Mechanics and prognostic value of left and right ventricular dysfunction in patients with systemic sclerosis.
Impairment of myocardial function is an important potential complication of systemic sclerosis (SSc) and associated with poor prognosis. The detection of left (LV) and right ventricular (RV) dysfunction may prompt specific therapeutic interventions. We sought to investigate the prognostic value of both LV and RV deformation in patients with SSc. Speckle tracking LV strain parameters [global longitudinal strain (GLS) and global circumferential strain (GCS)] and tricuspid annular peak systolic velocity (Ts') were measured in 103 patients with SSc and 103 age- and gender-matched controls. Subjects were followed for a median of 3.4 years for heart failure-specific admission or death, and the association of the study parameters with outcome was assessed using Cox proportional hazards models. GLS, GCS, and Ts' were significantly impaired in patients with SSc, even without pulmonary hypertension, compared with controls. GCS (r2 = 0.07, P = 0.03) but not GLS (r2 = 0.04, P = 0.11) was associated with systolic pulmonary artery pressure. During follow-up, SSc patients (n = 17, 17%) had more events than controls (n = 7, 7%, P = 0.04). In SSc patients, GCS (but not GLS), Ts', and 6-minute walk distance (6MWD) were significantly associated with outcome. 6MWD and Ts' (but not GCS) were independently associated with outcome. A model based on age, gender, 6MWD, and GCS was significantly improved by adding by adding Ts' (P = 0.02). RV dysfunction was associated with adverse outcome, independent of and incremental to clinical and LV deformation parameters in SSc. LV dysfunction appears to have less prognostic relevance than RV dysfunction.


Role of glutathione in Thiobencarb resistance in the European eel Anguilla anguilla.
Glutathione-dependent defense against xenobiotic toxicity is a multifaceted phenomenon that has been well characterized in mammals. In the present study, eels of species Anguilla anguilla were exposed to 15 ppm of the herbicide thiobencarb (S-4-chlorobenzyl diethylthiocarbamate) for 96 h. Eels exposed to the pesticide were grouped in 24-h intervals according to their time of death, while surviving intoxicated eels constituted another group (live animals). Glutathione content (GSx, GSH, GSSG) was determined in liver and muscle tissues of the dead and live (intoxicated) animals and compared to control values (nonexposed eels). The fish that died before 96 h of exposure were considered susceptible to thiobencarb, while those dead after 96 h and the surviving ones were called resistant. Hepatic glutathione (GSH) content in susceptible eels was lower than that in the control fish, while resistant eels presented GSH levels threefold higher than those of controls. Muscle glutathione levels in dead eels were practically unaffected, but there was a significant decrease in GSH levels in the surviving intoxicated eels. These results indicate that the eels that were able to induce glutathione synthesis in the liver due to the presence of thiobencarb in the medium demonstrated a greater longevity than those who lost glutathione homeostasis.


Mice lacking the immediate early gene Egr3 respond to the anti-aggressive effects of clozapine yet are relatively resistant to its sedating effects.
Immediate early genes (IEGs) of the early growth response gene (Egr) family are activated in the brain in response to stress, social stimuli, and administration of psycho-active medications. However, little is known about the role of these genes in the biological or behavioral response to these stimuli. Here we show that mice lacking the IEG transcription factor Egr3 (Egr3-/- mice) display increased aggression, and a decreased latency to attack, in response to the stressful social stimulus of a foreign intruder. Together with our findings of persistent and intrusive olfactory-mediated social investigation of conspecifics, these results suggest increased impulsivity in Egr3-/- mice. We also show that the aggression of Egr3-/- mice is significantly inhibited with chronic administration of the antipsychotic medication clozapine. Despite their sensitivity to this therapeutic effect of clozapine, Egr3-/- mice display a marked resistance to the sedating effects of acute clozapine compared with WT littermate controls. This indicates that the therapeutic, anti-aggressive action of clozapine is separable from its sedating activity, and that the biological abnormality resulting from loss of Egr3 distinguishes these different mechanisms. Thus Egr3-/- mice may provide an important tool for elucidating the mechanism of action of clozapine, as well as for understanding the biology underlying aggressive behavior. Notably, schizophrenia patients display a similar decreased susceptibility to the side effects of antipsychotic medications compared to non-psychiatric controls, despite the medications producing a therapeutic response. This suggests the possibility that Egr3-/- mice may provide insight into the neurobiological abnormalities underlying schizophrenia.


Serum concentrations of antibodies against vaccine toxoids in children exposed perinatally to immunotoxicants.
Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose-response relationship and possible vulnerable time windows of exposure are uncertain. In this study we applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity. The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children with regard to prenatal and postnatal PCB exposures. From a cohort of 656 singleton births formed in the Faroe Islands during 1999-2001, children were invited for examination with assessment of serum antibody concentrations at 5 years (before and after a booster vaccination) and at 7 years of age. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child's serum at 18 months of age. A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the antidiphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained 2 years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at 18 months of age. The strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an antidiphtheria antibody concentration below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum. Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure.


[Effects of intake of heated mixtures of glucose-lysine and glucose-methionine on bone calcium].
During food thermal treatment Maillard's reaction may occur, which implicates mainly the carbonyl groups of reductory sugars and amino protein groups. Maillard's reaction products (MRP) may interfere with mineral bioavailability because of modifications of their physical-chemical moiety in the food or the lumen, disrupting the absorption process or its normal metabolism. In this study, we sought to investigate MRP influence on issues related to Ca bioavailability in vitro and in vivo. Equimolar mixtures of glucose-lysine (GL) and glucose-methionine (GM) (40% moisture) were heated at 150 degrees C for 90 minutes (samples GL90 and GM90, respectively). In vitro solubility was measured by additioning each samples to a 3.75 mM Ca solution at intestinal pH and ionic strength; after shaking and centrifugation, soluble and insoluble calcium was determined. Three percent of GL90 and GM90 were individually added to the AIN93-G diet to obtain D-GL90 and D-GM90 diets. Three Wistar rats groups were fed for 21 days with both diets and with AIN93-G as control, carrying out calcium balance during last week and extirpating various organs after sacrifice. GM90 did not affect calcium solubility; GL90 reduced it slightly, remaining in both cases more than 94% soluble. D-GL90 and D-GM90 did not modify calcium bioavailability, with as effective usage as with the control diet (57.6 +/- 1.3%, 57.8 +/- 2.3% and 63.9 +/- 2.6% in control diet, D-GL90 and D-GM90, respectively). MRP intake produced, however, metabolic changes that decreased bone calcium, accumulating compensatorily in other organs.


Parallel fiber plasticity.
Cerebellar long-term depression (LTD) is classically observed when climbing fibers, originating from the inferior olive, and parallel fibers, axons of granule cells, are activated repetitively and synchronously. On the basis that the climbing fiber signals errors in motor performance, LTD provides a mechanism of learning whereby inappropriate motor signals, relayed to the cerebellar cortex by parallel fibers, are selectively weakened through their repeated, close temporal association with climbing fiber activity. LTD therefore provides a cellular substrate for error-driven motor learning in the cerebellar cortex. In recent years, it has become apparent that depression at this synapse can also occur without the need for concurrent climbing fiber activation provided the parallel fibers are activated in such a way as to mobilize calcium within the Purkinje cell. A form of long-term potentiation (LTP) has also been uncovered at this synapse, which similarly relies only upon parallel fiber activation. In brain slice preparations and contrary to expectation, each of these forms of parallel fiber induced plasticity, as well as classical LTD, does not remain confined to activated parallel fibers as previously thought, but both depression and potentiation have the capacity to spread to neighboring parallel fiber synapses several tens of microns away from the activated fibers. Here, the cellular mechanisms responsible for the induction and heterosynaptic spread of parallel fiber LTP and LTD are compared to those involved in classical LTD and the physiological implications that the heterosynaptic spread of plasticity may have on cerebellar signal processing are discussed.


International models. Home care in Canada.
Canada's exemplary health care system provides a great deal of medical coverage for its citizens, yet there are still some inconsistencies in delivery that need to be ironed out. This article takes a look at how home care is evolving in Canada and what the future holds for this growing industry.


Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes.
Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists regarding the optimum methods. The specific methods chosen to process optical mapping data are important because inappropriate data processing can affect the content of the data and thus alter the conclusions of the studies. Details of the different steps in processing optical imaging data, including image segmentation, spatial filtering, temporal filtering, and baseline drift removal, are provided in this review. We also provide descriptions of the common analyses performed on data obtained from cardiac optical imaging, including activation mapping, action potential duration mapping, repolarization mapping, conduction velocity measurements, and optical action potential upstroke analysis. Optical mapping is often used to study complex arrhythmias, and we also discuss dominant frequency analysis and phase mapping techniques used for the analysis of cardiac fibrillation.


Effectiveness of treatment with antihypertensive drugs and trends in mortality from stroke in the community.
A study was made of the changes in the treatment of hypertension, in the effectiveness of that treatment, and in mortality from cerebrovascular stroke in men and women in two counties in Finland. One of these counties was North Karelia, where a comprehensive cardiovascular programme based in the community had been launched in 1972. Cross sectional surveys in large representative samples of the middle aged populations were carried out in 1972, 1977, and 1982. Average annual mortality from stroke adjusted for age was calculated for the two year periods 1971-2, 1977-8, and 1980-1. The proportion of hypertensive men being effectively treated for their hypertension increased in both areas from 1972 to 1977 and further from 1977 to 1982. Mortality from stroke in middle aged men decreased in both areas during both observation periods. The proportion of hypertensive women being effectively treated greatly increased in both areas from 1972 to 1977. This was associated with a large decline in mortality from stroke. In North Karelia the proportion of women being effectively treated was remarkably high but decreased somewhat between 1977 and 1982; this decrease was associated with an increase in mortality from stroke in the women aged 35-64. These results support the idea that effective antihypertensive treatment in the community is a major determinant of mortality from stroke in both men and women.


Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation.
Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic" neoplasm. Single-agent immunotherapies have failed to demonstrate significant clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. We designed a neoadjuvant and adjuvant clinical trial comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg) as a means to study how the TME is altered by immunotherapy. Examination of resected PDACs revealed the formation of vaccine-induced intratumoral tertiary lymphoid aggregates in 33 of 39 patients 2 weeks after vaccine treatment. Immunohistochemical analysis showed these aggregates to be regulatory structures of adaptive immunity. Microarray analysis of microdissected aggregates identified gene-expression signatures in five signaling pathways involved in regulating immune-cell activation and trafficking that were associated with improved postvaccination responses. A suppressed Treg pathway and an enhanced Th17 pathway within these aggregates were associated with improved survival, enhanced postvaccination mesothelin-specific T-cell responses, and increased intratumoral Teff:Treg ratios. This study provides the first example of immune-based therapy converting a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm by inducing infiltration of T cells and development of tertiary lymphoid structures in the TME. Post-GVAX T-cell infiltration and aggregate formation resulted in the upregulation of immunosuppressive regulatory mechanisms, including the PD-1-PD-L1 pathway, suggesting that patients with vaccine-primed PDAC may be better candidates than vaccine-naïve patients for immune checkpoint and other immunomodulatory therapies.


Research resource: interactome of human embryo implantation: identification of gene expression pathways, regulation, and integrated regulatory networks.
A prerequisite for successful embryo implantation is adequate preparation of receptive endometrium and the establishment and maintenance of a viable embryo. The success of implantation further relies upon a two-way dialogue between the embryo and uterus. However, molecular bases of these preimplantation and implantation processes in humans are not well known. We performed genome expression analyses of human embryos (n = 128) and human endometria (n = 8). We integrated these data with protein-protein interactions in order to identify molecular networks within the endometrium and the embryo, and potential embryo-endometrium interactions at the time of implantation. For that, we applied a novel network profiling algorithm HyperModules, which combines topological module identification and functional enrichment analysis. We found a major wave of transcriptional down-regulation in preimplantation embryos. In receptive-stage endometrium, several genes and signaling pathways were identified, including JAK-STAT signaling and inflammatory pathways. The main curated embryo-endometrium interaction network highlighted the importance of cell adhesion molecules in the implantation process. We also identified cytokine-cytokine receptor interactions involved in implantation, where osteopontin (SPP1), leukemia inhibitory factor (LIF) and leptin (LEP) pathways were intertwining. Further, we identified a number of novel players in human embryo-endometrium interactions, such as apolipoprotein D (APOD), endothelin 1 (END1), fibroblast growth factor 7 (FGF7), gastrin (GAST), kringle containing trnasmembrane protein 1 (KREMEN1), neuropilin 1 (NRP1), serpin peptidase inhibitor clade A member 3 (SERPINA3), versican (VCAN), and others. Our findings provide a fundamental resource for better understanding of the genetic network that leads to successful embryo implantation. We demonstrate the first systems biology approach into the complex molecular network of the implantation process in humans.


An endogenous antigenic peptide bypasses the class I antigen presentation defect in RMA-S.
The RMA-S cell line was derived from the Raucher virus-induced murine cell line RBL-5 by ethylmethane sulfonate mutagenesis and anti-H-2 antibody plus complement selection (Ljunggren, H.-G., and K. Karre. 1985. J. Exp. Med. 162:1745). RMA-S is defective in the ability to present endogenously synthesized antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443; Ohlen, C., J. Bastin, H.-G. Ljunggren, L. Foster, E. Wolpert, G. Klein, A. R. M. Townsend, and K. Karre. 1990. J. Immunol. 145:52). This defect has been attributed to the inability of RMA-S to deliver antigenic peptides derived from antigens in the cytosol into the endoplasmic reticulum (ER), where they can associate with class I MHC molecules (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443). We show that RMA-S can present at least one endogenous antigen, vesicular stomatitis virus nucleoprotein (VSV-N), to class I MHC-restricted CTL. RMA-S presents VSV-N to CTL both when infected with VSV or transfected with the VSV nucleoprotein gene. The natural antigenic VSV nucleoprotein peptides purified from either RMA or RMA-S are indistinguishable when analyzed by high performance liquid chromatography. We also show that the genetic defect responsible for the RMA-S phenotype maps to the murine chromosome 17. This chromosome encodes the murine class I MHC genes as well as two genes, HAM-1 and -2, with homology to the adenosine triphosphate-dependent transporter superfamily (Monaco, J. J., S. Cho, and M. Attaya. 1990. Science [Wash. DC]. 250:1723). These results suggest that the system that delivers antigenic peptides from the cytosol to the ER in RMA-S may still be present and retain partial function.


[Surgery of the rolandic region guided by the peroperative localization of the primary motor cortex and neuro-navigation].
Surgery close to the central motor area carries the risk of a new or increased postoperative motor deficit. One reason is the difficulty of localizing the motor cortex when it is displaced by the tumor. Neurosurgeons have long recognised the need for anatomical and functional localisations during any procedure and nowhere is this more important than in and around the central region. For ten years, we have used modern imaging techniques which provide a wealth of information concerning anatomy and pathophysiology and a new method of intraoperative localization of the primary motor cortex based on the application of single anodal electric pulses to the brain surface. In fifty patients, lesions within or adjacent to the motor area were microsurgically resected using a minimally invasive surgical technique.


A retrospective examination of care pathways in individuals with treatment-resistant depression.
Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear. To explore the extent and nature of 'treatment gaps' (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK. Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced. Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment. There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.


The distance from the skin to the epidural space in a Chinese patient population.
The inter-relationship between age, height, weight and distance from the skin to the epidural space correlated with the patient's weight (r = 0.52, F = 23.96, P less than 0.001), and showed no correlation with patient's height (r = 0.18, F = 0.04, P greater than 0.05) or age (r = 0.13, F = 1.88, P greater than 0.05). The epidural space was found at a depth range of 3-7 cm, and 60% of patients had a depth of 4-5 cm. The results may be useful as a guideline for successful epidural blocks.


Tangential finger forces use mechanical advantage during static grasping.
When grasping and manipulating objects, the central controller utilizes the mechanical advantage of the normal forces of the fingers for torque production. Whether the same is valid for tangential forces is unknown. The main purpose of this study was to determine the patterns of finger tangential forces and the use of mechanical advantage as a control mechanism when dealing with objects of nonuniform finger positioning. A complementary goal was to explore the interaction of mechanical advantage (moment arm) and the role a finger has as a torque agonist/antagonist with respect to external torques (±0.4 N m). Five 6-df force/torque transducers measured finger forces while subjects held a prism handle (6 cm width × 9 cm height) with and without a single finger displaced 2 cm (handle width). The effect of increasing the tangential moment arm was significant (p < .01) for increasing tangential forces (in >70% of trials) and hence creating greater moments. Thus, the data provides evidence that the grasping system as a rule utilizes mechanical advantage for generating tangential forces. The increase in tangential force was independent of whether the finger was acting as a torque agonist or antagonist, revealing their effects to be additive.


Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates with respect to H1N1 and H3N2 isolates from previous seasonal epidemics.
The Influenza A pandemic sustained by a new H1N1 variant (H1N1v) started in Mexico and the USA at the end of April 2009 spreading worldwide in a few weeks. In this study we investigate the variability of the NS1 gene of the pandemic H1N1v strain with respect to previous seasonal strains circulating in humans and the potential selection of virus variants through isolation in cell culture. During the period April 27th 2009-Jan 15th 2010, 1633 potential 2009 H1N1v cases have been screened at our center using the CDC detection and typing realtime RT-PCR assays. Virus isolation on MDCK cells was systematically performed in 1/10 positive cases. A subset of 51 H1N1v strains isolated in the period May-September 2009 was selected for NS1 gene sequencing. In addition, 15 H1N1 and 47 H3N2 virus isolates from three previous seasonal epidemics (2006-2009) were analyzed in parallel. A low variability in the NS1 amino acid (aa) sequence among H1N1v isolates was shown (aa identity 99.5%). A slightly higher NS1 variability was observed among H1N1 and H3N2 strains from previous epidemics (aa identity 98.6% and 98.9%, respectively). The H1N1v strains were closely related (aa identity 92.1%) to swine reference strain (A/swine/Oklahoma/042169/2008). In contrast, substantial divergence (aa identity 83.4%) with respect to human reference strain A/Brevig Mission/1/1918 and previous epidemic strains H1N1 and H3N2 (aa identity 78.9% and 77.6%, respectively) was shown. Specific sequence signatures of uncertain significance in the new virus variant were a C-terminus deletion and a T215P substitution. The H1N1v NS1 gene was more conserved than that of previous epidemic strains. In addition, a closer genetic identity of H1N1v with the swine than the human reference strains was shown. Hot-spots were shown in the H1N1v NS1 aa sequence whose biologic relevance remains to be investigated.


Impact of bacterial sRNAs in stress responses.
Bacterial life is harsh and involves numerous environmental and internal challenges that are perceived as stresses. Consequently, adequate responses to survive, cope with, and counteract stress conditions have evolved. In the last few decades, a class of small, non-coding RNAs (sRNAs) has been shown to be involved as key players in stress responses. This review will discuss - primarily from an enterobacterial perspective - selected stress response pathways that involve antisense-type sRNAs. These include themes of how bacteria deal with severe envelope stress, threats of DNA damage, problems with poisoning due to toxic sugar intermediates, issues of iron homeostasis, and nutrient limitation/starvation. The examples discussed highlight how stress relief can be achieved, and how sRNAs act mechanistically in regulatory circuits. For some cases, we will propose scenarios that may suggest why contributions from post-transcriptional control by sRNAs, rather than transcriptional control alone, appear to be a beneficial and universally selected feature.


Yttrium 90 ibritumomab tiuxetan in lymphoma.
Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma (NHL) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns of associated toxicities and unclear long-term benefit. A comprehensive search for studies on 90Y-ibritumomab tiuxetan use in lymphoma was completed. The aims of this systematic review were to summarize and evaluate the evidence on: (1) the benefits and risks of this novel therapy; (2) predictors for response and toxicity; and (3) the role of dosimetry and imaging studies prior to treatment. A total of twenty trials investigating the use of 90Y-ibritumomab tiuxetan for the treatment of adult patients with NHL were identified. In trials of patients with relapsed or refractory indolent NHL, overall response rates ranged from 67 - 83%. In patients with follicular NHL refractory to the monoclonal antibody, rituximab, response rates remained high (74%). However, in rituximab-naïve patients with relapsed or refractory indolent or transformed NHL, the higher response rate seen with 90Y-ibritumomab tiuxetan therapy compared to rituximab monotherapy has not translated into clear improvements in time-to-progression or survival. 90Y-ibritumomab tiuxetan is an active agent in relapsed and refractory non-Hodgkin's lymphoma that should be considered in select patients.


NuRsing Research in the 21st Century: R You Ready?
Nurse scientists are adept at translating findings from basic science into useful clinical- and community-based interventions to improve health. Over time, the focus of some nursing research has grown to include the assessment and evaluation of genomic and other output from high-throughput, or "omic," technologies as indicators related to health and disease. To date, the growth in the application of omics technologies in nursing research has included calls to increase attention to omics in nursing school curricula and educational training opportunities, such as the Summer Genetics Institute offered by the National Institute of Nursing Research. However, there has been scant attention paid in the nursing literature to the complexity of data analysis or issues of reproducibility related to omics studies. The goals of this article are to (1) familiarize nurse scientists with tools that encourage reproducibility in omics studies, with a focus on the free and open-source data processing and analysis pipeline, and (2) provide a baseline understanding of how these tools can be used to improve collaboration and cohesion among interdisciplinary research team members. Knowledge of these tools and skill in applying them will be important for communication across disciplines and imperative for the advancement of omics research in nursing.


Surgery of the subthalamic nucleus: use of movement-related neuronal activity for surgical navigation.
THE BASAL GANGLIA have important roles in somatic motor, oculomotor, limbic, and associative functions. These functions are represented in anatomically distinct territories in each basal ganglion nucleus. During surgery of the subthalamic nucleus for Parkinson's disease, the primary goal is to influence the physiology of the motor territory without affecting nonmotor areas. This article describes the use of movement-related cellular activity during single-unit microelectrode mapping to identify and to navigate within the motor territory of the subthalamic nucleus.


[An assessment of the prognostic criteria for early recurrences of peptic hemorrhage].
The proposed prognostic system involves multivariate (step-by-step discriminatory) analysis allowing the risk for the coming early recurrent ulcerous bleedings to be assessed to an accuracy of 84%. Depending on the degree of the risk there have been identified three groups of patients: those of minimum, high and extremely high risk of recurrence of bleeding. The selection algorithm for time of surgical treatment of patients with acutely bleeding pyloroduodenal ulcers takes account of emergency operations (within 24 hours) for patients in the high and extremely high risk groups, allowing the specific weight of interventions at the height of the recurrent bleeding to be reduced from 31% to 14%.


Broad consent for biobanks is best - provided it is also deep.
As biobank research has become increasingly widespread within biomedical research, study-specific consent to each study, a model derived from research involving traditional interventions on human subjects, has for the sake of feasibility gradually given way to alternative consent models which do not require consent for every new study. Besides broad consent these models include tiered, dynamic, and meta-consent. However, critics have pointed out that it is normally not known at the time of enrolment in what ways samples deposited in a biobank may be used in future research and that, for a consent to be informed, exactly this kind of knowledge is required. Therefore, there is an ongoing debate about the ethical acceptability of going for less than study-specific consent. In light of this debate we address the question of how to best protect participants against relevant risks and violations of autonomy. We apply the central aims of the informed consent process to the unique circumstances of biobank research where samples and data in many cases are stored for long periods of time and reused in subsequent studies. Thereby we are able to formulate a set of criteria focusing both on the risk of informational harm and the potential violation of participants' values. We compare existing models of consent based on their ability to satisfy the criteria, and we find that the broad consent model offers the best level of protection for participants, although, it suffers from a few important deficiencies with regards to protection against participant value violations and long-term protection of autonomy, if it is applied without qualifications. For this reason, we propose modifications to the current broad consent model, in order to ensure that it provides protection of autonomy and participant values through strong ethical review and continuous communication. We conclude that a modified form of broad consent is ethically superior in biobank research, not only because it is most feasible but primarily because it offers the best available protection against the hazards facing research subjects in this form of research.


A case of early postmyocardial infarction syndrome.
A 65-year old woman was admitted with an inferior infarction. Six hours later she developed a pericarditis with specific ECG alterations in the anterior wall accompanied with pericardial and pleural effusion. This early form of true pericarditis after acute myocardial infarction can be explained as an exacerbation of a latent inflammation, whether or not triggered by the acute infarction.


[Clinico-anatomic variants of the course of cerebral hemisphere contusions].
An analysis of 237 cases of brain hemisphere contusions verified at operation or on autopsy has made if possible to distinguish between three variants of the traumatic disease which corresponded to the three pathoanatomical forms of the contusion. Convexital contusions (pathoanatomically-chiefly cortical or cortico-subcortical) ran the most favourable course and were characterized by distinct focal symptoms prevailing over slight, in most cases, general cerebral disturbances. Polarobasal contusions (anatomically - extensive or massive, i.e. penetrating down to subcortical ganglia or the lateral ventricles) ran a grave course and were characterized by progressing focal hemispheric symptoms in the presence of undulating development of general cerebral disturbances. Diffuse contusions of the brain hemispheres (anatomically small foci of destruction and hemorrhages in the cortex and the paraventricular divisions of the white matter) were characterized by prevalence of marked general cerebral disturbances over slight scattered focal symptoms.


Ras-related small GTPases RalA and RalB regulate cellular survival after ionizing radiation.
Oncogenic activation of Ras renders cancer cells resistant to ionizing radiation (IR), but the mechanisms have not been fully characterized. The Ras-like small GTPases RalA and RalB are downstream effectors of Ras function and are critical for both tumor growth and survival. The Ral effector RalBP1/RLIP76 mediates survival of mice after whole-body irradiation, but the role of the Ral GTPases themselves in response to IR is unknown. We have investigated the role of RalA and RalB in cellular responses to IR. RalA, RalB, and their major effectors RalBP1 and Sec5 were knocked down by stable expression of short hairpin RNAs in the K-Ras-dependent pancreatic cancer-derived cell line MIA PaCa-2. Radiation responses were measured by standard clonogenic survival assays for reproductive survival, gammaH2AX expression for double-strand DNA breaks (DSBs), and poly(ADP-ribose)polymerase (PARP) cleavage for apoptosis. Knockdown of K-Ras, RalA, or RalB reduced colony-forming ability post-IR, and knockdown of either Ral isoform decreased the rate of DSB repair post-IR. However, knockdown of RalB, but not RalA, increased cell death. Surprisingly, neither RalBP1 nor Sec5 suppression affected colony formation post-IR. Both RalA and RalB contribute to K-Ras-dependent IR resistance of MIA PaCa-2 cells. Sensitization due to suppressed Ral expression is likely due in part to decreased efficiency of DNA repair (RalA and RalB) and increased susceptibility to apoptosis (RalB). Ral-mediated radioresistance does not depend on either the RalBP1 or the exocyst complex, the two best-characterized Ral effectors, and instead may utilize an atypical or novel effector.


Acquired hemophilia a successfully treated with rituximab.
Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation.


IUD discontinuation rates, switching behavior, and user satisfaction: findings from a retrospective analysis of a mobile outreach service program in Pakistan.
In Pakistan, the uptake rate for the intrauterine device (IUD) is very low at 2.5%. The most popular modern contraceptive methods in Pakistan are female sterilization and use of condoms. The Marie Stopes Society established its mobile outreach service delivery program with the aim of increasing use of modern quality contraceptive services, including the long-term reversible IUD, by women living in hard-to-reach areas. The present study attempts to assess IUD discontinuation rates and associated factors, including switching behavior and level of satisfaction with this type of service delivery. Using a cross-sectional approach, we contacted 681 women who had received an IUD from the Marie Stopes Society mobile outreach program during July and August 2009. Successful interviews were conducted with 639 of these women using a structured questionnaire. The data were analyzed with Stata 11.2 using simple descriptive Chi-square and Cox proportional techniques. Analysis revealed that 19.4% (95% confidence interval 16.3-22.5) of the women discontinued use of their IUD at 10 months and, of these women, the majority (69.4%) cited side effects as the main reason for discontinuation. Other factors, such as geographical catchment province, age of the woman, history of contraceptive use before IUD insertion, and side effects following insertion of the device, were found to be significantly associated with IUD. Amongst the women who had their IUD removed, 56.5% did not switch to any other contraceptive method, while 36.3% switched to either short-term or traditional methods, such as withdrawal, rhythm, and folk methods. Degree of satisfaction with the device was also significantly associated with discontinuation. Early discontinuation and not switching to another contraceptive method increases the risk of unplanned pregnancy. Health care workers should be trained in managing clients' concerns about the IUD to prevent discontinuation and providing counseling services for clients to select an alternative contraceptive method if they decide to discontinue.


Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity.
Klinefelter syndrome (KS) (47,XXY) is the most common male sex chromosome aneuploidy. Diagnosis and clinical supervision remain a challenge due to varying phenotypic presentation and insufficient characterization of the syndrome. Here we combine health data-driven epidemiology and molecular level systems biology to improve the understanding of KS and the molecular interplay influencing its comorbidities. In total, 78 overrepresented KS comorbidities were identified using in- and out-patient registry data from the entire Danish population covering 6.8 million individuals. The comorbidities extracted included both clinically well-known (e.g. infertility and osteoporosis) and still less established KS comorbidities (e.g. pituitary gland hypofunction and dental caries). Several systems biology approaches were applied to identify key molecular players underlying KS comorbidities: Identification of co-expressed modules as well as central hubs and gene dosage perturbed protein complexes in a KS comorbidity network build from known disease proteins and their protein-protein interactions. The systems biology approaches together pointed to novel aspects of KS disease phenotypes including perturbed Jak-STAT pathway, dysregulated genes important for disturbed immune system (IL4), energy balance (POMC and LEP) and erythropoietin signalling in KS. We present an extended epidemiological study that links KS comorbidities to the molecular level and identify potential causal players in the disease biology underlying the identified comorbidities.


Determination of the structure form of the fourth ligand of zinc in Acutolysin A using combined quantum mechanical and molecular mechanical simulation.
Acutolysin A, which is isolated from the snake venom of Agkistrodon acutus, is a member of the SVMPs subfamily of the metzincin family, and it is a snake venom zinc metalloproteinase possessing only one catalytic domain. The catalytic zinc ion, in the active site, is coordinated in a tetrahedral manner with three imidazole nitrogen atoms of histidine and one oxygen atom. It is uncertain whether this oxygen atom is a water molecule or a hydroxide ion just from the three-dimensional X-ray crystal structure. The identity of the fourth ligand of zinc is theoretically determined for the first time by performing both combined quantum mechanical and molecular mechanical (QM/MM) simulation and high-level quantum mechanical calculations. All of the results obtained indicate that the fourth ligand in the active site of the reported X-ray crystal structure is a water molecule rather than a hydroxide anion. On the basis of these theoretical results, we note that the experimental observed pH dependence of the proteolytic and hemorrhagic activity of Acutolysin A can be attributed to the deprotonation of the zinc-bound water to yield a better nucleophile, the hydroxide ion. Structural analyses revealed structural details useful for the understanding of acutolysin catalytic mechanism.


Inclusion of gerodontology in dental curriculum: An urgent case for India.
The proportion of older adults is on the rise. Management of dental problems in this group is different from the general population, and hence requires special training. Gerodontology is yet to find its place in the Indian dental curriculum. A lack of training would result in inadequate care delivery. In this article, we share our views on the need for inclusion of the subject, potential challenges, and a guide for incorporation of gerodontology in undergraduate and postgraduate curriculum in the Indian dental institutes. We propose a framework based on the salient features of Kern's 6-step approach for curriculum development and Kotter's 8-step change management model. Some features are common to both the models. A combination of these models includes the following salient features: Problem identification and general needs assessment, beginning with a sense of urgency and targeted needs assessment, communication of the vision for change, working in guided coalitions and defining clear goals and objectives, adopting the relevant educational strategies, implementation strategies to enable change and generating short-term wins, evaluating the effectiveness of the curricular reform and sustaining and anchoring the change. The proposed framework may also be useful for countries where gerodontology is yet to be implemented.


Evaluating the potential of lignosulfonates and chitosans as alfalfa hay preservatives using in vitro techniques.
Our objectives were to compare the antifungal activity of 5 lignosulfonates, and 2 chitosans against fungi isolated from spoiled hay, and assess the effects of an optimized lignosulfonate, chitosan, and propionic acid (PRP) on high-moisture alfalfa hay. In experiment 1, we determined the minimum inhibitory concentration and minimum fungicidal concentration of 4 sodium lignosulfonates, 1 magnesium lignosulfonate, 2 chitosans, and PRP (positive control) against Aspergillus amoenus, Mucor circinelloides, Penicillium solitum, and Debaromyces hansenii at pH 4 and 6. Among sodium lignosulfonates, the one from Sappi Ltd. (NaSP) was the most antifungal at pH 4. However, chitosans had the strongest fungicidal activity with the exception of M. circinelloides at both pH 4 and 6. PRP had more antifungal effects than NaSP and was only better than chitosans for M. circinelloides. In experiment 2, we evaluated the effects of 3 additives (ADV): optimized NaSP (NaSP-O, UMaine), naïve chitosan (ChNv, Sigma-Aldrich), and PRP on high-moisture alfalfa hay. The experimental design was a randomized complete block design replicated 5 times. Treatment design was the factorial combination of 3 ADV× 5 doses (0, 0.25, 0.5, 1, and 2% w/w fresh basis). Additives were added to 35 g of sterile alfalfa hay (71.5 ± 0.23% DM), inoculated with a mixture of previously isolated spoilage fungi (5.8 log cfu/fresh g), and aerobically incubated in vitro for 23 d (25°C). After incubation, DM losses were reduced by doses as low as 0.25% for both NaSP-O and PRP (x¯=1.61) vs. untreated hay (24.0%), partially due to the decrease of mold and yeast counts as their doses increased. Also, hay NH3-N was lower in NaSP-O and PRP, with doses as low as 0.25%, relative to untreated hay (x¯=1.13 vs. 7.80% of N, respectively). Both NaSP-O and PRP increased digestible DM recovery (x¯=69.7) and total volatile fatty acids (x¯=94.3), with doses as low as 0.25%, compared with untreated hay (52.7% and 83.8 mM, respectively). However, ChNv did not decrease mold nor yeast counts (x¯=6.59 and x¯=6.16 log cfu/fresh g, respectively) and did not prevent DM losses relative to untreated hay. Overall, when using an alfalfa hay substrate in vitro, NaSP-O was able to prevent fungal spoilage to a similar extent to PRP. Thus, further studies are warranted to develop NaSP-O as a hay preservative under field conditions.


KSR/KSTR Guidelines for the Use of Diagnostic Imaging for COVID-19.
The Korean Society of Radiology and the Korean Society of Thoracic Radiology have prepared recommendations for the use of diagnostic imaging for COVID-19 in various clinical scenarios. We have tried to grasp the situation in the real world, aggregated opinions from the chest radiologists, and reviewed available references, in order to suggest the most reasonable recommendations possible at this moment. As circumstances change and new evidences emerge, the recommendations should immediately be modified accordingly.


Risk-associated mortality in patients with peritonitis due to Sandorica Koetjape seed ingestion: a retrospective study.
To identify the factor associated with the mortality ofpatients with peritonitis due to Sandoricum koetjape seed ingestion. Thirty patients who presented with peritonitis and had a history of Sandorica seed ingestion between September 2009 and August 2012 were retrospectively reviewed. Gender, age, comorbid, number of ingested seed, duration of symptom, body temperature, shock at initial admission, extent ofperitonitis, presence offree air under the dome of the diaphragm, white blood cell count, serum bicarbonate levels, resuscitation time, severity of intraabdominal contamination, perforated wound size, and operation methods were analyzed for their association with the mortality using Fisher s exact test. Odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the strength of association. All patients received a definite diagnosis of Sandorica seed-induced colon perforation intraoperatively. Six of 30 patients died during 28-day hospitalization. The result showed that shock at initial admission (OR 35.0, 95% CI 2.9-411.4, p= 0.002), serum bicarbonate levels less than 15 mmol/L (OR 19.0, 95% CI 1.7-201.6, p = 0.009), and severe intraabdominal contamination (OR 10.0, 95% CI 1.3-74.5, p = 0.029) were the significant factors associated with the mortality. The factor-associated mortality in patients with peritonitis due to Sandorica seed ingestion was consistent with a clinical picture of septic shock. Early recognition and treatment of hypotensive episode accompanying with surgical correction and control of infection is therefore a key to improve the mortality outcome of this group of patients.


[Oral health care for the elderly. More than care for the mouth only].
Dental treatment is changing to oral health care, integrating curative treatment and care. This development is based on the present state of oral health of elderly people. In the future, elderly persons are expected to receive adequate oral health care. This requires gerodontic knowledge and skills, as most oral health problems of elderly persons are chronical and related to ageing processes. For about 25% of elderly people substantially adapted oral health care is needed. This geriatric oral health care can be best provided in collaboration between dentists, dental hygienists and other careproviders. This procedure is already common practice in the care for the chronically ill. Then oral health care will become more than care for oral health.


The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.
The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein.


Protein complex formation with heat shock protein 90 in chronic hypoxia-induced pulmonary hypertension in newborn piglets.
Aberrant interactions between heat shock protein (Hsp)90 and its client proteins could contribute to pulmonary hypertension. We tested the hypotheses that 1) the interaction between Hsp90 and its known client protein, endothelial nitric oxide synthase (eNOS), is impaired in pulmonary resistance arteries (PRAs) from piglets with pulmonary hypertension caused by exposure to 3 or 10 days of hypoxia and 2) Hsp90 interacts with the prostanoid pathway proteins prostacyclin synthase (PGIS) and/or thromboxane synthase (TXAS). We also determined whether Hsp90 antagonism with geldanamycin alters the agonist-induced synthesis of prostacyclin and thromboxane or alters PRA responses to these prostaglandin metabolites. Compared with normoxic piglets, less eNOS coimmunoprecipitated with Hsp90 in PRAs from hypoxic piglets. Despite reduced Hsp90-eNOS interactions, dilation to ACh was enhanced in geldanamycin-treated PRAs from hypoxic, but not normoxic, piglets. In PRAs from all groups of piglets, PGIS and TXAS coimmunoprecipitated with Hsp90. Geldanamycin reduced the ACh-induced synthesis of prostacyclin and thromboxane and altered responses to the thromboxane mimetic U-46619 in PRAs from all groups. Although geldanamycin enhanced responses to prostacyclin in PRAs from both groups of hypoxic piglets, geldanamycin had no effect on prostacyclin responses in PRAs from either group of normoxic piglets. Our findings indicate that Hsp90 influences both prostanoid and eNOS signaling in the pulmonary circulation of newborn piglets and that the impact of pharmacological inhibition of Hsp90 on these signaling pathways is altered during exposure to chronic hypoxia.


Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux.
Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between PPA and autism phenotypes facilitated by signaling mechanisms in hippocampal neurons. Findings indicated autism-like pathogenesis associated with reduced dendritic spines in PPA-treated hippocampal neurons. To uncover the mechanisms underlying this loss, we evaluated autophagic flux, a functional readout of autophagy, using relevant biomedical markers. Results indicated that autophagic flux is impaired in PPA-treated hippocampal neurons. At a molecular level, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was activated and autophagic activity was impaired. We also observed that a MAPK inhibitor rescued dendritic spine loss in PPA-treated hippocampal neurons. Taken together, these results suggest a previously unknown link between PPA and autophagy in spine formation regulation in hippocampal neurons via MAPK/ERK signaling. Our results indicate that MAPK/ERK signaling participates in autism pathogenesis by autophagy disruption affecting dendritic spine density. This study may help to elucidate other mechanisms underlying autism and provide a potential strategy for treating ASD-associated pathology.


Microscale imaging of the preservation state of 5,000-year-old archaeological bones by synchrotron infrared microspectroscopy.
Archaeological bone materials record characteristic markers of life in prehistoric times (dating, climate, environment, diet, human migration) in their isotopic and chemical composition in addition to palaeontological, archaeozoological, anthropological and palaeogenetic information. Thus, the discovery and conservation of archaeological bone materials is of great importance to get access to this information. However, archaeological materials are altered by different postmortem processes and it appears necessary to estimate if the archaeological information is still reliable or if it has been modified during burial. As archaeological bone materials present a high structural hierarchy at the micro- and nanoscale, changes induced by diagenetic phenomena have to be observed at these scales. One method for revealing post mortem changes of the bone structure and composition at the microscale is synchrotron radiation micro-FTIR imaging (SR micro-FTIR). Thus, thin sections of about 5,000-year-old archaeological bones have been analysed in transmission mode at the IRIS beamline (BESSY II, HZB Berlin) to determine markers of the state of bone preservation at the microscale. The archaeological bone material comes from station 19 of the Neolithic site of the Chalain Lake. By using SR micro-FTIR it was possible to image characteristic bone structures, e.g. osteons (the constitutive histological unit of cortical bone), using the absorption band ratios corresponding to different chemical bone constituents (collagen content and quality, phosphate crystallinity, carbonate content). These data allow us to precisely evaluate the state of preservation of a 5,000-year-old bone at the histological level.


Tyrosine-Based Cross-Linking of Peptide Antigens to Generate Nanoclusters with Enhanced Immunogenicity: Demonstration Using the Conserved M2e Peptide of Influenza A.
A method of creating nanoclusters (NCs) from soluble peptide molecules is described utilizing an approach based on a tyrosine-tyrosine cross-linking reaction. A reactive tag comprising histidine and tyrosine residues was introduced at the termini of the peptide molecules. The cross-linking reaction led to the creation of dityrosine bonds within the tag, which allowed for the generation of peptide NCs. We show that it is essential for the reactive tag to be present at both the "N" and "C" termini of the peptide for cluster formation to occur. Additionally, the cross-linking reaction was systematically characterized to show the importance of reaction conditions on final cluster diameter, allowing us to generate NCs of various sizes. To demonstrate the immunogenic potential of the peptide clusters, we chose to study the conserved influenza peptide, M2e, as the antigen. M2e NCs were formulated using the cross-linking reaction. We show the ability of the clusters to generate protective immunity in a dose, size, and frequency dependent manner against a lethal influenza A challenge in BALB/c mice. Taken together, the data presented suggest this new cluster formation technique can generate highly immunogenic peptide NCs in a simple and controllable manner.


The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study.
An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples' decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest-posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision.


Trace level determination of selected sulfonylurea herbicides in wetland sediment by liquid chromatography electrospray tandem mass spectrometry.
Sulfonylurea herbicides are widely used in crop production on the Canadian prairies and a portion of these herbicides applied to cropland are inevitably lost to surrounding aquatic ecosystems. Little is known regarding the presence of sulfonylurea herbicides in wetlands located amongst cropland. This paper describes a new analytical method for the extraction and the determination of seven sulfonylurea herbicides (thifensulfuron-methyl, tribenuron-methyl, ethametsulfuron-methyl, metsulfuron-methyl, rimsulfuron, nicosulfuron and sulfosulfuron) in wetland sediment. The method provided > 85% analyte recovery from fortified sediment for six of the seven sulfonylurea herbicides with a limit of quantification (LOQ) of 1.0 microg kg(-1). Tribenuron-methyl had significantly lower recovery compared to the other six sulfonylurea herbicides (LOQ = 2 microg kg(-1)). Mean recovery standard deviations were < 10%. This methodology was used to quantify sulfonylurea herbicide residues in sediment samples collected from prairie wetlands situated within the agricultural landscape of Saskatchewan and Manitoba, Canada. This is the first-known detection of sulfonylurea herbicide residues in prairie wetland sediments. Ethametsulfuron-methyl, sulfosulfuron and metsulfuron-methyl, the three most environmentally persistent of the seven sulfonylurea herbicides monitored in the surveillance component of this study, were most frequently detected in wetland sediment with mean concentrations ranging from 1.2 to 10 microg kg(-1).


Elevated CEA and CA 19-9 Levels within the Normal Ranges Increase the Likelihood of CRC Recurrence in the Chinese Han Population.
This study aimed to determine if variations in the expression profiles of CA 19-9 and carcinoembryonic antigen (CEA) within the reference range could serve as possible biomarkers for postoperative CRC recurrence. This retrospective cohort investigation enrolled 2,596 cases of CRC that received curative surgery. Serum CEA/CA 19-9 were measured through chemiluminescence immunoassay (CLIA). During follow-up (median follow-up = 5.2 years), in total, 837 patients experienced recurrence. The fully adjusted hazard ratios (HRs) were significantly higher, ≥1 standard deviation (±SD), in patients with upregulated CEA/CA 19-9 levels (HRCEA = 7.06; HRCA 19 - 9 = 3.98) than in those with downregulated CEA/CA 19-9 levels. The likelihood of recurrence remained consistently greater in cases of elevated CEA/CA 19-9 levels during sensitivity analyses. The findings of this analysis showed that variations in CEA/CA 19-9 expression profiles within the reference range impact CRC recurrence.


Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma.
Fluorescence-guided surgery (FGS) of cancer is an emerging technology. We have previously shown the importance of resecting both the tumor and the tumor microenvironment (TME) for curative FGS. We also previously developed a syngeneic model using the mouse lymphoma cell line EL-4, expressing red fluorescent protein (EL-4-RFP), growing in green fluorescent protein (GFP) transgenic mice, which we have used in the present report to develop FGS of the tumor microenvironment. EL-4-RFP lymphoma cells were injected subcutaneously in C57/BL6 GFP transgenic mice. EL-4-RFP cells subsequently formed tumors by 35 days after cell transplantation. Using the portable hand-held Dino-Lite digital imaging system, subcutaneous tumors were resected by FGS. Resected tumor tissues were visualized with the Olympus FV1000 confocal microscope. Using the Dino-Lite, subcutaneous tumors and the tumor microenvironment were clearly visualized and resected. In the resected tumor, host stromal cells, including adipocyte-like cells and blood vessels with lymphocytes, were observed by confocal microscopy in addition to cancer cells by color-coded confocal imaging. The cancer cells and stromal cells in the TME were deeply intermingled in a highly-complex pattern. Color-coded FGS is an effective method to completely resect cancer cells along with the stromal cells in the TME which interact in a highly-complex pattern. Microscopically, cancer cells invade the TME and vice versa. To prevent tumor recurrence, it is necessary to resect the TME along with the tumor.


The effects of alpha male removal on the social behavior of a group of olive baboons (Papio anubis).
In captivity, the managers of primate populations have removed individuals from their groups for medical and social reasons, but there has been little documentation regarding the consequences of this extraction on the sociality of the remaining individuals. This study provides information about the social effect of the alpha male removal in a group of olive baboons (Papio anubis) maintained at the Station of Primatology of CNRS (France). Data on social behavior was collected before and after male removal and then compared. Moreover, this social information was used to calculate the individual dominance index and the group dominance ranking. Overall, our results indicate that females seem to respond to male removal showing a more affiliative and tolerant behavior. However, the results also highlight the different coping mechanisms of females with this new social context. Therefore, this information could be useful for managers of primate populations, allowing them to anticipate the response of captive groups when facing certain sociodemographic changes. In this regard, we recommended creating a detailed procedure before the removal of the individuals that considers the characteristics of the individuals.


Utility of adjuvant chemotherapy in patients receiving surgery and adjuvant radiotherapy for primary treatment of esthesioneuroblastoma.
Past research established that surgery plus adjuvant radiotherapy (S + AR) improves overall survival (OS) in esthesioneuroblastoma (ENB). However, it is unknown if the addition of adjuvant chemotherapy (AC) further improves survival. The primary objective of this study was to compare survival among patients treated with S + AR alone to patients who underwent S + AR + AC. Retrospective review of patient records. Thirty-eight patients met inclusion criteria for either S + AR or S + AR + AC treatment groups. The S + AR + AC group contained more patients with Kadish stage D disease, dural invasion, and positive histologic margins postsurgery. All S + AR + AC patients received platinum-based regimens, combined with etoposide in 67%. OS and recurrence-free survival did not differ between the two groups, even when restricting the analysis to patients with Kadish stages B and C disease. Patients who received platinum-based AC did not exhibit improved survival compared to S + AR alone. Further investigation, preferably prospective, into the optimal use of systemic therapy in ENB is warranted.


eHealth interventions for reducing cardiovascular disease risk in men: A systematic review and meta-analysis.
Men remain at a higher risk of developing cardiovascular disease (CVD) than women and behavioral risk factor modification is an important preventive measure. However, engaging men in behavior change interventions is challenging. Although men often indicate a preference for gender-specific information and support, this rarely occurs. eHealth interventions have the potential to address this gap, though their effectiveness for reducing CVD risk in men is unclear. Therefore, the aim of this systematic review and meta-analysis was to evaluate the effectiveness of eHealth interventions for reducing CVD risk in men. A search of published randomised controlled trials with no date restrictions up to July 2020 was conducted to identify those targeting at least two major CVD risk factors. Nine trials were identified and reviewed. Study quality ranged from low to unclear, with one trial at a high risk of bias. Compared to those in a control group or receiving printed materials, participants randomised to an eHealth intervention had statistically significant improvements in BMI (Z=-2.75, p=0.01), body weight (Z=-3.25, p=0.01), waist circumference (Z=-2.30, p=0.02) and systolic (Z=-3.57, p=0.01) and diastolic (Z=-3.56, p=0.01) blood pressure. Though less evident, there were also improvements in physical activity and diet in favour of the intervention group. This review suggests that eHealth interventions can reduce CVD risk in adult men through behavior change. However, we were unable to determine the association between intervention characteristics and outcomes. Also, overall, participant adherence to the intervention was poor. Both of these issues should be considered in future studies.


Sonophoresis Enhanced Transdermal Delivery of Cisplatin in the Xenografted Tumor Model of Cervical Cancer.
Transdermal drug delivery system has been researched for a long time because of its advantage in decreasing side effects such as nausea, vomiting, and gastrointestinal disturbance. Sonophoresis has been shown to be very effective in promoting the transdermal delivery of drugs. This study is on purpose to research the feasibility of sonophoresis promoting cisplatin in the treatment of cervical cancer and the optimum drug delivery mode. Thirty-two female nude-mice model of cervical cancer were randomly divided into 4 groups (n=8 in each group): control group without any intervention, low, medium and high concentration groups were treated with the corresponding cisplatin concentrations of 0.2mg/mL, 0.4mg/mL and 0.8mg/mL, respectively, with concurrent sonophoresis applied on the skin of local tumor, 1 mL at a time, once a day for a total of 5 days. Therapeutic pulsed ultrasound (TPU) was 1.0 MHz, 2.0 W/cm2 and 60-min duration. Weight of mice and tumor diameters were measured every day during the intervention. The concentration of cisplatin in tumors was detected by HPLC. Meanwhile, tumor, skin, liver and kidney gross structures and ultrastructure were observed in order to evaluate the effectiveness and safety of experimental conditions. In addition, apoptosis and proliferation-related factors (MPO, Caspase-3, PCNA) were detected by immunohistochemistry, immunofluorescence and TUNEL assay. The weight of nude mice in each group showed an increasing trend, except for a decrease of weight in the 0.8 mg/mL group. No obvious tumor inhibition effect was observed. Cisplatin was detected in the 0.4 mg/mL group and 0.8 mg/mL group, with relative concentrations of 0.081±0.033 mg/mL and 0.111±0.021 mg/mL, respectively. Both skin and kidney inflammation were observed in the 0.8 mg/mL group. The expression of MPO, caspase-3 and TUNEL was concentration dependent, with the highest expression in the 0.8 mg/mL group, followed by the 0.4 mg/mL group, with no significant differences between the control and the 0.2 mg/mL group. PCNA was highly expressed in both the control and 0.2 mg/mL groups but decreased in the 0.4 mg/mL and 0.8 mg/mL groups. Sonophoresis enhanced transdermal delivery of cisplatin in a xenograft tumor model of cervical cancer. Considering the occurrence of skin inflammation and renal injury caused by cisplatin, the recommended concentration to be administered is 0.4mg/mL.


A research on shape-controllable synthesis of Ag3PO4/AgBr and its degradation of ciprofloxacin.
Antibiotic ciprofloxacin is one of the commonly used broad spectrum fluoroquinolone human and veterinary drugs. Because of the overuse of human beings, the presence of ciprofloxacin has been detected in a variety of environmental matrices. To solve this problem, a facile, environmentally-friendly Ag3PO4/AgBr composite photocatalyst was synthesized by a simple precipitation method at room temperature in the presence of cetyltrimethyl ammonium bromide (CTAB). CTAB was served as surfactant and the source of bromide ions. The as-prepared Ag3PO4/AgBr microspheres were characterized by means of powder X-ray diffraction (XRD), scanning electron microscope (SEM) and UV-visible diffuse reflectance spectroscopy (UV-vis DRS). The results revealed that the Ag3PO4/AgBr sample (synthesized with CTAB, 0.8 g) exhibited the highest photocatalytic activity to the photodegradation rate of 96.36%. Moreover, mechanism detection experiment indicated that h+ was the major active species in the degradation process. So the enhanced photocatalytic activity of Ag3PO4/AgBr composites is attributed to its excellent separation of photogenerated electron-hole pairs through Ag3PO4/AgBr heterojunction. Also, Ag3PO4/AgBr heterojunction has a lower band gap compared to pure Ag3PO4 and pure AgBr, so higher efficiency of light harvesting is equipped.


[Information synthesis in key sections of the cortex as the basis of subjective experiences].
The main hypothesis developed in the paper proposes that the events of the subjective experience emerge as a result of the synthesis of three kinds of information in crucial for this mental function cortical areas. This information includes sensory one, information derived from memory and one coming from motivational centers. The hypothesis is based on researches of the brain mechanisms of perception and thinking. It has been shown that the sensation emerges as a result of the synthesis of information on physical parameters and of significance of the stimulus in the projection cortex neurons. This synthesis is provided by the circular spreading of the nerve impulses from the projection cortex to associative cortex, then to hippocampus and the hypothalamic motivation centers with the subsequent return of the impulsation to the projection cortex. It have been shown also that at thinking operations the cortical connections converge to define centers named the interaction foci. Their topography is specific for particular thinking operations. Thus in imaginative thinking the foci are located in temporo-parietal and in abstract-verbal thinking--in frontal cortex. It is proposed that the confrontation and the synthesis of information in the interaction foci result in decision making. The last part of the paper concerns the functional role of the subjective events and their possible influence on brain processes.


[Laser treatment of central retina diseases].
Review of literature is devoted to the most up-to-date retinal diseases such as diabetic macular edema and age macular degeneration affecting people of different age and leading to disability. Besides management of central serous retinopathy that affects younger patients is discussed. According to data of domestic and foreign studies common treatment options of central retina diseases along with therapeutic effect have adverse effects leading to damage of neurosensory retina. Thus despite of a great number of studies devoted to this problem a search of effective and safe treatment option of central retina diseases is still important.


Thyroid nodule with eggshell calcification and oncocytic thyroid cancer.
To report an interesting case of Hurthle cell cancer of the thyroid with eggshell calcification, including ultra-sonographic, surgical, histological, and immuno-histochemical findings and discussion of diagnostic and therapeutic strategies. A 62 year old asymptomatic man with negative history of radiation, referred for evaluation of a thyroid nodule, had a 3-4 cm firm, mobile nodule in the left lobe of his thyroid. US of the thyroid revealed a normal right lobe and a large heterogeneous mass that was iso- and hyper-echoic, with peripheral halo and intra-nodular and peripheral coarse calcifications, measuring 2.8 x 3.0 cm, in the left lobe. US-guided FNA revealed a richly cellular specimen with numerous sheets of Hurthle cells with nuclear pleomorphism and intranuclear vacuoles. At macroscopic examination after thyroidectomy, an encapsulated tumor mass measuring 5.0 x 3.5 x 2.6 cm was found to have replaced the entire left lobe. The capsule was thick and hard, preventing the specimen from being cut, and requiring 3 days of pretreatment with a decalcifying agent before sections could be made. Microscopic examination revealed oncocytic or Hurthle cell carcinoma with pericapsular and vascular invasion. The patient received radioiodine ablation and was placed on suppressive doses of levothyroxine. At follow up, the thyroid ultrasound and scan remain negative with undetectable thyroglobulin. We could not find any reports of Hurthle cell thyroid cancer with such coarse or eggshell calcification. Egg shell calcification does not exclude the presence of camcer.


Characterization of agonist radioligand interactions with porcine atrial A1 adenosine receptors.
The agonist radioligand (-)-N6-[125I]-p-hydroxyphenylisopropyl-adenosine ([ 125I]HPIA) was used to characterize adenosine recognition sites in porcine atrial membranes. [125I]HPIA showed saturable binding to an apparently homogeneous population of sites with a maximum binding capacity of 35 +/- 3 fmol/mg of protein and an equilibrium dissociation constant of 2.5 +/- 0.4 nM. Kinetic experiments were performed to address the molecular mechanism of [125I]HPIA binding in porcine atrial membranes. [125I]HPIA apparently interacts with the cardiac adenosine receptor in a simple bimolecular reaction. A kinetically derived [125I] HPIA dissociation constant (2.4 nM) was in good agreement with that parameter measured at equilibrium. Guanyl nucleotides negatively modulated [125I]HPIA binding by increasing its rate of dissociation. This finding is consonant with the formation of a ternary complex in porcine atrial membranes, consisting of ligand, receptor, and guanyl nucleotide-binding protein. Prototypic adenosine receptor agonists and antagonists inhibited specific binding in a manner consistent with the labeling of an A1 adenosine receptor. The results of these experiments suggest that the adenosine receptor present in porcine atrial membranes, as labeled by [125I]HPIA, is of the A1 subtype.


Reconstruction of skeletal movement using skin markers: comparative assessment of bone pose estimators.
The assessment of the accuracy of the pose estimation of human bones and consequent joint kinematics is of primary relevance in human movement analysis. This study evaluated the performance of selected pose estimators in reducing the effects of instrumental errors, soft tissue artifacts and anatomical landmark mislocations occurring at the thigh on the determination of the knee kinematics. The pattern of a typical knee flexion-extension during a gait cycle was fed into a knee model which generated a six-components knee kinematics and relevant marker trajectories. The marker trajectories were corrupted with both instrumental noise and soft tissue artifacts. Two different cluster configurations (4 and 12-marker cluster) were investigated. Four selected pose estimators, a Geometrical method, a SVD-based method, and the Pointer Cluster Technique in the optimized and non optimized version, were analyzed. The estimated knee kinematics were compared to the nominal kinematics in order to evaluate the accuracy of the selected pose estimators. Results have shown that optimal pose estimators perform better than traditional geometric pose estimators when soft tissue artifacts are present. The use of redundant markers improved in some cases the estimation of the dynamics of the kinematics patterns, while it does not reduce the offsets from the nominal kinematics curves. Overall, the best performance was obtained by the SVD-based pose estimator, while the performance of the PCT pose estimator in its optimal version was not satisfactory. However, the knee kinematics errors reached 5 deg for rotations and 10 mm for translations). Given the favorable experimental conditions of this study (soft tissue artifacts determined from a young, healthy and non overweight subject), the errors found in estimating the knee kinematics have to be considered unsatisfactory even if the best performing pose estimator is used. Therefore, it is the authors' opinion that the movement analysis research community should make additional efforts in the search of more subject specific error models to increase the accuracy of joint kinematics estimations.


A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport.
The Rab27a GTPase regulates diverse processes involving lysosome-related organelles, including melanosome motility in melanocytes, and lytic granule release in cytotoxic T lymphocytes. Toward an understanding of Rab27a function, we searched for proteins that interact with Rab27a(GTP) using the yeast two-hybrid system and identified JFC1/Slp1, a protein of unknown function. JFC1/Slp1 and related proteins, including melanophilin, contain a conserved amino-terminal domain similar to the Rab3a-binding domain of Rabphilin-3. We used several methods to demonstrate that this conserved amino-terminal domain is a Rab27-binding domain. We show that this domain interacts directly, and in a GTP-dependent manner with Rab27a. Furthermore, overexpression of this domain in melanocytes results in perinuclear clustering of melanosomes, suggesting that this region is sufficient for interaction with, and perturbation of function of, Rab27a in a physiological context. Thus, we identified a novel family of Rab27-binding proteins. We also show that melanophilin associates with Rab27a and myosin Va on melanosomes in melanocytes, and present evidence that a domain within the carboxyl-terminal region of melanophilin interacts with the carboxyl-terminal tail of the melanocyte-specific splice isoform of myosin Va. Thus, melanophilin can associate simultaneously with activated Rab27a and myosin Va via distinct regions, and serve as a linker between these proteins.


PGE2 release by bradykinin in human airway smooth muscle cells: involvement of cyclooxygenase-2 induction.
Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2 release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2 antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.


A bipolar coaxial microprobe for safe transvitreal diathermy.
We present a new 22-gauge transvitreal bipolar diathermy microprobe. With the use of the coaxial principle, the current flows only at the probe's end surfaces. Because of its small size and end-on coagulation effect, and when used in conjunction with a low-frequency diathermy unit, the probe can be used safely on vessels lying directly on the retinal surface and close to the optic nerve head. We report three cases to demonstrate the usefulness of this instrument.


User-friendly 3D bioassays with cell-containing hydrogel modules: narrowing the gap between microfluidic bioassays and clinical end-users' needs.
Cell-containing hydrogel modules as cell-hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of the simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond the current 2D cell-culture systems.


[Ablation of slow pathway in a patient with persistent left superior vena cava].
We describe a case of successful radiofrequency ablation of slow pathway in a 54 year-old woman with persistent left superior vena cava. The ablation was performed using anatomical approach, outside the ostium of coronary sinus.


Attempt to prevent the development of diabetes in non-obese diabetic mice by oral vanadate administration.
Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM. To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice. Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice. Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83 +/- 0.67 vs. 4.44 +/- 0.83 mmol/L, P < 0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104 +/- 27 vs. 151 +/- 36 mumol/L, P < 0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups. This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.


Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease.
The authors compared the effects of deep brain stimulation (DBS) in the globus pallidus internus (GPi) with those in the subthalamic nucleus (STN) in patients with Parkinson disease (PD) in whom electrodes had been bilaterally implanted in both targets. Eight of 14 patients with advanced PD in whom electrodes had been implanted bilaterally in both the GPi and STN for DBS were selected on the basis of optimal DBS effects and were studied 2 months postsurgery in off- and on-stimulus conditions and after at least 1 month of pharmacological withdrawal. Subcutaneous administration of an apomorphine test dose (0.04 mg/kg) was also performed in both conditions. Compared with the off status, the results showed less reduction in the Unified PD Rating Scale Section III scores during DBS in the GPi (43.1%) than during DBS of the STN (54.5%) or DBS of both the STN and GPi (57.1%). The difference between the effects of DBS in the GPi compared with that in the STN or simultaneous DBS was statistically significant (p < 0.01). In contrast, no statistical difference was found between DBS in the STN and simultaneous DBS in the STN and GPi (p < 0.9). The improvement induced by adding apomorphine administration to DBS was similar in all three stimulus modalities. The abnormal involuntary movements (AIMs) induced by apomorphine were almost abolished by DBS of the GPi, but were not affected by stimulation of the STN. The simultaneous stimulation of STN and GPi produced both antiparkinsonian and anti-AIM effects. The improvement of parkinsonian symptoms during stimulation of the GPi, STN, and both nuclei simultaneously may indicate a similar DBS mechanism for both nuclei in inducing antiparkinsonian effects, although STN is more effective. The antidyskinetic effects produced only by DBS of the GPi, with or without STN, may indicate different mechanisms for the antidyskinetic and antiparkinsonian activity related to DBS of the GPi or an additional mechanism in the GPi. These findings indicate that implantation of double electrodes for DBS should not be proposed as a routine procedure, but could be considered as a possible subsequent choice if electrode implantation for DBS of the STN does not control AIMs.


Inflammatory bowel disease pathobiology: the role of the interferon signature.
The pathogenesis of inflammatory bowel disease (IBD) is still unclear, but includes both inflammatory and autoimmune reactions. Current methodological approaches could better elucidate the cytokine pathways and the genetics involved in the etiopathogenesis of this disease. Interferons (IFNs) are cytokines that play a key role in autoimmune/inflammatory disorders because of their pro- and anti-inflammatory properties as well as their immunoregulatory functions. An increased expression of IFN-regulated genes, widely known as an IFN signature, has been reported in blood and tissue from patients with autoimmune disorders. In this review, we present the function as well as the clinical and therapeutic potential of the IFN signature. Current data demonstrate that the IFN signature can be used as a biomarker that defines disease activity in autoimmune diseases, although this has not been thoroughly studied in IBD. Consequently, further investigation of the IFN signature in IBD would be essential for a better understanding of its actions.


Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma.
We aimed to determine the prognostic value of bcl-2, c-myc and survivin in synovial sarcoma cases and to evaluate the relationship between the conventional morphological findings with prognosis. In this study, we evaluated 81 synovial sarcoma cases referred to our tertiary tumor center during a period of 20 years. We applied bcl-2, c-myc and survivin immunohistochemically and investigated the relationship with prognosis for those 65 cases with follow-up. The relationship between the conventional morphological findings (mitosis, necrosis, grade) with prognosis was also investigated. Five-year disease free survival rate was 44% and ten-year progression free survival rate was 38%, reflecting the aggressive behavior of synovial sarcoma. Tumor grade (according to FNCLCC) was the most significant prognostic input in this study. We obtained a significant difference between grade II (40 cases) and grade III (24 cases) group regarding progression-free survival and overall survival (p < 0.001 and p < 0.001 respectively). Grade II was divided into two groups according to mitotic index and necrosis (grade IIa and IIb) and there was a significant difference between them regarding prognosis (p=0.013 for progression free survival, p=0.003 for overall survival). There was a significant relationship between bcl-2 negative plus focally weak positive cases (9 cases) and focally strong cases (21 cases) and diffuse strong cases (35 cases) (p=0.042 and p=0.016 respectively). There was a significant relation between c-myc negative cases (25 cases) and nuclear positive cases (17 cases) regarding overall survival (p=0.043) and between c-myc negative cases and cytoplasmic positive cases (23 cases) regarding progression free survival (p=0.05). The relation between survivin and prognosis was not significant. Tumor grade was the most significant prognostic parameter in this study. The grade IIa group (with less than 10 mitoses in 10 HPF, without necrosis) had a better prognosis than both the grade IIb and III groups. The grade IIb group was closer to grade III regarding the prognosis. Bcl-2 and c-myc (nuclear and/or cytoplasmic) immunohistochemical positivity had prognostic value but this finding has to be confirmed by large series.


Psychological and physical health of mostly heterosexuals: a systematic review.
We reviewed whether mostly heterosexuals, a sexual orientation group characterized by a small amount of same-sex sexuality, differ from heterosexuals and bisexuals on a variety of mental and physical health outcomes (e.g., internalizing problems, body dissatisfaction and disordered eating, obesity, sexual/reproductive health, physical health), health risk behaviors (e.g., substance use, sexual risk taking), and risk and protective factors (e.g., victimization, stressful/risky environment, socioeconomic status, personal and social relationships, gender nonconformity). A narrative and quantitative literature review was conducted of 60 papers covering 22 samples from five Western countries. Individual, mean, and median effect sizes (Cohen ds) were calculated whenever possible. Mostly heterosexuals reported higher levels of risk in most reviewed outcomes compared to heterosexuals (unweighted mean effect sizes ranged from 0.20 to 0.50) but typically somewhat lower than bisexuals (unweighted mean effect sizes ranged from -0.10 to -0.30). Various risk factors frequently reduced, but rarely eliminated, health disparities between mostly heterosexuals and heterosexuals. Findings are discussed through the lens of three potential explanations of elevated health risks among nonheterosexuals: minority stress, nonheterosexual lifestyles, and common causes. Because data on many outcomes were scarce or missing, particularly for men and in comparison with bisexuals, further research is needed.


Doppler velocimetry indices of human immunodeficiency virus-positive pregnant women and their controls at Aminu Kano Teaching Hospital, Kano.
Nigeria is among the countries having a large number of human immunodeficiency virus (HIV)-infected people in Africa with growing number of HIV-positive children, mainly infected by their mothers. Traditional tests diagnose high-risk fetuses very late. Doppler sonography has a potential for detecting high at-risk fetus at a much early stage, so that appropriate measures could be instituted to improve outcomes. This study compared umbilical artery velocimetric parameters among HIV-positive women on highly active antiretroviral therapy (HAART) and their matched controls to determine the possible abnormalities and correlates. This was a comparative study that was conducted among HIV-positive pregnant women and their matched controls (HIV-negative pregnant women matched for gestational age and parity) at Aminu Kano Teaching Hospital. History and physical examination, transabdominal ultrasound examination were done on each subject to obtain the basic obstetric parameters. Detailed evaluations of the umbilical arteries on gray scale and duplex Doppler protocols using a 3.5-MHz curvilinear transducer were also done. The data were analyzed using SPSS Version 19.0. Independent samples t-test was used for continuous data. Chi-square test and Fisher's exact test were used for categorical data. P < 0.05 was considered statistically significant. The mean age ± standard deviation (SD) was 30.8 ± 5.50 and 27.6 ± 5.34 for HIV and control groups, respectively. The mean amniotic fluid indices and that of estimated fetal weight for the HIV and control groups showed no statistically significant difference between the two groups. The mean (±SD) umbilical artery diameter of the HIV-infected mothers is wider than their negative controls. The study showed no statistically significant difference between the Doppler indices of HIV-positive pregnant women on HAART and their matched controls.