Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures.
Recent evidence has suggested that atypical antipsychotic drugs regulate synaptic plasticity. We investigated whether some atypical antipsychotic drugs (olanzapine, aripiprazole, quetiapine, and ziprasidone) altered the expression of synapse-associated proteins in rat hippocampal neuronal cultures under toxic conditions induced by B27 deprivation. A typical antipsychotic, haloperidol, was used for comparison. We measured changes in the expression of various synaptic proteins including postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP). Then we examined whether these drugs affected the dendritic morphology of hippocampal neurons. We found that olanzapine, aripiprazole, and quetiapine, but not haloperidol, significantly hindered the B27 deprivation-induced decrease in the levels of these synaptic proteins. Ziprasidone did not affect PSD-95 or BDNF levels, but significantly increased the levels of SYP under B27 deprivation conditions. Moreover, olanzapine and aripiprazole individually significantly increased the levels of PSD-95 and BDNF, respectively, even under normal conditions, whereas haloperidol decreased the levels of PSD-95. These drugs increased the total outgrowth of hippocampal dendrites via PI3K signaling, whereas haloperidol had no effect in this regard. Together, these results suggest that the up-regulation of synaptic proteins and dendritic outgrowth may represent key effects of some atypical antipsychotic drugs but that haloperidol may be associated with distinct actions.


Hydrogen spillover mechanism on covalent organic frameworks as investigated by ab initio density functional calculation.
The hydrogen spillover mechanism, including the H chemisorption, diffusion, and H(2) associative desorption on the surface of COFs and H atoms migration from metal catalyst to COFs, have been studied via density functional theory (DFT) calculation. The results described herein show that each sp(2) C atom on COFs' surface can adsorb one H atom with the bond length d(C-H) between 1.11 and 1.14 Å, and the up-down arrangement of the adsorbed H atoms is the most stable configuration. By counting the chemisorption binding sites for these COFs, we can predict the saturation storage densities. High hydrogen storage densities show that the gravimetric uptakes of COFs are in the range of 5.13-6.06 wt%. The CI-NEB calculations reveal that one H atom diffusing along the C-C path on HHTP surface should overcome the 1.41-2.16 eV energy barrier. We chose tetrahedral Pt(4) cluster and HHTP as the representative catalyst and substrate, respectively, to study the H migration from metal cluster to COFs. At most, two H atoms can migrate from Pt(4) cluster to HHTP substrate. The migration reaction is an endothermic process, undergoing an activation barrier of 1.87 eV and 0.57 eV for the first and second H migration process, respectively. Three types of H(2) associative desorption from hydrogenated COFs were studied: (I) the two H adatoms recombining to one H(2) molecule with a recombination barrier of 4.28 eV, (II) the abstraction of adsorbed H atoms by gas-phase hydrogen atoms through ER type recombination reactions with a recombination barrier of 1.05 eV, (III) the H(2) desorption through the reverse spillover mechanism with an energy barrier of 2.90 eV.


CXCL13 and TH1/Th2 cytokines in the serum and cerebrospinal fluid of neurosyphilis patients.
Neurosyphilis is a chronic infectious disease with involvement of central nervous system infection by Treponema pallidum. This study was to investigate the contents of B lymphocyte chemokine 1 (BLC-1/chemokine [C-X-C motif] ligand 13), Th1 cytokines (Interleukin [IL]-2, IL-12, and Interferon [IFN]-γ), and Th2 cytokines (IL-6 and IL-10) in serum and cerebrospinal fluid (CSF) of HIV-negative patients with neurosyphilis before and after treatment, aiming to elucidate roles of CXCL13 and Th1/Th2 cytokines in immune response to and pathogenesis of neurosyphilis.Enzyme-linked immunosorbent assay was employed to detect the contents of CXCL13, IL-2, IL-12, IFN-γ, IL-6, and IL-10 in serum and CSF of 47 HIV-negative patients with neurosyphilis, 36 syphilis patients without neurological involvement and 23 controls (noninfectious intracranial disease) before, 3 and 12 months after treatment with high dose penicillin.Results showed that there was no significant difference in blood CXCL13 content among 3 groups (P > .05); CSF CXCL13 content in neurosyphilis patients was significantly higher than in other 2 groups (P < .001), and positively related to leucocyte count, protein concentration, and IgG index. IL-6 and IL-10 contents of the serum and CSF in neurosyphilis patients were markedly higher than in other 2 groups (P < .05 or .01), but IL-2, IL-12, and IFN-γ of the serum and CSF were significantly lower than in other 2 groups (P < .05 or .01). The IL-6, IL-10, IL-2, IL-12, and IFN-γ contents of the serum and CSF were comparable between control group and syphilis group (P > .05). CSF CXCL13 content was positively related with IL-6 and IL-10 content, while negatively related to IL-12 content in neurosyphilis patients. CSF IL-6 content was negatively related with IL-12 content. In neurosyphilis patients, the CSF CXCL13 content reduced significantly at 3 and 12 months (P < .001), the CSF IL-2 and IL-12 contents increased significantly at 12 months, and CSF IL-6 contents reduced significantly at 12 months after treatment (P < .05 or .01).It is concluded that neurosyphilis patients did not have normal immune function. CXCL13 and Th1/Th2 cytokines are involved in the immune response of neurosyphilis patients. CSF CXCL13 and Th1/Th2 cytokines contents may be used for the diagnosis and evaluation of therapeutic efficacy of neurosyphilis.


[Chapter 7. The frozen embryo in the light of a jurist : beyond qualification].
The legal qualification of the embryo does not pose any particular difficulties : this human being is a bodily thing of human nature, devoid of legal personality.However the freezing affects its humanity : it is no more than a thing made in laboratory, out of time. Stored in liquid nitrogen, it does not die, so storage must be ended.As long as they respond to a specific parental project, the one for which they were made and kept, the frozen embryos are identified by this given project.They are unique and not interchangeable. On the other hand, without a parental project, frozen embryos that can be accommodated by any infertile couple or those given to research, become interchangeable gender things.Although human beings, they are treated as the elements and products of the human body, human things.


Positive mood and helping behavior: a test of six hypotheses.
Past research has shown rather consistently that positive mood states lead to increased helpfulness. In an expanded analysis of the published literature, we examined six distinct views about this relation: the focus of attention, objective self-awareness, separate process, social outlook, mood maintenance, and concomitance hypotheses. For each of 61 positive affect conditions in which it was possible to generate an effect-size estimate corresponding to the relative degree of helpfulness exhibited by positive mood subjects (compared with neutral affect subjects), judges assessed the contextual levels of variables relevant to each of the six hypotheses by reading the Method section of each article. Higher-order partial correlation coefficients were then calculated to isolate the independent contribution of each of the theoretically relevant variables to the variation among the 61 effect sizes. The results support the focus of attention, separate process, social outlook, and mood maintenance hypotheses, and partially support the objective self-awareness and concomitance hypotheses.


Universal Machine Learning Interatomic Potentials: Surveying Solid Electrolytes.
We apply ab initio molecular dynamics (AIMD) with on-the-fly machine learning (ML) of interatomic potentials using the sparse Gaussian process regression (SGPR) algorithm for a survey of Li diffusivity in hundreds of ternary crystals as potential electrolytes for all-solid-state batteries. We show that models generated for these crystals can be easily combined for creating more general and transferable models which can potentially be used for simulating new materials without further training. As examples, universal potentials are created for Li-P-S and Li-Sb-S systems by combining the expert models of the crystals which contained the same set of elements. We also show that combinatorial models of different ternary crystals can be directly applied for modeling composite quaternary ones (e.g., Li-Ge-P-S). This hierarchical approach paves the way for modeling large-scale complexity by a combinatorial approach.


Reliability and validity of the Turkish version of the fibromyalgia rapid screening tool (FiRST).
[Purpose] An easy-to-use, psychometrically validated screening tool for fibromyalgia is needed. This study aims to evaluate the reliability and validity of the Turkish version of the Fibromyalgia Rapid Screening Tool by correlating it with 2013 American College of Rheumatology alternative diagnostic criteria and the Hospital Anxiety and Depression Scale. [Subjects and Methods] Subjects were 269 Physical Medicine and Rehabilitation clinic outpatients. Patients completed a questionnaire including the Fibromyalgia Rapid Screening Tool (twice), 2013 American College of Rheumatology alternative diagnostic criteria, and the Hospital Anxiety and Depression Scale. Scale reliability was examined by test-retest. The 2013 American College of Rheumatology alternative diagnostic criteria was used for comparison to determine criterion validity. The sensitivity, specificity, and positive and negative likelihood ratios were calculated according to 2013 American College of Rheumatology alternative diagnostic criteria. Logistic regression analysis was conducted to find the confounding effect of the Hospital Anxiety and Depression Scale on Fibromyalgia Rapid Screening Tool to distinguish patients with fibromyalgia syndrome. [Results] The Fibromyalgia Rapid Screening Tool was similar to the 2013 American College of Rheumatology alternative diagnostic criteria in defining patients with fibromyalgia syndrome. Fibromyalgia Rapid Screening Tool score was correlated with 2013 American College of Rheumatology alternative diagnostic criteria subscores. Each point increase in Fibromyalgia Rapid Screening Tool global score meant 10 times greater odds of experiencing fibromyalgia syndrome. [Conclusion] The Turkish version of the Fibromyalgia Rapid Screening Tool is reliable for identifying patients with fibromyalgia.


Patients' rights and the law of contract in eighteenth-century England.
The study of 34 lawsuits between practitioners and patients shows how the law relating to contracts was brought to bear on convicts over medical practice in eighteenth-century England. It shows that patients in this period had rights, and explores them though the practice of the courts. The article illuminates two substantial changes: the decline of the contract of cure, and the creation of the patient's right to disregard bills for fees from physicians and apothecaries. It argues that the common law created a medical market-place that was differentiated by the legal status of the patient, and that this affected the character of many healing relationships, even though the legal scrutiny of a patient-practitioner encounter was a relatively infrequent occurrence. The inability of married women and minors to make contracts, along with the legal and customary responsibility of employers for the health of servants and apprentices, meant that many patients in eighteenth-century England were not the autonomous consumers of medical care that existing histories of the patient in this period suggest. The essay thus investigates the impact of the law on the culture of medicine, whilst using legal sources to address questions about power in healing relationships.


Neurilemmoma showing a unique growth pattern in the lateral chest wall: both inside and outside the thoracic cavity.
We report the first case of the intercostal neurilemmoma showing a unique growth pattern in the lateral chest wall (both inside and outside the thoracic cavity). Usually, intrathoracic neurilemmoma is found in the posterior mediastinum and bulge from the inner surface of the bony thorax toward the thoracic cavity. This unique growing pattern of neurilemmoma arising from intercostal nerve was clearly demonstrated by computed tomography and ultrasonography.


Purification of linearized template plasmid DNA decreases double-stranded RNA formation during IVT reaction.
After the COVID-19 pandemic, messenger RNA (mRNA) has revolutionized traditional vaccine manufacturing. With the increasing number of RNA-based therapeutics, valuable new scientific insights into these molecules have emerged. One fascinating area of study is the formation of double-stranded RNA (dsRNA) during in vitro transcription (IVT) which is considered a significant impurity, as it has been identified as a major trigger in the cellular immune response pathway. Therefore, there is a growing importance placed to develop and optimize purification processes for the removal of this by-product. Traditionally, efforts have primarily focused on mRNA purification after IVT through chromatographic separations, with anion exchange and reverse phase chromatography emerging as effective tools for this purpose. However, to the best of our knowledge, the influence and significance of the quality of the linearized plasmid have not been thoroughly investigated. Plasmids production involves the growth of bacterial cultures, bacterial harvesting and lysis, and multiple filtration steps for plasmid DNA purification. The inherent complexity of these molecules, along with the multitude of purification steps involved in their processing, including the subsequent linearization and the less-developed purification techniques for linearized plasmids, often result in inconsistent batches with limited control over by-products such as dsRNA. This study aims to demonstrate how the purification process employed for linearized plasmids can impact the formation of dsRNA. Several techniques for the purification of linearized plasmids based on both, resin filtration and chromatographic separations, have been studied. As a result of that, we have optimized a chromatographic method for purifying linearized plasmids using monolithic columns with C4 chemistry (butyl chains located in the surface of the particles), which has proven successful for mRNAs of various sizes. This chromatographic separation facilitates the generation of homogeneous linearized plasmids, leading to mRNA batches with lower levels of dsRNA during subsequent IVT processes. This finding reveals that dsRNA formation is influenced not only by RNA polymerase and IVT conditions but also by the quality of the linearized template. The results suggest that plasmid impurities may contribute to the production of dsRNA by providing additional templates that can be transcribed into sequences that anneal with the mRNA molecules. This highlights the importance of considering the quality of plasmid purification in relation to dsRNA generation during transcription. Further investigation is needed to fully understand the mechanisms and implications of plasmid-derived dsRNA. This discovery could shift the focus in mRNA vaccine production, placing more emphasis on the purification of linearized plasmids and potentially saving, in some instances, a purification step for mRNA following IVT.


Suppression by thymidine-requiring mutants of Escherichia coli K-12.
Thymidine-requiring strains of Escherichia coli isolated by trimethoprim selection often simultaneously acquire the ability to suppress bacteriophage T4 nonsense mutations. Suppression is lost in Thy+ revertants and recombinants, but is sometimes retained in thyA plasmid-bearing transformants. Suppression is restricted in Strr derivatives of the Thy- mutants, indicating that suppression occurs at the level of translation.


A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.
Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.


Differential inhibitory effects of indomethacin, dexamethasone, and interferon-gamma (IFN-gamma) on IL-11 production by rheumatoid synovial cells.
IL-11, a member of the IL-6 type cytokines, has some biological activity related to the joint destruction in rheumatoid arthritis (RA), such as induction of osteoclast differentiation. However, its expression and regulation in rheumatoid inflamed joints has not been clarified. In the present study we examined the capacity of fresh rheumatoid synovial cells (fresh RSC) to produce IL-11, and the effect of indomethacin, dexamethasone and IFN-gamma on IL-11 production. Fresh RSC obtained from eight patients with RA produced large amounts of IL-11, measured by ELISA, and showed strong expression of IL-11 mRNA, determined by Northern blotting. Indomethacin inhibited the production of IL-11 by about 55%. Prostaglandin E2 (PGE2) completely prevented the inhibition, suggesting that IL-11 production by fresh RSC was in part mediated by PGE2. Dexamethasone inhibited the production of IL-11 by more than 80%. Interestingly, the inhibition was not abolished by PGE2. IFN-gamma inhibited the production of IL-11 from IL-1alpha-stimulated cultured rheumatoid synovial fibroblasts, although IFN-gamma did not inhibit the production of IL-11 by fresh RSC. These results suggest that the production of IL-11 by rheumatoid synovia was differentially regulated by PGE2 and IFN-gamma, and that treatment with indomethacin or dexamethasone decreased the level of IL-11 at inflammatory joints in patients with RA.


T-cell receptor gene homologs are present in the most primitive jawed vertebrates.
The phylogenetic origins of T-cell immunity and T-cell antigen receptor (TCR) genes have not been established. A PCR approach using short, minimally degenerate oligodeoxynucleotide primers complementing conserved variable region segments amplifies TCR-like products from the genomic DNA of Heterodontus francisci (horned shark), a representative phylogenetically primitive cartilaginous fish. One of these products has been used as a probe to screen a Heterodontus spleen cDNA library and a clone was identified that is most related at the nucleotide sequence and predicted peptide levels to higher vertebrate TCR beta-chain genes. Genomic analyses of the TCR homologs indicate that recombining variable and joining region segments as well as constant region exons are encoded by extensive gene families, organized in the multicluster form, characteristic of both the immunoglobulin heavy- and light-chain gene loci in the cartilaginous fishes. Greater numbers of homologous products were identified when a probe complementing the putative constant region of the TCR homolog was used to screen the same cDNA library. A high degree of intergenic variation is associated with the putative variable region segments of these isolates. Direct evidence is presented for TCR-like genes, which presumably are associated with T-cell function, at the earliest stages in the phylogenetic emergence of jawed vertebrates.


[Relation of capsaicin-sensitive neurones to the effect of electro-acupuncture analgesia].
In this experiment, the rats treated with capsaicin (50 mg/kg) s. c. on day 2 of liqe were used 12 weeks after injection. The levels of substance P(SP) in sciatic nerves and dorsal spinal cords were measured with radioimmunoassay to evaluate the extent of C-afferent fibers damaged by capsaicin. The results as follows: (1) the levels of SP in the sciatic nerve and the dorsal spinal cord are decreased by 69% and by 62% respectively, indicating the degeneration of the primary C-afferent fibers is very massive; (2) the average of basal tail-flick latency (immersing in 50 degrees C water) is prolonged 105% as compared with the control; (3) after electro-acupuncture, the average of tail-flick latency of the capsaicin treated rats is increased by 81%, while that of the vehicle treated rats increased by 54%. These data suggest that C-afferent fibers substantially mediate the transmission of noxious thermal stimuli, but is unnecessary for the transmission of acupuncture message to induce analgesia.


The value of specific IgG4 determination in childhood allergy to egg in relation to specific IgE and the provocation test.
The value of IgG4 determination in food allergy shows conflicting results in the medical literature. Our pediatric study was carried out in two phases. The first compared the percentage of detection and agreement of specific IgE (RAST) and IgG4 (FAST) for egg white and egg yolk in 104 patients with possible hypersensitivity to egg and positive skin tests. The second, in 22 new patients, compared IgG4 determination with the oral provocation test (OPT; the diagnostic "gold standard"). In the first phase, the percentage of positive cases for both antibodies was almost identical, but little agreement was observed between them. In the second phase, the sensitivity, specificity and agreement with the OPT were higher for IgE than for IgG4. Thus, we conclude that IgG4 levels may be high in food allergy, but their detection seems to have little diagnostic value in allergy to egg proteins in children.


Cryopreservation of bull sperm: effects of extender supplemented with different cryoprotectants and antioxidants on sperm motility, antioxidant capacity and fertility results.
The objectives of this study were to compare glycerol (G) and ethylene glycol (EG) at different concentrations and trehalose (T) or cysteine (C; with/without) in Tris extender for cryopreservation of bull semen. Twenty-four ejaculates obtained from three bulls were included in the study. Each ejaculate was divided into four equal aliquots and diluted using both of the Tris extenders with G (5% or 7%) or EG (3% or 5%). After that, each extenders were divided into three equal aliquots and diluted using both of the 5 mM C or 25 mM T, and control (without additives) was cooled to 4 ° C and frozen in 0.25 ml French straws. The addition of 3% and 5% EG without antioxidants resulted in the least Computer-Assisted Sperm motility Analysis (CASA) motility as compared with the other groups. Treatment with 25 mM T in 3% EG beneficially effected acrosome morphology as compared with the other groups. Also, treatment with 3% EG with 25 mM T and 5% EG resulted in a greater rate of total abnormalities. Treatment with 3% G yielded a slightly greater percentage of membrane integrity by Hypo-Osmotic Swelling Test (HOST) assessment than that of the other groups. Treatment with 3% EG with 5 mM C resulted in the greatest concentration of malondialdehyde (MDA). The glutathione peroxidase (GPx) antioxidant activity was increased in the C-treatment groups when compared to the other groups. Treatment with 5% EG and 5 mM C resulted in less chromatin damage and detrimental impacts on tail moment. Treatment with 5% EG led to greater non-return rates of inseminated cows. However, this result was not considered to be statistically important.


In situ reaction mechanism studies on ozone-based atomic layer deposition of Al(2)O(3) and HfO(2).
The mechanisms of technologically important atomic layer deposition (ALD) processes, trimethylaluminium (TMA)/ozone and tetrakis(ethylmethylamino)hafnium (TEMAH)/ozone, for the growth of Al(2)O(3) and HfO(2) thin films are studied in situ by a quadrupole mass spectrometer coupled with a 300 mm ALD reactor. In addition to released CH(4) and CO(2), water was detected as one of the reaction byproduct in the TMA/O(3) process. In the TEMAH/O(3) process, the surface after the ozone pulse consisted of chemisorpted active oxygen and -OH groups, leading to the release of H(2)O, CO(2), and HNEtMe during the metal precursor pulse.


Researching chronic childhood illness: the example of childhood cancer.
To provide an overview of issues raised by conducting research in the area of chronic childhood illness, using the example of childhood cancer. This literature review used informal methods. Children with cancer and their families may participate in a wide variety of studies in different research traditions, including social science studies, epidemiological, biological and genetic research, and clinical trials. Different concerns about research participation have been raised in these different contexts. Sociological debate has tended to characterize exclusion from research as a manifestation of assumptions of poor competence on the part of children, and to see inclusion in research as a means of restoring proper balance in power relations and giving children a voice. The ethical imperative within clinical research, on the other hand, has been in favour of protection of individuals from risk or direct harm. Lack of consensus on issues such as the status of children's consent for research participation persists, in part because debates have taken place within rather than across disciplinary boundaries, and in part because of a tendency to debate issues as ethical principles in an empirical vacuum. The lack of research on the experiences and views of those asked to take part in childhood cancer research is striking. It is important that debates about the involvement of children in research are informed by high-quality social science research and by interdisciplinary dialogue.


Interdisciplinary rehabilitation of a primary intraosseous carcinoma including orthodontic archform management.
Squamous cell carcinomas arising from keratocystic odontogentic tumors are a rare phenomenon in head and neck cancer, accounting for only 1.45% of oral squamous cell carcinomas, and are classified as primary intraosseous carninomas. This cancer is locally aggressive, has a high potential for recurrence, and requires radical resection and subsequent rehabilitation. This case report describes a patient diagnosed with this uncommon tumor who was treated by dental specialists at Mayo Clinic. During convalescence, orthodontic changes to the maxillary dental archform were observed secondary to alterations in the soft tissue equilibrium following mandibulectomy and reconstruction with a microvascular fibula free flap. This highlights the need for treatment plan adaptability, the role of orthodontists in maintenance or treatment of pre-resection archforms, and the interdisciplinary nature necessary in managing the complex oncologic, functional, and esthetic needs in patients undergoing treatment for head and neck cancer.


Low-risk polycythemia vera and essential thrombocythemia: management considerations and future directions.
Thrombotic events are a distinctive feature of the myeloproliferative neoplasms (MPNs) polycythemia vera (PV) and essential thrombocythemia (ET). Patients with these MPNs may also experience a poor quality of life secondary to symptom burden, as well as progression of disease to acute leukemia or myelofibrosis. Over the years, various risk stratification methods have evolved in order to attempt to predict thrombotic risk, which is the largest contributor of morbidity and mortality in these patients. More than half of PV and ET patients are low- or intermediate-risk disease status at the time of diagnosis. While therapeutic development is presently focused on high-risk patients, there is a paucity of therapies, outside of aspirin and therapeutic phlebotomy, which can reduce the thrombotic risk or delay disease progression in low-risk patients. In this review, we first describe the various complications that patients with PV and ET experience, and then detail our evolving understanding of risk stratification in these diseases. We then highlight the available evidence on the management of low-risk PV and ET and include a description of novel therapies currently under investigation in this space. We conclude with recommendations for future directions to advance our understanding and improve the treatment of low-risk PV and ET.


MCM6 is a Poor Prognostic Biomarker and Promotes Progression in Breast Cancer.
Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear. MCM6 expression in patients with breast cancer was examined through The Cancer Genome Atlas (TCGA) database, immunohistochemistry, Quantitative Real-Time PCR (qRT‒PCR) and Western blotting. The prognostic factors were assessed by the Kaplan‒Meier method and Cox regression. On the basis of the key factors selected by multivariable Cox regression analysis, a nomogram risk prediction model was adopted for clinical risk assessment. The TCGA database was utilized to determine how MCM6 is correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, along with tumor mutation burden (TMB) and methylation. The impact of MCM6 on carcinoma cells was investigated in terms of proliferation, cell cycle as well as migrating and invasive behavior through CCK assays, flow cytometry, wound healing assays, Transwell assays and xenotransplantation experiments. MCM6 expression was upregulated, which is closely associated with the size of the tumor (p = 0.001) and lymph node metastasis (p = 0.012) in patients with breast cancer. Multivariate analysis revealed MCM6 to be an independent risk factor for prognosis in patients with breast carcinoma. The nomograph prediction model included MCM6, age, ER, M and N stage, which displayed good discrimination with a C index of 0.817 and good calibration. Overexpression of MCM6 correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, tumor mutation burden (TMB), and methylation. Silencing MCM6 significantly inhibited proliferation, prolonged the G1 phase of the cell cycle, and restrained the proliferation, migration and invasive behavior of cancerous cells and inhibited tumor growth in vivo. Our research shows that MCM6 is highly expressed in breast cancer and can be used as an independent prognostic factor, which is expected to become a new target for the treatment of breast cancer in the future.


[The ultrastructure of the synapses in the upper layers of the cat cerebral cortex after applying strychnine].
Ultrastructure of axo-dendritic and axo-spinous synapses in upper layers of cat brain gyrus suprasylvii was studied in 10, 30 and 90 min application of 0.1% strychnine nitrate and also 2.5 and 5 hrs after 90 min long use of strychnine. Portion of active synaptic contacts was found to grow higher in 10 and 30 min application and smaller during and 2.5 hrs after 90 min application. However, synaptic vesicles number is sharply reduced beginning from min 30 of application and only on 5th postapplication hr reaches initial level. Application of strychnine does not cause changes in synapse active zone length and presynaptic terminals section area. Reorganisations in pre- and postsynaptic terminals most acutely manifested in 90 min application are reversible--on 5th postapplication hr synapse ultrastructure turns into similar to that of control material.


[Clinical misdiagnosis analysis of valproate encephalopathy].
To analyze the clinical and laboratory characteristics of postoperative patients of valproate encephalopathy (VHE), summarize the diagnostic and treatment experiences, discuss the reason of misdiagnosis and improve the level of early diagnosis. A total of 12 VHE patients diagnosed after an application of valproate were recruited from January 2010 to April 2013. The characteristics of clinical manifestations and laboratory examinations were retrospectively analyzed. Among them, the misdiagnoses included intracranial hemorrhage (n = 1), secondary brain edema (n = 1), postoperative cerebral infarction (n = 1), postoperative epileptic deterioration (n = 4), electrolyte disorder (n = 2), intracranial infection (n = 1), vasospasm (n = 1) and non-specific (n = 1). All patients had disturbance of consciousness associated with elevated blood ammonia. The symptoms of VHE were not correlated with the dosage and concentration of valproate. VHE was more likely to occur in patients treated with valproic acid sodium injection or other antiepileptic drugs. The symptoms dramatically improved after a withdrawal of valproate. VHE should be considered in postoperative neurosurgical valproate-treated patients with unknown disturbance of consciousness. Timely diagnosis is needed and valproate should be withdrawn to avoid serious consequences.


Modeling natural images using gated MRFs.
This paper describes a Markov Random Field for real-valued image modeling that has two sets of latent variables. One set is used to gate the interactions between all pairs of pixels, while the second set determines the mean intensities of each pixel. This is a powerful model with a conditional distribution over the input that is Gaussian, with both mean and covariance determined by the configuration of latent variables, which is unlike previous models that were restricted to using Gaussians with either a fixed mean or a diagonal covariance matrix. Thanks to the increased flexibility, this gated MRF can generate more realistic samples after training on an unconstrained distribution of high-resolution natural images. Furthermore, the latent variables of the model can be inferred efficiently and can be used as very effective descriptors in recognition tasks. Both generation and discrimination drastically improve as layers of binary latent variables are added to the model, yielding a hierarchical model called a Deep Belief Network.


[Clinical results and modification of left ventricular function after emergency revascularization for acute myocardial infarction].
Results of emergency revascularization for evolving myocardial infarction have been evaluated in 43 consecutive patients operated between January 1985 and March 1988. Time interval between onset of symptoms and coronary bypass averaged 6.7 +/- 0.5 hours (0.75-48). Intravenous or intracoronary thrombolysis was attempted pre-operatively in 26 cases. Overall hospital mortality was 6.9% (3/43) but this decreased to only 2.7% if patients in cardiogenic shock were excluded. Follow-up averaged 20.6 +/- 9.5 months (4-42). Actuarial survival was 82.9 +/- 7.3% at 36 months. Of the 36 survivors, 28 were free from angina and reinfarction at control. Nineteen patients were evaluated with angiography at follow-up (averaging 10.1 +/- 5.7 months). Left ventricular and regional ejection fraction were calculated on pre- and post-operative angiograms; regional ejection fraction was determined with the centerline method. Left ventricular ejection fraction increased from 0.49 +/- 0.15 to 0.52 +/- 0.19 (NS), regional ejection fraction improved from 0.20 +/- 0.1 to 0.27 +/- 0.16 (35% increment, p less than 0.05). The analysis of left ventricular and regional ejection fraction variations with the time elapsed from the onset of symptoms to surgery identified two subgroups of patients: those operated within and after six hours. In the first subgroup, left ventricular ejection fraction increased from 0.52 +/- 0.16 to 0.62 +/- 0.13 (p less than 0.005) and regional ejection fraction from 0.19 +/- 0.08 to 0.36 +/- 0.14 (89% increment, p less than 0.0005). In the second subgroup, both left ventricular and regional ejection fractions decreased from 0.44 +/- 0.13 to 0.36 +/- 0.11 (NS) and from 0.20 +/- 0.13 to 0.12 +/- 0.08 (NS), respectively. These results lead to the conclusion that improved left ventricular performance may be achieved in selected groups of patients if they undergo surgery within six hours of the onset of pain.


Linguistic Validation of the Pediatric Versions of the Sheehan Suicidality Tracking Scale (S-STS).
The United States Food and Drug Administration meta-analysis of registration trials of antidepressants found that emergent suicidality under the age of 25 years increases with decreasing age. This led to boxed warnings for antidepressants and the recommendation for careful assessment and monitoring of suicidality in children and adolescents. To address this need, we describe the development of a pediatric suicidality assessment and tracking scale and a novel, empirically based approach to its age-appropriate linguistic validation. Starting with the adult version of the Sheehan-Suicidality Tracking Scale, we collaborated with reading specialists who use the sight word lists of Dolch and Fry and the grade level vocabulary lists of Beck, Farr, and Strickland to adapt the adult version to each age group. Our approach resulted in the development and documentation of a process for linguistically validating three age-appropriate pediatric versions of the Sheehan-Suicidality Tracking Scale from the adult version of the scale: one for 6- to 8-year-olds, a second for 9- to 12-year-olds, and a third for 13- to 17-year-olds. Further reliability and cognitive debriefing studies are needed in diverse demographic, ethnic, and cultural groups to make the pediatric versions of the Sheehan-Suicidality Tracking Scale more reliable, more generalizable, and more useful.


[The role of goitrogenic factors distinct from iodine deficiency in the etiology of goiter].
The main cause of endemic and sporadic goiter is a deficiency in the dietary supply of iodine. However, iodine deficiency is not the only cause of goiter. This paper reviews present knowledge on the role of naturally occurring goitrogens in the etiology of goiter. Vegetables from the Cruciferae family, chronic consumption of poorly detoxified cassava containing large amounts of cyanogenic glucosides, flavonoids, humic substances originating from the organic residues in the soil are clearly involved in the etiology of endemic goiter. Iodine excess, especially in the newborn infants, lithium and thiocyanate overload resulting from smoking habits can be responsible for the development of goiter in non endemic areas.


Orthopedic management of acquired cerebrospasticity in childhood.
Of 221 children with head injuries and resultant deep coma followed for long-term problems, 156 became totally independent, functional individuals, only 61 lacking normal cognition and speech. Reconstructive surgical procedures for residual spasticity was necessary in 45 patients. Achilles lengthenings were the most common procedure performed; after Achilles lengthenings, toe flexor releases were most often required. Twenty children had anoxia from drowning or anesthesia problems; 7 of these had spastic hip deformities or dislocations, all within 6 months of the anoxic event. Progressive cerebrospastic syndromes and post-infectious cerebrospasticity most often require orthotic devices for their orthopedic management.


The state of shared decision making in Malaysia.
Shared decision making (SDM) activities in Malaysia began around 2010. Although the concept is not widespread, there are opportunities to implement SDM in both the public and private healthcare sectors. Malaysia has a multicultural society and cultural components (such as language differences, medical paternalism, strong family involvement, religious beliefs and complementary medicine) influence medical decision making. In terms of policy, the Ministry of Health has increasingly mentioned patient-centered care as a component of healthcare delivery while the Malaysian Medical Council's guidelines on doctors' duties mentioned collaborative partnerships as a goal of doctor-patient relationships. Current research on SDM comprises baseline surveys of decisional role preferences, development and implementation of locally developed patient decision aids, and conducting of SDM training workshops. Most of this research is carried out by public research universities. In summary, the current state of SDM in Malaysia is still at its infancy. However, there are increasing recognition and efforts from the academic institutions and Ministry of Health to conduct research in SDM, develop patient decision support tools and initiate national discussion on patient involvement in decision making.


Evaluation of In Vitro Antiamoebic Activity of Antimicrobial Agents Against Clinical Acanthamoeba Isolates.
The aim of this study was to elucidate in vitro antiamoebic activity of antimicrobial agents at short exposure times similar to those used for actual treatment against Acanthamoeba strains isolated from patients with keratitis. The 5 clinical Acanthamoeba isolated in Japan were used in this study. Identification of genotypes for the Acanthamoeba isolates was performed using partial 18S ribosomal DNA (rDNA), including the ASA.S1 region sequences. Fluconazole, miconazole, itraconazole, voriconazole, amphotericin B, natamycin (pimaricin), and micafungin (antifungal agents), and chlorhexidine (a biguanide disinfectant), and sulfamethoxazole and paromomycin (antibacterial agents) were used to determine the antiamoebic activity against Acanthamoeba, which were determined by 50% and 90% growth inhibitory concentrations (IC50 and IC90) following exposing to each drug at 25°C for 7 days and 12 h. Among the tested antimicrobial agents, natamycin strongly inhibited the growth of all Acanthamoeba isolates at low concentration in both the 7-day (IC90 = 4.1 μg/mL) and 12-h (IC90 = 11.6 μg/mL) assays. Additionally, sulfamethoxazole exhibited strong antiamoebic activity (IC90 = 9.8 μg/mL) at low concentration in the 7-day assay. Our findings showed that natamycin ophthalmic solution might be an effective agent against Acanthamoeba keratitis. Additionally, frequent administration of sulfamethoxazole ophthalmic solution or systemic sulfamethoxazole-trimethoprim is also considered as an effective treatment for Acanthamoeba keratitis.


Scoping study of detecting high harmonic fast waves in NSTX-U hot core plasma directly using beam emission spectroscopy.
In this paper, we used radio frequency (RF) full wave simulation to explore the feasibility of generating a density beat oscillation formed by high harmonic fast waves (HHFWs) in the National Spherical Tokamak Experiment-Upgrade (NSTX-U) and of measuring it numerically with 2D beam emission spectroscopy (BES). This oscillation is of interest as it can be used to determine the injected RF fields. We began by computing HHFW fields in NSTX-U under a variety of experimental conditions and antenna configurations with Petra-M, a 3D RF wavefield solver. These fields were then used to evaluate the amplitude of δne,beat/ne0 in the volume of measurement, which we predict to be between 5 × 10-10 and 10-9, although it is highly dependent on plasma parameters. Trends in magnetic field, core temperature, core density, and antenna phasing are presented, and the parameters most suitable to this measurement are identified. Finally, we developed a synthetic BES diagnostic to compare the experimental BES signal against.


Stiripentol.
Stiripentol (STP) is a new antiepileptic compound made by Biocodex. It recently proved to increase the GABAergic transmission in vitro in an experimental model of immature rat. Clinical studies were based on the fact that STP also acts as an inhibitor of CYP3A4, CYP1A2, and CYP2C19 in vivo in epileptic patients. Whereas the studies in adult patients were disappointing, the trials conducted in pediatric populations demonstrated a specific efficacy of STP in severe myoclonic epilepsy in infancy, Dravet syndrome, when combined with valproate and clobazam. Based on these results, STP was granted orphan drug status in the European Union for the treatment of Dravet syndrome. The French experience in compassionate use suggests that STP might also be of benefit when combined with carbamazepine in pediatric patients with pharmacoresistant partial epilepsy. The interactions of STP with a large number of drugs need to be carefully taken into account, with doses of the combined antiepileptic drugs adjusted to improve the tolerability of the therapeutic association.


Quality of Acute Care and Long-Term Quality of Life and Survival: The Australian Stroke Clinical Registry.
Uncertainty exists over whether quality improvement strategies translate into better health-related quality of life (HRQoL) and survival after acute stroke. We aimed to determine the association of best practice recommended interventions and outcomes after stroke. Data are from the Australian Stroke Clinical Registry during 2010 to 2014. Multivariable regression was used to determine associations between 3 interventions: received acute stroke unit (ASU) care and in various combinations with prescribed antihypertensive medication at discharge, provision of a discharge care plan, and outcomes of survival and HRQoL (EuroQoL 5-dimensional questionnaire visual analogue scale) at 180 days, by stroke type. An assessment was also made of outcomes related to the number of processes patients received. There were 17 585 stroke admissions (median age 77 years, 47% female; 81% managed in ASUs; 80% ischemic stroke) from 42 hospitals (77% metropolitan) assessed. Cumulative benefits on outcomes related to the number of care processes received by patients. ASU care was associated with a reduced likelihood of death (hazard ratio, 0.49; 95% confidence interval, 0.43-0.56) and better HRQoL (coefficient, 21.34; 95% confidence interval, 15.50-27.18) within 180 days. For those discharged from hospital, receiving ASU+antihypertensive medication provided greater 180-day survival (hazard ratio, 0.45; 95% confidence interval, 0.38-0.52) compared with ASU care alone (hazard ratio, 0.64; 95% confidence interval, 0.54-0.76). HRQoL gains were greatest for patients with intracerebral hemorrhage who received care bundles involving discharge processes (range of increase, 11%-19%). Patients with stroke who receive best practice recommended hospital care have improved long-term survival and HRQoL.


The open, the closed, and the empty: time-resolved fluorescence spectroscopy and computational analysis of RC-LH1 complexes from Rhodopseudomonas palustris.
We studied the time-resolved fluorescence of isolated RC-LH1 complexes from Rhodopseudomonas palustris as a function of the photon fluence and the repetition rate of the excitation laser. Both parameters were varied systematically over 3 orders of magnitude. On the basis of a microstate description we developed a quantitative model for RC-LH1 and obtained very good agreement between experiments and elaborate simulations based on a global master equation approach. The model allows us to predict the relative population of RC-LH1 complexes with the special pair in the neutral state or in the oxidized state P(+) and those complexes that lack a reaction center.


World Trade Center psychological exposures and trauma related disorders: PTSD and adjustment disorders.
The relationship between exposure to the World Trade Center (WTC) disaster and elevated rates of trauma related psychiatric illnesses in 9/11 responders and survivors has been well documented. This paper is part of a series to promote the practice of evidence-based medicine when managing persons with WTC-related conditions and focuses on "Trauma and Stressor Related Disorders," a diagnostic category that includes posttraumatic stress disorder (PTSD) and adjustment disorder. It offers background on 9/11-related trauma exposure, a summary of research findings from this cohort, and is followed by brief diagnostic and treatment information from selected clinical practice guidelines.


The Impact on the Healing of Bioactivation with Argon Plasma of a Xenogeneic Graft with Adequate Fixation but Poor Adaptation to the Recipient Site: An Experimental Study in Rabbits.
To evaluate the impact on healing of bioactivation with argon plasma of a xenogeneic graft with adequate fixation but poor adaptation to the native host bone. Xenogeneic grafts were either treated with argon plasma or left untreated and randomly secured with a titanium screw to both lateral aspects of the mandible angle of rabbits. A discrepancy was obtained between the xenograft and the mandible due to the convexity of the recipient site. Collagen membranes were placed on the grafts. Thirty animals were included and euthanized in groups of 10 after 2, 6, and 10 weeks, respectively. Histomorphometric evaluations were performed on ground sections. Newly formed bone was the primary outcome, while the distance between the peak of new bone inside the graft and the upper surface of the graft, the xenograft percentages, and the area of the xenograft were considered as secondary variables. The Wilcoxon test was applied for statistical analyses. After 2 weeks of healing, gaps of ~0.5 mm were observed at the interface between the graft and the recipient sites, and new bone was mainly located in the interface and within the inferior regions of the grafts. New bone increased over time in all regions, including those in the upper zones of the graft, reaching proportions of 20.3% ± 6.5% and 19.3% ± 7.4% (P = .484) after 10 weeks in the plasma and control groups, respectively. The mean distance between the peak of new bone inside the graft and the upper surface of the graft decreased between 2 and 10 weeks of healing from 1.4 mm to 0.4 mm and from 1.7 mm to 0.3 mm at the plasma and control sites, respectively. The xenogeneic grafts of both groups were incorporated into the recipient sites by newly formed bone that presented a growth close to the upper surface of the graft. The bioactivation with argon plasma did not improve healing.


Primers on molecular pathways. The glycogen synthase kinase-3beta.
Despite tremendous scientific effort, conventional treatment approaches have had little impact on the course of pancreatic ductal adenocarcinoma. Therefore, urgency is needed to understand the molecular mechanisms underlying the development of pancreatic cancer with the hope that this will lead to preventative and treatment strategies to improve the outcome of the disease. Numerous factors contribute to progression of this disease, including constitutively active NF kappa B, which has been shown to positively influence cancer cell survival, proliferation, invasion, metastasis and chemoresistance. Recently, the cytoplasmic serine/threonine protein kinase glycogen synthase kinase-3beta (GSK-3beta) was found to regulate NF kappa B activation and the proliferation and survival of pancreatic cancer cells. Moreover, recent studies in other human malignancies have implicated GSK-3beta as a regulator of cancer cell proliferation, survival and chemoresistance through distinct mechanisms. Thus, GSK-3beta has emerged as a viable therapeutic target in the treatment of several human neoplasms.


Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder.
Heart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala. Respiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9-18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest. There were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects. RSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula's role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those.


NORTH AMERICAN BLACK BEAR mtDNA PHYLOGEOGRAPHY: IMPLICATIONS FOR MORPHOLOGY AND THE HAIDA GWAII GLACIAL REFUGIUM CONTROVERSY.
The controversial role of Haida Gwaii (Queen Charlotte Islands) as a biological refugium on the northwestern coast of North America has been widely discussed for more than fifty years. The presence of morphologically divergent subspecies on Haida Gwaii is one of the major lines of evidence suggesting this archipelago's role as a refugium during the Wisconsin. However, since morphological distinction can be derived postglacially as well as in extended isolation, such evidence is ambiguous. To examine this question, we did a phylogenetic analysis of cytochrome b sequences (719 bp) of black bear (Ursus americanus), one of the distinctive endemics of Haida Gwaii, and compared these with conspecifics from across North America, focusing primarily on the northwestern coast. We found that the Haida Gwaii bear are indistinguishable from coastal bear of British Columbia and Vancouver Island, but are highly distinct from continental bear. Coastal and continental bears differ by 24 synapomorphies and an average sequence divergence of 3.6%. The coastal mitochondrial lineage occurs in each of the three recognized coastal subspecies suggesting that the morphological characteristics differentiating these taxa may be postglacially derived. The data are consistent with recent suggestions that a glacial refugium existed on the now submerged continental shelf connecting Haida Gwaii, Vancouver Island, and the coastal fringe of mainland British Columbia. This refugium would have been an additional source for postglacial recolonization of northwestern North America.


An autopsy report of a rare pediatric lung tumor: pleuropulmonary blastoma.
An autopsy report of pleuropulmonary blastoma (PPB) is described in a two-and-a-half-year-old male child who died within a few days of starting chemotherapy. Autopsy revealed a large tumor almost occupying the whole of left hemithorax with widespread extension to pleura. The diagnosis was confirmed to be PPB, type III on autopsy.


Tumor immunohistochemistry and preoperative magnetic resonance imaging features predict local recurrence of giant cell tumor of bone following intralesional curettage.
Giant cell tumor of bone (GCTB) is among the most prevalent types of tumor of the bone in East and Southeast Asia. The high rate of local recurrence following intralesional curettage poses a challenge for the clinical treatment of GCTB. In the present study, the expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL) in GCTB was investigated by immunohistochemical staining. A correlation between expression and preoperative magnetic resonance imaging (MRI) features was identified. The patients were followed up for ≥2 years after intralesional curettage. The rates of local recurrence were compared among different groups. A total of 74 cases of GCTB in the proximal tibia or distal femur were investigated. MRI features were retrospectively examined by correlation analysis. The expression of MMP-9 was demonstrated to be associated with cystic changes and the 'paint brush borders' sign (P<0.05), and positively associated with the expression of RANKL (P<0.05) and VEGF (P<0.05). Cystic changes, the 'paint brush borders' sign and adjacent soft tissue invasion were associated with high rates of local recurrence (P<0.05) and were therefore identified as significant risk factors. Pathologically, the 'paint brush borders' sign was demonstrated to be indicative of local invasion of the bone. These findings may be useful for predicting local recurrence of GCTB, and may provide important insight into the preoperative MRI features and molecular expression patterns of GCTB tumors.


Neutrophil stimulation by recombinant cytokines and a factor produced by IL-1-treated human synovial cell cultures.
Neutrophil accumulation and activation are early events in the inflammatory response in vivo. Using human recombinant forms of the putative inflammatory mediators interleukin-1 (IL-1) and tumour necrosis factor (TNF alpha) we were unable to detect direct effects on human neutrophil locomotion or intracellular free calcium concentration ([Ca2+]i) in vitro. Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to stimulate significant locomotion, but was unable to elevate neutrophil [Ca2+]i. In contrast, supernatant from cultured human synovial cells that had been treated with human recombinant IL-1 alpha (28 pM) released a factor that stimulated both neutrophil locomotion and elevated neutrophil [Ca2+]i. Our studies demonstrate that the production of this factor is time-dependent, requiring exposure of the synovial cells to IL-1 for more than 4 hr, is not influenced by cyclo-oxygenase or lipo-oxygenase inhibition, but can be abolished by dexamethasone (100 nM) or actinomycin D (0.8 microM). The factor has a molecular weight above 10,000 and does not cross-react with anti-C5a antisera. IL-1 beta and TNF alpha were also able to stimulate its production. Our findings suggest that the neutrophil accumulation that is known to occur in response to IL-1 in vivo may be a consequence of the local production of such a factor.


[Preventive effect of zeolite in VX poisoning in rats].
In the present paper the effect of zeolite tuff (61% clinoptilolite) was investigated on cholinesterase activity in brain, liver, spleen, femoral muscle, heart, stomach, duodenum, colon and erythrocytes in sewer-rats after peroral intoxication with VX substance (65.5 micrograms/kg). Fig. 1 shows the ChE activity in the tissues and erythrocytes in the animals of control group and in the group of animals after intoxication with VX substance. The highest activity in the control group was found in brain and duodenum. The enzyme activity in the femoral muscle had the lowest values. A significant decrease in the ChE activity (P < 0.001 or P < 0.01) occurred in all the investigated samples in the group of animals intoxicated with the VX substance. highest enzyme inhibition was observed in erythrocytes (97.9%), stomach (97.9%), brain (95.4%) and liver (94.7%) if compared with the control group. The relatively lowest inhibition was found out in duodenum and colon. In the group administered zeolite before intoxication (1.0 g/kg five minutes before intoxication) the ChE activity was significantly higher in almost all investigated samples than in the group without zeolite (P < 0.001 or P < 0.01)-Fig. 2. The duodenum is an exception, in which the ChE activity in the zeolite group was lower than in the zeolite-free group (P < 0.001), as well as the colon, in which there were no significant differences in the activity between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)


An assay method for glycogen debranching enzyme using new fluorogenic substrates and its application to detection of the enzyme in mouse brain.
An assay method for glycogen debranching enzyme involving fluorogenic dextrins as substrates was developed. Two dextrins were prepared from 6-O-alpha-D-glucosyl-alpha-cyclodextrin and glucose by taking advantage of the action of Bacillus macerans cyclodextrin glucanotransferase, and converted by pyridylamination to fluorogenic derivatives. Structural analysis of the fluorogenic dextrins by FAB-MS, partial acid hydrolysis, and glucoamylase digestion revealed that they were Glcalpha1-4(Glcalpha1-6)Glcalpha1-4Glcalpha1- 4Glcalpha1-4Glc-PA (FD6) and Glcalpha1-4Glcalpha1-4(Glcalpha1-6)Glcalpha1- 4Glcalpha1-4Glcalpha1-4G lc-PA (FD7). Using the glycogen debranching enzyme from rabbit muscle, FD6 and FD7 were, respectively, hydrolyzed to PA-maltopentaose and PA-maltohexaose, in addition to glucose, showing that these two fluorogenic dextrins are suitable substrates for assaying the glycogen debranching enzyme. An assay method involving the separation and quantification by HPLC of the characteristic fluorogenic products was successfully applied to determination of the distribution of the enzyme activity in mouse cerebrum.


Protection by selenium against gentamicin-induced acute renal damage in the rat.
Gentamicin has been shown to induce renal tubular damage in man and laboratory animals and to result in elevated urinary excretion of some enzymes associated with specific cell regions in the kidney. In the present investigation, the possible protective effect of selenium against gentamicin-induced renal damage was tested by measuring the urinary excretion of some enzymes in the presence and absence of selenium. Our results show that a prior subcutaneous injection of selenium to rats for two days followed by a simultaneous S.C. injection of gentamicin and selenium resulted in a marked reduction in the excretion of such biochemical systems as the urine volume, urinary proteins, alkaline and acid phosphatases, beta-glucuronidase, muramidase, and glutamate dehydrogenase. Renal functional studies revealed that selenium-treated rats suffered less adverse effects compared to rats treated with gentamicin alone. Urinary acid phosphatase, beta-glucuronidase and muramidase, the three lysosomal enzymes tested, appeared to respond most readily to protection by selenium.


Regulation of breathing movements in fetal sheep by prostaglandin E2.
In fetal sheep, plasma prostaglandin (PG) E2 concentrations are high, and fetal breathing movements (FBM) occur intermittently, primarily during low-voltage fast electrocortical activity (LVFA). There is evidence suggesting that prostaglandins, specifically PGE2, may regulate FBM. To define the physiological role of PGE2 in regulation of FBM, we infused meclofenamate (0.9 mg X kg-1 X h-1), a prostaglandin synthetase inhibitor, into six fetal sheep to suppress endogenous prostaglandin production. Afterward, PGE2 was added in mean doses of 9, 18, 36, and 90 ng X kg-1 X min-1. Meclofenamate decreased PGE2 concentrations and increased FBM, especially during high-voltage slow electrocortical activity (HVSA). Addition of PGE2 reversed the effects of meclofenamate, increasing PGE2 concentrations and decreasing FBM, especially during HVSA. The response to PGE2 was dose dependent; the overall incidence of FBM and incidences of FBM during HVSA and LVFA were inversely correlated with both the infused PGE2 dose and the mean PGE2 concentration. At higher doses of PGE2, FBM occurred intermittently and only during LVFA; thus PGE2 infusion restored the physiological pattern of FBM. These results indicate that PGE2 regulates FBM by inhibiting FBM during HVSA.


Book of Abstracts of the 21th European Conference on Eye Movements in Leicester 2022.
Contents Keynotes: Iain Gilchrist: Integrative Active Vision p 5 Ziad Hafed: A Vision for orienting in Primate Oculomotor Control Circuitry p 6 Fatema Ghasia: Miniscule Eye Movements Play a Major Role in Binocular Vision Disorders p.7 Miriam Spering: Eye Movements as a Window into Human Decision-Making p.8 Monica S. Castelhano: Explorations of how Scene Context and Previous Experience Dynamically Influence Attention and Eye Movement Guidance p.9 Symposia: Eye Tracking and the Visual Arts p.19 Eye Movements during Text Processing and Multiline Reading p.23 Unstable Fixation and Nystagmus with a Focus on the Next Generation of Researchers p.84 Eye Movements as a measure of Higher-Level Text Processing p.97 Eye Movements in Memory Processes Between Working Memory and Long-Term Memory p.178 Symposium to Honour Alexander Pollatsek's Legacy to Eye Movement Research p.204 Talks: Reading p.30 Parafoveal Processing p.36 Cinical and Applied p.39 Visual Search p.92 Eye Movement Control in Reading I & II p.104 & 116 & 225 Reading Development p.110 Decision-Making p.122 Eye-tracking Methods p.128 Real World and Virtual Reality p.134 Chinese Reading p.185 Special Populations p.191 Visuo-motor p.195 Bilingual Reading p.201 & 217 Reading Comprehension p.219 Pupillometry p.235 Poster sessions: Attention p.44 & 139 Cognition p. 49 Visuo-Motor p.62 Memory p.145 Methods p.150 Reading p. 57 & 155 Real World p.169 Social Cognition p.173.


3,5-Diarylimidazo[1,2-a]pyridines as Color-Tunable Fluorophores.
A new protocol for the synthesis of color-tunable fluorescent 3,5-diarylimidazo[1,2-a]pyridines has been achieved via palladium-catalyzed C-H amination of pyridinium zwitterions. Based on experimental results and computational analysis, we extracted a high correlation of photophysical properties with the theoretical concept and predicted emission wavelengths of 3,5-diarylimidazo[1,2-a]pyridines. The emission wavelengths of imidazo[1,2-a]pyridines increase as a function of the electron-withdrawing nature of the substituent on the C5-aryl group of imidazo[1,2-a]pyridine as a result of inductive effects on the LUMO levels. Varying the substituent on the C3-aryl group imidazo[1,2-a]pyridine changes the HOMO levels. Combining these two sites, the HOMO and LUMO levels can be tuned fairly decoupled from each other. This conceptual trend is demonstrated across a series where the C3 and C5 positions were functionalized independently and then utilizes a combination strategy where both sites are used to prepare fluorophores with a large window of emission wavelengths. In view of the biological properties of imidazo[1,2-a]pyridines, the developed method provides an efficient approach for understanding and preparing strongly fluorescent bioprobes.


[PROGNOTIC FACTORS EFFECTING MORTALlTY IN TRAUMATIC DIAPHRAGMA INJURY].
Traumatic diaphragma rupturesare difficult to diagnose and generally with associated organe injuries. The aim ofthe study is to evaluate the factors effect on mortality. Twenty-three patients with traumatic diaphragma injuries, admitted to our hospital were retrospectively evaluated for demographics, diagnosis, otherorgan injuries, treatment, mortalityand morbidity. All patients were male and the mean age was 24.7 10.0. The diaphragma injuries were observed during laparatomy in 19 patients (%82.6), during laparatomy and thoracotomy in 2 (%8.7). The injuries were diagnosed with fluid drainage from thorax tube during peritoneal lavage in 2 patients (%8. 7). All patients, but one, had other organ injuries (%95.7), most commonly in stomach, spleen and liver. Seven patients died during peroperative or postoperative peiod (%30.4). When these seven patients were compared to survived patients, it was observed that age and trauma score were statistically related to mortality rate (p<0.05), but the lenght ofthe diaphragmatic injury was not related to mortality rate (p > 0.05). Traumatic diaphragma injuries are generally diagnosed during laparatomy and associated with other organ injuries. The high mortality rate in patients with traumatic diaphragma injuries, is not related to the characteristics ofthe diaphragma injury, but it is closely related to concomitant problems such as patient is age and trauma score.


Selecting β-glucosidases to support cellulases in cellulose saccharification.
Enzyme end-product inhibition is a major challenge in the hydrolysis of lignocellulose at a high dry matter consistency. β-glucosidases (BGs) hydrolyze cellobiose into two molecules of glucose, thereby relieving the product inhibition of cellobiohydrolases (CBHs). However, BG inhibition by glucose will eventually lead to the accumulation of cellobiose and the inhibition of CBHs. Therefore, the kinetic properties of candidate BGs must meet the requirements determined by both the kinetic properties of CBHs and the set-up of the hydrolysis process. The kinetics of cellobiose hydrolysis and glucose inhibition of thermostable BGs from Acremonium thermophilum (AtBG3) and Thermoascus aurantiacus (TaBG3) was studied and compared to Aspergillus sp. BG purified from Novozyme®188 (N188BG). The most efficient cellobiose hydrolysis was achieved with TaBG3, followed by AtBG3 and N188BG, whereas the enzyme most sensitive to glucose inhibition was AtBG3, followed by TaBG3 and N188BG. The use of higher temperatures had an advantage in both increasing the catalytic efficiency and relieving the product inhibition of the enzymes. Our data, together with data from a literature survey, revealed a trade-off between the strength of glucose inhibition and the affinity for cellobiose; therefore, glucose-tolerant BGs tend to have low specificity constants for cellobiose hydrolysis. However, although a high specificity constant is always an advantage, in separate hydrolysis and fermentation, the priority may be given to a higher tolerance to glucose inhibition. The specificity constant for cellobiose hydrolysis and the inhibition constant for glucose are the most important kinetic parameters in selecting BGs to support cellulases in cellulose hydrolysis.


THE DEPENDENCE OF THE PHOTOPUPIL RESPONSE ON FLASH DURATION AND INTENSITY.
The changes in pupil size were recorded by infrared pupillographic methods in response to light flashes of different durations and intensities for a 13 degree 34 minute centrally fixated circular field. For such stimuli, the threshold intensities for (rod) vision and for the pupil response were found to be about the same. The response amplitudes were related to the logarithm of the flash energy, the reciprocity law remaining valid up to about one-half second. The curve relating flash energy and pupil response was clearly divisible into two parts commensurate with the duplex character of the human retina. A similar dichotomy appears in curves relating response amplitude to response latency. Since the pupil response is determined by total flash energy, intense long flashes produce larger pupil responses than shorter (and perceptually brighter) ones of the same intensity.


OryR is a LuxR-family protein involved in interkingdom signaling between pathogenic Xanthomonas oryzae pv. oryzae and rice.
Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight in rice, contains a regulator that is encoded in the genome, designated OryR, which belongs to the N-acyl homoserine lactone (AHL)-dependent quorum-sensing LuxR subfamily of proteins. However, we previously reported that X. oryzae pv. oryzae does not make AHLs and does not possess a LuxI-family AHL synthase and that the OryR protein is solubilized by a compound present in rice. In this study we obtained further evidence that OryR interacts with a rice signal molecule (RSM) and that the OryR concentration increases when rice is infected with X. oryzae pv. oryzae. We also describe three OryR target promoters which are regulated differently: (i) the neighboring proline iminopeptidase (pip) virulence gene, which is positively regulated by OryR in the presence of the RSM; (ii) the oryR promoter, which is negatively autoregulated independent of the RSM; and (iii) the 1,4-beta-cellobiosidase cbsA gene, which is positively regulated by OryR independent of the RSM. We also found that the RSM for OryR is small, is not related to AHLs, and is not able to activate the broad-range AHL biosensor Agrobacterium tumefaciens NT1(pZLQR). Furthermore, OryR does not regulate production of the quorum-sensing diffusible signal factor present in the genus Xanthomonas. Therefore, OryR has unique features and is an important regulator involved in interkingdom communication between the host and the pathogen.


Solitary dermal leiomyosarcomas in 12 ferrets.
Twelve 3-6-year-old ferrets (8 males, 3 females, 1 unknown) were presented with single cutaneous nodules. These dermal tumors were characterized histologically by nodular proliferation of neoplastic smooth muscle fibers with marked anisokaryosis and a mitotic rate of >2 mitoses per 10 high-power fields. Neoplastic cells stained strongly for vimentin in all tumors and for smooth muscle actin and desmin in all but 1 tumor. Histologic and immunohistochemical findings suggested a diagnosis of piloleiomyosarcoma for these tumors. Excision was curative in all animals available for follow-up. However, 3 of 5 animals developed adrenal disease within 7 months after removal of the dermal leiomyosarcoma.


Emerging siRNA Design Principles and Consequences for Biotransformation and Disposition in Drug Development.
After two decades teetering at the intersection of laboratory tool and therapeutic reality, with two siRNA drugs now clinically approved, this modality has finally come into fruition. Consistent with other emerging modalities, initial proof-of-concept efforts concentrated on coupling pharmacologic efficacy with desirable safety profiles. Consequently, thorough investigations of siRNA absorption, distribution, metabolism, and excretion (ADME) properties are lacking. Advancing ADME knowledge will aid establishment of in vitro-in vivo correlations and pharmacokinetic-pharmacodynamic relationships to optimize candidate selection through discovery and translation. Here, we outline the emerging siRNA design principles and discuss the consequences for siRNA disposition and biotransformation. We propose a conceptual framework for siRNA ADME evaluation, contextualizing the site of biotransformation product formation with PK-PD modulation, and end with a discussion around safety and regulatory considerations and future directions for this modality.


Genetic diversity of Plasmodium Vivax in South of Iran: A cross-sectional study.
Despite declining the number of malaria cases in Iran, increased prevalence of malaria is supposed to be due to migration from eastern neighboring countries of Iran, which are abundant in Plasmodium vivax (P. vivax). The circumsporozoite protein (CSP) of the P. vivax, is one of the candidate antigens for antimalaria vaccine. The diversity of P. vivax populations circulating in Iran has been investigated by using circumsporozoite protein (CSP) in this study. A hundred and eighteen blood samples were collected from patients diagnosed with P. vivax malaria from south of Iran during 2007-2008. All samples were analyzed by using nested PCR/ RFLP and 18 were sequenced. Genotyping of Pvcsp gene showed that VK210 type was predominant (95%) in south of Iran. Sequence analysis of Pvcsp gene revealed 6 distinct allelic variants in VK210 type. The present data indicate that there is some degree of genetic diversity among P. vivax populations in Hormozgan province of Iran. It seems that in neighbors of Iran, VK210 type is predominant, probably due to similar vector of malaria in these regions.


[Videoendoscopic ligation of the internal seminal veins in bilateral varicocele].
Varicocele diagnosis should be based not only on physical methods but on ultrasound dopplerography as well (flebography or scrotal thermography) to detect a subclinical form and bilateral process. Bilateral varicocele (BV) occurs more often than is diagnosed. It results in more changes in spermogram and is a prognostic infertility factor. Bilateral pain, impairment of spermatogenesis and infertility are indications for bilateral ligation of the seminal veins in BV patients. Bilateral ligation is much more effective than unilateral. Laparoscopic and microsurgical methods are most effective and low invasive in correction of BV and present a method of choice in the treatment of such patients.


Daxx plays a novel role in T cell survival but is dispensable in Fas-induced apoptosis.
Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas. It was proposed that Daxx mediates a parallel apoptotic pathway that is independent of FADD and caspase 8, but signals through ASK1-mediated apoptotic pathway. However, because the deletion of Daxx leads to embryonic lethality, the in vivo function of Daxx has not been properly analyzed. In the current study, analysis was performed using a conditional mutant mouse in which Daxx was deleted specifically in T cells. The data show that Daxx-/- T cells were able to undergo normal Fas-induced apoptosis. While containing normal thymocyte populations, the T cell-specific Daxx-/- mice have a reduced peripheral T cell pool. Importantly, Daxx-deficient T cells displayed increased death responses upon activation through TCR stimulation. These results unequivocally demonstrated that Daxx does not mediate Fas-induced apoptosis, but rather that it plays a critical role in survival responses in primary mature T cells.


[Current problems in the microbiological control of food].
The paper deals with a number of aspects of current interest and significance on the subject of the microbiological testing of food with particular reference to the role of research institutes. The main objectives of microbiological testing of food are essentially two: (i) to establish the absence of a human health hazard due to microbial contamination of food (food safety); and (ii) to define the quality standard of food (food quality). As far as the first of these objectives is concerned, the outcome of the assay necessarily emerges not only from identification of pathogens but also from definition of their pathogenicity and virulence characteristics and of critical factors for their transmission. Alongside the classic pathogens, evidence has recently been found indicating that four additional bacteria, namely Yersinia enterocolitica, Campylobacter jejuni, Vibrio cholerae non 0-1 and Listeria monocytogenes, also play an important role in food-borne disease. The most characteristic biological, ecological and epidemiologic aspects related to human food-borne disease are described for these bacteria. As regards the second objective, i.e. food quality, stress is laid on the role played by microbial indicators and their predictivity for pathogenic micro-organisms, which does not always exist. This depends on three basic differential factors: (i) biological characteristics giving rise to different diffusion, dilution and extinction phenomena, or, on the other hand, multiplication of such pathogens in the environment and in food; (ii) resistance to the natural inactivation mechanisms, whether of a general or specific nature, of each alimentary substrate; and (iii) the ecological and epidemiological pattern. By way of examples, two experiences indicating the lack of predictivity of the faecal indicators for enterovirus and Vibrio cholerae non 0-1 are reported. Nevertheless, standard microbiological testing for mesophilic flora and indicators are fundamental instruments in the analysis of food quality at all stages of production (supply of raw materials, good manufacturing practices, characteristics of the product during shelf life), and this type of testing, when performed by industrial-scale food producers, may guarantee a high standard of food quality and its progressive improvement.


Enhanced ferromagnetism in a Mn(3)C(12)N(12)H(12) sheet.
Based on a recent experimental study on the Ni3 C12 S12 sheet [J. Am. Chem. Soc. 2013, 135, 2462] and a theoretical study on the Mn3 C12 S12 sheet [Nanoscale- 2013, 5, 10404], by using density functional theory combined with a thermodynamic model, it is shown that when sulfur atoms are replaced by NH groups the resulting Mn3 C12 N12 H12 sheet can exhibit strong ferromagnetism with a Curie temperature of 450 K. The enhanced ferromagnetism is due to two main factors: the reduced lattice constant and nitrogen is more effective in mediating magnetic couplings through p-d exchange interactions. Furthermore, it is also confirmed that the Mn3 C12 N12 H12 sheet is kinetically and thermally stable, and displays half metallicity.


The use of immunosuppression in autoimmune hepatitis: A current literature review.
Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre's approach to treatment of AIH in the context of a contemporary review of the literature.


Opsoclonus-myoclonus syndrome following rotavirus gastroenteritis.
Opsoclonus-myoclonus syndrome (OMS) is a rare neurologic disorder characterized by opsoclonus, myoclonus, ataxia and behavioral disturbance. In the pathogenesis, an autoimmune process with infectious or paraneoplastic trigger has been suggested. We describe the case of a 22-month-old girl with OMS following rotavirus gastroenteritis. Rotavirus should be considered in the differential diagnosis of OMS in children.


National health accounts in developing countries: appropriate methods and recent applications.
Better information on the financing of the health sector is an essential basis for wise policy change in the area of health sector reform. Analysis of health care financing should begin with sound estimates of national health expenditure--total spending, the contributions to spending from different sources and the claims on spending by different uses of the funds. The member countries of the OECD have successfully established such comparative health expenditure accounts in terms of standardized definitions of the uses of funds and breakdowns by public and private sector sources. This has resulted in important research on health system differences which could explain variations in the level and composition of financing. The United States has developed a more detailed approach called National Health Accounts, which expands the OECD method into a more disaggregated 'sources and uses' matrix. In the developing countries, analysis of health expenditures has been much less systematic, despite several decades of calls by international researchers for more attention. This paper reviews previous work done in developing countries and proposes renewed attention to national health expenditures, adapting the recent experience of the United States. Because most developing countries have more pluralistic health financing structures than are found in most industrialized countries, an enhanced and adapted version of the 'sources and uses' matrix method is proposed. This method should be modified to address the relevant categories of expenditures prevalent in the developing countries. Examples of recent applications of such 'national health accounts' from the Philippines, Egypt, India, Mexico, Colombia and Zambia are presented. Experience to date suggests that development of sound estimates using this method in low and middle income countries is feasible and affordable. National health accounts estimates can significantly influence policy. They provide decision makers with a holistic picture of the health sector, showing the actual emphasis of spending and the roles of different payers. They also provide a consistent framework for modelling reforms and for monitoring the effects of changes in financing and provision. An easy to use software tool has been developed for training and data management. Regional networks of collaborating national groups are proposed as a first step in expanding use of the method and to gain both national and cross-national comparative benefits.


Ten reasons to screen women at risk of lung cancer.
This opinion piece reviews major reasons for promoting lung cancer screening in at-risk women who are smokers or ex-smokers, from the age of 50. The epidemiology of lung cancer in European women is extremely worrying, with lung cancer mortality expected to surpass breast cancer mortality in most European countries. There are conflicting data as to whether women are at increased risk of developing lung cancer compared to men who have a similar tobacco exposure. The sharp increase in the incidence of lung cancer in women exceeds the increase in their smoking exposure which is in favor of greater susceptibility. Lung and breast cancer screening could be carried out simultaneously, as the screening ages largely coincide. In addition, lung cancer screening could be carried out every 2 years, as is the case for breast cancer screening, if the baseline CT scan is negative.As well as detecting early curable lung cancer, screening can also detect coronary heart disease and osteoporosis induced by smoking. This enables preventive measures to be taken in addition to smoking cessation assistance, to reduce morbidity and mortality in the female population. Key points • The epidemiology of lung cancer in European women is very worrying.• Lung cancer is becoming the leading cause of cancer mortality in European women.• Women benefit greatly from screening in terms of reduced risk of death from lung cancer.


The effect of repeated administration of delta9-tetrahydrocannabinol on serotonin metabolism in the rat brain.
The level of serotonin (5-HT) was increased in the whole rat brain as well as in the hypothalamus plus midbrain region at 0.5 hr after the fifth or sixth daily dose of delta9-tetrahydrocannabinol (THC), 20.0 mg/kg, i.p., respectively. A decreased rate of 5-HT synthesis was also observed. A slight development of tolerance was indicated by the fact that elevation of 5-HT was smaller than that seen after a single dose (1).


Learning to nurse: the family as the unit of care.
How can we prepare nurses who will have as their focus of practice, the health of the family unit? This paper describes the learning outcomes which were generated from a short term experience in a curriculum where the major thrust is learning to nurse families in a health promoting way. Students were provided with experience with families who were undergoing an important family event, e.g., coping with the short term hospitalization of a child. An exploration and analysis of these experiences revealed for students the content of nursing families who are in the process of dealing with this particular event of family living. This content related to the acquisition of nursing skills of an interpersonal, technical and decision-making nature as well as the development of knowledge which provides the basis for nursing the family as the unit of care.


Semicarbazide-sensitive amine oxidase: role in the vasculature and vasodilation after in situ inhibition.
1. The characteristics of semicarbazide-sensitive amine oxidase (SSAO) are reviewed and the unknown physiological or pathological role of this enzyme emphasized. 2. The various mechanisms of action proposed for the vasodilator drug hydralazine are considered. In particular, the inhibitory action on various enzymes, related or not to cardiovascular function, are discussed. 3. Studies linking inhibition of SSAO to hydralazine hypotension are reviewed and a general hypothesis relating both actions is presented. The hypothesis postulates that (a). vascular SSAO is involved in the regulation of vascular tone, and (b). hydralazine vasodilation is the consequence of vascular SSAO inhibition. 4. Evidence supporting these postulates is presented and vascular SSAO inhibition is proposed as a novel mechanism of vasodilation.


Dietary zinc intake of a group of long-stay mentally handicapped women: some bioavailability considerations.
Dietary factors affecting zinc bioavailability were evaluated according to their relative distribution in the individual daily meals making up the basic diet of 17 institutionalized, mentally handicapped adult women. Mean intake values of zinc, phytate, nonstarch polysaccharides (NSP), calcium, protein, and energy were calculated from a dietary survey of 7 consecutive days, which also served to obtain values for the two zinc bioavailability predictor formulas, phytate/Zn millimolar ratio and [Ca][phytate]/[Zn][energy] ratio. Mean daily zinc intake was 8.5 +/- 1.8 mg, with noon and evening meals accounting for the highest contribution to this value (45% and 35%, respectively), whereas breakfast meals' contribution was 16%. The mean protein intake was 55 +/- 13 g, with noon and evening meals being the major contributors to total daily intake (42% and 38%, respectively). Breakfast meals accounted for 77% of daily phytate intake, giving a respective phytate/Zn millimolar ratio of 20.4 +/- 7.6 and a [Ca][phytate]/[Zn][energy] ratio of 336 +/- 127 mmol/Mcal. Values for both ratios based on noon and evening meals were negligible in comparison. The mean daily NSP intake was 9.8 +/- 4.2 g, with 53% of total daily intake supplied from breakfast meals, whereas noon and evening meals accounted for 30% and 14%, respectively. The results, while suggesting that zinc bioavailability is unlikely to be adversely affected, indicated that dietary fiber intake levels are probably inadequate, particularly in view of the nonambulant condition and low physical activity prevalent in such individuals, who may, as a consequence, be susceptible to health disorders associated with impaired bowel function and constipation.


Thrombotic thrombocytopenic purpura: a ten-year experience.
Splenectomy, corticosteroids, and antiplatelet agents have improved survival in thrombotic thrombocytopenic purpura (TTP). In 1974 we reported the successful treatment in 5 of 6 patients using splenectomy, corticosteroids, and average molecular weight dextran. This report describes a 10-yr experience with TTP at Mount Sinai Hospital (MSH). Twenty patients with TTP were seen. Possible inciting factors included pregnancy, oral contraceptives, and surgery. Splenectomy was performed in 18 patients and typical findings of TTP were found in 14 (78%). Fifteen patients were treated with splenectomy, corticosteroids, and average molecular weight dextran. Two of the 15 patients received, in addition, ASA and dipyridamole and a third received only dipyridamole. Thirteen of the 15 (87%) have survived and remain disease-free.


Aspirin Use for Primary Prevention of Cardiovascular Disease in Older Patients: A Review of Clinical Guidelines and Updated Evidence.
OBJECTIVE: To provide an up-to-date review of current guidelines, previous trials, and new trials regarding aspirin use in primary prevention of cardiovascular (CV) disease in the elderly population. DATA SOURCES: A PubMed search of articles published through April 2019 was performed using a combination of the following words: aspirin, bleeding, cardiovascular, elderly, hemorrhage, myocardial infarction, primary prevention, stroke. STUDY SELECTION/DATA EXTRACTION: Relevant randomized controlled trials, meta-analyses, and guidelines were assessed for the use of aspirin in primary prevention of CV disease in older patients. References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results. DATA SYNTHESIS: The role of aspirin for primary prevention of CV disease in older adults is not well defined. As a result, the guideline recommendations for the use of aspirin in this setting are inconsistent. In 2018, the ARRIVE, ASCEND, and ASPREE studies were published. These studies tried to address some of the inconsistencies regarding the use of aspirin in primary prevention of CV disease. This article reviews the current recommendations along with previous and recent studies for aspirin use for primary prevention in older adults. CONCLUSION: The role of aspirin for primary prevention of CV disease in older adults should be individualized based on patient's risk factors, including risk of CV disease and likelihood of bleeding. Updated evidence provides more guidance regarding which patient populations will benefit from therapy.


Molecular epidemiology of integron-associated antibiotic resistance genes in clinical isolates of enterobacteriaceae.
The epidemiology of integron-mediated antibiotic-resistant genes in clinical enterobacteria from a single location was investigated. Forty-nine isolates (kindly provided by Dr. D. Sirot, Clermont-Ferrand, France) were selected for transferable resistance to aminoglycosides or to other antibiotics. Total DNA prepared from these strains was screened for the presence of conserved segments of integrons by PCR. The nature and frequency of inserted resistance gene cassettes were determined by direct nucleotide sequencing and were related to the resistances expressed by the strain. Integron hot-spots were present in 59% of the strains from 6 species, in either one or two copies. For amplicons sequenced, one or two antibiotic-resistant genes were found in various combinations, and were always expressed at the phenotypic level. They included the aminoglycoside resistance genes ant(3")-Ia and aac(6')-Ib (75%), as well as dhfr-I,-VII (21.4%) and blaOXA-1 (3.6%). Almost half of the transferable resistance to aminoglycosides (53%) was mediated by integron hot-spots in strains characterized at the nucleotide level. The proportion rose to 100% for the AAC(6')-I resistance profile. This study emphasizes the important contribution of integrons to aminoglycoside resistance within enterobacteria from a clinical setting.


Gut bacterial composition in a mouse model of Parkinson's disease.
The mechanism of neurodegeneration in Parkinson's disease (PD) remains unknown but it has been hypothesised that the intestinal tract could be an initiating and contributing factor to the neurodegenerative processes. In PD patients as well as in animal models for PD, alpha-synuclein-positive enteric neurons in the colon and evidence of colonic inflammation have been demonstrated. Moreover, several studies reported pro-inflammatory bacterial dysbiosis in PD patients. Here, we report for the first time significant changes in the composition of caecum mucosal associated and luminal microbiota and the associated metabolic pathways in a rotenone-induced mouse model for PD. The mouse model for PD, induced by the pesticide rotenone, is associated with an imbalance in the gut microbiota, characterised by a significant decrease in the relative abundance of the beneficial commensal bacteria genus Bifidobacterium. Overall, intestinal bacterial dysbiosis might play an important role in both the disruption of intestinal epithelial integrity and intestinal inflammation, which could lead or contribute to the observed alpha-synuclein aggregation and PD pathology in the intestine and central nervous system in the oral rotenone mouse model of PD.


Physical therapy for persons with vestibular disorders.
Persons with vestibular disorders experience symptoms of dizziness and balance dysfunction, resulting in falls, as well as impairments of daily life. Various interventions provided by physical therapists have been shown to decrease dizziness and improve postural control. In the present review, we will focus on the role of physical therapy in the management of vestibular symptoms in patients with peripheral and central vestibular disorders. Persons with both acute and chronic central and peripheral vestibular disorders improve with vestibular rehabilitation. New interventions during the past 5 years have been designed to enhance recovery from problems with balance and dizziness. Examples include the use of virtual reality, vibrotactile feedback, optokinetic flow, YouTube videos, and innovative methods to change the gain of the vestibulo-ocular reflex (VOR). Patients with central and peripheral vestibular disorders benefit from physical therapy interventions. Advances in physical therapy interventions include new methods to stimulate adaptation of the VOR and the vestibulospinal systems.