs show an increase in IgG4+ plasma cells within affected tissues. Histological sections of pancreas, liver, kidney, salivary gland and conjunctiva were obtained from ECSs with idiopathic chronic inflammatory disease affecting those tissues. Tissue samples from age-matched dogs of other breeds with similar diseases were also sampled. Control diseased tissue samples, from dogs without a suspected immune-mediated disease, were included. A subset of ECSs and dogs of other breeds presented with disease in more than one organ. Immunohistochemistry was performed with primary reagents detecting total IgG and three of the four canine IgG subclasses (IgG2, IgG3 and IgG4). Normal sections of pancreas and liver showed an absence of labelled plasma cells of any subclass. Normal kidney and salivary gland sections showed the presence of a few labelled plasma cells (<10 plasma cells/high-power field). Fourteen tissue sections from 12 ECSs and seven sections from six dogs of other breeds showed elevated numbers of IgG4+ plasma cells and IgG4+:IgG+ ratios >40%. Individual dogs (ECSs and other breeds) showed marked increases in IgG4+ cells. There were no significant differences in the number of IgG4+ plasma cells between ECSs and dogs of other breeds for affected pancreas, liver, salivary glands and conjunctiva. Kidney sections had more IgG4+ cells, for both ECSs and dogs of other breeds, than did sections from other organs. Dogs of other breeds had significantly more IgG4+ plasma cells in affected kidneys than ECSs. In conclusion, several ECSs and dogs of other breeds fulfilled the histological criteria for the diagnosis of IgG4-RD, supporting the existence of a multiorgan immune-mediated disease in ECSs and some dogs of other breeds.