Estradiol's effects on learning and neuronal morphology vary with route of administration.
Estrogen's effects on performance and neuronal morphology are variable, and the reasons for this variability are not yet understood. In this study, the authors compared the effects of 2 delivery routes of 17 beta-estradiol on spatial learning and dendritic spine densities in young ovariectomized rats; estradiol was administered by implanted capsules or by daily oral gavage. Estradiol treatment via capsules improved performance in the radial-arm water maze and increased spine densities on dendrites of CA1 pyramidal neurons in the hippocampal formation. In contrast, daily oral administration of estradiol did not affect either measure. These data demonstrate that estradiol delivery is a critical variable in animal studies and that clinical studies comparing the effects of different estradiol treatment routes on cognition are warranted.


Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina.
Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.


Increased Expression of a myo-Inositol Methyl Transferase in Mesembryanthemum crystallinum Is Part of a Stress Response Distinct from Crassulacean Acid Metabolism Induction.
The facultative halophyte Mesembryanthemum crystallinum responds to osmotic stress by switching from C(3) photosynthesis to Crassulacean acid metabolism (CAM). This shift to CAM involves the stress-initiated up-regulation of mRNAs encoding CAM enzymes. The capability of the plants to induce a key CAM enzyme, phosphoenolpyruvate carboxylase, is influenced by plant age, and it has been suggested that adaptation to salinity in M. crystallinum may be modulated by a developmental program that controls molecular responses to stress. We have compared the effects of plant age on the expression of two salinity-induced genes: Gpdl, which encodes the photosynthesis-related enzyme glyceraldehyde 3-phosphate dehydrogenase, and Imtl, which encodes a methyl transferase involved in the biosynthesis of a putative osmoprotectant, pinitol. Imtl mRNA accumulation and the accompanying increase in pinitol in stressed Mesembryanthemum exhibit a pattern of induction distinct from that observed for CAM-related genes. We conclude that the molecular mechanisms that trigger Imtl and pinitol accumulation in response to salt stress in M. crystallinum differ in some respects from those that lead to CAM induction. There may be multiple signals or pathways that regulate inducible components of salinity tolerance in this facultative halophyte.


Relevant parameters for describing the oxygenation status of solid tumors.
Several studies using different methods of pO2 measurement have shown that in many tumor entities tissue oxygenation is quite heterogeneous and thus cannot be sufficiently described by a single value. This study presents those distribution parameters which are mandatory to describe the complete oxygenation status of a solid tumor. In determining the oxygenation status different aspects of relevancy have to be taken into account. First, several parameters are necessary to characterize the location, the spread, and the shape of the pO2 distribution from a statistical point of view (statistical parameters). In addition, parameters for the description of the biological relevance of the tumor oxygenation have to be considered (biological parameters). These parameters reflect the role of oxygenation for the metabolic microenvironment and the biological behavior of the tumor as well as the significance under therapeutic and diagnostic aspects. Finally, some parameters are necessary to assess the quality of pO2 measurement itself (quality parameters). By combining all pO2 readings from one tumor a statistical distribution is obtained, which is in many tumors asymmetrically shifted towards low pO2 values. In order to describe the location, spread, and shape of this distribution the following parameters should be stated: median, mean, 10% and 90% percentile, minimum, maximum and 10 to 90% interpercentile range. For data presentation these values can be combined in a box-whiskers plot. In order to reflect the importance of tumor oxygenation under diagnostic, therapeutic or cell-biological aspects the fraction of pO2 readings < or = 2.5 mm Hg, < or = 5 mm Hg, and < or = 10 mm Hg should be stated. Where negative pO2 readings occur in a study, the fraction of pO2 readings < 0 mm Hg as well as the most negative pO2 value should be presented in order to assess the quality of the pO2 measurement. For a comprehensive description of the oxygenation status of solid tumors the following distribution parameters should be stated: median, mean, 10% and 90% percentile, minimum, maximum, 10 to 90% interpercentile range, fraction of pO2 readings < 0 mm Hg, < or = 2.5 mm Hg, < or = 5 mm Hg, and < or = 10 mm Hg as well as the most negative pO2 reading.


Motor disturbance and brain functional imaging in Parkinson's disease.
18F-Dopa positron emission tomography (PET) provides a sensitive means of quantitating the loss of nigrostriatal dopaminergic fibres in Parkinson's disease and so can be used to diagnose its presence and to objectively follow the rate of disease progression. It can also be used, in principle, to determine the efficacy of putative neuroprotective agents and has already been extensively used to monitor the viability of striatal transplants of fetal mesencephalic tissue. Loss of dopaminergic projections produces significant changes in the patterns of both resting and activated cortical function. H2(15)O PET activation studies have suggested that the akinesia of Parkinson's disease is associated with failure to activate the supplementary motor and dorsal prefrontal areas, brain regions particularly involved in motor preparation and decision making. Activation of these cortical areas can be restored by administering dopaminergic medication, implanting the striatum with fetal mesencephalic tissue, and by pallidotomy. This article reviews the insight that PET studies have provided into the pathophysiology of Parkinson's disease.


Association between immunosuppressive therapy and course of mild interstitial lung disease in systemic sclerosis.
Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Little is known about the benefits of immunosuppressive drugs in mild ILD. Our aim was to determine whether use of CYC or MMF was associated with an improved ILD course in patients with normal or mildly impaired lung function. A retrospective cohort of SSc subjects with ILD, disease duration below seven years and no exposure to CYC or MMF prior to the baseline visit was constructed from the Canadian Scleroderma Research Group registry. Subjects were categorized as having mild ILD if baseline forced vital capacity (FVC % predicted) was >85%. The primary exposure was any use of CYC or MMF at the baseline visit. FVC at one year was compared between exposed and unexposed subjects, using multivariate linear regression. Out of 294 eligible SSc-ILD subjects, 116 met criteria for mild ILD. In this subgroup, mean (s.d.) disease duration was 3.7 (2.0) years. Thirteen (11.2%) subjects were exposed to CYC or MMF at baseline. The one-year FVC was higher in exposed subjects compared with unexposed subjects, by a difference of 8.49% (95% CI: 0.01-16.98%). None of the exposed subjects experienced clinically meaningful progression over two years, whereas 24.6% of unexposed subjects did. In this real-world setting, CYC/MMF exposure at baseline was associated with higher FVC values and a lower risk of progression among subjects with mild ILD. These data suggest a window of opportunity to preserve lung function in SSc-ILD.


Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19.
The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19. We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels. Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens. For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.


Prevention of runting and cachexia by a chimeric TNF receptor-Fc protein.
Tumor necrosis factor alpha (TNF) is an important mediator of septic shock and cachexia. A soluble form of the human type 2 TNF receptor, constructed by joining the Fc region of human IgG1 to the TNF receptor, prevents weight loss in nude mice bearing a TNF-secreting tumor. This soluble receptor was also used to treat TNF transgenic mice which were runting and died before reaching reproductive age. After continuous treatment with soluble TNF receptor, the TNF transgenic mice grew to normal size and reproduced. Thus, soluble TNF may be useful in counteracting the detrimental systemic effects of TNF in a clinical setting.


Body weight and dietary factors in Huntington's disease patients compared with matched controls.
A longitudinal study using medical records has confirmed that, even when eating high energy diets, loss of body weight is characteristic of Huntington's disease patients in comparison with a group of matched control subjects. Further analysis showed that although some Huntington's disease patients initially may gain weight rapidly after a period in hospital, they eventually lose weight to below their admission levels. This pattern was not seen in the control group. The findings are discussed in terms of striatal pathology.


Sparse direct adaptive equalization based on proportionate recursive least squares algorithm for multiple-input multiple-output underwater acoustic communications.
In this paper, the sparse direct adaptive equalization based on the recently developed proportionate recursive least squares (PRLS) adaptive filtering algorithm is investigated for multiple-input multiple-output (MIMO) underwater acoustic (UWA) communications. First, performance analysis is made for the PRLS, and simulation results show its gain over a standard recursive least squares algorithm under sparse systems. The fast implementation of the PRLS, named the proportionate stable fast transversal filters (PSFTF), is revisited to implement a direct adaptive decision-feedback equalizer which outperforms the existing PSFTF direct adaptive linear equalizer. The PSFTF direct adaptive equalizers (DAEs) are then compared with the selective zero-attracting stable fast transversal filter DAEs (SZA-SFTF-DAEs) enabled by the SZA-SFTF adaptive filtering algorithm. The SZA-SFTF algorithm is designed with the zero-attracting sparsity-promoting principle, which is in parallel to the proportionate updating principle used to design the PSFTF algorithm. Experimental results of an at-sea MIMO UWA communication trial show that PSFTF-DAEs outperform the SZA-SFTF-DAEs.


Pre-Sodiated Ti3C2Tx MXene Structure and Behavior as Electrode for Sodium-Ion Capacitors.
Layered titanium carbide (Ti3C2Tx) MXene is a promising electrode material for use in next-generation electrochemical capacitors. However, the atomic-level information needed to correlate the distribution of intercalated cations with surface redox reactions, has not been investigated in detail. Herein we report on sodium preintercalated MXene with high sodium content (up to 2Na per Ti3C2Tx formula) using a solution of Na-biphenyl radical anion complex (E0 ≈ -2.6 SHE). Multiple sodiation sites and formation of a two-dimensional sodium domain structure at interfaces/surfaces is identified through combined computational simulations with neutron pair distribution function analysis. The induced layer charges and the redox process characterized by the density-functional tight-binding method on a local scale are found to greatly depend on the location of sodium ions. Electrochemical testing of the pre-sodiated MXene as an electrode material in a sodium-ion capacitor shows excellent reversibility and promising performance, indicating the feasibility of chemical preintercalation as an approach to prepare MXene electrodes for ion capacitors.


Quantiferon-TB Gold: performance for ruling out active tuberculosis in HIV-infected adults with high CD4 count in Côte d'Ivoire, West Africa.
To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT). Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml. Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion. A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases. ClinicalTrials.gov NCT00495651.


Women's experiences of social support during the first year following primary breast cancer surgery.
The aim of this qualitative follow-up study was to describe women's individual experiences of social support during their first year after primary breast cancer surgery. Individual semi-structured interviews with 10 women 1 year after surgery analysed by Kvales' meaning condensation method. Sharing experiences, being understood as an individual, continuity, and information and explanations were themes identified. Sharing mutual experiences increased the women's knowledge regarding cancer, increased experience of support and minimised rumination. After 1 year, the women felt that the network around them had 'normalised' and was less supportive. Being seen as a person, not as 'a diagnosis being treated', and continuity of professional support were important, giving feelings of security and trust. The women felt uncertainty after loss of professional support post-treatment. Information and explanations regarding treatment and treatment-related problems were essential. Mutual sharing of experiences is an important part of social support. Continuity, availability, information and respect were essential aspects of experienced professional support.


Isolation and comparative analysis of potential stem/progenitor cells from different regions of human umbilical cord.
Human umbilical cord (hUC) blood and tissue are non-invasive sources of potential stem/progenitor cells with similar cell surface properties as bone marrow stromal cells (BMSCs). While they are limited in cord blood, they may be more abundant in hUC. However, the hUC is an anatomically complex organ and the potential of cells in various sites of the hUC has not been fully explored. We dissected the hUC into its discrete sites and isolated hUC cells from the cord placenta junction (CPJ), cord tissue (CT), and Wharton's jelly (WJ). Isolated cells displayed fibroblastoid morphology, and expressed CD29, CD44, CD73, CD90, and CD105, and showed evidence of differentiation into multiple lineages in vitro. They also expressed low levels of pluripotency genes, OCT4, NANOG, SOX2 and KLF4. Passaging markedly affected cell proliferation with concomitant decreases in the expression of pluripotency and other markers, and an increase in chondrogenic markers. Microarray analysis further revealed the differences in the gene expression of CPJ-, CT- and WJ-hUC cells. Five coding and five lncRNA genes were differentially expressed in low vs. high passage hUC cells. Only MAEL was expressed at high levels in both low and high passage CPJ-hUC cells. They displayed a greater proliferation limit and a higher degree of multi-lineage differentiation in vitro and warrant further investigation to determine their full differentiation capacity, and therapeutic and regenerative medicine potential.


[Case Report on a Woman with Epilepsy Who Took Lacosamide during Pregnancy and Gave Birth to a Healthy Infant].
Lacosamide is a novel antiepileptic drug. Although many antiepileptic drugs reportedly pose a risk to fetuses, patients with epilepsy are advised to continue their medications during pregnancy. There have been few reports on lacosamide use during pregnancy, and its effects on the fetus remain unclear. Here, we report a case of lacosamide use during pregnancy. The 33-year-old patient was treated with oral lacosamide (400 mg/d) for symptomatic partial epilepsy. She was concomitantly treated with folic acid (5 mg/d) beginning 4 days before her last menstrual cycle. She was also concomitantly treated with oral perampanel (2 mg/d) at 5-7 weeks' gestation for seizure control but discontinued perampanel after the pregnancy was discovered. She progressed through her pregnancy with only mild seizures. Fetal growth was normal and ultrasonography revealed no external malformations. The patient had an elective cesarean section at 37 weeks and 2 days owing to a previous post-cesarean pregnancy. Her baby boy weighed 3025 g; his Apgar score was 8 and 9, 1 and 5 min, respectively, and his umbilical artery blood pH was 7.348. He had no congenital anomalies and no neonatal drug withdrawal symptoms. This suggests that lacosamide may have a low risk of teratogenicity and fetal toxicity. Thus, this case is valuable for clinicians who are considering the administration of antiepileptic drugs during pregnancy. In the future, more reports on the use of lacosamide during pregnancy should be collected.


[Helping the highly dependent smokers].
Many smokers have difficulty in stopping smoking, either motivated to stop or forced for health, economic or statutory reasons. They have in common a heavy tobacco dependence and a high level of cigarette consumption. Often they combined factors impairing success in the attempt to stop smoking : e. g. anxio-depressive disorders, use of psychoactive substances, socio-economic deprivation. Smoking cessation specialists must optimize their interventions in order to improve the care of these highly dependent smokers.


Population-based reference values of handgrip strength and functional tests of muscle strength and balance in men aged 70-80 years.
With aging, the incidence of falls and fractures increases. There has during the last decades been secular changes in demographics so that the proportion of elderly increases in society. Hence, there is an increasing need for clinicians to be able to make a solid appraisal of the elderly patient's functional capacity, as to identify individuals with an increased risk to fall. If high risk individuals could be targeted fall preventive strategies might be implemented in specific risk cohorts. This would require reference values for muscle strength tests and functional tests, in order to defined high risk individuals performing inferior. From the MrOS Sweden cohort, 999 subjects aged 70-80 years were evaluated. Muscle strength and functional performance was tested by timed-stands test, 6-m and 20-cm narrow walk tests and Jamar handgrip strength test. Normative data is presented. With increasing age, there was a 10-18% successively decline in performance throughout the entire age span. This study provides reference values for handgrip strength and functional muscle tests in 70-80 years old men. The decline in the test values with increasing age, infer the use of age-specific normative data when using these tests both in clinical and research settings.


A Mixed Methods Evaluation of the Feasibility and Acceptability of an Adapted Cardiac Rehabilitation Program for Home Care Patients.
Home care clinicians have an opportunity to improve care for post-hospitalization patients with cardiovascular disease. This mixed methods study examined the feasibility and acceptability of an adapted cardiac rehabilitation (CR) program for the home care setting. Surveys measuring patient self-care and knowledge were administered to patients (n = 46) at baseline and at 30-day follow-up. Semi-structured interviews were conducted with patients (n = 28) and home care clinicians (n = 11) at completion of the program. All survey indicators demonstrated a trend towards improvement, with a statistically significant increase in the self-care management subscale (p = 0.002). Qualitative analyses identified three patient themes (self-awareness, nutrition, motivation) and three clinician themes (systematic approach, motivation, patient selection process). Incorporating CR into the home care setting proved to be a feasible and acceptable approach to increasing access to CR services among elderly patients.


Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease.
Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I-containing particles: those that also contain apoA-II [Lp(AI w AII)] and those that do not [Lp(AI w/o AII)]. These particles were isolated by immunoaffinity chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL) with symptomatic coronary artery disease (CAD), from 17 NL men without any symptoms of CAD (healthy controls), and from 10 NL men with entirely normal coronary arteriograms (CAD-free controls). The distributions of particle size in these two subpopulations were determined by gradient gel electrophoresis and densitometric scanning. Approximately half of the Lp(AI w AII) particles in all subjects were distributed in the 8.2-9.2 nm interval. For patients with CAD, a greater fraction of the particles were small, in the 7.0-8.2 nm interval [33% in CAD vs. 26% in CAD-free controls (P less than 0.01) and 19% in healthy controls (P less than 0.0001)], and a smaller fraction of the particles were in the 9.2-11.2 nm interval (14% in CAD vs. 24% in CAD-free control (P less than 0.002) and healthy control groups (P less than 0.001). The Lp(AI w/o AII) of both control groups were primarily composed of two discrete subpopulations in the 8.2-9.2 nm and the 9.2-11.2 nm intervals. In CAD patients there were fewer particles in the 9.2-11.2 nm size interval (23% in CAD vs. 33% in CAD-free controls (P less than 0.005) and 36% in healthy controls (P less than 0.0001), and more particles in the smallest 7.0-8.2 nm size interval (32% in CAD vs. 23% in CAD-free controls (P less than 0.01) and 18% in healthy controls (P less than 0.001]. Thus, the spectrum of HDL particle sizes in patients with CAD tends to be shifted toward the smaller particle when compared with the two control groups. This was observed in both NL and HL patients with HDL cholesterol (CH) values in the normal range. As a group, CAD patients had lower HDL (42 +/- 7 mg/dl) and HDL2 (6 +/- 4 mg/dl) CH than healthy (HDL: 49 +/- 7, HDL2: 12 +/- 6 mg/dl) and CAD-free (HDL: 51 +/- 9, HDL2: 12 +/- 6 mg/dl) controls. When controls and patients were compared for their frequencies of abnormal HDL CH levels and particle sizes, abnormalities in HDL and HDL2 CH levels were not significantly more frequent (twofold) among CAD patients than among controls.(ABSTRACT TRUNCATED AT 400 WORDS)


Phytochrome Control of Germination of Rumex crispus L. Seeds Induced by Temperature Shifts.
High germination of curly dock (Rumex crispus L.) seeds is evident after suitable imbibition and temperature shift treatment, but germination at constant temperatures fails without an input of far red-absorbing form of phytochrome. Preliminary imbibitions at high temperatures (30 C) sharply reduce germination induced by temperature shifts. High germination may be restored by low energies of red radiation, or by brief far red adequate for the photosteady state. Prolonged far red during imbibition also nullifies temperature shift-induced germination. After prolonged far red, high germination may be restored by red radiation of an energy dependent upon the duration of the far red treatment. The evidence supports the conclusion that dark germination induced by temperature shifts arises from the interaction of pre-existent far red-absorbing form of phytochrome in the mature seeds with the temperature shift.


A multivariate discrete failure time model for the analysis of infant motor development.
We develop a multivariate discrete failure time model for the analysis of infant motor development. We use the model to jointly evaluate the time (in months) to achievement of three well-established motor milestones: sitting up, crawling, and walking. The model includes a subject-specific latent factor that reflects underlying heterogeneity in the population and accounts for within-subject dependence across the milestones. The factor loadings and covariate effects are allowed to vary flexibly across milestones, and the milestones are permitted to have unique at-risk intervals corresponding to different developmental windows. We adopt a Bayesian inferential approach and develop a convenient data-augmented Gibbs sampler for posterior computation. We conduct simulation studies to illustrate key features of the model and use the model to analyze data from the Nurture study, a birth cohort examining infant health and development during the first year of life.


Sodium Stimulates Growth of Panicum coloratum through Enhanced Photosynthesis.
A sodium-requiring C(4) plant, Panicum coloratum Walt. cv Kabulabula, was grown with and without sodium. Rate of nitrogen uptake and photosynthesis were measured during the recovery from sodium deficiency. The beneficial effect of sodium on growth was apparent irrespective of nitrogen source, ammonium- or nitrate-nitrogen. The leaf photosynthetic rate ((14)CO(2) fixation) doubled by sodium within 1 hour of the application.


Maternal Near Miss and Quality of Obstetric Care in a Tunisian Tertiary Level Maternity.
This study aimed to determine the frequency and the nature of maternal near miss (NM) events in a population of women attending a tertiary level maternity hospital in Tunisia and to evaluate the care level of this institution according to indicators proposed by the World Health Organization (WHO). We opted for a retrospective medical chart review of cases of NM and maternal mortality that occurred in the year 2010 at the Farhat Hached Maternity University Hospital. NM cases were defined based on the WHO criteria 2009. There were 9957 deliveries, 58 NM events and one case of maternal death. Haemorrhagic (74.1%) and hypertensive disorders (20.7%) were the leading causes of NM. The study showed a low Maternal NM Ratio of 5.86/1000 live births, a relatively low mortality index of 1.7 % and Severe Maternal Outcome Ratio of 5.96/1000 live births. This was the first study to document NM in a Tunisian public maternity. The WHO approach allowed a systematic monitoring of quality of maternal health care. There is a low frequency of maternal morbidity and mortality at the level of this facility. But, more efforts are still needed to document NM events in other types of care facilities in Tunisia.


Metal-Organic Coordination Strategy for Obtaining Metal-Decorated Mo-Based Complexes: Multi-dimensional Structural Evolution and High-Rate Lithium-Ion Battery Applications.
Multi-dimensional metal oxides have attracted great attention in diverse applications due to their intriguing performances. However, their structural design remains challenging, particularly that based on organic chelation chemistry. Although metal-organic complexes with different architectures have been reported, their structure formation mechanisms are not well understood because of the complex chelation processes. Herein, we introduce a new metal-organic coordination strategy to construct metal-decorated (Ni, Co, Mn) Mo-based complexes ranging from 2D nanopetals to 3D microflowers. The chelating process of the metal-organic complex can be tuned by a surfactant, giving rise to different structures, and then a further metal can be appended. Thus, different metal (oxide)-decorated MoO2 /C-N structures were designed, enabling an extremely high lithium storage capability of 1018 mA h g-1 and rate capacities of up to 10 A g-1 over 1000 cycles. Relationships between electrochemical behavior and structure have been analyzed kinetically. A high-rate lithium-ion battery has been assembled from Ni-MoO2 /C-N and an Ni-rich layered oxide as the anode and cathode, respectively. We believe that this general metal-organic coordination strategy should be applicable to other multi-functional materials with superior capabilities.


STATIC STRETCHING DOES NOT REDUCE VARIABILITY, JUMP AND SPEED PERFORMANCE.
Stretching is often part of the warm-up routine prior to athletic participation; however, controversial evidence exists on the effects of stretching on countermovement jump (CMJ) and sprint performance. Additionally, analysis of variability between repeated tasks is useful for monitoring players, to analyze factors that could affect the performance, and to guide clinical decisions for training strategies. The purpose of this study was to examine whether static stretching (SS) prior to CMJ and 20-meter (20-m) sprint would affect performance, and to investigate whether SS affects an athlete's ability to perform these tasks consistently. Twenty-two trained healthy athletes (23.2 ± 5.0 years) attended, randomly, two testing sessions, separated by 48 hours. At session one, all participants underwent 10 minutes of dynamic running warm-up followed by the experimental tasks (three CMJ and three 20-m sprint), whereas five minutes of stretching was added after the warm-up routine at session two. All participants performed the same experimental tasks in both sessions. The stretching protocol consisted of five stretching exercises for each lower limb. The paired-samples t-test revealed no significant differences between the stretching protocol condition and no stretching condition for the 20-m sprint (t(21)=.920; p=.368) and CMJ (t(21)=.709; p=.486). There were no significant differences in trial-by-trial variability on 20-m sprint (t(21)=1.934; p=.067) and CMJ scores (t(21)=.793; p=.437) as result of SS. The SS protocol did not modify jumping and running ability in trained healthy athletes. The SS prior to training or competition may not cause detrimental effects to athletic performance. Level III, Nonrandomized controlled trial.


Tranylcypromine addiction: a case report and review.
The authors report a case of tranylcypromine addiction and review the literature on the subject. Since the drug was first marketed in 1960, a total of 18 cases have been described. Predisposing risk factors and potential mechanisms for addiction are discussed. Given the current trend toward using tranylcypromine more frequently and in higher therapeutic doses for refractory depression, a greater index of suspicion for self-medication with this drug is warranted.


Acute pancreatitis in patients over 80 years.
To evaluate the occurrence, aetiology and outcome of acute pancreatitis (AP) in patients over 80 years of age, compared with those between 61 and 79 years old. Retrospective analysis. University hospital, Finland. Subgroups of 22 patients 80 years old or over and 139 patients 61-79 years old out of 1058 episodes of AP between 1982 and 1990. Mortality, morbidity, and hospital stay. The percentage of patients aged 80 or more varied from 0 in 1982 to 3% in 1990; 13 (59%) were women compared with 47 (34%) in the 61-79 year old group (p = 0.03). AP in the older group was more likely to be necrotising 9/22 (41%) compared with 23/139 (17%), p = 0.02) and to have been caused by biliary disease 15/22 (68%) compared with 54/139 (39%), (p = 0.01). The overall mortality was 9/22 (41%) in the 80 years and over group and 24/139 (17%) in patients aged 61-79 years (p = 0.02). All 9 patients in their eighties with necrotising pancreatitis died. Neither the mode of treatment nor the Glasgow prognostic scoring had any relation to mortality in the older group. AP in patients of 80 or more is a serious disease with a high mortality irrespective of standard treatment.


[Establishment and characterization of a new squamous cell carcinoma cell line CS1213 from the human uterine cervix].
To establish a human cervical carcinoma cell line. A primary culture was initiated from malignant tissue collected by dissection of cervical biopsy specimens. Characterizing cells in culture which included morphological observation, biological and karyotypic analysis, experimental tumorigenesis and the expression of p53, bcl-2 and Ki67 genes was carried out. The new established cervical carcinoma cell line (CS1213) had been maintained in culture for over 170 generations. The cells which were nonadherent had a common, rounded appearance with a cell cycle time of 25-hour and a 19 colony formation rate in soft agar. Electron micrographs demonstrated abundant tonofilaments in the cytoplasm. The karyotype showed a hyperdiploid feature with a main chromosome stem number ranged from 80 to 88. The culture was not contaminated by mycoplasma and had a distinct lactic acid dehydrogenase isozyme pattern. High expression level of p53 (31.9%), bcl-2 (89.3%) and Ki67 (33.7%) proteins was detected by flow cytometry. The xenogeneic tumors were grown in nude mice with the histological structure of the original one. The novel CS1213 cells have the characteristics of human cervical squamous cells and could be used as an appropriate cellular model system for studying tumor invasion and metastasis.


Binding sites for abundant nuclear factors modulate RNA polymerase I-dependent enhancer function in Saccharomyces cerevisiae.
The 190-base pair (bp) rDNA enhancer within the intergenic spacer sequences of Saccharomyces cerevisiae rRNA cistrons activates synthesis of the 35S-rRNA precursor about 20-fold in vivo (Mestel,, R., Yip, M., Holland, J. P., Wang, E., Kang, J., and Holland, M. J. (1989) Mol. Cell. Biol. 9, 1243-1254). We now report identification and analysis of transcriptional activities mediated by three cis-acting sites within a 90-bp portion of the rDNA enhancer designated the modulator region. In vivo, these sequences mediated termination of transcription by RNA polymerase I and potentiated the activity of the rDNA enhancer element. Two trans-acting factors, REB1 and REB2, bind independently to sites within the modulator region (Morrow, B. E., Johnson, S. P., and Warner, J. R. (1989) J. Biol. Chem. 264, 9061-9068). We show that REB2 is identical to the ABF1 protien. Site-directed mutagenesis of REB1 and ABF1 binding sites demonstrated uncoupling of RNA polymerase I-dependent termination from transcriptional activation in vivo. We conclude that REB1 and ABF1 are required for RNA polymerase I-dependent termination and enhancer function, respectively, Since REB1 and ABF1 proteins also regulate expression of class II genes and other nuclear functions, our results suggest further similarities between RNA polymerase I and II regulatory mechanisms. Two rDNA enhancers flanking a rDNA minigene stimulated RNA polymerase I transcription in a "multiplicative" fashion. Deletion mapping analysis showed that similar cis-acting sequences were required for enhancer function when positioned upstream or downstream from a rDNA minigene.


The pathology of fresh and cryopreserved homograft heart valves: an analysis of forty explanted homograft valves.
Tissue degeneration reduces the durability of aortic and pulmonary homograft heart valves. Homograft valves can evoke cellular and humoral immune responses that might be detrimental to the valve tissue. Analyzing explanted homograft valves helps in understanding the different factors that eventually lead to tissue degeneration. A total of 40 homografts was acquired from patients whose grafts had been explanted because of stenosis (n = 22), insufficiency (n = 8), paravalvular leakage (n = 4), other technical problems (n = 4), noncardiac death (n = 1), and stenosis with endocarditis (n = 1). The period of implantation varied from 14 days to 16 years (median, 4 years). Cryopreserved valves (n = 31) were, in the majority, derived from beating-heart donors, whereas the fresh valves were sterilized with antibiotics and stored at 4 degrees C for an average of 32 days. Four unimplanted cryopreserved valves, 1 native aortic valve, and 1 native pulmonary valve were used as references. Analysis included macroscopy, light microscopy with routine hematoxylin and eosin staining (cellularity and tissue structure), and immunohistochemical studies to allow identification of macrophages (CD68) and T lymphocytes (CD3), endothelial cells, leukocyte adhesion molecules (CD54, CD106, and CD62E), and immunoglobulin (IgG) and complement factor (C3) depositions. In situ hybridization for the Y chromosome was performed in 10 cases, with host-donor sex mismatch, to distinguish between host and donor cells. The outcomes of histology and immunohistochemistry were related to clinical factors, such as implantation time and reason for explantation. In the first year after implantation, a strong reduction in cellularity of the valve tissue was observed, with almost acellular tissues after 1 year. Trilaminar tissue architecture disappeared with the same speed, whereas endothelial cells were almost absent in all explants. Macrophages and T lymphocytes were encountered in 85% and 78% of the leaflets, respectively. Expression of leukocyte adhesion molecules was low in almost all grafts, and IgG and C3 depositions were not increased. Valve tissue cellularity consisted mainly of ingrown host cells when the implantation time exceeded 1 year. During the first year of implantation, homograft valves rapidly lose their cellular components and normal tissue architecture. A low-grade inflammatory response was observed, but no convincing evidence of immune-mediated injury was found.


Characterization of glutamine synthetase isoforms from chlorella.
Ion-exchange chromatography of extracts derived from Chlorella sorokiniana mutant strain (oxygen resistant) yielded two separate activity peaks of glutamine synthetase (GS). GS(I) and GS(II) were purified 220- and 187-fold and have molecular weights of approximately 398,000 and 360,000, respectively. Both enzymes are composed of eight identical subunits with a subunit molecular weight of 47,000 for GS(I) and 43,000 for GS(II). The amino acid composition, catalytic, and immunological properties for both enzymes are similar.


The effect of low-dose chemotherapy on the tumor microenvironment and its antitumor activity combined with anti-PD-1 antibody.
Aim: This study aimed to explore the effects of low-dose chemotherapy in the tumor microenvironment (TME) on a gastric cancer xenograft and its antitumor activity combined with the anti-PD-1 antibody. Materials & methods: Mice with gastric cancer were divided into four groups. The body weight and tumor volume of the mice were recorded. The TME was analyzed using flow cytometry. Results: Low-dose paclitaxel increased the PD-L1 expression level and the number of CD8+ T cells, but not the CD4+ T and myeloid-derived suppressor cells or PD-1+ CD8+ T cells in the TME. Low-dose 5-fluorouracil reduced the number of myeloid-derived suppressor cells and PD-1+ CD8+ T cells, but the PD-L1 expression level and the number of CD4+ T and CD8+ T cells did not change in the TME. The anti-PD-1 antibody inhibited tumor growth, but the combination therapy did not show superior antitumor activity. Conclusion: Low-dose chemotherapy altered the TME but failed to improve the responses to the anti-PD-1 antibody.


Isolation of a nitric oxide synthase from the protozoan parasite, Leishmania donovani.
A soluble nitric oxide synthase (NOS) activity was purified 2800-fold from Leishmania donovani, the causative parasite of visceral leishmaniasis, by two-step affinity and anion-exchange chromatography. The purified enzyme ran as a prominent band of 110 kDa on SDS-PAGE whereas gel filtration experiments estimated the native molecular mass to be 230 +/- 20 kDa indicating that the native enzyme exists as a dimer. The enzyme activity required NADPH and was blocked by EGTA. The enzyme kinetics, cofactor requirements, inhibition studies and Western blot analysis with brain anti-NOS antibody suggest its similarity with mammalian NOS isoform I.


Inhibitory effects of ionophore A23187 on the release of thyroid hormone and colloid reabsorption in mouse thyroid glands.
The effect of the ionophore A23187 on a. the release of thyroid hormone from perifused mouse thyroid glands and b. the morphological changes in follicular epithelial cells was evaluated. A23187 at a concentration of 5 mumol/l significantly inhibited both the TSH- and the forskolin-stimulated release of T3 and T4. In the presence of 3-isobutyl-1-methylxanthine or (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) RO 20-1724, A23187 did not affect the forskolin-stimulated release of cAMP, but did inhibit the release of T3 and T4 stimulated by forskolin. Light and electron microscopic evaluation of the follicular epithelial cells of mouse thyroid tissues following 1-h stimulation with forskolin showed numerous pseudopods engulfing luminal colloid of various size and the presence of reabsorbed colloid droplets in the apical cytoplasm. Quantitative electron microscopic analysis revealed that the addition of the ionophore A23187 reduced the number of reabsorbed colloid droplets to one eighth in follicular epithelial cells. These observations suggest that the increase in intracellular Ca2+ induced by the ionophore A23187 inhibits the TSH-stimulated thyroid hormone release independently of the cAMP level, and that the suppression of thyroid hormone release may be due to an inhibition of colloid reabsorption.


Pre-athletic training students perform better on written tests with teacher-centered instruction.
There are many different methods of instruction used in the academic setting. Little experimental research exists examining which mode is more effective in educating students. The purpose of this study was to compare scores obtained on the written and the practical examinations of students on a single topic taught through either a teacher-centered format or a student-centered format. A 2 x 2 x 6 factorial design was used in this study. Independent variables were teaching style (teacher-centered instruction and student-centered instruction), order (first or second), and learning style (competitive, collaborative, participant, avoidant, dependent, and independent). The dependent variables were the scores obtained on a written and a practical examination of gait and crutch fitting. Forty pre-athletic training students in their first semester of their first year (16 males, 24 females) participated in this study. The Grasha-Reichmann Student Learning Style Scale was used to determine the learning styles of the subjects. The total subject pool was divided randomly into two groups, one taught by teacher-centered instruction and the other by student-centered instruction. Both groups took the same written and practical examinations, and scores were recorded. A 2 x 2 x 6 fixed model multivariate analysis of variance was performed. A difference was observed for teaching style (F2,21 = 5.35, p = 0.01), on the combination of written and practical exam scores. A difference also was observed on the written examination scores with the teacher-centered format producing better results (p < 0.05); but teacher-centered format scores did not differ from student-centered scores on the practical examination (p > 0.05). Teacher-centered instruction improves written test performance compared with student-centered instruction. When initially teaching a skill, direct teacher involvement may help students learn and perform better.


[Subdiaphragmatic bronchogenic cyst in the left crus of diaphragm: report of a case].
A 39-year-old man who had a subdiaphragmatic bronchogenic cyst in the left crus of diaphragm received surgical treatment. The cyst was located in the retroperitoneum just below the diaphragm and was adhered to the left crus of diaphragm and unconnected with any other structures. The surgically resected cyst was 50 x 25 x 22 mm diameter and the wall was thin and contained white turbid mucus. Histologically, the cyst consisted of ciliated epithelium, mucus glands, smooth muscle, cartilage and this evidence established the final diagnosis of bronchogenic cyst. The post operative course was uneventful and the patient was discharged 10 days after operation. This is the 4th reported case of a subdiaphragmatic bronchogenic cyst in the Japanese literature.


Emergence of high drug resistant bacterial isolates from patients with health care associated infections at Jimma University medical center: a cross sectional study.
The rates of resistant microorganisms which complicate the management of healthcare associated infections (HAIs) are increasing worldwide and getting more serious in developing countries. The objective of this study was to describe microbiological features and resistance profiles of bacterial pathogens of HAIs in Jimma University Medical Center (JUMC) in Ethiopia. Institution based cross sectional study was carried out on hospitalized patients from May to September, 2016 in JUMC. Different clinical specimens were collected from patients who were suspected to hospital acquired infections. The specimens were processed to identify bacterial etiologies following standard microbiological methods. Antibacterial susceptibility was determined in vitro by Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Overall, 126 bacterial etiologies were isolated from 118 patients who had HAIs. Of these, 100 (79.4%) were gram negative and the remaining were gram positive. The most common isolates were Escherichia coli 31(24.6%), Klebsiella species 30(23.8%) and Staphylococcus aureus 26 (20.6%). Of 126 bacterial isolates, 38 (30.2%), 52 (41.3%), and 24 (19%) were multidrug-resistant (MDR, resistant to at least one agent in three or more antimicrobial categories), extensively drug resistant (XDR, resistant to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories), pan-drug resistant (PDR, resistant to all antibiotic classes) respectively. More than half of isolated gram-negative rods (51%) were positive for extended spectrum beta-lactamase (ESBL) and/or AmpC; and 25% of gram negative isolates were also resistant to carbapenem antibiotics. The pattern of drug resistant bacteria in patients with healthcare associated infection at JUMC is alarming. This calls for coordinated efforts from all stakeholders to prevent HAIs and drug resistance in the study setting.


Analysis of Factors Affecting Post-Stroke Fatigue: An Observational, Cross-Sectional, Retrospective Chart Review Study.
Post-stroke fatigue (PSF) is one of the most common emotional and mood disorders in stroke survivors. Several studies have suggested associations between PSF and various factors. However, they describe conflicting results. Therefore, this study aimed to evaluate the factors affecting PSF. We retrospectively reviewed the medical records of 178 hospitalized stroke patients. The collected data were compared between the PSF and control groups. To evaluate the association between factors and PSF, regression analysis was conducted. A total of 96 patients (53.9%) were assigned to the PSF group, and 82 patients were assigned to the control group. Age, neurological deficits, cognitive dysfunction, degree of depression, hs-CRP, and ESR differed significantly between the two groups. For both types of stroke, multiple linear regression analyses showed that degree of depression and degree of inflammation were significantly associated with PSF. Through subgroup analysis, multiple linear regression analyses showed that the degree of depression in ischemic and hemorrhagic stroke and the platelet-to-lymphocyte ratio in hemorrhagic stroke had a significant association with PSF. In conclusion, post-stroke depression and degree of inflammation could be clinically significant predictors of PSF in all types of stroke patients. However, larger, prospective studies are required to obtain more concrete results.


Micropropagation of Elaeis guineensis Jacq. 'Dura': Comparison of three basal media for efficient regeneration.
Three basal plant tissue culture media, namely, N6, MS, and modified Y3, were compared to optimize micropropagation protocol for E. guineensis. Full strength media were used separately to regenerate plantlets directly using immature zygotic embryos (IZEs), and through somatic embryogenesis of calli obtained from IZEs. The plantlets regenerated by direct regeneration on three media were examined for shoot length and rooting percentage. For the induction of callus, somatic embryogenesis, and rooting modified Y3 medium was the most effective. In conclusion, the results indicate that modified Y3 medium is the most suitable for direct regeneration, callus induction and somatic embryogenesis in E. guineensis.


Eosinophilic infiltration of the liver in primary biliary cirrhosis: a morphological study.
Eosinophils and their secretory proteins are important in necroinflammatory processes. In this study we surveyed eosinophilic infiltration of the liver in 176 liver biopsy specimens from patients with primary biliary cirrhosis. A considerable number of eosinophils were found in the portal tracts in 51 of these specimens (29%), whereas this finding occurred in only 2 of 50 (4%) specimens from patients with viral chronic active hepatitis. Eosinophilic infiltration of the portal tracts was focal. These eosinophils were immunohistochemically shown to contain the secreted form of eosinophilic cationic protein. Grades of eosinophilic infiltration of the portal tracts were higher in those livers with higher grades of lymphoplasmacytic infiltration, granulomas and florid duct lesion in the portal tracts, and they were lower in those livers with higher grades of bile duct disappearance and orcein-positive granuoles in hepatocytes. In the livers of patients with primary biliary cirrhosis, eosinophils were abundant around the damaged bile ducts, around the portal vein branches and at the marginal regions, and they were scattered in the portal tracts, whereas only the last pattern was seen in viral chronic active hepatitis. Peripheral blood eosinophils tended to be increased in primary biliary cirrhosis patients with higher grades of eosinophilic infiltration of the portal tracts. Eosinophilic infiltration of the portal tracts may play a role in immunological injuries of the interlobular bile ducts in primary biliary cirrhosis.


Hypovitaminosis D3 in menopausal women in a tertiary care hospital in Delhi.
Blood samples from 126 menopausal women, seeking treatment for different ailments at a tertiary care, multidisciplinary hospital in Delhi, India, were examined for their vitamin D(3), quantified by 25-hydroxvitamin D (25-OH-D) level. Using a direct ELISA kit, the 25-OH-D levels were measured and were found to be sufficient in 30 (23.8%) cases, adequate in 10 cases (7.9%) and deficient in 86 cases (68.2%). Severe hypo-vitaminosis in menopausal women in the Indian subcontinent ought to be treated with oral or parenteral supplementation. Point-of-care assay formats are needed for quantification of 25-OH-D levels at healthcare centers.


Upregulation of hepatic glucose 6-phosphatase gene expression in rats treated with an inhibitor of glucose-6-phosphate translocase.
The multicomponent hepatic glucose 6-phosphatase (Glc-6-Pase) system catalyzes the terminal step of hepatic glucose production and plays a key role in the regulation of blood glucose. We used the chlorogenic acid derivative S 3483, a reversible inhibitor of the glucose-6-phosphate (Glc-6-P) translocase component, to demonstrate for the first time upregulation of Glc-6-Pase expression in rat liver in vivo after inhibition of Glc-6-P translocase. In accordance with its mode of action, S 3483-treatment of overnight-fasted rats induced hypoglycemia and increased blood lactate, hepatic Glc-6-P, and glycogen. The metabolic changes were accompanied by rapid and marked increases in Glc-6-Pase mRNA (above 35-fold), protein (about 2-fold), and enzymatic activity (about 2-fold). Maximal mRNA levels were reached after 4 h of treatment. Glycemia, blood lactate, and Glc-6-Pase mRNA levels returned to control values, whereas Glc-6-P and glycogen levels decreased but were still elevated 2 h after S 3483 withdrawal. The capacity for Glc-6-P influx was only marginally increased after 8.5 h of treatment. Prevention of hypoglycemia by euglycemic clamp did not abolish the increase in Glc-6-Pase mRNA induced by S 3483 treatment. A similar pattern of hypoglycemia and possibly of associated counterregulatory responses elicited by treatment with the phosphoenolpyruvate carboxykinase inhibitor 3-mercaptopicolinic acid could account for only a 2-fold induction of Glc-6-Pase mRNA. These findings suggest that the significant upregulation of Glc-6-Pase gene expression observed after treatment of rats in vivo with an inhibitor of Glc-6-P translocase is caused predominantly either by S 3483 per se or by the compound-induced changes of intracellular carbohydrate metabolism.


Variation in seed size is structured by dispersal syndrome and cone morphology in conifers and other nonflowering seed plants.
Seed size varies tremendously in plants and its evolution is influenced by multiple ecological and biological factors that are difficult to disentangle. In this study, we focus on understanding the role of seed dispersal by animals in the evolution of seed size in conifers, the most diverse extant nonflowering seed plant group. Relationships among seed size, dispersal syndrome, climate and cone morphology were analyzed across conifers using quantitative models of character evolution and phylogenetic regression techniques. Dispersal syndrome is a more consistent predictor of seed size within major extant conifer clades than climate. Seeds are generally larger in animal-dispersed than wind-dispersed species, and particular cone morphologies are consistently associated with specific ranges in seed size. Seed size and cone morphology evolve in a correlated manner in many animal-dispersed conifers, following a trade-off that minimizes the total size of the dispersal unit. These relationships are also present in other nonflowering seed plant groups, and have been important in the evolution of seeds and cones at least over the Cenozoic and perhaps over much of the later Mesozoic.


Biliary and nonbiliary contributions to reverse cholesterol transport.
The process of reverse cholesterol transport (RCT) is critical for disposal of excess cholesterol from the body. Although it is generally accepted that RCT requires biliary secretion, recent studies show that RCT persists in genetic or surgical models of biliary insufficiency. Discovery of this nonbiliary pathway has opened new possibilities of targeting the intestine as an inducible cholesterol excretory organ. In this review we highlight the relative contribution and therapeutic potential for both biliary and nonbiliary components of RCT. Recently, the proximal small intestine has gained attention for its underappreciated ability to secrete cholesterol in a process called transintestinal cholesterol efflux (TICE). Although this intestinal pathway for RCT is quantitatively less important than the biliary route under normal physiological conditions, TICE is highly inducible, providing a novel therapeutic opportunity for treatment of atherosclerotic cardiovascular disease (ASCVD). In fact, recent studies show that intestine-specific activation of RCT protects against ASCVD in mice. It is well known that the small intestine plays a gatekeeper role in the maintenance of cholesterol balance. Through integrated regulation of cholesterol absorption and TICE, the small intestine is a key target for new therapies against ASCVD.


Tyrosine kinase inhibitor resistance: a case report on chronic myeloid leukemia and Gilbert's syndrome.
Although tyrosine kinase inhibitors (TKI) are commonly used as targeted treatment options for chronic myeloid leukemia (CML), its use is associated to UGT1A1 polymorphisms and, consequently, are related to a higher risk of manifesting Gilbert's syndrome, a genetic disorder associated to hyperbilirubinemia. The report of concomitant condition of CML and Gilbert's Syndrome is uncommon. Therefore, the aim of this study was to report the clinical case of a patient diagnosed with CML and subsequently, with Gilbert's Syndrome. A 34-year-old female was diagnosed with CML. On physical examination, spleen and liver were palpable, indicating hepatosplenomegaly. Laboratory findings of peripheral blood showed leukocytosis (165,190/mm3), 6% of blasts and a bone marrow biopsy showed hypercellularity by granulocytic series with moderate maturation delay. After diagnosis, the patient immediately started chemotherapy with the TKI Imatinib. One year after treatment, due to the partial response, the therapy was changed to Nilotinib, resulting in a complete response. Despite the absence of hyperbilirubinemia, a genetic study by polymerase chain reaction (PCR) verified a positivity for Gilbert's Syndrome. TKIs are also inhibitors of the enzyme UDPGT1, leading to deficient glucuronidation, causing manifestation of Gilbert's Syndrome. This report demonstrates the case of a patient that, besides having two coexisting conditions that could cause hyperbilirubinemia, did not have bilirubin alterations and it highlights the importance of having genetic investigations in cancer patients, in order to identify secondary diseases that could worsen the course of treatment.


The Efficacy of an Initial Prednisone Monotherapy Regimen on PLA2R-associated Idiopathic Membranous Nephropathy.
The aim of this study was to evaluate the efficacy and safety of prednisone monotherapy for phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN). This was a retrospective cohort study involving 32 patients enrolled between January 2017 and June 2019 at Beijing Friendship Hospital, Capital Medical University, Beijing, China. Seventeen patients received prednisone monotherapy, and 15 received the Ponticelli regimen. The primary outcome was nephrotic syndrome remission at 12th month. The secondary outcomes were the incidence of adverse events and recurrence over the 12-month follow-up. At 12th month, 16/17 patients (94.1%) in the prednisone monotherapy group and 14/15 patients (93.3%) in the Ponticelli regimen group achieved remission (p = 0.19). The adverse events occurred in 9/17 and 9/15 of the patients receiving prednisone monotherapy and the Ponticelli regimen, respectively (p = 0.74). Four and three patients relapsed in the prednisone monotherapy and Ponticelli regimen groups, respectively (p = 0.99). Initial prednisone monotherapy had similar efficacy and safety compared with the Ponticelli regimen for PLA2R-associated IMN. Key Words: PLA2R-associated idiopathic membranous nephropathy, Ponticelli regimen, Prednisone monotherapy.


Multifocal conduction block in a patient with sarcoid neuropathy: successful treatment with intravenous immunoglobulin.
A 54-year-old-woman with sarcoidosis presented with progressive symmetric, predominantly distal weakness and sensory dysfunction with areflexia in all four limbs. Nerve conduction studies showed multifocal conduction blocks in several nerves. Oral steroids were ineffective; however, intravenous immunoglobulin (IVIG) therapy rapidly and repeatedly improved the patient's neurologic symptoms with a resolution of the conduction blocks. Multifocal conduction blocks are not frequently reported in patients with sarcoid neuropathy, but they may respond to early treatment with IVIG.


Pentobarbital desensitization in a 3-month-old child.
Barbiturates, a class of medications commonly used as antiepileptics and sedatives, are known to cause adverse reaction, with the most commonly reported immune-mediated reactions being anticonvulsant hypersensitivity syndrome. Other types of allergic reactions such as immediate hypersensitivity reactions also can occur. We present a 3-month-old child with refractory generalized convulsive status epilepticus who required pentobarbital therapy in the context of phenobarbital sensitivity because of progressive generalized seizures unresponsive to other aggressive therapies. Skin tests to pentobarbital and phenobarbital were negative. In the intensive care unit setting, intravenous pentobarbital desensitization was performed without reaction. To our knowledge, this is the first reported protocol for pentobarbital desensitization.


Highly diastereoselective construction of fused carbocycles from cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers: scope, mechanism, and origin of diastereoselectivity.
Cyclopropane rings true: By selecting the appropriate substituents on the ester and silyl groups, fused cyclopentane derivatives with multiple contiguous stereocenters can be synthesized with excellent diastereoselectivity through Cu(II)/bisoxazoline-catalyzed intermolecular [3+2] cycloaddition reactions of cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers (see scheme).


Mutagenicity and metabolism of dimethyl phthalate and its binding to epidermal and hepatic macromolecules.
As an active ingredient in insect repellents, dimethyl phthalate (DMP) had previously been shown to produce chromosomal aberrations in the livers of rats following subchronic application of the phthalate to skin. When we tested DMP in the Ames mutagenesis assay, it produced in bacterial tester strain TA100 (but not TA98) a dose-related mutagenic response that was abolished by NAD- and NADP-independent metabolism associated with rat liver microsomal preparations (S9). In a host-mediated mutagenesis assay, rats were injected ip with DMP (2 g/kg body weight); urine was collected for 24 h, extracted, and analyzed for mutagenic activity and phthalic acid-containing derivatives. The extracted urine was not mutagenic to TA100 and contained an equivalent of 1.96 mg phthalate/ml urine. More than 97% of the phthalic acid-containing derivatives present in the extracted urine consisted of the nonmutagenic metabolite of DMP, monomethyl phthalate (MMP). In vitro experiments showed that rat liver homogenates hydrolyzed 93% of carbonyl-labeled 14C-DMP (7.7 mM) to MMP in 2 h and bound 0.07 nmol of [14C]phthalate/mg liver macromolecules. By contrast, rat epidermal homogenates metabolized only 5% and bound 38-fold higher levels of carbonyl-labeled 14C-DMP (2.66 nmol/mg of macromolecules), with no detectable binding to nucleic acids. Compared to epidermis and plasma, liver had a fivefold higher rate of DMP monoesterase activity (1240 nmol/h/mg protein), which, when inhibited by 67%, resulted in a 4.4-fold increase in phthalate-bound hepatic macromolecules (0.31 vs. 0.07 nmol of carbonyl-labeled 14C-DMP/mg macromolecules). In addition to MMP, formaldehyde was produced during the metabolism of DMP by liver. When ethanol was used to inhibit the oxidation of DMP-derived methanol by hepatic homogenates, there resulted a 74% reduction in the accumulation of formaldehyde and similar reductions of 71 and 73% in the binding of methyl-labeled 14C-DMP to nucleic acids and macromolecules. (Methyl-labeled, unlike carbonyl-labeled, 14C-DMP yields a 14C-labeled methanol when hydrolyzed.) These results indicate that the DMP diester is a weak bacterial mutagen, which binds to epidermal and hepatic macromolecules other than nucleic acids, and that although the rapid hepatic metabolism of DMP to its monoester (MMP) and methanol affords protection against higher levels of phthalate binding as well as against DMP-induced bacterial mutagenesis, it also oxidizes DMP-derived methanol to formaldehyde, a metabolite that binds macromolecules, including nucleic acids.


Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium. To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses. Immunization with PfCelTOS resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with P. berghei sporozoites in a proportion of both inbred and outbred mice. The biological activity of CelTOS-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. The results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species.


When advanced cancer patients won't eat: family responses.
We conducted a grounded theory study examining nutritional care experiences in advanced cancer from the perspective of patients (n = 13), families (n = 23), and health care providers (n = 11) (McClement, 2001). That work generated an inductively derived model that captured important information about adult family members' perceptions and behaviour regarding the nutritional care their terminally ill adult relative received while hospitalized on an inpatient palliative care unit, and has been reported elsewhere (McClement et al, 2003). This article provides a more detailed description of one of the major sub-processes of the model regarding family member responses to declining oral intake and weight loss in a terminally ill relative-the sub-process of 'letting nature take its course: it's best not to eat.' The strategies family members use when letting nature take its course, and the consequences of these strategies for patients, family members and health care providers are reported. Implications for practice and research are provided.


Erratum: Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids using Extracellular Flux Analysis.
An erratum was issued for: Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids using Extracellular Flux Analysis. The Representative Results section was updated. Figure 5 was updated from: Figure 5: Single or sequential injection of mitochondrial respiratory compounds. Cancer-cell-derived spheroids of MCF-7, HEPG2/C3A, SK-OV-3, and A549 were placed into wells of an XFe96 spheroid microplate in XF RPMI and probed for OCR using the Agilent Seahorse XFe96 analyzer. OCR was measured 5x, after which 2 µg/mL oligomycin (injection Port A: green trace) or 5 µM BAM15 (injection Port A: blue trace or injection port B: green trace) to inhibit the mitochondrial ATP synthase and determine maximal respiratory capacity, respectively. Kinetic OCR data are expressed as % basal (A-D). Maximal respiratory capacity (OCRmax) was calculated as a factor of basal OCR by the equation: OCRmax = OCRBAM15 / OCRbasal. OCRmax was obtained from OCR averages across measurement cycles 8-10 post BAM15 injection with (green bars) and without (blue bars) oligomycin. Data are averages ± SEM from 3-8 individual well replicates across the spheroid assay microplate. Abbreviations: OCR = oxygen consumption rate. Please click here to view a larger version of this figure. to: Figure 5: Single or sequential injection of mitochondrial respiratory compounds. Cancer-cell-derived spheroids of MCF-7, HEPG2/C3A, SK-OV-3, and A549 were placed into wells of an XFe96 spheroid microplate in XF RPMI and probed for OCR using the Agilent Seahorse XFe96 analyzer. OCR was measured 5x, after which 2 µg/mL oligomycin (injection Port A: green trace) or 5 µM BAM15 (injection Port A: blue trace or injection port B: green trace) to inhibit the mitochondrial ATP synthase and determine maximal respiratory capacity, respectively. Kinetic OCR data are expressed as % basal (A-D). Maximal respiratory capacity (OCRmax) was calculated as a factor of basal OCR by the equation: OCRmax = OCRBAM15 / OCRbasal. OCRmax was obtained from OCR averages across measurement cycles 8-10 post BAM15 injection with (green bars) and without (blue bars) oligomycin. Data are averages ± SEM from 3-8 individual well replicates across the spheroid assay microplate. Abbreviations: OCR = oxygen consumption rate. Please click here to view a larger version of this figure.


The TECH@HOME study, a technological intervention to reduce caregiver burden for informal caregivers of people with dementia: study protocol for a randomized controlled trial.
It is estimated that global dementia rates will more than triple by 2050 and result in a staggering economic burden on families and societies. Dementia carries significant physical, psychological and social challenges for individuals and caregivers. Informal caregiving is common and increasing as more people with dementia are being cared for at home instead of in nursing homes. Caregiver burden is associated with lower perceived health, lower social coherence, and increased risk of morbidity and mortality. The aim of this trial is to evaluate the effects of information and communication technology (ICT) on caregiver burden among informal caregivers of people with dementia by reducing the need for supervision. This randomized controlled trial aims to recruit 320 dyads composed of people with dementia living in community settings and their primary informal caregivers. In the intervention group, people with dementia will have a home monitoring kit installed in their home while dyads in the control group will receive usual care. The ICT kit includes home-leaving sensors, smoke and water leak sensors, bed sensors, and automatic lights that monitor the individual's behavior. Alerts (text message and/or phone call) will be sent to the caregiver if anything unusual occurs. All study dyads will receive three home visits by project administrators who have received project-specific training in order to harmonize data collection. Home visits will take place at enrollment and 3 and 12 months following installation of the ICT kit. At every home visit, a standardized questionnaire will be administered to all dyads to assess their health, quality of life and resource utilization. The primary outcome of this trial is the amount of informal care support provided by primary informal caregivers to people with dementia. This is the first randomized controlled trial exploring the implementation of ICT for people with dementia in a large sample in Sweden and one of the first at the international level. Results hold the potential to inform regional and national policy-makers in Sweden and beyond about the cost-effectiveness of ICT and its impact on caregiver burden. ClinicalTrials.gov, NCT02733939 . Registered on 10 March 2016.


Firing rate homeostasis counteracts changes in stability of recurrent neural networks caused by synapse loss in Alzheimer's disease.
The impairment of cognitive function in Alzheimer's disease is clearly correlated to synapse loss. However, the mechanisms underlying this correlation are only poorly understood. Here, we investigate how the loss of excitatory synapses in sparsely connected random networks of spiking excitatory and inhibitory neurons alters their dynamical characteristics. Beyond the effects on the activity statistics, we find that the loss of excitatory synapses on excitatory neurons reduces the network's sensitivity to small perturbations. This decrease in sensitivity can be considered as an indication of a reduction of computational capacity. A full recovery of the network's dynamical characteristics and sensitivity can be achieved by firing rate homeostasis, here implemented by an up-scaling of the remaining excitatory-excitatory synapses. Mean-field analysis reveals that the stability of the linearised network dynamics is, in good approximation, uniquely determined by the firing rate, and thereby explains why firing rate homeostasis preserves not only the firing rate but also the network's sensitivity to small perturbations.


[Diaphragm reconstruction after extrapleural pneumonectomy].
Extrapleural pneunonectomy with resection of the diaphragm only offers acceptable therapeutic results in patients with malignant diseases of the pleura and the lung. The standard procedures for diaphragm reconstruction consist of the use of biomaterials and prosthetic patches. We retrospectively reviewed techniques and results in 4 patients where the pedicled latissimus dorsi flap, the expanded polytetrafluoroethylene (ePTFE) sheet and the composite mesh sheet consisting of the ePTFE sheet and 2 layers of polypropylene mesh sheets were successfully used to replace the resected diaphragm. When we evaluated such biomaterials and prosthetic patches, the ePTFE sheet was superior in the time of reconstruction to other materials although it was expensive. The pedicled latissimus dorsi flap did not apply to patient with poor muscle volume. In conclusion, the ePTFE sheet widely applies to every patient who requires diaphragm reconstruction after extrapleural pneumonectomy.


Systemic contact dermatitis in children: how an avoidance diet can make a difference.
Systemic contact dermatitis is an under-recognized skin reaction that occurs secondary to systemic (oral, intravenous, intramuscular, inhaled, or subcutaneous) exposure to a hapten in a previously sensitized individual. Medicaments are the most common cause of SCD in the adult population, but other chemicals like nickel, cobalt, balsam of Peru, and formaldehyde have been implicated as well. Few reports in children exist to date. Dietary restriction has shown to be of some benefit in managing some adult patients. We present a case series of 8 pediatric patients diagnosed with SCD from the contact dermatology clinic, who showed marked improvement of their dermatitis after adequate dietary avoidance. We review common presentations of chemicals causing SCD in children and potential dietary modifications.


Dicer1 is essential for female fertility and normal development of the female reproductive system.
The ribonuclease III endonuclease, Dicer1 (also known as Dicer), is essential for the synthesis of the 19-25 nucleotide noncoding RNAs known as micro-RNAs (miRNAs). These miRNAs associate with the RNA-induced silencing complex to regulate gene expression posttranscriptionally by base pairing with 3'untranslated regions of complementary mRNA targets. Although it is established that miRNAs are expressed in the reproductive tract, their functional role and effect on reproductive disease remain unknown. The studies herein establish for the first time the reproductive phenotype of mice with loxP insertions in the Dicer1 gene (Dicer1fl/fl) when crossed with mice expressing Cre-recombinase driven by the anti-müllerian hormone receptor 2 promoter (Amhr2Cre/+). Adult female Dicer1fl/fl;Amhr2Cre/+ mice displayed normal mating behavior but failed to produce offspring when exposed to fertile males during a 5-month breeding trial. Morphological and histological assessments of the reproductive tracts of immature and adult mice indicated that the uterus and oviduct were hypotrophic, and the oviduct was highly disorganized. Natural mating of Dicer1fl/fl;Amhr2Cre/+ females resulted in successful fertilization as evidenced by the recovery of fertilized oocytes on d 1 pregnancy, which developed normally to blastocysts in culture. Developmentally delayed embryos were collected from Dicer1fl/fl; Amhr2Cre/+ mice on d 3 pregnancy when compared with controls. Oviductal transport was disrupted in the Dicer1fl/fl;Amhr2Cre/+ mouse as evidenced by the failure of embryos to enter the uterus on d 4 pregnancy. These studies implicate Dicer1/miRNA mediated posttranscriptional gene regulation in reproductive somatic tissues as critical for the normal development and function of these tissues and for female fertility.


Validity of estimating limb muscle volume by bioelectrical impedance.
The present study aimed to investigate the validity of estimating muscle volume by bioelectrical impedance analysis. Bioelectrical impedance and series cross-sectional images of the forearm, upper arm, lower leg, and thigh on the right side were determined in 22 healthy young adult men using a specially designed bioelectrical impedance acquisition system and magnetic resonance imaging (MRI) method, respectively. The impedance index (L(2)/Z) for every segment, calculated as the ratio of segment length squared to the impedance, was significantly correlated to the muscle volume measured by MRI, with r = 0.902-0.976 (P < 0.05). In these relationships, the SE of estimation was 38.4 cm(3) for the forearm, 40.9 cm(3) for the upper arm, 107.2 cm(3) for the lower leg, and 362.3 cm(3) for the thigh. Moreover, isometric torque developed in elbow flexion or extension and knee flexion or extension was significantly correlated to the L(2)/Z values of the upper arm and thigh, respectively, with correlation coefficients of 0.770-0.937 (P < 0.05), which differed insignificantly from those (0.799-0.958; P < 0.05) in the corresponding relationships with the muscle volume measured by MRI of elbow flexors or extensors and knee flexors or extensors. Thus the present study indicates that bioelectrical impedance analysis may be useful to predict the muscle volume and to investigate possible relations between muscle size and strength capability in a limited segment of the upper and lower limbs.


Genotype analysis of hepatitis delta virus from hepatitis B surface antigen-positive patients using PCR-RFLP in Tehran, Iran.
Hepatitis delta virus is a unique human pathogen responsible for some 20 million infections globally. This virus is dependent on hepatitis B virus for transmission and propagation. Currently, at least three genotypes of hepatitis delta virus with different geographic distribution and clinical manifestations are described. In this study, hepatitis delta virus RNA of 35 patients' sera were analyzed by RT- semi-nested polymerase chain reaction. Based on genomic differences of hepatitis delta antigen coding region of hepatitis delta virus RNA among hepatitis delta virus RNA-positive sera, the polymerase chain reaction products were digested with restriction enzymes and studied by restriction fragment length polymorphism. Out of 35 samples, 13 (38.46%) were positive for hepatitis delta virus RNA by RT- semi-nested polymerase chain reaction. All polymorphisms were shown to be genotype I. Out of 13 hepatitis delta virus RNA-positive (13/35), eight were HBeAg negative. Our data indicated that hepatitis delta virus isolates in Tehran are exclusively genotype I.


Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat.
Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.


Dracohodin Perochlorate Stimulates Fibroblast Proliferation via EGFR Activation and Downstream ERK/CREB and PI3K/Akt/mTOR Pathways In Vitro.
In recent years, an increasing number of natural plant extracts have been determined to be potential drugs for various illnesses. In this study, we investigated the effects of dracorhodin perchlorate (DP) on fibroblast proliferation, which is crucial for wound healing. Cell proliferation assays were performed by different concentrations of DP, and the cell viability was detected by CCK-8 kits. After DP treatment for 24 h, the cell cycle was checked by flow cytometer. EGFR and downstream signaling pathways ERK1/2 and PI3K were examined with DP treatment by western blot. We further determined the effects of the related inhibitors on DP-induced relative protein phosphorylation and cell proliferation. The results showed that 3 μg/mL of DP promoted cell proliferation most significantly at treatment lengths of 24 h, and the percentage of cells in the S + G2 phase increased compared to those of the control group. In western blot detection, we found that DP significantly upregulated EGFR phosphorylation and activated the downstream ERK/CREB and PI3K/Akt/mTOR signaling pathway. Moreover, the results also showed that AG1478 abolished DP-induced relative protein activation and cell proliferation. When U0126 or LY294002 pretreated cells alone, DP-induced p-ERK or p-PI3K downstream proteins and cell proliferation were suppressed compared to those of the control group, but EGFR was not affected. In addition, ICG001 and BEZ235 collectively eliminated DP-induced fibroblast proliferation. Our findings suggest that DP-promoted fibroblast proliferation is stimulated by p-EGFR-induced activation of the ERK1/2-CREB and PI3K/Akt/mTOR pathways. Our present study explored the mechanism of DP-promoted fibroblast proliferation and provided a new basis for wound healing.


Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28.
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VT in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VT and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.


[Mechanism of lumen loss of the left circumflex ostium after main vessel stent implantation: observations by intravascular ultrasound].
To explore the mechanism of lumen loss of the left circumflex ostium after main vessel stent implantation. Twenty-eight patients undergoing provisional T technique were enrolled in this study. Intravascular ultrasound (IVUS) examination was performed before and after main vessel stenting and kissing balloon post-dilatation to evaluate the geometrical changes of the vessels. The CSA of LCX ostium lumen decreased significantly from 5.9∓2 mm(2) to 4.9∓1.9 mm(2) (P<0.01) after the procedure, and the CSA of LCX ostium P and M increased from 5.4∓2.9 mmmm(2) to 5.7∓2.9 mm(2) (P=0.21) after the main vessel stenting. The changes in LCX ostium lumen CSA was correlated with the changes of LCX ostium EEM CSA but not the LCX ostium P and M CSA. After kissing balloon post-dilatation, the CSA of LCX ostium lumen increased from 4.9∓1.9 mm(2) to 5.5∓1.9 mm(2) (P<0.01) , and the CSA of LCX ostium P and M showed no obvious changes (5.7∓2.9 mmmm(2) vs 5.7∓2.6 mmmm(2), P=0.89). The changes of LCX ostium lumen CSA were correlated with the those of the LCX ostium EEM CSA (R=0.432, P=0.02). After stent implantation from the LMCA to the LAD, most of lumen losses of the LCX are due to carina shift, and in occasional cases, plaque shift occurs from the distal LMCA to the ostium of the LCX. Kissing balloon technique can adjust carina shift but can not improve plaque shift.


Inhibitory molecules in signal transduction pathways of cardiac hypertrophy.
Cardiac hypertrophy is induced by a variety of diseases, such as hypertension, valvular diseases, myocardial infarction, and endocrine disorders. Although cardiac hypertrophy may initially be a beneficial response that normalizes wall stress and maintains normal cardiac function, prolonged hypertrophy is a leading cause of heart failure and sudden death. A number of studies have elucidated molecules responsible for the development of cardiac hypertrophy, including the mitogen-activated protein (MAP) kinases pathway, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and calcium/calmodulin-dependent protein phosphatase calcineurin pathway. These molecules may be targets for therapies designed to prevent the progression of cardiac hypertrophy. Numerous studies have focused on characterization of the intracellular signal transduction molecules that promote cardiac hypertrophy in order to clarify the molecular mechanisms, but there have been only a few reports on the inhibitory regulators of hypertrophic response. Recently, several molecules have attracted much attention as endogenous inhibitory regulators of cardiac hypertrophy. Enhancement of these inhibitory regulators would also seem to be a potential approach for the pharmacological treatment of hypertrophy. In this review, we summarize the inhibitory molecules of cardiac hypertrophy.


Managing and Retrieving Bilingual Documents Using Artificial Intelligence-Based Ontological Framework.
In recent times, artificial intelligence (AI) methods have been applied in document and content management to make decisions and improve the organization's functionalities. However, the lack of semantics and restricted metadata hinders the current document management technique from achieving a better outcome. E-Government activities demand a sophisticated approach to handle a large corpus of data and produce valuable insights. There is a lack of methods to manage and retrieve bilingual (Arabic and English) documents. Therefore, the study aims to develop an ontology-based AI framework for managing documents. A testbed is employed to simulate the existing and proposed framework for the performance evaluation. Initially, a data extraction methodology is utilized to extract Arabic and English content from 77 documents. Researchers developed a bilingual dictionary to teach the proposed information retrieval technique. A classifier based on the Naïve Bayes approach is designed to identify the documents' relations. Finally, a ranking approach based on link analysis is used for ranking the documents according to the users' queries. The benchmark evaluation metrics are applied to measure the performance of the proposed ontological framework. The findings suggest that the proposed framework offers supreme results and outperforms the existing framework.


Colloid-wall interaction in a nematic liquid crystal: the mirror-image method of colloidal nematostatics.
The new area of nematic colloidal systems (or nematic emulsions) has been greatly guided by the fruitful analogy between the colloidal nematostatics and electrostatics. The elastic charge density representation of the colloidal nematostatics [V. M. Pergamenshchik and V. O. Uzunova, Eur. Phys. J. E 23, 161 (2007); Phys. Rev. E 76, 011707 (2007)] develops this analogy at the level of charge density and Coulomb interaction. It shows, however, that the colloidal nematostatics in three dimensions substantially differs from the electrostatics both in its mathematical structure and physical implications: the elastic charge and multipoles are dyads; similar charges attract while opposite charges repel each other, and so on. In this paper we consider the interaction between an elastic charge and elastic dipole with a nematic surface (wall) at which the director alignment is fixed. Using the mirror image method of electrostatics as a guiding idea, we develop the mirror image method in the nematostatics for arbitrary director tilt at the wall. A wall is shown to induce a repulsive 1R{4} force on the elastic dipole which, in general, is accompanied by its reorientation. External torque on the colloid induces an elastic charge therein and triggers switching to the 1R{2} repulsion. The dyadic nature of an elastic dipole is shown to be essential: a particle-wall interaction potential cannot be obtained in phenomenological theories with a single component dipole. In the introductory sections we discuss connection between the director-mediated interaction in two and three dimensions and the electrostatic interaction and consider different symmetries of elastic dipoles. Conservation of the torque components exerted upon colloids is shown to play the role of Gauss' theorem and determines the elastic charge dyad.


Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase.
Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in proliferation and epithelial-mesenchymal transition (EMT) of cancer cells, but much less is understood about their contribution to interactions with other signaling events. Recent studies have indicated that crosstalk between TGF-β and Ras signaling makes a contribution to TGF-β-mediated EMT. Here, we demonstrate that Jumonji domain containing-3 (JMJD3 also called KDM6B) promotes TGF-β-mediated Smad activation and EMT in Ras-activated lung cancer cells. JMJD3 in lung cancer patients was significantly increased and JMJD3 expression in lung tumor tissues was correlated with expression of K-Ras or H-Ras in particular, and its expression was regulated by Ras activity in lung cancer cells. JMJD3 promotes TGF-β-induced Smad activation and EMT in Ras-activated lung cancer cells through the induction of syntenin, a protein that regulates TGF-β receptor activation upon ligand binding. Tissue array and ChIP analysis revealed that JMJD3 epigenetically induces syntenin expression by directly regulating H3K27 methylation levels. Mechanical exploration identified a physical and functional association of JMJD3 with syntenin presiding over the TGF-β in Ras-activated lung cancer cells. Taken together, these findings provide new insight into the mechanisms by which JMJD3 promotes syntenin expression resulting in oncogenic Ras cooperation with TGF-β to promote EMT.


[Permanent determinants of international migration of the Polish population].
The author examines historical trends and determinants of international migration in Poland. "The leading role is ascribed by the author to sociodemographic conditions.... There are presented types of temporary and permanent migration and educational level of migrants, with a special stress on a 'brain-drain' phenomenon as a result of existing international migratory processes." (SUMMARY IN ENG AND RUS)


Evaluation of Happy Sport, an Emotional Education Program for Assertive Conflict Resolution in Sports.
Interpersonal conflicts occur in any kind of social relation, including the field of sports. Proper emotional management can improve athletes' well-being, coexistence, and performance. This study presents the initial results of the gamified emotional education program Happy Sport in a sample of athletes in the field of non-formal education. The study sample consists of 194 athletes from the benjamín and alevín categories (3rd- to 6th-grade primary school children). A quasi-experimental pre-intervention and post-intervention design with a control group is followed using the Games and Emotions Scale (GES), Social Support Scale, Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA), and Bullying in Sports Questionnaire. Statistically significant differences were found across participants in the experimental group between the pre- and post-intervention evaluations for the variables satisfaction and bullying. An analysis of the competencies related to emotion regulation revealed significant results for the experimental group for both scales (cognitive reappraisal and expressive suppression). The results show that after a training session with the gamified software Happy Sport, children's satisfaction increased and bullying levels decreased. Changes in cognitive reappraisal and expressive suppression may also be explained by the training received.