Drosophila eye size is determined by Innexin 2-dependent Decapentaplegic signalling.
Organogenesis relies on specific genetic and molecular programmes, which orchestrate growth and cellular differentiation over developmental time. This is particularly important during Drosophila eye development in which cell-cell inductive events and long-range signalling have to be integrated to regulate proper cell proliferation, differentiation and morphogenesis. How these processes are coordinated is still not very well understood. Here we identify the gap junction protein Innexin2 (Inx2) as an important regulator of eye development. Depleting inx2 during eye development reduces eye size whereas elevating inx2 levels increases eye size. Loss- and gain-of-function experiments demonstrate that inx2 is required functionally in larval eye disc cells where it localises apico-laterally. inx2 regulates disc cell proliferation as well as morphogenetic furrow movement and as a result the amount of differentiated photoreceptors. inx2 interacts genetically with the Dpp pathway and we find that proper activation of the Dpp pathway transducer Mad at the furrow and expression of Dpp receptors Thickveins and Punt in the anterior disc compartment require inx2. We further show that inx2 is required for the transcriptional activation of dpp and punt in the eye disc. Our results highlight the crucial role of gap junction proteins in regulating morphogen-dependent organ size determination.


Detection of intracochlear damage during cochlear implant electrode insertion using extracochlear measurements in the gerbil.
An intraoperative monitoring algorithm during cochlear implant electrode insertion could be used to detect trauma and guide electrode placement relative to surviving hair cells. The aim of this report was to assess the feasibility of using extracochlear recording sites to monitor acoustically evoked responses from surviving hair cells and neural elements during implantation in an animal model. Animal experiments. The normal-hearing gerbil was used. Two recording methods, one using a lock-in amplifier and another using Fourier analysis of recorded signals, were used to obtain frequency-specific information about the responses to tones. Amplitude and threshold determinations were made at the round window and at three extracochlear sites. To induce intracochlear damage, a platinum-iridium wire was inserted through the round window. The wire was advanced, and changes in the potentials were correlated with cochlear contact. Anatomic integrity was assessed using cochlea whole mount preparations. In general, the lock-in amplifier showed greater sensitivity and lower thresholds at higher frequencies relative to the Fourier method. Also, the lock-in amplifier was more resistant to masking effects. Both systems were able to detect loss of cochlear potentials secondary to intracochlear trauma. Histologic damage was seen in all cases and corresponded to electrophysiologic changes. Impact of electrodes on cochlear structures affecting cochlear performance could be detected from several extracochlear sites. The lock-in amplifier demonstrated greater sensitivity and resistance to noise when compared to the fast Fourier transform recording paradigm. The latter showed greater flexibility of detecting and separating hair cell and neural potentials.


Clinical features and outcome of MLL gene rearranged acute lymphoblastic leukemia in infants with additional chromosomal abnormalities other than 11q23 translocation.
The treatment outcome for infant acute lymphoblastic leukemia (ALL) with positive MLL gene rearrangements remains poor. We analyzed whether additional chromosomal abnormalities (ACA) other than 11q23 translocation could affect the disease behavior and its prognosis. Eighteen of seventy-four patients with infant acute lymphoblastic leukemia showed ACA, including three-way translocations in four, other novel translocations in four, and complex structural chromosomal changes in four. Only age less than 6 months and positive central nervous system leukemia were significant prognostic factors by multivariate analysis. However, overall survival rates were worse in patients with ACA compared to those with non-ACA. Genetic alterations induced by additional chromosomal changes may be associated with disease progression and poorer overall survival rates in infants with MLL-rearranged ALL.


Editor's Choice - Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis.
The aim was to summarise the evidence from published epidemiological studies investigating the efficacy of statin therapy on long term survival in patients after abdominal aortic aneurysm (AAA) repair. This study was a systematic review with critical appraisal and meta-analysis of observational studies. A systematic literature search was carried out throughout February 2020, revealing 14 eligible cohort studies of which 11 were judged to be of high quality. A random effects model was used to synthesise results, and heterogeneity between studies examined by subgroup and meta-regression analyses considering patient and study related variables. Small study effect was evaluated. The pooled estimate showed that statin treatment among 69 790 AAA patients with a median follow up of 3.1 years was associated with a 35% relative reduction in total mortality (rate ratio 0.65, 95% confidence interval 0.57-0.73) with moderate heterogeneity (I2 = 68%) and no small study effect. Evidence from this systematic review indicates a beneficial effect of statins on long term survival in patients treated by AAA repair.


Carcinogens stimulate phosphorylation of ethanolamine derived from increased hydrolysis of phosphatidylethanolamine in C3H/101/2 fibroblasts.
Many human tumors contain high concentrations of ethanolamine phosphate (EtnP). An important question is whether increased formation of EtnP is merely the consequence of cell transformation, or is it associated with the process of carcinogenesis. Here we show that in C3H/10T1/2 embryonic fibroblasts, an established cellular model for the study of carcinogenesis, the environmental carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) (0.1-1 microgram/ml concentration; 24 h treatment), stimulate phosphorylation of ethanolamine derived from increased hydrolysis of phosphatidylethanolamine. The results suggest that increased formation of EtnP is associated with the early stages of carcinogenesis. This observation may have prognostic value.


[Diagnostics of drug allergies and intolerances].
The prevalence of hypersensitivity reactions to drugs is increasing. Currently, this affects more than 7% of the world population. Nonsteroidal anti-inflammatory drugs (NSAID) and beta-lactam antibiotics (BLA) are by far the most common pharmaceutical preparations involved in hypersensitivity reactions to drugs. Misdiagnoses are frequent and BLA allergies present a danger that can lead to adverse health outcomes. Therefore, delabeling (exclusion of a suspected diagnosis) is paramount for those affected. Following the occurrence of uncomplicated maculopapular exanthemas, outpatient oral drug provocation can be safely considered in children without prior skin tests. Immediate perioperative reactions are rare. The approach to studying these complex reactions requires collaboration between allergologists and anesthesiologists to provide the best possible care for these patients.


Dynamic studies of a fibronectin type I module pair at three frequencies: Anisotropic modelling and direct determination of conformational exchange.
A detailed analysis of the (15)N relaxation of a pair of modules from fibronectin is presented. The overall dimensions of the protein structure can be approximated by a cylinder with an axial ratio D(∥)/D(⊥) of 1.9. T(1), T(2) and NOE data, collected at three (15)M frequencies (50.6, 60.8 and 76 MHz), can be fitted satisfactorily to a Lipari-Szabo model, taking anisotropy into account. A method for analysing the exchange contribution to relaxation is presented. This contribution depends upon the predicted B (inf0) (sup2) frequency dependence in the fast exchange limit of these exchange terms. Using this analysis, relatively slow conformational exchange contributions are detected around one of the disulphide bonds in the first module of the pair.


Fungal cell wall dynamics and infection site microenvironments: signal integration and infection outcome.
Upon entrance into the host, fungi encounter a myriad of host effector products and microenvironments that they sense and adapt to for survival. Alterations of the structure and composition of the cell wall is a major fungal adaptation mechanism to evade these environments. Here we discuss recent findings of host-microenvironmental induced fungal cell wall changes, including structure, composition, and protein content, and their effects on host immune responses. A take home message from these recent studies is an emerging understanding of how integration of multiple signals, of both fungal and host responses to dynamic infection site microenvironments, determines outcomes of infection. A challenge moving forward is to further understand these mechanisms and harness them for therapeutic benefit.


Presence of MHC-I and B-7 molecules in rat and human glioma cells expressing antisense IGF-I mRNA.
Tumor cells frequently express the insulin-like growth factor I (IGF-I). Recently we demonstrated that rat glioma cells when transfected with a vector encoding antisense IGF-I cDNA lost tumorigenicity and induced a tumor specific immune response involving CD8+ lymphocytes. Here we show that the cultured transfected cell lines, rat C-6 glioma, human primary glioma and mouse teratocarcinoma, expressed an increased level of MHC-I and of co-signaling B-7 molecules. This increased expression of MHC-I and B-7, demonstrated by 51Cr release complement dependent cytoxicity assay and by immunostaining flow cytometry analysis, could contribute to the final immune recognition of glioma immunogenicity.


Bilayer graphene/HgCdTe based very long infrared photodetector with superior external quantum efficiency, responsivity, and detectivity.
We present a high-performance bilayer graphene (BLG) and mercury cadmium telluride (Hg1-x Cd x=0.1867Te) heterojunction based very long wavelength infrared (VLWIR) conductive photodetector. The unique absorption properties of graphene enable a long carrier lifetime of charge carriers contributing to the carrier-multiplication due to impact ionization and, hence, large photocurrent and high quantum efficiency. The proposed p+-BLG/n-Hg0.8133Cd0.1867Te photodetector is characterized and analyzed in terms of different electrical and optical characteristic parameters using computer simulations. The obtained results are further validated by developing an analytical model based on drift-diffusion, tunneling and Chu's methods. The photodetector has demonstrated a superior performance including improved dark current density (∼1.75 × 10-14 µA cm-2), photocurrent density (∼8.33 µA cm-2), internal quantum efficiency (QEint ∼ 99.49%), external quantum efficiency (QEext ∼ 89%), internal photocurrent responsivity (∼13.26 A W-1), external photocurrent responsivity (∼9.1 A W-1), noise equivalent power (∼8.3 × 10-18 W), total noise current (∼1.06 fA), signal to noise ratio (∼156.18 dB), 3 dB cut-off frequency (∼36.16 GHz), and response time of 9.4 ps at 77 K. Furthermore, the effects of different external biasing, light power intensity, and temperature are evaluated, suggesting a high QEext of 3337.70% with a bias of -0.5 V near room temperature.


Structural basis of transposon end recognition explains central features of Tn7 transposition systems.
Tn7 is a bacterial transposon with relatives containing element-encoded CRISPR-Cas systems mediating RNA-guided transposon insertion. Here, we present the 2.7 Å cryoelectron microscopy structure of prototypic Tn7 transposase TnsB interacting with the transposon end DNA. When TnsB interacts across repeating binding sites, it adopts a beads-on-a-string architecture, where the DNA-binding and catalytic domains are arranged in a tiled and intertwined fashion. The DNA-binding domains form few base-specific contacts leading to a binding preference that requires multiple weakly conserved sites at the appropriate spacing to achieve DNA sequence specificity. TnsB binding imparts differences in the global structure of the protein-bound DNA ends dictated by the spacing or overlap of binding sites explaining functional differences in the left and right ends of the element. We propose a model of the strand-transfer complex in which the terminal TnsB molecule is rearranged so that its catalytic domain is in a position conducive to transposition.


Dendritic cells in Listeria monocytogenes infection.
Dendritic cells (DCs) represent a unique collection of innate immune cells present throughout the body as distinct subpopulations generally sharing the functions of pathogen recognition, cytokine production, and antigen presentation. A large body of work in recent years has examined DC functions during infection with Listeria monocytogenes (Lm), particularly in the murine model. Here, I review several aspects of DC biology in this model, with particular emphasis on the role DCs play in the establishment of a productive Lm infection and the role of DCs as cytokine producers and antigen-presenting cells in this system.


[Experiences with autogenic training groups (author's transl)].
According to I. H. Schultz, "Autogenic Training" has helped many children with psychosomatic symptoms. The children's symptoms were obviously influenced by disturbed family-situations and so we invited both children and parents to the "Autogenic Training". The treatment was carried out in two parallel groups, 6 children, 3 parents and 3 mothers. The process and the "outcome" of ten group-sessions are described.


Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model.
Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals. We tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells. We also determined if the alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model. In TE-671 cells, all three alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence. 1.0 μM alpha conotoxin GI shifted the concentration-effect curves of anabasine and myosmine to the right, and decreased maximal responses. Neither of the conotoxins blocked the actions of lobeline in TE-671 cells. In the day 40 pregnant goats, 0.8 mg/kg anabasine abolished fetal movement at 30 and 60 min after dosing and fetal movement was reduced by lobeline and myosmine. The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR. All three alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these alkaloids to cause multiple congenital contracture-type defects in developing fetuses.


Combination of biological pretreatment with liquid hot water pretreatment to enhance enzymatic hydrolysis of Populus tomentosa.
A novel stepwise pretreatment of combination of fungal treatment with liquid hot water (LHW) treatment was conducted to enhance the enzymatic hydrolysis of Populus tomentosa. The results showed that lignin and cellulose increased with the elevating temperature, while significant amount of hemicellulose was degraded during the LHW pretreatment. A highest hemicellulose removal of 92.33% was observed by combination of Lenzites betulina C5617 with LHW treatment at 200°C, which was almost 2 times higher than that of sole LHW treatment at the same level. Saccharification of poplar co-treated with L. betulina C5617 and LHW at 200°C resulted in a 2.66-fold increase of glucose yield than that of sole LHW treatment, and an increase (2.25-fold) of glucose yield was obtained by the combination of Trametes ochracea C6888 with LHW. The combination pretreatment performed well at accelerating the enzymatic hydrolysis of poplar wood.


Visual field defects in normal-tension and high-tension glaucoma.
Differences in visual field characteristics between normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) have not been established. This study re-examined the problem by pointwise between-group comparison of data obtained with the Humphrey 30-2 program. Sixty-eight NTG cases with maximum intraocular pressure (IOP) of 21 mmHg or lower and 62 HTG cases with maximum IOP of 25 mmHg or greater with a mean deviation (STATPAC) greater than -10 decibels (dB) were included. Age, refraction, mean deviation, or sex ratio were matched between the two groups. Total deviation (STATPAC), the difference between the measured threshold and the age-corrected normal reference at each test point of the 30-2 program, was used for pointwise between-group comparisons. Another parameter, total deviation - mean total deviation, was introduced to normalize the total deviation by the overall visual field damage as an index of disease stage. Mean total deviation is the average of total deviations across the test field. Further, logistic discriminant analysis was applied to confirm that the difference at a questioned test point was due to the difference of disease type, but not disease stage, between the two groups. Comparison using total deviation and total deviation - mean total deviation gave similar results, which were collaborated by logistic discriminant analysis. For a given amount of visual field damage, an area just above the horizontal meridian was significantly more depressed in NTG, while HTG had significantly more diffuse visual field damage. Visual field defect of NTG differs from that of HTG, which may suggest that different regions of the optic disc are more susceptible to damage in NTG.


Associated joint pathology in the anterior cruciate ligament-deficient knee with emphasis on a classification system and injuries to the meniscocapsular ligament-musculotendinous unit complex.
This article defines the anterior cruciate ligament-deficient knee in terms of capsular instabilities. This definition lends itself to a better assessment of the associated pathology consisting of torn capsular ligaments, torn medial and lateral menisci, chondral fractures, subluxation of the patella, and acute contusion of the peroneal nerve. The specific incidence of torn medial meniscus was 70 per cent, with a torn lateral meniscus identified 77 per cent of the time.


Evaluation of CT techniques for reducing artifacts in the presence of metallic orthopedic implants.
Metallic intramedullary orthopedic implants generate artifacts that can markedly degrade transaxial CT images. The artifacts, typically seen as starburst streaking, result primarily from reconstructions involving missing projection data. Two approaches are clinically available to reduce the artifacts around orthopedic implants. These are (a) the imaging of implants with lower attenuation coefficients or smaller path lengths (less attenuating objects) and (b) the planar reformatting of image data. The sizing accuracy of these two approaches was quantified using phantoms and the efficacy using cadaveric femoral specimens. Results demonstrated that metal artifacts may be reduced and accurate bony dimensional data obtained.


[Changes in RNA synthesis in neurons depending on the intensity of their synaptic activity].
A prolonged synaptic activation of the frog spinal motoneurons increases the intensity of 3H-uridine incorporation into nuclei and nucleoli of the nerve cells. The higher the frequency of neuronal synaptic activation, the higher the incorporation intensity during the post-activation period.


Sodium-Glucose Co-Transporter 2 Inhibitors and Fracture Risk.
Patients with type 2 diabetes mellitus (T2DM) appear to have increased risk for fractures. In this context, the finding that canagliflozin, a sodium-glucose co-transporter-2 (SGLT) inhibitor, increased the risk for fracture compared with placebo in the Canagliflozin Cardiovascular Assessment Study (CANVAS), a large randomized controlled trial (RCT) in patients with established cardiovascular disease or multiple cardiovascular risk factors, created concern. In the present review, we summarize the data regarding the association between SGLT2 inhibitors and fracture risk in patients with T2DM. In contrast to the findings reported in CANVAS, canagliflozin did not affect the risk of fracture in a more recent, large RCT in patients with diabetic nephropathy. In addition, empagliflozin and dapagliflozin, other members of this class, also do not appear to affect the incidence of fracture. Moreover, there is no clear pathogenetic mechanism through which SGLT2 inhibitors increase the risk for fractures. Therefore, available data are inconclusive to attribute to these drugs a direct responsibility for bone fractures.


Constructing molecular bridge for high-efficiency and stable perovskite solar cells based on P3HT.
Poly (3-hexylthiophene) (P3HT) is one of the most attractive hole transport materials (HTMs) for the pursuit of stable, low-cost, and high-efficiency perovskite solar cells (PSCs). However, the poor contact and the severe recombination at P3HT/perovskite interface lead to a low power conversion efficiency (PCE). Thus, we construct a molecular bridge, 2-((7-(4-(bis(4-methoxyphenyl)amino)phenyl)-10-(2-(2-ethoxyethoxy)ethyl)-10H-phenoxazin-3-yl)methylene)malononitrile (MDN), whose malononitrile group can anchor the perovskite surface while the triphenylamine group can form π-π stacking with P3HT, to form a charge transport channel. In addition, MDN is also found effectively passivate the defects and reduce the recombination to a large extent. Finally, a PCE of 22.87% has been achieved with MDN-doped P3HT (M-P3HT) as HTM, much higher than the efficiency of PSCs with pristine P3HT. Furthermore, MDN gives the un-encapsulated device enhanced long-term stability that 92% of its initial efficiency maintain even after two months of aging at 75% relative humidity (RH) follow by one month of aging at 85% RH in the atmosphere, and the PCE does not change after operating at the maximum power point (MPP) under 1 sun illumination (~45 oC in N2) over 500 hours.


Chromatin condensation of Xist genomic loci during oogenesis in mice.
Repression of maternal Xist (Xm-Xist) during preimplantation in mouse embryos is essential for establishing imprinted X chromosome inactivation. Nuclear transplantation (NT) studies using nuclei derived from non-growing (ng) and full-grown (fg) oocytes have indicated that maternal-specific repressive modifications are imposed on Xm-Xist during oogenesis, as well as on autosomal imprinted genes. Recent studies have revealed that histone H3 lysine 9 trimethylation (H3K9me3) enrichments on Xm-Xist promoter regions are involved in silencing at the preimplantation stages. However, whether H3K9me3 is imposed on Xm-Xist during oogenesis is not known. Here, we dissected the chromatin states in ng and fg oocytes and early preimplantation stage embryos. Chromatin immunoprecipitation experiments against H3K9me3 revealed that there was no significant enrichment within the Xm-Xist region during oogenesis. However, NT embryos with ng nuclei (ngNT) showed extensive Xm-Xist derepression and H3K9me3 hypomethylation of the promoter region at the 4-cell stage, which corresponds to the onset of paternal Xist expression. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Although the condensed Xm-Xist genomic locus relaxed during early preimplantation phases, the extent of the relaxation across Xm-Xist loci derived from normally developed oocytes was significantly smaller than those of paternal-Xist and ngNT-Xist genomic loci. Furthermore, Xm-Xist from 2-cell metaphase nuclei became derepressed following NT. We propose that chromatin condensation is associated with imprinted Xist repression and that skipping of the condensation step by NT leads to Xist activation during the early preimplantation phase.


Cross-Jurisdiction Comparative Research in Work Disability Prevention: Introduction to the Special Series.
The systems that societies construct to support work disability prevention can have powerful effects on both the experiences of people with work disability as well as their health and employment outcomes. Comparative studies between jurisdictions provide an opportunity to gain insights into these system level impacts, by comparing system features, processes and experiences; and by determining if jurisdictional variation affects outcomes. In turn, this can prompt policy and practice reform. Reflecting the diversity of work disability systems globally, there is growing interest in cross-jurisdiction comparative research in the field. This special series presents seven articles addressing important methodological and conceptual aspects of comparative research in work disability prevention, and presents practical examples of how jurisdictions vary and the impact this can have on workers.


Comparison of direct medical care costs between patients receiving care in a designated palliative care unit and the usual care units.
The need for palliative services is increasing throughout Thailand. A few palliative care units have been established in the nation so far. An economic evaluation of palliative care units has never been explored. This study compared between the medical costs of terminally ill patients receiving palliative care in a palliative care unit and the usual care units during their final admissions. This study was a retrospective observational study comparing the costs of care for patients who died in a tertiary hospital. The study group comprised patients who died in a palliative care unit, then matched with deceased patients from other units by diagnosis-related groups. Patients not indicating of having received palliative care in the medical records were excluded. The direct medical costs of the patients' care and their data were collected from the finance department database and by medical chart review. Data were entered into the SPSS statistical database. The costs of the control group were calculated from the day when palliative care was initiated RESULTS: The total cost of care was significantly lower in the palliative care unit by 45 percent. The cost reduction notably was from the shorter length of stay and lower expenditure on medication and investigations in the palliative care unit. The utilization of aggressive treatment was higher in the usual units. The palliative care unit was associated with cost savings in caring for terminally ill patients in a tertiary hospital in Thailand.


Paliperidone extended-release: a review of efficacy and tolerability in schizophrenia, schizoaffective disorder and bipolar mania.
Paliperidone extended-release (ER), a once-daily, oral, atypical antipsychotic, has been available in the USA and the EU for the treatment of schizophrenia for more than 2 years and was recently (July 2009) approved in the USA for treatment of schizoaffective disorder. Additional data on its efficacy and safety, including that for additional indications, is emerging. This review provides a background on the compound and summarizes recent data available on treatment of schizophrenia, including comparative data with other antipsychotics, and efficacy and safety data from clinical trials in schizoaffective and bipolar disorders. The reader will gain knowledge of the compound and the existing clinical data so far for paliperidone ER. Paliperidone ER is effective for the treatment of schizophrenia and is at present the only antipsychotic approved in the USA for treatment of schizoaffective disorder. Its efficacy and tolerability profile in treating patients with schizophrenia or schizoaffective disorder indicates that paliperidone ER offers an important treatment option among atypical antipsychotic therapy for these patients.


Parallel analysis of miRNAs and mRNAs suggests distinct regulatory networks in Crassostrea gigas infected by Ostreid herpesvirus 1.
Since 2008, the aquaculture production of Crassostrea gigas was heavily affected by mass mortalities associated to Ostreid herpesvirus 1 (OsHV-1) microvariants worldwide. Transcriptomic studies revealed the major antiviral pathways of the oyster immune response while other findings suggested that also small non-coding RNAs (sncRNA) such as microRNAs might act as key regulators of the oyster response against OsHV-1. To explore the explicit connection between small non-coding and protein-coding transcripts, we performed paired whole transcriptome analysis of sncRNA and messenger RNA (mRNA) in six oysters selected for different intensities of OsHV-1 infection. The mRNA profiles of the naturally infected oysters were mostly governed by the transcriptional activity of OsHV-1, with several differentially expressed genes mapping to the interferon, toll, apoptosis, and pro-PO pathways. In contrast, miRNA profiles suggested more complex regulatory mechanisms, with 15 differentially expressed miRNAs (DE-miRNA) pointing to a possible modulation of the host response during OsHV-1 infection. We predicted 68 interactions between DE-miRNAs and oyster 3'-UTRs, but only few of them involved antiviral genes. The sncRNA reads assigned to OsHV-1 rather resembled mRNA degradation products, suggesting the absence of genuine viral miRNAs. We provided data describing the miRNAome during OsHV-1 infection in C. gigas. This information can be used to understand the role of miRNAs in healthy and diseased oysters, to identify new targets for functional studies and, eventually to disentangle cause and effect relationships during viral infections in marine mollusks.


Identification and cross-species comparisons of CYP2F subfamily genes in mammals.
The cytochrome P450 2F (CYP2F) subfamily genes are currently known only from cDNA sequences in human, mouse, rat and goat. Compared to other divisions of the CYP2 gene family, the CYP2F subfamily is unusual in having few genes per species and in being selectively expressed in lung tissues. Sequencing genomic DNAs from human and gorilla has allowed us to determine the number of CYP2F subfamily loci in these species, the sources of known human transcripts, and the functional status of CYP2F loci in both primates. This information will make accurate genotyping of the functional and medically significant CYP2F1 gene possible in humans. Comparisons across multiple species show that the sequences of CYP2F subfamily genes are very conserved in mammals for intronic as well as exonic DNA.


Brain-based learning in design and visual arts education: a bibliometric assessment of Scopus indexed literature.
This study aims to critically review, quantify, and assess research outcomes on brain-based learning with an evidence-based study on Scopus indexed literature, with a focus to understand the evolution structure and growth, detect trends, subject development, and most importantly, identify the gaps in the published body of literature that relates brain-based learning to design and visual arts education. Various scientometric tools were used to map, visualize, and analyze 186 research publications, indexed in Scopus in a twenty-year timespan '2001-2021'. Annual publication trends, relevant sources, prolific authors, authorship patterns, productive organizations and countries, funding agencies, keyword co-occurrence analysis, and thematic evolution mapping on brain-based learning publications were examined in this study. Despite the significance to apply brain-based learning strategies in design and visual arts education to boost students' knowledge and creative skills, the findings show a decline in quantities and growth patterns in brain-based learning research directed towards design disciplines in the past twenty years. Among the identified (186) documents published in (128) sources, with (1013) citations, the study detected only (57) research (30%) that were related to 'design education,' including those focusing on 'instructional design, 'and 'syllabus design' whereas only (3) articles were in 'design and visual arts' disciplines. These rather small numbers reflect the big gap in the current body of literature that associates brain-based learning with creativity-based disciplines, specifically in design and visual arts education. This infers the necessity to direct the attention of academics, researchers, and educationalists in the fields of design and arts towards brain-based learning applications, research and pedagogy.


A novel peroxisome proliferator-activated receptor gamma ligand improves insulin sensitivity and promotes browning of white adipose tissue in obese mice.
Nuclear receptor Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a promising target for the treatment of type 2 diabetes. The antidiabetic drug thiazolidinediones (TZDs) are potent insulin sensitizers as full agonists of PPARγ, but cause unwanted side effects. Recent discoveries have shown that TZDs improve insulin sensitivity by blocking PPARγ phosphorylation at S273, which decouples the full agonism-associated side effects. PPARγ ligands that act through the blockage of PPARγ phosphorylation but lack the full agonist activity would be expected to improve insulin sensitivity without TZD-associated side effects, however, chemicals that carry such traits and bind to PPARγ with high-affinity are lacking. Moreover, TZDs are known to promote white-to-brown adipocyte conversion and energy expenditure and appear to require their full agonism on PPARγ for this activity. It is unknown whether a partial or non-TZD agonist of PPARγ is capable of promoting browning effect. In this study, we developed a novel non-TZD partial agonist of PPARγ and investigated its function on insulin sensitivity and white-to-brown conversion and energy expenditure in diet-induced obese mice. A novel indole-based chemical WO95E was designed via medicinal chemistry and tested for PPARγ binding and activity and for the effect on PPARγ phosphorylation. Diet-induced obese mice were administered with WO95E for 4 weeks. Insulin sensitivity, glucose tolerance, body weight, fat tissue weight, adipocyte size, morphology, energy expenditure, and expression levels of genes involved in PPARγ activity, thermogenesis/browning, and TZD-related side effects were evaluated. WO95E binds to PPARγ with high affinity and acts as a PPARγ partial agonist. WO95E inhibits PPARγ phosphorylation and regulates PPARγ phosphorylation-dependent genes. WO95E ameliorates insulin resistance and glucose tolerance in mice of diet-induced obesity, with minimal TZD use-associated side effects. We found that WO95E promotes white-to-brown adipocyte conversion and energy expenditure and hence protects against diet-induced obesity. WO95E decreases the size of adipocytes and suppresses adipose tissue inflammation. WO95E also suppresses obesity-associated liver steatosis. WO95E improves insulin sensitivity and glucose homeostasis and promotes browning and energy expenditure by acting as a novel PPARγ phosphorylation inhibitor/partial agonist. Our findings suggest the potential of this compound or its derivative for the therapeutic treatment of insulin resistance and obesity.


The metabotropic glutamate receptor 1 is not involved in the facilitation of glutamate release in cerebrocortical nerve terminals.
In this study we have addressed the identification of the metabotropic glutamate receptor (mGluR) involved in the facilitation of glutamate release in nerve terminals from the cerebral cortex. mGluR1 and 5 are coupled to phosphoinositide hydrolysis and the activation of these receptors with the specific agonist 3,5-dihydroxyphenylglycine (DHPG) enhances the release of glutamate. We have examined whether mGluR1 is responsible for this modulatory effect by preparing nerve terminals from mGluR 1 deficient mice. The Ca2+-dependent glutamate release evoked by a submaximal depolarization is enhanced by the agonist DHPG in nerve terminals from both wild and mutant mice. This result is consistent with the finding that the mGluR agonist also induces a similar increase in the levels of diacylglycerol (DAG) in the nerve terminals from wild and mutant mice. Moreover, the activity-dependent switch from facilitation to inhibition of release, observed when a second stimulation of the receptor is applied shortly after (5 min) the first pulse, was also observed in the mutant mice. These results indicate therefore, that the facilitation of glutamate release is unlikely to be due to the activation of mGluR1 but related to another phosphoinositide coupled mGluR.


Hemodynamic actions of bepridil during treatment of stable angina pectoris.
Bepridil, a new calcium-entry blocker, was evaluated in 13 patients with chronic stable angina in a single-blind trial that was placebo controlled within patients. Its antianginal effects were recorded and left ventricular (LV) function was assessed at rest and during exercise by gated blood pool scintigraphy. Mean anginal frequency was significantly reduced from 7.3 to 3.4 episodes/week (p less than 0.01). Total work performed increased from 336 to 625 kpm (p less than 0.01). Supine resting LV end-diastolic volume index, end-systolic volume index, stroke volume index, cardiac index and ejection fraction (EF) were not altered by bepridil. During supine exercise, the EF decreased from 60 to 55 during placebo therapy. Despite an increase in total work, the mean EF increased from 60 to 62 (p less than 0.05 versus exercise on placebo) during exercise with bepridil therapy. Maximal exercise stroke volume index and cardiac index were significantly greater during bepridil therapy. Exercise resulted in new or increased LV wall motion abnormalities in 7 of 13 patients during placebo therapy. During bepridil therapy, only 4 new or increased wall motion abnormalities were noted despite the increase in total work performed. Therefore, bepridil is an effective antianginal agent, allowing an increase in exercise workload while preserving LV performance.


Study on thermal decomposition characteristics of AIBN.
It is found that the results such as observed in the differential scanning calorimeter (DSC), which show the major thermal decomposition (TD) of a self-reactive material, lack the detail to reveal what happens at the initial stage of a reaction. The reaction at this stage is corresponding to the handling condition of storage or transportation, often possibly having the potential to be developed to a runaway reaction. This paper examined and compared the thermal behaviors of AIBN at various working conditions in calorimeters and Dewar vessels. The mechanism that affects the initial reaction and self-heating behavior of the given material was clarified. Near its onset decomposition temperature, physical processes, such as sublimation or melting interfered the initial reaction of AIBN. The mutuality of the physical effect and the chemical reaction made AIBN behave differently under different measuring conditions, and as the result, quasi-autocatalysis or TD possibly occurs in the same sample at the handling temperature range. The heat accumulation storage tests in two Dewar vessels presented completely different self-heating behaviors due to this mechanism and heat transfer capability of the vessels.


Impact of the pharmacist on a multidisciplinary team in an antimicrobial stewardship program: a quasi-experimental study.
Antimicrobial stewardship programs (ASP) have been implemented to promote rational use of antimicrobial drugs. Multidisciplinary teams are needed to form effective committees. Assess the impact of ASP, with and without the presence of a pharmacist, in a cardiology hospital in Brazil. The program started with an infectious disease (ID) physician, and after 22 months, a pharmacist started to work in the ASP team. We present data related to: stage 1-before the program implementation; stage 2-with the ID physician; and stage 3 with the inclusion of a pharmacist. Analysis was made by segmented regression of time series. After the start of ASP there was a significant reduction of consumption of all antimicrobials. The pharmacist contributed to the significant reduction in consumption of fluoroquinolones, clindamycin and ampicillin/sulbactam and in increase in total cephalosporins use in stage 3. Adherence rate to the ASP team recommendations was 64.1%. There was a significant reduction of 69% in hospital antibiotics costs. A non-expensive ASP in a limited resource country resulted in reductions in antimicrobial consumption and costs. The multidisciplinary team contributed to maximize the impact of interventions.


Transcriptome revealing the dual regulatory mechanism of ethylene on the rhynchophylline and isorhynchophylline in Uncaria rhynchophylla.
Rhynchophylline (RIN) and isorhynchophylline (IRN) are extracted from Uncaria rhynchophylla, which are used to treat Alzheimer's disease. However, the massive accumulation of RIN and IRN in U. rhynchophylla requires exogenous stimulation. Ethylene is a potential stimulant for RIN and IRN biosynthesis, but there is no study on the role of ethylene in RIN or IRN synthesis. This study investigated the regulation of ethylene in RIN and IRN biosynthesis in U. rhynchophylla. An increase in the content of RIN and IRN was observed that could be attributed to the release of ethylene from 18 mM ethephon, while ethylene released from 36 mM ethephon reduced the content of RIN and IRN. The transcriptome and weighted gene co-expression network analysis indicated the up-regulation of seven key enzyme genes related to the RIN/IRN biosynthesis pathway and starch/sucrose metabolism pathway favored RIN/IRN synthesis. In comparison, the down-regulation of these seven key enzyme genes contributed to the reduction of RIN/IRN. Moreover, the inhibition of photosynthesis is associated with a reduction in RIN/IRN. Photosynthesis was restrained owing to the down-regulation of Lhcb1 and Lhcb6 after 36 mM ethephon treatment and further prevented supply of primary metabolites (such as α-D-glucose) for RIN/IRN synthesis. However, uninterrupted photosynthesis ensured a normal supply of primary metabolites at 18 mM ethephon treatment. AP2/ERF1, bHLH1, and bHLH2 may positively regulate the RIN/IRN accumulation, while NAC1 may play a negative regulatory role. Our results construct the potential bidirectional model for ethylene regulation on RIN/IRN synthesis and provide novel insight into the ethylene-mediated regulation of the metabolism of terpenoid indole alkaloids.


Intraspinal juxta-facet cysts: a case of bilateral ganglion cysts.
Juxta-facet cysts are relatively uncommon intraspinal lesions, causing radiculopathy, neurogenic claudication or myelopathy. To the best of our knowledge, only 4 cases of bilateral synovial or ganglioncysts were described. We report the 5th case of bilateral ganglioncysts of the lumbar spine. Generally, juxta-facet cysts should be differentiated from other intraspinal lesions, such as herniated discs, meningiomas and neurinomas. Correct preoperative diagnosis is necessary for adequate treatment, namely the (microscopic) resection of the cyst. After adequate treatment, complete recovery may be expected.


Anti-vascular endothelial growth factor dosing frequency and visual outcomes in macular oedema following branch retinal vein occlusion.
To determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice. Study eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year). Among 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (-3.0 vs 0.7 letters, respectively; p < 0.001). In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.


A Novel Approach Based on Data Redundancy for Feature Extraction of EEG Signals.
Feature extraction and classification for electroencephalogram (EEG) in medical applications is a challenging task. The EEG signals produce a huge amount of redundant data or repeating information. This redundancy causes potential hurdles in EEG analysis. Hence, we propose to use this redundant information of EEG as a feature to discriminate and classify different EEG datasets. In this study, we have proposed a JPEG2000 based approach for computing data redundancy from multi-channels EEG signals and have used the redundancy as a feature for classification of EEG signals by applying support vector machine, multi-layer perceptron and k-nearest neighbors classifiers. The approach is validated on three EEG datasets and achieved high accuracy rate (95-99 %) in the classification. Dataset-1 includes the EEG signals recorded during fluid intelligence test, dataset-2 consists of EEG signals recorded during memory recall test, and dataset-3 has epileptic seizure and non-seizure EEG. The findings demonstrate that the approach has the ability to extract robust feature and classify the EEG signals in various applications including clinical as well as normal EEG patterns.


Functional volumetric analysis of striatum using F-18 FP-CIT PET in patients with idiopathic Parkinson's disease and normal subjects.
We applied a simple isocontour volume-of-interest (VOI) method to analyze the whole striatum in an F-18 FP-CIT PET image and to investigate the usefulness of the method in differentiating healthy subjects from idiopathic Parkinson's disease (IPD) patients and the correlation of the value of functional volume parameters with the motor symptoms in patients with IPD. Forty-three IPD patients and 23 age-matched healthy controls underwent F-18 FP-CIT PET. Using a dedicated workstation, VOIs for the whole striatum were drawn automatically with the gradient delineation method. The SUVmax, SUVmean, functional volume (FV), striatal volume activity (SVA), striatal-specific binding (SSB), and volume-specific uptake ratio (VSUR) were compared between the IPD patients and the normal subjects. In the IPD patients, the correlation between the clinical factor and the functional parameters was assessed. The SUVmax, SUVmean, FV, SVA, SSB, and VSUR were significantly lower in the IPD patients than in the normal subjects. In the receiver operating characteristic analysis, those parameters had significant and good-to-excellent accuracy. In the patients with IPD, a moderate negative correlation was revealed between the SUVmax and H&Y stage, the SUVmean and H&Y stage, SVA and H&Y stage, the VSUR and H&Y stage, the FV and bradykinesia, and the SVA and bradykinesia. The functional volumetric analysis of the striatum based on simple isocontour VOI was a useful method of analyzing the F-18 FP-CIT PET image. Not only can it be easily applied in daily clinical practice, but it can also be used as a clinical parameter to discriminate IPD and to correlate it with the disease severity.


Chinese patients' response to doctor-patient relationship stimuli: evidence from an event-related potential study.
With improvements in medical technology, the doctor-patient relationship should be further improved. However, disputes between doctors and patients have increased, with the two groups frequently hurting each other. Therefore, we sought to explore the perception of Chinese patients regarding the stimuli of doctor-patient relationships with different valence. We used event-related potential (ERP) to explore the brain electrical activity of 19 undergraduate participants who had a clinical experience in the previous 6 months where they perceived negative, neutral, and positive doctor-patient relationships. The ERPs were recorded, and the early ERP components (P2) and late positive potential (LPP) were measured. Compared with the stimuli of negative doctor-patient relationships, those of positive doctor-patient relationships would attract more attention and have larger P2 amplitude; LPP was larger for the stimuli of negative doctor-patient relationships than neutral ones in the 500-800 ms, while in the 1100-1500 ms, the stimuli of neutral doctor-patient relationships elicited larger LPP amplitude than positive ones. Patients paid more attention to the stimuli of positive doctor-patient relationships because they expected to have the same positive relationship. Although threatening elements in negative doctor-patient relationships would catch patients' attention and make them have implicit emotional regulation, neutral stimuli with poker-faced doctors would cause lasting attention. These results illustrate the patients' real perception of the different valence of doctor-patient relationship stimuli.


Ambulation without wheelchairs for paraplegics with complete lesions.
Some salient features of the physical training programme for paraplegics at the State Rehabilitation Institute in Oslo are mentioned. A ten-year follow-up study of 42 clients with complete lesions (TI-L3) is presented. After an intensive physical training programme of some 10--15 weeks 74 per cent were able to climb and go down 20 standard stairs and 71 per cent were able to walk 100 metres indoors with crutches. The authors stress the importance of ambulations independent of wheelchairs whenever this is possible.


[Therapeutic interruption of pregnancy in the 4th month shortly after the patient underwent heart transplantation for obstructive hypertrophic heart disease].
We describe here therapeutic abortion of 16 weeks in a woman with a recently transplanted heart. Abortion was inevitable owing to the brief interval (4 months) from heart transplantation, for heavy immunosuppression with risk of congenital anomalies, and mother's will. Abortion was procured under general anaesthesia and without complications. The fetus weighted 70 gm, with good maternal outcome.


A novel fluorescence chamber for the determination of volume changes in human CaSki cell cultures attached on filters.
The objective of the study was to test the hypothesis that, in the cultured human cervical epithelium, CaSki, the effect of calcium mobilizing agents on transepithelial electrical conductance (GTE), is the result of cell volume decrease. CaSki cells attached on filters were loaded with fura-2, and measurements of fluorescence at the isosbestic wavelength 360 nm (excitation/emission [F360/510]) were made in a newly designed fluorescence chamber; this design allowed us also to determine changes in cytosolic calcium ([Ca2+]i). The experimental conditions were similar to those used to measure changes in paracellular permeability in the Ussing chamber, and they enabled us to compare the time-course of changes in [Ca2+]i, in F360/510, and in GTE. Hypertonicity increased, and hypotonicity decreased F360/510 and GTE, without having an effect on [Ca2+]i, and the changes in F360/510 and in GTE correlated linearly. Metabolism, bleaching, and extrusion of intracellular fura-2 were minimal, indicating that the changes in F360/510 reflect changes in dye concentration. Hypertonicity decreased, and hypotonicity increased the size of dispersed CaSki cells, suggesting that osmolarity-induced changes in F360/510 reflect changes in size of the attached cells. Ionomycin increased [Ca2+]i, F360/510, and GTE, but the increases in [Ca2+]i preceded those in F360/510 and GTE. The calcium chelator BAPTA blocked the ionomycin-induced increase in [Ca2+]i, F360/510, and in GTE. Preincubation with 4-acetamido-4'isothiocyanatostilbene-2,2'disulfonic acid (SITS) augmented the ionomycin-induced increase in [Ca2+]i, but blocked the increases in F360/510 and in GTE. Pretreatment of cells with hypertonic solution abrogated the increases in F360/510 and in GTE in response to ionomycin, but had little effect on the ionomycin-induced increase in [Ca2+]i. On the basis of these results we suggest that the ionomycin-induced increase in GTE is mediated by [Ca2+]i-dependent chloride secretion and osmotic water loss.


Designing Graphs that Promote Both Risk Understanding and Behavior Change.
Graphs show promise for improving communications about different types of risks, including health risks, financial risks, and climate risks. However, graph designs that are effective at meeting one important risk communication goal (promoting risk-avoidant behaviors) can at the same time compromise another key goal (improving risk understanding). We developed and tested simple bar graphs aimed at accomplishing these two goals simultaneously. We manipulated two design features in graphs, namely, whether graphs depicted the number of people affected by a risk and those at risk of harm ("foreground+background") versus only those affected ("foreground-only"), and the presence versus absence of simple numerical labels above bars. Foreground-only displays were associated with larger risk perceptions and risk-avoidant behavior (i.e., willingness to take a drug for heart attack prevention) than foreground+background displays, regardless of the presence of labels. Foreground-only graphs also hindered risk understanding when labels were not present. However, the presence of labels significantly improved understanding, eliminating the detrimental effect of foreground-only displays. Labels also led to more positive user evaluations of the graphs, but did not affect risk-avoidant behavior. Using process modeling we identified mediators (risk perceptions, understanding, user evaluations) that explained the effect of display type on risk-avoidant behavior. Our findings contribute new evidence to the graph design literature: unlike what was previously feared, we demonstrate that it is possible to design foreground-only graphs that promote intentions for behavior change without a detrimental effect on risk understanding. Implications for the design of graphical risk communications and decision support are discussed.


A Comprehensive Multidisciplinary Management Plan Is Effective in Reducing the Prevalence of Overweight and Obesity in Childhood and Adolescence.
Obesity in childhood and adolescence represents a major health problem of our century. In Greece, 30-35% of children and adolescents are overweight or obese. Objective and Hypotheses: To investigate the effectiveness of a comprehensive multidisciplinary personalized management plan at reducing the prevalence of overweight and obesity in childhood and adolescence. One thousand (n = 1,000) children and adolescents aged 2-18 years (mean age ± SD: 10.09 ± 2.86 years; 520 females, 480 males) were studied prospectively. Subjects were classified as obese (n = 579, 57.9%), overweight (n = 295, 29.5%) or having a normal body mass index (BMI) (n = 126, 12.6%) according to the International Obesity Task Force cutoff points. All subjects were evaluated by a multidisciplinary team at frequent intervals, received personalized advice on diet and exercise and were studied prospectively for 1 year. Detailed clinical evaluation and laboratory investigations were performed at the beginning and at the end of the study. At initial evaluation, 57.9% of subjects were obese, 29.5% overweight and 12.6% of normal BMI. Indices of cardiometabolic disease were higher in obese than in overweight and normal-BMI subjects. Following 1 year of multidisciplinary management interventions, the prevalence of obesity decreased by 16.8%, the prevalence of normal BMI increased by 8.2%, and all cardiometabolic indices improved significantly. A personalized multidisciplinary management plan is effective at reducing the prevalence of obesity in childhood and adolescence.


The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface.
The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal-fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G-negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity.


The mechanical strength of bone in different rat models of experimental osteoporosis.
In order to discover good parameters for experimental osteoporosis, we measured the failure load of the femoral neck and the bending strength of the tibia in orchidectomized (ORC) (20 rats for 4 weeks), ovariectomized (OVX) (28 rats for 6 weeks), and immobilized (IMM) (33 rats for 3 weeks) rats. Each of these operations led to a significant decrease in trabecular bone volume when compared with corresponding controls (p < 0.001). The ash weight of femurs was significantly decreased in ORC (p < 0.05) and IMM (p < 0.001) rats, but not in OVX rats. Growth of the femur was somewhat slower in ORC (p < 0.05) and IMM rats (p < 0.05), but not in OVX animals. All three osteoporosis models showed significant decreases in the maximal load of the femoral neck (ORC: 23.9%, p < 0.001; OVX: 15.8%, p < 0.001; IMM: 27.7%, p < 0.001), as well as in energy absorption (ORC: 43.9%, p < 0.001; OVX: 28.3%, p < 0.001; IMM: 45.3%, p < 0.001). In tibia orchidectomy reduced maximal strength and energy absorption significantly (10%, p < 0.01; 27.8%, p < 0.01), but ovariectomy decreased only maximal load (8.7%, p < 0.01) and immobilization only energy absorption (18.0%, p < 0.01). Our results suggest that the mechanical strength of the femoral neck is a sensitive indicator of bone loss in all three osteoporosis models.


Use of a swine bioassay and a RT-PCR assay to assess the risk of transmission of swine hepatitis E virus in pigs.
The objective of this study was to assess the risk of transmission of swine hepatitis E virus (swine HEV) to naïve pigs by inoculation with tissues or feces collected from pigs infected experimentally with swine HEV. Seventy-five, 3-week-old pigs were assigned randomly to 24 groups of 3-4 pigs and inoculated with homogenates of tissues (liver, heart, pancreas, or skeletal muscle) or a suspension of feces from swine HEV-infected pigs collected at 3, 7, 14, 20, 27, or 55 days post inoculation (DPI). Each inoculum was prepared as a 10% suspension (w/v) in PBS buffer and tested by a semi-quantitative RT-PCR for swine HEV RNA and by the swine bioassay. The inoculation route was intravenous for liver, heart and pancreas, and via stomach tube for skeletal muscle and fecal suspension. The liver homogenate inocula and feces collected at 3-7 and 14-20 DPI were positive for swine HEV RNA by RT-PCR. The pigs inoculated with liver homogenates collected at 3-7 and 14-20 DPI developed anti-HEV antibodies and swine HEV RNA was detected in their sera. Pigs inoculated with heart, pancreas, skeletal muscle homogenates or fecal suspensions failed to develop anti-HEV antibodies. These findings suggest that there is a potential risk of transmission of swine HEV via liver tissue from infected pigs in the early stages (3-20 DPI) of infection and the in vitro RT-PCR assay correlates well with the swine bioassay.


[A scanning method for detecting colorectal tumors].
To develop a method for survey of colorectal tumors. Mucus obtained by digital rectal examination was smeared on a slice to react with peanut agglutinin labeled by Horseradish-peroxidase. Brown color was noted in positive reaction. In detecting colorectal tumors, the sensitivity and specificity of the method was 88.2% and 92.5% respectively. The method is effective in detecting colorectal tumors in humans.


Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.
To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. A randomized controlled study. A university research laboratory. Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. Detection threshold for a vibrotactile stimulus. The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.


Src-family tyrosine kinase fyn phosphorylates phosphatidylinositol 3-kinase enhancer-activating Akt, preventing its apoptotic cleavage and promoting cell survival.
Phosphatidylinositol 3-kinase enhancer-activating Akt (PIKE-A) binds Akt and upregulates its kinase activity, preventing apoptosis. PIKE-A can be potently phosphorylated on tyrosine residues 682 and 774, leading to its resistance to caspase cleavage. However, the upstream tyrosine kinases responsible for PIKE-A phosphorylation and subsequent physiological significance remain unknown. Here, we show that PIKE-A can be cleaved by the active apoptosome at both D474 and D592 residues. Employing fyn-deficient mouse embryonic fibroblast cells and tissues, we demonstrate that fyn is essential for phosphorylating PIKE-A and protects it from apoptotic cleavage. Active but not kinase-dead fyn interacts with PIKE-A and phosphorylates it on both Y682 and Y774 residues. Tyrosine phosphorylation in PIKE-A is required for its association with active fyn but not for Akt. Mutation of D into A in PIKE-A protects it from caspase cleavage and promotes cell survival. Thus, this finding provides a molecular mechanism accounting for the antiapoptotic action of src-family tyrosine kinase.


Removal of oral debris and bacteria during supervised tooth brushing.
To investigate foam generation during brushing, and the oral debris and bacteria removal efficacy of an experimental gel-to-foam dentifrice compared to a commercially-available dentifrice after brushing. Thirty-four subjects participated in this blinded, crossover study. After a wash-out period prior to each session of product use, subjects reported to the site having abstained from oral hygiene, eating and drinking from 22:00 h on the evening prior to treatment visits. The subjects brushed with a weighed dose of assigned paste and were asked to expectorate their toothpaste slurry into a collection vessel at 30 and 60 seconds during supervised brushing. The expectorated foam was measured immediately, after which subjects rinsed with 10 ml of sterile water and expectorated into the same vessel. Samples were placed on ice and immediately transported to the laboratory for analysis. Bacteria (total anaerobes and VSC-producing bacteria) were enumerated using appropriate selective media. To calculate the amount of debris, a measured portion of the sample was deposited onto a pre-weighed dish and weighed. Dishes were dried thoroughly and weighed again after cooling. Use of the gel-to-foam dentifrice resulted in 105% greater foam volume compared with use of the control dentifrice (p < 0.0001). Further, the gel-to-foam dentifrice removed 15.77% more debris than the control dentifrice (p-value = 0.0342). There was greater removal of total anaerobes and VSC-producing bacteria by the gel-to-foam dentifrice versus the control dentifrice (p-value < 0.0001). Single use of a gel-to-foam dentifrice generated a greater volume of foam and removed a greater amount of oral debris and bacteria during brushing than a standard dentifrice.


Cholinergic and adrenergic neuroreceptors in urinary tract of female dogs. Evaluation of function with pharmacodynamics.
Our preliminary pharmacodynamic studies on the lower urinary tract of adult female dogs indicate that cholinergic and adrenergic (alpha and beta) neuroreceptors in the urethra appear to coordinate the detrusor and urethral function during micturition. Urethral resistance measured as urethral pressure was easily altered with various pharmacologic agents. However, only bethanechol elicited detrusor response measured as intravesical pressure. The possible clinical usefulness of various drugs is outlined. Our results indicate the therapeutic value of ephedrine sulfate and propranolol in stress urinary incontinence; phenoxybenzamine in neurogenic vesical dysfunction and functional outlet obstruction; phenoxybenzamine plus bethanechol in atonic neurogenic bladder; and imipramine in enuresis.


Impact of history of febrile convulsions on the risk difference of febrile convulsions with the tetravalent measles-mumps-rubella-varicella vaccine: Post-hoc exploratory analysis of results from a matched-cohort study.
This post-hoc analysis of data from a matched cohort study investigated the risk of febrile convulsions (FC) 5-12 days post-first dose of measles-mumps-rubella-varicella vaccine (MMRV) in a low-risk population, compared to measles-mumps-rubella (MMR) and varicella (V) vaccines administered separately. The low-risk population excluded children with personal history of FC (Scenario 1) and children with personal or/and family history (≥1 parent/sibling) of FC (Scenario 2). Incidence of FC post-MMRV in Scenario 2 (excluding at risk children) (36.3-49.5/100,000) and post-MMR+V in the whole cohort including children with personal/family history of FC (43.6/100,000) were similar. The risk difference of FC increased by 0.2 case/100,000 in Scenario 1 and decreased by 5.3-8.6 cases/100,000 of vaccinated children in Scenario 2, compared to the whole cohort. The overall risk of FC post-first dose MMRV vaccination could be lowered by administering MMRV only to children with no personal or family history of FC.


Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas.
Small, noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. We used comparisons of global miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in our patient population. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient among 736 miRNAs that were evaluated. This result has been previously observed by other groups; however, we extend this finding with the unique observation that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, we found that oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls. We conclude that miR-375 represents a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor's invasive properties.


Response of the lens to oxidative-osmotic stress.
Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H2O2 present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity. We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K+ in the lenses under the double stress. Apparently, the slightly decreased 86Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the 86Rb efflux was found in these lenses, however.


Security of quantum key distribution from generalised entropy accumulation.
The goal of quantum key distribution (QKD) is to establish a secure key between two parties connected by an insecure quantum channel. To use a QKD protocol in practice, one has to prove that a finite size key is secure against general attacks: no matter the adversary's attack, they cannot gain useful information about the key. A much simpler task is to prove security against collective attacks, where the adversary is assumed to behave identically and independently in each round. In this work, we provide a formal framework for general QKD protocols and show that for any protocol that can be expressed in this framework, security against general attacks reduces to security against collective attacks, which in turn reduces to a numerical computation. Our proof relies on a recently developed information-theoretic tool called generalised entropy accumulation and can handle generic prepare-and-measure protocols directly without switching to an entanglement-based version.


A meta-analysis of mismatch negativity in children with attention deficit-hyperactivity disorders.
Mismatch negativity (MMN) is an optimal neurophysiological signal to assess the integrity of auditory sensory memory and involuntary attention switch. The generation of MMN is independent of overt behavioral requirements, concentration or motivation, and thus serves as a suitable tool to study the perceptual function in children with attention deficit-hyperactivity disorders (ADHD). It remains unclear whether ADHD children showed altered MMN responses. Therefore we performed a meta-analysis of peer-reviewed MMN studies that had targeted both typically developed and ADHD children to examine the pooled effect size. The published articles between 1990 and 2014 were searched in PubMed, Medline, Cochrane, and CINAHL. The mean effect size and a 95% confidence interval (CI) were estimated. Six studies, consisting of 10 individual investigations, were included in the final analysis. A significant effect size of 0.28 was found (p=0.028, 95% CI at 0.03-0.53). These results were also free from publication bias or heterogeneity. In conclusion, our meta-analysis results suggest ADHD children demonstrated a reduced MMN amplitude compared to healthy controls.


Parathyroid storm: immediate recognition and pathophysiological considerations.
A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling.


Silk fibroin for skin injury repair: Where do things stand?
Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. STATEMENT OF SIGNIFICANCE: Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.


Patients' and providers' experiences with video consultations used in the treatment of older patients with unipolar depression: A systematic review.
WHAT IS KNOWN ON THE SUBJECT?: Depression is the most common cause of mental illness amongst older people. As a result of the growth of the older population, it is expected that an increasing number of older people will need treatment. Depression can be effectively treated-but fewer than half of those who are affected receive treatment. Barriers to receiving treatment are lack of resources and trained healthcare providers, social stigma, incorrect diagnoses and long distances to treatment facilities. There is an increased need for alternative ways of treating patients with depression. The use of video consultations has shown to be a viable option for delivering mental health care to older patients. Use of video consultations allows patients to receive treatment in their own homes. None of the existing reviews have focused on satisfaction with the use of video consultations amongst older people with depression. This paper provides knowledge regarding the use of video consultations, especially for older people with depression. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: No previous review has sought to understand the use of video consultations in mental health care to older patients with depression. The results show that video consultations support mental health practice, especially as a useful alternative when face-to-face therapy is not possible. An initial scepticism from participants quickly disappeared when video consultations were experienced in action. The challenges associated with the use of video consultations seem to consist of technical problems and lack of support from staff. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health practitioners should consider the use of video consultations because it can support mental health practice, especially as a useful alternative when face-to-face therapy is not possible. ABSTRACT: Introduction Depression is the leading cause of mental illness amongst an ageing population and fewer than half of those who are affected receive treatment. There is an increased need for alternative ways of treating patients; the use of video consultations has been shown to be a viable option for delivering mental health care. However, none of the existing reviews have focused on satisfaction with the use of video consultations amongst older people with depression and providers. Aim To conduct a systematic review of the existing literature focusing on patients' and providers' experiences of video consultations for depression. Method Eight scientific databases were searched. In all, 3,537 articles were identified and, of these, 21 peer-reviewed articles were included in this review. Results The results show that video consultations support mental health practice, especially as a useful alternative when face-to-face therapy is not possible. Any initial scepticism quickly disappeared when video consultations were experienced in action. The challenges seem to consist of technical problems and lack of support from staff. Discussion The experiences and satisfaction of older people with depression seem to be positive, although methodological limitations and deficiencies of the reviewed articles should be considered. More qualitative research is needed, and future studies should focus on specific diagnoses and providers' experiences. Implications for practice Video consultations support mental health practice, especially as a useful alternative when face-to-face therapy is not possible.


The role of cyclic AMP in parathyroid hormone action in the toad bladder.
Parathyroid hormone (PTH) inhibited active transport of inorganic phosphate and stimulated an increase in cyclic AMP concentration in the urinary bladder of the toad, Bufo marinus. Active transport of phosphate in the toad bladder was also inhibited by an analog of cyclic AMP (dibutyryl cyclic AMP) and by other drugs (pitressin and theophylline) which increase toad bladder intracellular cyclic AMP concentration. These data support the concept that cyclic AMP may be the mediator of PTH-induced phosphate transport inhibition in the toad bladder.


Cell type-specific labeling of newly synthesized proteins by puromycin inactivation.
Puromycin and its derivative O-propargyl puromycin (OPP) have recently found widespread use in detecting nascent proteins. Use of these metabolic labels in complex mixtures of cells leads to indiscriminate tagging of nascent proteomes independent of cell type. Here, we show how a widely used mammalian selection marker, puromycin N-acetyltransferase, can be repurposed for cell-specific metabolic labeling. This approach, which we named puromycin inactivation for cell-selective proteome labeling (PICSL), is based on efficient inactivation of puromycin or OPP in cells expressing puromycin N-acetyltransferase and detection of translation in other cell types. Using cocultures of neurons and glial cells from the rat brain cortex, we show the application of PICSL for puromycin immunostaining, Western blot, and mass spectrometric identification of nascent proteins. By combining PICSL and OPP-mediated proteomics, cell type-enriched proteins can be identified based on reduced OPP labeling in the cell type of interest.


Muscle phenotype of a rat model of Duchenne muscular dystrophy.
Our aim was to assess key muscle imaging and contractility parameters in the Duchenne muscular dystrophy (DMD) rat model (Dmd-KO rat), which have not yet been characterized sufficiently. We performed in-vivo magnetic resonance imaging (MRI) for thigh and leg muscles, and performed hematoxylin and eosin (H&E) staining and in-vivo muscle contractility testing in specific hindlimb muscles. MRI prior to testing muscle contractility revealed multiple, unevenly distributed focal hyperintensities in the Dmd-KO rat quadriceps and tibialis anterior muscles. H&E staining showed corresponding areas of inflammation and ongoing regeneration. In-vivo contractile testing showed maximal force generated by Dmd-KO muscles was significantly lower, and susceptibility to injury was ~ two-fold greater in the Dmd-KO rats compared to wild-type (WT) rats. Together, the MRI findings, histological findings, and the low strength and high susceptibility to injury in muscles support use of the Dmd-KO rat as an animal model of DMD.


Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools.
Early detection strategies and improvements in cancer treatment have dramatically reduced the cancer mortality rate in the United States (US). However, cardiovascular (CV) side effects of cancer therapy are frequent among the 17 million cancer survivors in the US today, and cardiovascular disease (CVD) has become the second leading cause of morbidity and mortality among cancer survivors. Circulating biomarkers are ideal for detecting and monitoring CV side effects of cancer therapy. Here, we summarize the current state of clinical studies on conventional serum and plasma CVD biomarkers to detect and prevent cardiac injury during cancer treatment. We also review how novel exploratory tools such as genetic testing, human stem cell-derived cardiomyocytes, Omics technologies, and artificial intelligence can elucidate underlying molecular and genetic mechanisms of CV injury and to improve predicting cancer therapy-related cardiotoxicity (CTRC). Current regulatory requirements for biomarker qualifications are also addressed. We present generally applicable lessons learned from published studies, particularly on how to improve reproducibility. The combination of conventional circulating biomarkers and novel exploratory tools will pave the way for precision medicine and improve the clinical practice of prediction, detection, and management of CTRC.


Pathological alterations of strial capillaries in dominant white spotting W/Wv mice.
Dominant white spotting W/W(v) and W(v)/W(v) mice are well-known mutants that lack strial intermediate cells in their cochlea and manifest hereditary sensorineural hearing loss. We recently reported marked thickening of and IgG deposition on the basement membrane of strial capillaries in W/W(v) mutant mice, similar to observations made in aged animals and in animals with autoimmune sensorineural hearing loss. The present study aimed to clarify the age-dependent changes in these pathological findings of strial capillaries in the W/W(v) mice. Male WBB6F1 +/+ and dominant white spotting W/W(v) mutant mice were sacrificed by transcardiac perfusion with paraformaldehyde solution. The cochlear ducts were isolated and subjected to light- and electron-microscopy, immunohistochemistry, immunoelectron microscopy. Alternatively, lanthanum chloride tracer examination in the isolated cochlear ducts was performed in order to compare the permeability of the strial capillaries between +/+ and W/W(v) mice. In the W/W(v) mice, thickening of and IgG deposition on the basement membrane of strial capillaries were observed as early as 1 week after birth and became more noticeable with age. Deposited IgG was preferentially localized to the thickened basement membrane and was also observed in partially the intercellular space between adjacent of endothelial cells. In addition, pinocytotic vesicles both in the apical and basal lesions of such cells also showed IgG deposition. Lanthanum chloride was retained along apical plasma membrane of the endothelial cells in the +/+ mice but penetrated through the endothelial layer in the W/W(v) mice. These results indicate that active transport via pinocytotic vesicles as well as increased permeability of strial capillaries in the W/W(v) mice occur in the early stage after birth, resulting in the morphological alterations in the strial capillaries of these mice.


Expression of SOCS1 and CXCL12 Proteins in Primary Breast Cancer Are Associated with Presence of Circulating Tumor Cells in Peripheral Blood.
Circulating tumor cells (CTCs) are independent prognostic factors in the primary and metastatic breast cancer patients and play crucial role in hematogenous tumor dissemination. The aim of this study was to correlate the presence of CTCs in peripheral blood with the expression of proteins in tumor tissue that have a putative role in regulation of cell growth and metastatic potential. This prospective study included 203 primary breast cancer patients treated by definitive surgery. CTCs were detected by quantitative real-time PCR for the expression of epithelial (CK19) or epithelial-to-mesenchymal transition-inducing transcription factor genes (TWIST1, SNAIL1, SLUG, and ZEB1). Expression of APC, ADAM23, CXCL12, E-cadherin, RASSF1, SYK, TIMP3, BRMS1, and SOCS1 proteins in primary breast tumor tissue was evaluated by immunohistochemistry. CTCs with epithelial markers were found in 17 (9.2%) patients. Their occurrence was associated with inhibition of SOCS1 expression (odds ratio [OR] = 0.07; 95% confidence interval [CI], 0.03-0.13; P < .001). CTCs with positive epithelial-to-mesenchymal transition markers were detected in 30 (15.8%) patients; however, no association with analyzed protein expressions was found. Overall, CTCs were detected in 44 (22.9%) patients. Presence of any CTC marker was significantly associated with positive CXCL12 expression (OR = 3.08; 95% CI, 1.15-8.26; P = .025) and lack of SOCS1 expression (OR = 0.10; 95% CI, 0.04-0.25; P < .001) in patient's tumor tissues. As both CXCL12 and SOCS1 proteins are involved in cytokine signaling, our results provide support for the hypothesis that aberrant signaling cross talk between cytokine and chemokine responses could have an important role in hematogenous dissemination of tumor cells in breast cancer.


Patients with schizophrenia are less prone to interpret virtual others' empathetic questioning as helpful.
Individuals with schizophrenia are impaired in their neurocognition and present cognitive biases. These impairments may lead to a deficit in recognizing helping intentions of others. To investigate recognition of help, we designed a card-guessing game (Virtual Help Recognition Paradigm) involving two successive virtual agents asking questions to the participant at different moments of the game. These questions were either empathetic (i.e. on the subject's feelings) or non-empathetic (i.e. on technical aspects of the game). We assessed how much the participant felt that the virtual agent had helped him and, her attitude and personality traits. We measured how much the participant trusted the virtual agent with a monetary allocation procedure. Twenty individuals with schizophrenia and twenty healthy controls were recruited. The controls' ratings demonstrated that they interpreted empathetic questioning as helping and rewarded it positively with an increased monetary allocation. Participants with schizophrenia had a reduced perception of the differences between the two agents. Only the rating concerning the "interest/attention" of the agent toward these participants yielded significant differences among conditions. Hypothetically, individuals with schizophrenia take into account the fact they are the object of another's attention, but may fail to infer a helping intention and to behave accordingly.


Molecular prevalence of Enterocytozoon bieneusi in stray cats of İzmir, Türkiye.
The phylum Microsporidia contains obligate single celled parasites that can infect many vertebrate hosts including humans. Enterocytozoon bieneusi is considered as the most diagnosed species in humans. E. bieneusi has also been detected in many animals such as cats, dogs and cattle. Among these animals, cats are carriers of type D and IV which are the most common human pathogenic genotypes of E. bieneusi. In Türkiye, the prevalence of E. bieneusi in stray cats is not well known. Therefore, in this study, the molecular prevalence of E. bieneusi in stray cats (n = 339) was determined by Real-Time PCR targeting ribosomal DNA ITS (internal transcribed spacer) region of E. bieneusi. Initially, the analytical sensitivity of Real-Time PCR was determined by a plasmid control and then E. bieneusi DNA was investigated in fecal samples of stray cats. The results showed that the analytical sensitivity of Real-Time PCR targeting ITS region of E. bieneusi was ≤1 copy plasmid/reaction. Analysis of fecal samples revealed that the molecular prevalence of E. bieneusi was 50.15% (170/339). Overall, these results showed that the Real-Time PCR successfully detected E. bieneusi in cat's fecal samples and stray cats can be an important source for transmission of E. bieneusi to humans and other animals.


Local therapy for cytomegalovirus retinopathy.
We sought to understand better the efficacy and risks of local therapies (direct placement of drug into the eye) for the treatment of cytomegalovirus retinopathy. This understanding can be used to design rational treatment regimens, to formulate indications for use of local therapy, and to establish criteria for assessment of future results in this area. We collected information about local therapies through a review of published literature. Intraocular injection of ganciclovir and foscarnet and implantation of intraocular devices that slowly release ganciclovir are able to decrease the activity of cytomegalovirus retinopathy lesions and prevent their enlargement for variable periods of time. The time to disease progression (lesion enlargement) may be longer with intraocular devices than with current treatments using intravenously administered antiviral drugs. Local therapies have many advantages (for example, convenience, reduced cost, and lack of systemic toxicity), but there are potential disadvantages, including endophthalmitis, increased rates of retinal detachment, and development of nonocular cytomegalovirus disease and cytomegalovirus retinopathy in fellow, uninvolved eyes. Local therapies are effective for the treatment of cytomegalovirus retinopathy, but their relative risks and benefits, when compared with those of intravenous drug therapy, have yet to be fully evaluated. We anticipate that local therapy will be an important treatment modality for selected patients with cytomegalovirus retinopathy. Indications include the use of local therapy as an alternative therapy for patients who are unable to receive systemic therapy (intolerance to intravenous or oral medication, or lack of intravenous access) and as supplementation in patients whose retinal disease is incompletely controlled by maximum tolerated systemic medications. The use of local therapy as sole initial treatment in lieu of systemic therapy remains controversial. Its most useful role may be in conjunction with oral forms of antiviral drugs now in development.


Oesophageal resection for high-grade dysplasia in Barrett's oesophagus.
The aims of this study were to evaluate the prevalence of invasive cancer in patients with high-grade dysplasia in Barrett's oesophagus and to verify whether a second endoscopy with multiple biopsies could improve the accuracy of preoperative diagnosis. In addition, the mortality, morbidity and survival rates in patients with high-grade dysplasia having oesophageal resection were recorded. Fifteen patients were observed from 1982 to 1998; the first seven patients were offered primary oesophageal resection after diagnosis. The other eight patients underwent a second endoscopy with a median of 12 biopsies examined. All later underwent oesophageal resection. Invasive adenocarcinoma was found in five patients, with a minimal difference between the first and second periods (two of seven versus three of eight). There were no perioperative deaths. Early morbidity was observed in eight patients and late morbidity in four. The actuarial survival rate was 79 per cent at 5 years. The Karnofsky status was unchanged from preoperative values in 13 of 15 patients after a median follow-up of 46 months. These patients with high-grade dysplasia had a 33 per cent probability of harbouring invasive oesophageal carcinoma but even a second endoscopy failed to identify patients with invasive tumour. Oesophagectomy was performed with no deaths and remains a rational treatment in patients fit for surgery.


Baclofen in the treatment of post-amputation autonomous stump movements.
Baclofen at 20-40 mg/day was used to successfully treat two post-amputation patients who developed continuous complex involuntary movements of the proximal extremity. These autonomous movements were otherwise recalcitrant to therapy and were felt to arise from neural generators intrinsic to the spinal cord. Baclofen is known to be useful for spasticity of spinal etiology and now appears to be indicated for treatment of involuntary autonomous movements in post-amputation patients.


T2-FLAIR Mismatch Sign in Pediatric Low-Grade Glioma.
No qualitative imaging feature currently predicts molecular alterations of pediatric low-grade gliomas with high sensitivity or specificity. The T2-FLAIR mismatch sign predicts IDH-mutated 1p19q noncodeleted adult gliomas with high specificity. We aimed to assess the significance of the T2-FLAIR mismatch sign in pediatric low-grade gliomas. Pretreatment MR images acquired between January 2001 and August 2018 in pediatric patients with pediatric low-grade gliomas were retrospectively identified. Inclusion criteria were the following: 1) 0-18 years of age, 2) availability of molecular information in histopathologically confirmed cases, and 3) availability of preoperative brain MR imaging with non-motion-degraded T2-weighted and FLAIR sequences. Spinal cord tumors were excluded. Three hundred forty-nine patients were included (187 boys; mean age, 8.7 [SD, 4.8] years; range, 0.5-17.7 years). KIAA1549-B-Raf proto-oncogene (BRAF) fusion and BRAF p.V600E mutation were the most common molecular markers (n = 148, 42%, and n = 73, 20.7%, respectively). The T2-FLAIR mismatch sign was present in 25 patients (7.2%). Of these, 9 were dysembryoplastic neuroepithelial tumors; 8, low-grade astrocytomas; 5, diffuse astrocytomas; 1, a pilocytic astrocytoma; 1, a glioneuronal tumor; and 1, an angiocentric glioma. None of the 25 T2-FLAIR mismatch pediatric low-grade gliomas were BRAF p.V600E-mutated. Fourteen of 25 pediatric low-grade gliomas with the T2-FLAIR mismatch sign had rare molecular alterations, while the molecular subtype was unknown for 11 tumors. The T2-FLAIR mismatch sign was not observed in the common molecular alterations, BRAF p.V600E-mutated and KIAA1549-BRAF fused pediatric low-grade gliomas, while it was encountered in pediatric low-grade gliomas with rare pediatric molecular alterations.