[Genetics and obesity in man].
This brief review constitutes a synthesis of some of the research conducted in our laboratory about the role of inheritance in human variation observed for subcutaneous fat, total fat mass and subcutaneous fat distribution. Our first studies were of the genetic epidemiology type and were conducted on a cohort of 1,698 subjects from 409 families of French descent living in the greater Québec city area. These studies have shown that heritability of the amount of subcutaneous fat was almost zero, while the additive genetic effect reached about 25% of human variation, after statistical control over the effects of age and gender, for total fat mass and regional subcutaneous fat distribution. On the other hand, there are considerable individual differences in the response to overfeeding and those that pertain to body weight and body composition, and the various components of daily energy expenditure in subjects kept inactive, are mainly determined by the genotype. These findings come from a study on the response to chronic overfeeding, sustained for 22 consecutive days, undertaken with 6 pairs of identical twins. In general, our research shows that there are individuals who are more at risk of becoming obese because of undetermined genetic characteristics but that are apparently associated somehow with the various components of habitual energy expenditure.


Production of thermal insulation blocks from bottom ash of fluidized bed combustion system.
The issues of disposal and environmental problems are increased by the generation of bottom ash from the thermal power plants day by day; hence, its recycling is required. The present study aimed to make thermal insulation blocks using as raw material bottom ash and iron ore slime as a binder and to characterize their engineering properties. Two different fineness values of bottom ash were considered with varying amounts of iron ore slime (0-10%) to make the blocks. Blocks were dried followed by firing at 1000, 1100 and 1200°C, respectively. Cold crushing strength, density and thermal conductivity of these fired blocks showed increasing behaviour with firing temperature, fineness of bottom ash and iron ore slime content. In contrast, a reverse trend was observed in the case of porosity. With increasing firing temperature, the formation of lower melting phases like iron silicate followed by iron aluminium silicate was observed, which imparts the strength inside the blocks. The coarser particles of bottom ash increase the interparticle spaces, which enhances the apparent porosity, resulting in higher thermal insulation property in the blocks. Blocks having better thermal insulation property could be possible to make effectively from coarse bottom ash by adding iron ore slime as a binder.


Development and validation of a sensitive LC-MS-MS assay for the quantification of betulonic acid in rat plasma.
A rapid, sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of betulonic acid in rat plasma. The plasma samples were prepared by protein precipitation. Chromatographic separation was achieved on an Agela MG-C18 analytical column (50 × 2.1 mm, 5 µm) using methanol-water-formic acid (80:20:0.1, v/v/v) as the mobile phase with a constant flow rate of 0.6 mL/min. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring mode. The calibration curves were linear over a concentration range of 3.00-3,000 ng/mL for the analyte. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all concentrations. The method was successfully applied for the estimation of betulonic acid in rat plasma from a preclinical pharmacokinetics study.


Legionella pneumophila-induced blastogenesis of murine lymphoid cells in vitro.
Legionella pneumophilia antigen preparations, either killed whole cell vaccine, a soluble sonic extract, or a purified large-molecular-weight somatic antigen, stimulated blastogenic responses by splenocytes from both normal and Legionella-sensitized mice. Graded amounts of the bacterial preparations, when added to cultures of normal spleen cells, resulted in increased uptake of thymidine into cellular DNA, indicating that the preparations were mitogenic for normal mouse splenocytes. Spleen cells from mice injected with graded numbers of living bacteria showed blastogenic responsiveness to Legionella preparations generally at a higher level than spleen cells from normal animals. The heightened blastogenic response was mainly evident with spleen cells obtained from mice injected with living bacteria 2 to 3 weeks earlier. Splenocytes from mice infected with legionella less than 1 to 2 weeks or for more than 4 to 5 weeks responded generally similar to those obtained from uninjected mice, indicating that sensitization with living organisms had a relatively short duration. Spleen cell suspensions responding to the L. pneumophila antigens appeared to be mainly B-lymphocytes since cell suspensions from athymic nude mice deficient in T-cells responded as well as cells from conventional mice. Furthermore, passage of splenocytes over nylon wool columns to obtain B-cell-enriched preparations resulted in cell populations capable of responding to Legionella antigen. The cell fractions rich in T-cells were much less capable of responding to the Legionella antigens. In addition, treatment of spleen cell populations with antitheta serum plus complement failed to inhibit the blastogenic response, whereas the same spleen cell preparations treated with anti-mouse immunoglobulin serum plus complement markedly diminished blastogenic responsiveness, again consistent with the likelihood that B-lymphocytes were the major cell class responding to the Legionella preparations.


NURR1 involvement in recombinant tissue-type plasminogen activator treatment complications after ischemic stroke.
Despite the effectiveness of recombinant tissue-type plasminogen activator (r-tPA) during the acute phase of ischemic stroke, the therapy remains limited by a narrow time window and the occurrence of occasional vascular side effects, particularly symptomatic hemorrhages. Our aim was to investigate the mechanisms underlying the endothelial damage resulting from r-tPA treatment in ischemic-like conditions. Microarray analyses were performed on cerebral endothelial cells submitted to r-tPA treatment during oxygen and glucose deprivation to identify novel biomarker candidates. Validation was then performed in vivo in a mouse model of thromboembolic stroke and culminated in an analysis in a clinical cohort of patients with ischemic stroke treated with thrombolysis. The transcription factor NURR1 (NR4A2) was identified as a downstream target induced by r-tPA during oxygen and glucose deprivation. Silencing NURR1 expression reversed the endothelial-toxicity induced by the combined stimuli, a protective effect attributable to reduced levels of proinflammatory mediators, such as nuclear factor-kappa-beta 2 (NF-κ-B2), interleukin 1 alpha (IL1α), intercellular adhesion molecule 1 (ICAM1), SMAD family member 3 (SMAD3), colony stimulating factor 2 (granulocyte-macrophage; CSF2). The detrimental effect of delayed thrombolysis, in conditions in which NURR1 gene expression was enhanced, was confirmed in the preclinical stroke model. Finally, we determined that patients with stroke who had a symptomatic hemorrhagic transformation after r-tPA treatment exhibited higher baseline serum NURR1 levels than did patients with an asymptomatic or absence of cerebral bleedings. Our results suggest that NURR1 upregulation by r-tPA during ischemic stroke is associated with endothelial dysfunction and inflammation and the enhancement of hemorrhagic complications associated to thrombolysis.


Manganese in Drinking Water and Cognitive Abilities and Behavior at 10 Years of Age: A Prospective Cohort Study.
Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown. We prospectively evaluated the effects of W-Mn, from fetal life to school age, on children's cognitive abilities and behavior. We assessed cognitive abilities and behavior in 1,265 ten-year-old children in rural Bangladesh using the Wechsler Intelligence Scale for Children (WISC-IV) and the Strengths and Difficulties Questionnaire (SDQ), respectively. Manganese in drinking water used during pregnancy and by the children at 5 y and 10 y was measured using inductively coupled plasma mass spectrometry. The median W-Mn was 0.20 mg/L (range 0.001–6.6) during pregnancy and 0.34mg/L (<0.001–8.7) at 10 y. In multivariable-adjusted linear regression analyses, restricted to children with low arsenic (As) exposure, none of the W-Mn exposures was associated with the children's cognitive abilities. Stratifying by gender (p for interaction in general <0.081) showed that prenatal W-Mn (3 mg/L) was positively associated with cognitive ability measures in girls but not in boys. W-Mn at all time points was associated with an increased risk of conduct problems, particularly in boys (range 24–43% per mg/L). At the same time, the prenatal W-Mn was associated with a decreased risk of emotional problems [odds ratio (OR)=0.39 (95% CI: 0.19, 0.82)] in boys. In girls, W-Mn was mainly associated with low prosocial scores [prenatal W-Mn: OR=1.48 (95% CI: 1.06, 1.88)]. Elevated prenatal W-Mn exposure was positively associated with cognitive function in girls, whereas boys appeared to be unaffected. Early life W-Mn exposure appeared to adversely affect children's behavior. https://doi.org/10.1289/EHP631.


Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma.
Intrinsic asthma is characterized by an increased number of activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchial mucosa. This study was carried out to investigate the expression of alpha GM-CSF receptor (alpha GM-CSFr) messenger RNA and protein in the bronchial mucosa of patients with intrinsic or atopic asthma and of control subjects and to correlate the expression of alpha GM-CSFr to the number of EG2+ cells (eosinophils) and CD68+ cells (macrophages) and pulmonary function. Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic subjects) were recruited, and FEV1 (percent predicted) and PC20 were measured before bronchoscopy. Endobronchial biopsy specimens were obtained and examined for membrane-bound alpha GM-CSFr by using in situ hybridization and immunocytochemistry. alpha GM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens from all four groups studied. There was no significant difference in the number of cells expressing alpha GM-CSFr mRNA and protein in patients with atopic asthma compared with atopic and nonatopic control subjects. However, the numbers of alpha GM-CSFr mRNA- and protein-positive cells were significantly higher in nonatopic patients with asthma compared with atopic patients with asthma and atopic and nonatopic control subjects (p < 0.001). In the patients with intrinsic asthma, the number of alpha GM-CSFr mRNA-positive cells per millimeter of basement membrane correlated with numbers of CD68+ cells (r2 = 0.87, p < 0.001) but not with EG2+ cells, and colocalization studies demonstrated that 80% of the cells expressing alpha GMCSFr mRNA were CD68+. The expression of GM-CSF was also significantly increased in patients with intrinsic asthma compared with those with atopic asthma and control subjects (p < 0.05). In addition, in intrinsic asthma, there was a correlation between alpha GM-CSFr mRNA and FEV1 (r2 = 0.61, p < 0.05). These results demonstrate that elevated numbers of cells expressing alpha GM-CSFr can be detected in nonatopic asthma but not in atopic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma.


Myofibroblast-Mediated Contraction.
Myofibroblast-mediated contraction is viewed as a cycle of four steps. The first step is stimulation of myofibroblasts by lysophospholipids leading to the activation of G proteins and ending with contraction of the actin-myosin complex. The next step is the transmission of the intracellular contractile force at the focal adhesions of myofibroblasts; a step that involves talin, vinculin, paxillin, Hic-5, and the integrin receptors. In the third step, fibronectin will act as the extracellular link between the integrin receptors and the extracellular collagen. Finally, "sensing" tension and the maintenance of myofibroblast activity represent the fourth step. The clinical relevance of each step is then discussed in the form of modalities to prevent excessive scarring/fibrosis.


A Review of the Design and Performance of Catalysts for Hydrothermal Gasification of Biomass to Produce Hydrogen-Rich Gas Fuel.
Supercritical water gasification has emerged as a promising technology to sustainably convert waste residues into clean gaseous fuels rich in combustible gases such as hydrogen and methane. The composition and yield of gases from hydrothermal gasification depend on process conditions such as temperature, pressure, reaction time, feedstock concentration, and reactor geometry. However, catalysts also play a vital role in enhancing the gasification reactions and selectively altering the composition of gas products. Catalysts can also enhance hydrothermal reforming and cracking of biomass to achieve desired gas yields at moderate temperatures, thereby reducing the energy input of the hydrothermal gasification process. However, due to the complex hydrodynamics of supercritical water, the literature is limited regarding the synthesis, application, and performance of catalysts used in hydrothermal gasification. Hence, this review provides a detailed discussion of different heterogeneous catalysts (e.g., metal oxides and transition metals), homogeneous catalysts (e.g., hydroxides and carbonates), and novel carbonaceous catalysts deployed in hydrothermal gasification. The article also summarizes the advantages, disadvantages, and performance of these catalysts in accelerating specific reactions during hydrothermal gasification of biomass, such as water-gas shift, methanation, hydrogenation, reforming, hydrolysis, cracking, bond cleavage, and depolymerization. Different reaction mechanisms involving a variety of catalysts during the hydrothermal gasification of biomass are outlined. The article also highlights recent advancements with recommendations for catalytic supercritical water gasification of biomass and its model compounds, and it evaluates process viability and feasibility for commercialization.


Effect of catheter ablation on the left ventricular mass index and other echocardiograph parameters in atrial fibrillation patients: comparison with antiarrhythmic drug treatment.
Catheter ablation (CA) is reported to improve left ventricular (LV) function in patients with atrial fibrillation (AF). This study compared the effects of CA and antiarrhythmic drug treatment (AT) on LV remodeling and other echocardiography parameters in AF. We performed a non-randomized prospective study involving 72 drug-resistant AF patients who were treated with either CA (n = 42) or who declined CA and continued on AT (n = 30). Baseline and follow-up (mean 20.7 ± 7.5 months) echocardiography was performed in all patients. The maintenance of sinus rhythm was determined based on clinical interview, electrocardiography, and 24-h Holter and event recording. There were no significant differences between the two groups in regard to demographic features, blood pressure, and medication. CA was superior to AT with respect to sinus rhythm maintenance, LV ejection fraction, left atrium (LA) diameter, and LA volume index. In addition, CA resulted in decreases in the LV mass [from 190.5 ± 36.1 to 179.3 ± 32.4 g (p = 0.02)] and the LV mass index [from 104.2 ± 20.5 to 98.2 ± 18.3 g/m(2) (p = 0.03)]. No parameter improved in AT patients. These improved echocardiographic parameters were observed in both groups with maintained sinus rhythm. Reverse LV remodeling after CA may include a reduction in the LV mass index, which appears to be associated with sinus rhythm maintenance.


First principles reaction discovery: from the Schrodinger equation to experimental prediction for methane pyrolysis.
Our recent success in exploiting graphical processing units (GPUs) to accelerate quantum chemistry computations led to the development of the ab initio nanoreactor, a computational framework for automatic reaction discovery and kinetic model construction. In this work, we apply the ab initio nanoreactor to methane pyrolysis, from automatic reaction discovery to path refinement and kinetic modeling. Elementary reactions occurring during methane pyrolysis are revealed using GPU-accelerated ab initio molecular dynamics simulations. Subsequently, these reaction paths are refined at a higher level of theory with optimized reactant, product, and transition state geometries. Reaction rate coefficients are calculated by transition state theory based on the optimized reaction paths. The discovered reactions lead to a kinetic model with 53 species and 134 reactions, which is validated against experimental data and simulations using literature kinetic models. We highlight the advantage of leveraging local brute force and Monte Carlo sensitivity analysis approaches for efficient identification of important reactions. Both sensitivity approaches can further improve the accuracy of the methane pyrolysis kinetic model. The results in this work demonstrate the power of the ab initio nanoreactor framework for computationally affordable systematic reaction discovery and accurate kinetic modeling.


ILAE/IBE/WHO Global Campaign Against Epilepsy: a partnership that works.
Epilepsy can hijack the lives of many persons of all ages. It is an unpredictable disease that can manifest itself in seizures, brain damage and cognitive and psychiatric disabilities, although some people with epilepsy can have a relatively normal life. People with epilepsy are among the most vulnerable in any society because the disease is misunderstood and often stigmatizing. Thus, many patients and their families are reluctant to admit that they suffer from epilepsy. This in turn affects public policy in terms of patient care, early diagnosis, medical research, advocacy, cure and their very lives. A survey to evaluate the results of Global Campaign Against Epilepsy activities on a national level was performed in 2009. Data from the demonstration projects have already changed the public policies in several countries. On the occasion of the launch of phase II of the Campaign, the WHO Director General stated: 'The collaboration between the IBE, ILAE and WHO has shown that when people with different backgrounds and roles come together with a shared purpose, creativity is released and expertise is used in innovative and constructive ways'. Indeed, this partnership led to many activities and all over the world to many people 'standing up for epilepsy'.


What is new in mediastinal staging?
Appropriate staging is of utmost importance in nonsmall cell lung cancer (NSCLC), as the pathologic stage dictates both overall prognosis and appropriate therapeutic pathways. This article seeks to review the current recommendations for mediastinal staging of NSCLC and available modalities to achieve this. Landmark publications pertaining to recent advancements in NSCLC treatments are also highlighted and the role of specific bronchoscopic modalities for tissue acquisition are reviewed. Recent advancements in the treatment of NSCLC have made accurate mediastinal staging more important than ever. Guidelines and recommendations outlining patients that warrant invasive mediastinal staging are available and a systematic approach should be utilized when sampling is performed. Ensuring the adequacy of tissue for the growing number of molecular biomarkers that must be tested has been the focus of many recent studies. Appropriate mediastinal staging is crucial for the management of patients with NSCLC as is obtaining adequate tissue for diagnostic and therapeutic purposes. EBUS-TBNA is sufficient for the diagnosis of nonsmall cell and small cell lung carcinomas, but EBUS-guided intranodal forceps and cryobiopsy may provide more optimal specimen for patients with benign disease, such as sarcoidosis, or in cases of lymphoma. Further studies are necessary to better delineate the role of these techniques in the diagnosis and staging of mediastinal diseases before they become the primary diagnostic modalities.


Modulation of parkinsonian tremor by radial nerve palsy.
We analyzed rest and postural hand tremors in a Parkinson's disease patient who developed and recovered from a right radial nerve palsy at the spiral groove, and found that, despite complete paralysis of all extensors below the elbow, tremor frequencies remained unchanged while tremor amplitudes actually increased. This provides compelling evidence for a central generation of parkinsonian tremor frequency that is not influenced by the effects of peripheral modulation. In addition, the increase in tremor amplitudes may be due to disinhibited flexor activity caused by normally operating spinal segmental mechanisms interacting with central tremor generators programmed to alternate between antagonist muscles. Peripheral treatment of tremors--with muscle paralysis or botulinum toxin, for example--therefore may not be effective in stopping tremor oscillations in Parkinson's disease and may even worsen tremor amplitudes if all antagonists of a tremoring joint are not treated equally.


Healthcare waste management in Asian developing countries: A mini review.
Healthcare waste encompasses a significant quantity of hazardous substances. Poor healthcare waste management can result in serious environmental and human health risks. Asian developing countries are densely populated, and some are highly resource constrained. These countries commonly fail to practice appropriate healthcare waste management. Moreover, facilities in these countries extensively lack proper waste segregation, collection, safe storage, transportation, and disposal. This mini-review recapitulates key issues of healthcare waste management confronting Asian developing countries. Regulations, legislation, and policies are found to be recent, and their implementation varies from one another. Variation in waste generation rate is common. Contradictory methods of waste measurement used by researchers leave these variations questionable. The absence of waste management training programmes roots ignorance among staff and handlers, which leads to unsafe waste handling and causes different health risks. Unsafe and illegal recycling of hazardous waste is a threat to human health, also landfilling is often confused with open dumping, causing environmental damage. Outdated incineration plants need to be replaced with autoclaving, steam sterilisation, and comparatively reasonable new practice of pyrolysis to avoid the emission of toxic gases. The significance of proper healthcare waste management cannot be ignored, especially in Asian developing countries; substantial improvements are required in order to protect the environment and human health from serious risks.


Successful treatment of multiple relapsed-refractory Langerhans cell histiocytosis with cyclosporine.
Langerhans cell histiocytosis is a rare hematologic disorder and patients who fail first-line treatment have a poor prognosis, and require more intensive treatment. We present an infant diagnosed with multisystem Langerhans cell histiocytosis refractory to multimodal therapy who was successfully treated with cyclosporine. Cyclosporine might be an effective alternative drug as nonmyelosuppressive rescue therapy for multiple relapsed-refractory Langerhans cell histiocytosis that has not achieved remission with cladribine and cytarabine therapy.


Dexmedetomidine reduces enteric glial cell injury induced by intestinal ischaemia-reperfusion injury through mitochondrial localization of TERT.
This study was performed to uncover the effects of dexmedetomidine on oxidative stress injury induced by mitochondrial localization of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) following intestinal ischaemia-reperfusion injury (IRI) in rat models. Following establishment of intestinal IRI models by superior mesenteric artery occlusion in Wistar rats, the expression and distribution patterns of TERT were detected. The IRI rats were subsequently treated with low or high doses of dexmedetomidine, followed by detection of ROS, MDA and GSH levels. Calcein cobalt and rhodamine 123 staining were also carried out to detect mitochondrial permeability transition pore (MPTP) and the mitochondrial membrane potential (MMP), respectively. Moreover, oxidative injury of mtDNA was determined, in addition to analyses of EGC viability and apoptosis. Intestinal tissues and mitochondria of EGCs were badly damaged in the intestinal IRI group. In addition, there was a reduction in mitochondrial localization of TERT, oxidative stress, whilst apoptosis of EGCs was increased and proliferation was decreased. On the other hand, administration of dexmedetomidine was associated with promotion of mitochondrial localization of TERT, whilst oxidative stress, MPTP and mtDNA in EGCs, and EGC apoptosis were all inhibited, and the MMP and EGC viability were both increased. A positive correlation was observed between different doses of dexmedetomidine and protective effects. Collectively, our findings highlighted the antioxidative effects of dexmedetomidine on EGCs following intestinal IRI, as dexmedetomidine alleviated mitochondrial damage by enhancing the mitochondrial localization of TERT.


Clinical characteristics and ABO blood groups in COVID-19 patients, Saudi Arabia.
This study assessed the proportion of ABO blood groups and clinical characteristics among Saudi patients with coronavirus disease 2019 (COVID-19) in Jazan, Saudi Arabia.This retrospective cohort study included 404 Saudi adults with COVID-19, confirmed by the real-time reverse transcription-polymerase chain reaction. The participants were selected randomly between July 1, 2020, and July 31, 2020, from the Health Electronic Surveillance Network system, which contains the primary data on COVID-19 infections in Jazan.Blood type O (62.4%) represented the highest proportion in COVID-19 Saudi patients followed by the other blood groups which distributed as follows: blood type A (25.5%), blood type B (10.1%), and blood type AB (2%). Men, and people aged 18-44 years, represented the higher percentage than women and those of a younger age. The majority of the patients with COVID-19 had clinical symptoms (88.4%), and the remainder (11.6%) were asymptomatic. Ninety four percent of the patients had mild COVID-19 symptoms and self-isolated at home. Only 6.4% of the cases were severe and admitted to hospital. There was no significant association between a specific ABO blood group and COVID-19 clinical symptoms (P = .950), incubation period (P = .780), disease duration (P = .430), and disease severity (P = .340). Old age and diabetes were the significant predictors of COVID-19 severity and hospital admission (P = .010).Blood group O represented the highest proportion of COVID-19 Saudi patients as it is the most common blood group in Saudi individuals in Jazan. However, no specific blood group was associated with COVID-19 severity and hospital admission. Old age and diabetes mellitus were shown to be significant predictors of severe COVID-19 and hospital admission.


Identifying the Genes Responsible for Iron-Limited Condition in Riemerella anatipestifer CH-1 through RNA-Seq-Based Analysis.
One of the important elements for most bacterial growth is iron, the bioavailability of which is limited in hosts. Riemerella anatipestifer (R. anatipestifer, RA), an important duck pathogen, requires iron to live. However, the genes involved in iron metabolism and the mechanisms of iron transport are largely unknown. Here, we investigated the transcriptomic effects of iron limitation condition on R. anatipestifer CH-1 using the RNA-Seq and RNA-Seq-based analysis. Data analysis revealed genes encoding functions related to iron homeostasis, including a number of putative TonB-dependent receptor systems, a HmuY-like protein-dependent hemin (an iron-containing porphyrin) uptake system, a Feo system, a gene cluster related to starch utilization, and genes encoding hypothetical proteins that were significantly upregulated in response to iron limitation. Compared to the number of upregulated genes, more genes were significantly downregulated in response to iron limitation. The downregulated genes mainly encoded a number of outer membrane receptors, DNA-binding proteins, phage-related proteins, and many hypothetical proteins. This information suggested that RNA-Seq-based analysis in iron-limited medium is an effective and fast method for identifying genes involved in iron uptake in R. anatipestifer CH-1.


5-hydroxydopa, a new compound in the Raper-Mason scheme of melanogenesis.
Oxidation of tyrosine or dopa by tyrosinase leads to the formation of 5-OH-dopa, a compound previously unknown in melanogenesis. 5-OH-dopa, first detected as an unknown compound on HPLC of the dopa-tyrosinase incubate, was purified by Al2O3-adsorption, semipreparative HPLC, and ion-exchange chromatography. 5-OH-dopa was identified by comparison with the authentic compound in several chromatographic systems, by electrochemical oxidation studies and by mass spectrometry.


Stressful life events and major depressive disorders.
This study examined the relationship between stressful life events (SLE) and recurrent major depressive disorders. Three groups of 50 subjects were assessed: Patients with recurrent major depressive disorder with melancholic features; patients with borderline personality disorder; and healthy controls. Interviews for AXIS I and II DSM-IV Disorders were used for diagnosis. The Israel Psychiatric Epidemiology Research Interview Life Event Scale and the Coddington Life Events Schedule were used to measure life events and were confirmed with an interview. Beck Depression Inventory was also administered. The proportions of loss-related events in childhood and in the year preceding the first episode were higher in the depressed group than in the control groups during the same time period. Proportions of SLE, uncontrolled and independent events were also more common in the depressed patients in the year preceding the first episode. No category of SLE differentiated the groups following the first depressive episode. The study's conclusion is that SLE play an important role in the onset of depressive disorders. There are specific kinds of SLE that occur in childhood and in the year preceding the first episode. SLE has a less significant role in the maintenance of this illness.


Typical state of an isolated quantum system with fixed energy and unrestricted participation of eigenstates.
This work describes the statistics for the occupation numbers of quantum levels in a large isolated quantum system, where all possible superpositions of eigenstates are allowed provided all these superpositions have the same fixed energy. Such a condition is not equivalent to the conventional microcanonical condition because the latter limits the participating eigenstates to a very narrow energy window. The statistics is obtained analytically for both the entire system and its small subsystem. In a significant departure from the Boltzmann-Gibbs statistics, the average occupation numbers of quantum states exhibit in the present case weak algebraic dependence on energy. In the macroscopic limit, this dependence is routinely accompanied by the condensation into the lowest-energy quantum state. This work contains initial numerical tests of the above statistics for finite systems and also reports the following numerical finding: when the basis states of large but finite random matrix Hamiltonians are expanded in terms of eigenstates, the participation of eigenstates in such an expansion obeys the newly obtained statistics. The above statistics might be observable in small quantum systems, but for the macroscopic systems, it rather re-enforces doubts about self-sufficiency of nonrelativistic quantum mechanics for justifying the Boltzmann-Gibbs equilibrium.


Down-regulation of systemin after herbivory is associated with increased root allocation and competitive ability in Solanum nigrum.
After simulated herbivory, inflicted by a treatment involving wounding and the application of Manduca sexta oral secretions (OS) to mechanical wounds (OS-elicitation), transcripts of the systemin-precursor, prosystemin, are down-regulated in black nightshade (Solanum nigrum). Since S. nigrum silenced in prosystemin expression (IRSys) has unaltered herbivore resistance but produced more above-ground biomass and berries than did wild-type (WT) competitors in a pilot experiment, we examine the hypothesis that systemin helps the plant to tolerate rather than resist folivory. When plants competed, IRSys plants produced significantly more berries than did WTs. Berry production of OS-elicited and unelicited WTs did not differ, but OS-elicited WTs that were additionally treated with systemin (systemin-augmented OS-elicited WTs) produced fewer berries than did unelicited WT competitors. When root-competition was prevented by a barrier, no differences in berry production were found. Growth experiments revealed that OS-elicited WTs and IRSys plants produced more roots than did untreated WTs, whereas systemin-augmented OS-elicited WTs did not. Microarray analyses of leaves revealed that fitness differences were associated with the transcriptional regulation of sugar and spermine metabolism. We propose that down-regulation of systemin after herbivory is associated with increased root allocation which allows plants to more effectively compete with conspecifics and may allow plants to compensate for tissue losses during herbivory.


[Immunopathological mechanism of spleen damage in acute disseminated MCMV infection].
To explore the immunopathological mechanism of spleen damage in acute disseminated infection of murine cytomegalovirus (MCMV) in vivo by observing the association of virus titers and the expressions of caspase-1 and pro-inflammatory factors (IL-1β and IL-18) with the degree of pathological damage of the spleen. BALB/c mice (n=24) were randomly divided into 2 groups (n=12 per group), experimental group and control group. The control mice were sham-infected. The experimental mice were infected with MCMV Smith for establishing the models of acute disseminated MCMV infection. Three mice of each group were randomly chosen to be killed on day 3, 7, 14 and 28 after infection, respectively. Viral titers in the spleen tissues were determined using a standard plaque assay; the expression of caspase-1 in the splenocytes was detected by Western blot; the expressions of IL-1β and IL-18 in the spleen tissues were observed by immunohistochemical staining; the degree of spleen histological damage was observed by HE staining and graded by a semiquantitative method. Viral titers in the spleen peaked on day 3, but quickly diminished on day 7 and virus was not detected in the spleen on day 14 after infection. Compared with the normal control group, the protein levels of caspase-1 in MCMV-infected mice were markedly elevated on day 3 (P<0.01), and then dropped slowly; the expressions of IL-1β and IL-18 in the spleen tissues gradually increased to the climax on day 7, then decreased on day 14 and turned to the normal on day 28. However, the pathological condition of the spleen in infected mice deteriorated gradually until day 14, and then showed obviously the signs of recovery on day 28. The spleen damage was aggravated following the elevation of IL-1β and IL-18 expressions and alleviated after they declined. MCMV infection would stimulate the increase of caspase-1 expression and the production of pro-inflammatory factors (IL-1β and IL-18). IL-1β and IL-18 not only exert antiviral effect, but also might be involved in the immunopathological injury of spleen tissue during the acute disseminated MCMV infection.


[Hyperactivity and prescription of Ritalin in the canton of Vaud (Switzerland), 2002].
The estimated prevalence of Attention Deficit Hyperactivity Disorder (ADHD) reported in European countries is 2 to 5% of school age children. Political concern has been expressed in Switzerland about possible over treatment with methylphenidate. The purpose of this research, commissioned by the regional public health authority, was to assess the prescription of methylphenidate (Ritalin) for children as a treatment of ADHD. The regional health authority collected all prescriptions of Ritalin delivered in pharmacies during 2002. Data available from prescriptions and analyzed were: age, sex and place of residence of the patient, dosage prescribed, date of prescription, place of practice and medical specialization of doctors. Only patients living in the canton of Vaud and aged less than 20 years were included in the analysis. Six hundred and ninety-seven patients, aged less than 20 years, received Ritalin in 2002. The mean age was 12.1 years (median: 12 years; range: 3-19), 15% were female. These patients represented 0.74% of the 5-14 years old population living in the canton of Vaud. Eighty percent of patients had a prescription from a specialist (pediatrician or psychiatrist) during the year. Less than 1% of the young population receives methylphenidate in the canton of Vaud. Dosage complies with the recommendations of the Swiss Medic Compendium. The large majority of patients receive prescriptions for methylphenidate from specialists. A new study based on the 2005 data will be conducted to follow changes in the prescription of Ritalin.


Combination of MD Simulations with Two-State Kinetic Rate Modeling Elucidates the Chain Melting Transition of Phospholipid Bilayers for Different Hydration Levels.
The phase behavior of membrane lipids plays an important role in the formation of functional domains in biological membranes and crucially affects molecular transport through lipid layers, for instance, in the skin. We investigate the thermotropic chain melting transition from the ordered Lβ phase to the disordered Lα phase in membranes composed of dipalmitoylphosphatidylcholine (DPPC) by atomistic molecular dynamics simulations in which the membranes are subject to variable heating rates. We find that the transition is initiated by a localized nucleus and followed by the propagation of the phase boundary. A two-state kinetic rate model allows characterizing the transition state in terms of thermodynamic quantities such as transition state enthalpy and entropy. The extrapolated equilibrium melting temperature increases with reduced membrane hydration and thus in tendency reproduces the experimentally observed dependence on dehydrating osmotic stress.


FYCO1: linking autophagosomes to microtubule plus end-directing molecular motors.
In mammalian cells, autophagosomes are transported along microtubule tracks to fuse with late endosomes or lysosomes. Autophagosomal membranes harbor the lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) and phosphatidylethanolamine-conjugated ATG8/LC3/GABARAP family proteins. The small GTPase Rab7 is implicated in autophagosomal transport and fusion. We have recently reported that a previously uncharacterized protein FYVE and coiled-coil domain-containing 1 (FYCO1) functions as an adapter linking autophagosomes to microtubule plus end-directed molecular motors. FYCO1 binds to both LC3, PtdIns(3)P and Rab7, and contains a domain responsible for microtubule plus end-dependent transport. When cells are depleted for FYCO1, autophagosomes accumulate in perinuclear clusters, whereas overexpression of FYCO1 redistributes Rab7-positive vesicles to microtubule plus ends at the cell periphery. FYCO1 is likely selectively recruited to autophagosomal membranes via a mechanism involving a conformational change upon LC3-LIR interaction to expose the FYVE domain for PtdIns(3)P binding.


Stanniocalcin 2 is a negative modulator of store-operated calcium entry.
The regulation of cellular Ca(2+) homeostasis is essential for innumerable physiological and pathological processes. Stanniocalcin 1, a secreted glycoprotein hormone originally described in fish, is a well-established endocrine regulator of gill Ca(2+) uptake during hypercalcemia. While there are two mammalian Stanniocalcin homologs (STC1 and STC2), their precise molecular functions remain unknown. Notably, STC2 is a prosurvival component of the unfolded protein response. Here, we demonstrate a cell-intrinsic role for STC2 in the regulation of store-operated Ca(2+) entry (SOCE). Fibroblasts cultured from Stc2 knockout mice accumulate higher levels of cytosolic Ca(2+) following endoplasmic reticulum (ER) Ca(2+) store depletion, specifically due to an increase in extracellular Ca(2+) influx through store-operated Ca(2+) channels (SOC). The knockdown of STC2 expression in a hippocampal cell line also potentiates SOCE, and the overexpression of STC2 attenuates SOCE. Moreover, STC2 interacts with the ER Ca(2+) sensor STIM1, which activates SOCs following ER store depletion. These results define a novel molecular function for STC2 as a negative modulator of SOCE and provide the first direct evidence for the regulation of Ca(2+) homeostasis by mammalian STC2. Furthermore, our findings implicate the modulation of SOCE through STC2 expression as one of the prosurvival measures of the unfolded protein response.


Genome-Wide Association Study of Muscle Glycogen in Jingxing Yellow Chicken.
Glucose metabolism plays an important role in many normal and pathological physiological processes in the body. The breakdown and synthesis of muscle glycogen provides ATP for muscle activities. A genome-wide association study for muscle glycogen was performed in 473 Jingxing yellow chickens to identify significant single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs) involved in muscle glycogen metabolism. A total of nine SNPs (p < 1/699341) and three INDELs (p < 1/755733) reached a significant level of potential association. The following results were obtained through a series of analyses, including additive effects and gene function annotation. Two significant SNPs were found in introns 12 and 13 of copine 4 (CPNE4) on chromosome 2. The wild-type and mutant individuals had significant differences in glycogen metabolism at two loci (p < 0.01 for both). Individuals carrying two mutations had increased muscle glycogen content. According to the gene annotation of chromosome 11, there is a significant INDEL in intron 6 of naked cuticle homolog 1 (NKD1). After the INDEL mutation, the glycogen content increased significantly. There was a significant difference between wild-type and mutant individuals (p < 0.01). These mutations likely affecting two genes (CPNE4 and NKD1) may affect glycogen storage in a pleiotropic manner. Gene annotation indicates that CPNE4 and NKD1 may affect the process of glucose metabolism. Our findings contribute to understanding the genetic regulation of muscle glycogen metabolism and provide theoretical support.


Partial distal pancreatectomy with a hand-held CO2 laser. An experimental study.
Partial distal pancreatectomy was performed in dogs with CO2 laser. Results were compared with those obtained with use of diathermy and scalpel. Postoperative hyperamylasemia appeared in all the animals. The highest peaks in the laser and scalpel groups were found on the fifth postoperative day, after which they gradually returned to normal; the highest levels appeared in the diathermy group on the 21st day, and returned to normal only after 56 days. Pancreatography showed a sealed duct in the laser and diathermy groups although no duct ligation was performed. Histological study of the laser group disclosed initial thermal injury at the cut section with no damage to the nearby parenchyma, followed later by a smooth, thin scar. In the diathermy and scalpel groups, the injured zone became enlarged later by active parenchymal and interlobular inflammation in the underlying tissue.


Ploidy-dependent growth and binucleation in cultured rat hepatocytes.
The proliferative activity of rat hepatocytes, cultured in the presence of epidermal growth factor (EGF) and insulin, was examined by immunostaining of S-phase cells labeled with bromodeoxyuridine (BrdU) in culture. Proliferation rates of the different hepatocellular ploidy and nuclearity classes were measured by fluorescence image cytometry or by microscope counting of immunostained cells. Effects of EGF and insulin were largely additive, the binuclear cells being more growth factor-dependent (showing less growth in the absence of factors) than the mononuclear cells. A serial warm-washing procedure was used to remove excess BrdU from the culture medium, allowing the study of hepatocellular binucleation by a BrdU pulse-chase approach. A high rate of binucleation was detected (50%, possibly suggesting a quantal mechanism), indicating that the hormones induce a binucleating (polyploidizing) type of growth similar to that normally observed in the liver of growing rats. The highest proliferative activity (labeling index) in the hepatocyte cultures was found among the diploid cells, independent of the degree of mitogenic stimulation. The labeling index was inversely correlated with ploidy, suggesting that the ability of hepatocytes to proliferate decreases with increasing polyploidization.


Metabotropic glutamate receptors differentially regulate GABAergic inhibition in thalamus.
Thalamic interneurons and thalamic reticular nucleus (TRN) neurons provide inhibitory innervation of thalamocortical cells that significantly influence thalamic gating. The local interneurons in the dorsal lateral geniculate nucleus (dLGN) give rise to two distinct synaptic outputs: classical axonal and dendrodendritic. Activation of metabotropic glutamate receptors (mGluRs) by agonists or optic tract stimulation increases the output of these presynaptic dendrites leading to increased inhibition of thalamocortical neurons. The present study was aimed to evaluate the actions of specific mGluRs on inhibitory GABA-mediated signaling. We found that the group I mGluR (mGluR(1,5)) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) or optic tract stimulation produced a robust increase in spontaneous IPSCs (sIPSCs) in thalamocortical neurons that was attenuated by the selective mGluR(5) antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). In contrast, the group II mGluR (mGluR(2,3)) agonists (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or (2S,2'R,3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV) suppressed the frequency of sIPSCs. In addition, mGluR(1,5) agonist DHPG produced depolarizations and mGluR(2/3) agonists APDC or L-CCG-I [(2S,1'S,2'S)-2-(carboxycyclopropyl)glycine] produced hyperpolarizations in dLGN interneurons. Furthermore, the enhanced sIPSC activity by optic tract stimulation was reduced when paired with corticothalamic fiber stimulation. The present data indicate that activation of specific mGluR subtypes differentially regulates inhibitory activity via different synaptic pathways. Our results suggest that activation of specific mGluR subtypes can upregulate or downregulate inhibitory activity in thalamic relay neurons, and these actions likely shape excitatory synaptic integration and thus regulate information transfer through thalamocortical circuits.


Mast cells impair the development of protective anti-tumor immunity.
Mast cells have emerged as critical intermediaries in the regulation of peripheral tolerance. Their presence in many precancerous lesions and tumors is associated with a poor prognosis, suggesting mast cells may promote an immunosuppressive tumor microenvironment and impede the development of protective anti-tumor immunity. The studies presented herein investigate how mast cells influence tumor-specific T cell responses. Male MB49 tumor cells, expressing HY antigens, induce anti-tumor IFN-γ(+) T cell responses in female mice. However, normal female mice cannot control progressive MB49 tumor growth. In contrast, mast cell-deficient c-Kit(Wsh) (W(sh)) female mice controlled tumor growth and exhibited enhanced survival. The role of mast cells in curtailing the development of protective immunity was shown by increased mortality in mast cell-reconstituted W(sh) mice with tumors. Confirmation of enhanced immunity in female W(sh) mice was provided by (1) higher frequency of tumor-specific IFN-γ(+) CD8(+) T cells in tumor-draining lymph nodes compared with WT females and (2) significantly increased ratios of intratumoral CD4(+) and CD8(+) T effector cells relative to tumor cells in W(sh) mice compared to WT. These studies are the first to reveal that mast cells impair both regional adaptive immune responses and responses within the tumor microenvironment to diminish protective anti-tumor immunity.


Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro.
Replication of mixtures of two or more human immunodeficiency virus type 1 (HIV-1) variants would be expected to result in the eventual selection of the fittest virus due to Darwinian competition among the variants. The relative proportions of known HIV-1 variants (which may differ only by a single nucleotide from a standard "wild-type" virus, HIV-1HXB2) in mixed viral cultures were quantified by analysis of automated sequence signals of reverse transcriptase PCR products. With this method, the relative levels of replicative fitness of several zidovudine (3'-azidothymidine)-resistant HIV-1HXB2 variants were estimated under controlled in vitro conditions by measuring the rate of change in the proportions of viral variants as they replicated in cell cultures both in the presence and in the absence of drug selection pressure. These variants were engineered to contain commonly observed zidovudine resistance mutations in the HIV-1 reverse transcriptase (M41L, K70R, T215Y, and M41L+T215Y). In the absence of zidovudine, all variants tested displayed reduced replicative fitness compared to wild-type HIV-1HXB2. The order of relative fitness was wild type > K70R >> T215Y = M41L+T215Y > M41L. Mixed cultures in the presence of zidovudine showed a dose-dependent selection pressure against the wild-type virus which varied according to the resistance profile of each virus. The information gathered from this approach provides insight into competition among multiple HIV-1 variants, which likely occurs in vivo with drug selection pressure, and may be applicable in more complex mathematical models for predicting the emergence of HIV-1 variants after the initiation of antiretroviral therapy.


Nine years' experience of needle localized breast biopsy in a university hospital: results and evaluation of the role of the surgeon in decision making.
Needle localized breast biopsy is an effective means of detecting breast cancer in its early stages. We analysed the indications for needle localized biopsies, evaluated the results, and determined the surgeon's role in the decision-making process. The needle localized open biopsy results of 350 patients were assessed. Malignancy was encountered in 7 of 56 patients in whom the radiologist suggested follow-up due to mammographical images, although a surgeon performed a biopsy with the assessment of the patient's historical and clinical findings (12.5%). Biopsy failure rates were higher for office-based ambulatory patients (9.1%) than for those patients who underwent biopsies in an operating theatre (1.9%; P < .05). Patients undergoing operating theatre biopsies under local anaesthesia showed statistically significant failure rates compared with those under general anaesthesia (p = .04). The rate of malignancy of micro-calcification was highest in patients younger than 40 years of age (64.3%), while spicular lesions were commonly malignant in patients over 50 years of age. From our experience, we suggest that needle localized biopsies should be performed in the operating theatre with the patient under general anaesthesia. Although both micro-calcifications and spicular lesions have a high rate of malignancy in all decades, micro-calcifications are more prevalent in younger patients while spicular lesions prevail in older patients. The final decision, to follow-up or biopsy, should be based on a patient's clinical and historical perspective and not only on the guidance of the mammography report.


Tioman virus, a paramyxovirus of bat origin, causes mild disease in pigs and has a predilection for lymphoid tissues.
Disease manifestation, pathology, and tissue tropism following infection with Tioman virus (TioPV), a newly isolated, bat-derived paramyxovirus, was investigated in subcutaneously (n = 12) and oronasally (n = 4) inoculated pigs. Pigs were either asymptomatic or developed pyrexia, but all of the animals produced neutralizing antibodies. The virus (viral antigen and/or genome) was detected in lymphocytes of the thymus, tonsils, spleen, lymph nodes and Peyer's patches (ileum), tonsillar epithelium, and thymic epithelioreticular cells. Virus was isolated from oral swabs but not from urine. Our findings suggest that the pig could act as an intermediate or amplifying host for TioPV and that oral secretion is a possible means of viral transmission.


The aquiferous systems of three marine demospongiae.
The aquiferous systems of three common, coastal, marine Demospongiae, Halichondria panicea (Pallas), Haliclona permollis (Bowerbank) and Microciona Prolifera (Ellis and Solander), are analyzed by measurements of cross-sectional areas of conducting elements. The patterns in demosponges of extremely different organizational morphologies are found to be quantitatively similar. The porocyte nature of the ostia is established for all three species. Choanocyte chamber densities range from 1 to 1.8 × 107 chambers ml-1 with 57 to 95 choanocytes per chamber (means). Cross-sectional area of the intervillar space of the choanocyte collars is calculated to be 12 to 56 times the lateral surface area of the specimen. Velocities of water movement through specific elements of the aquiferous system are calculated from cross-sectional area data and measured oscular flow of Haliclona permollis. The calculated Reynolds numbers lie below the critical value and fluid flow is thus considered laminar throughout the aquiferous systems of these sponges.


Development, validation and field application of an RNA-based growth index in juvenile plaice Pleuronectes platessa.
A general mechanism relating RNA concentration and growth rate is derived from four physiological assumptions and developed into a growth index for juvenile plaice Pleuronectes platessa. The index describing instantaneous growth rates (G, day⁻¹) in the laboratory with the lowest Akaike information criterion with small-sample bias adjustment was a function of RNA concentration (R, g(RNA)g⁻¹(wet mass)), temperature (T, ° K), body mass (M, g) and DNA concentration (D, g(DNA)g⁻¹(wet mass)): G = β₀ + β(R) R + β(T)T + β(T2)T² + β(M)M + β(D)D + β(RT)RT. RNA concentration began to respond to changes in feeding conditions within 8 days, suggesting that the index reflects growth rate in the short-term. Furthermore, the index distinguished between rapid growth and negative growth of juvenile P. platessa measured directly in laboratory and field enclosures, respectively. An application of the RNA-based growth index at two beaches on the west coast of Scotland suggested that the growth of juvenile P. platessa varies considerably in space and time and is submaximum in late summer.


Interactions of alkaline phosphatase and the cell wall of Pseudomonas aeruginosa.
Spheroplasts prepared by lysozyme treatment of cells of Pseudomonas aeruginosa, suspended in 20% sucrose or 0.2 m MgCl(2), were examined in detail. Preparation of spheroplasts in the presence of 0.2 m Mg(2+) released periplasmic alkaline phosphatase, whereas preparation in the presence of 20% sucrose did not, even though untreated cells released phosphatase when suspended in sucrose in the absence of lysozyme. Biochemical characterizations of the sucrose-lysozyme preparations indicated that lysozyme mediated a reassociation of the released phosphatase with the spheroplasts. In addition, the enzyme released from whole cells suspended in 20% sucrose (which represents 20 to 40% of the cell-bound phosphatase) reassociates with the cells in the presence of lysozyme. Electron microscopic examinations of various preparations revealed that phosphatase released in sucrose reassociated with the external cell wall layers in the presence of lysozyme, that sucrose-lysozyme prepared spheroplasts did not dissociate phosphatase which remained in the periplasm of sucrose-washed cells, and that phosphatase was never observed to be associated with the cytoplasmic membrane. A model to account for the binding of P. aeruginosa alkaline phosphatase to the internal portion of the tripartite layer of the cell wall rather than to the cytoplasmic membrane or peptidoglycan layer is presented.


Adaptive phase calibration of a microphone array for acoustic holography.
Previous work has indicated that a limitation on the performance of a circular microphone array for holographic sound field recording at low frequencies is phase mismatch between the microphones in the array. At low frequencies these variations become more significant than at mid-range and high frequencies because the high order phase mode responses at low frequencies are lower in amplitude. This paper demonstrates the feasibility of a "self-calibration" method. The basis of the calibration is to estimate the location of one or more wide-band sources using mid-range frequencies and to use this source location information to perform correction to the array at low frequencies. In its simplest form the calibration must be performed in an anechoic environment, since multipath effects at widely differing frequencies are uncorrelated. The approach is first demonstrated in such an environment using recordings from an array of high quality microphones. The technique is then extended to an adaptive calibration that can be used in an environment that is somewhat reverberant. The validity of the adaptive approach is demonstrated using recordings from an array of inexpensive microphones.


Cryptic species diversity in the Hypsolebiasmagnificus complex, a clade of endangered seasonal killifishes from the São Francisco River basin, Brazilian Caatinga (Cyprinodontiformes, Aplocheilidae).
A great diversity of animal species adapted to life in the semi-arid Caatinga of northeastern Brazil, including seasonal killifishes, has been reported in the last three decades. More recently, field and molecular data have shown a high occurrence of cryptic species. The killifish group herein analysed, the Hypsolebiasmagnificus species complex, is endemic to the middle and southern portion of the Caatinga, occupying about 120 km along the floodplains of the middle São Francisco River and some adjacent tributaries. Species of this complex are rare and presently considered threatened with extinction, being uniquely found in pools protected by trees and bushes. Single-locus delimitation methods were used to test species limits of populations displaying different colour patterns along the whole distribution of the complex. All analyses consistently supported the three nominal species and two new, herein described: H.gardneri Costa, sp. n., from the floodplains of the middle São Francisco River and H.hamadryades Costa, sp. n., from the Gorotuba River floodplains. The phylogenetic analysis highly supports H.hamadryades as sister to a clade comprising H.gardneri and H.harmonicus. Our field observations suggest that H.hamadryades is a miniature species. This study indicates that the H.magnificus complex comprises cryptic species apparently endemic to small areas and extremely vulnerable to environmental changes, deserving high concern.


Plasma renin activity and aldosterone concentration in sodium-depleted cattle following ACTH or metoclopramide injection.
Adrenocorticotropic hormone (ACTH) treatment (7 micrograms X kg-1 body weight) induced an increase in plasma aldosterone concentration in both Na-deficient heifers (following saliva loss after right parotid duct cannulation) and Na-replete heifers, but had no significant effect on plasma renin activity in either of these groups. The dopamine antagonist, metoclopramide, injected i.v. (1 mg X kg-1 body weight) did not modify plasma renin activity, aldosterone or cortisol concentrations in either group. These results indicate that dopamine did not play a major role in the regulation of aldosterone secretion in Na-replete or Na-depleted heifers.


Analysis of antigenic determinants on human monocytes and macrophages.
Mo1, 2, 3, and 4, and Plt-1 are a series of five distinct antigens detected on the surface of human peripheral blood monocytes by mouse monoclonal antibodies. Mo2 and 3 are restricted to the monocyte-macrophage series, while Mo1, as previously reported, is also expressed by human granulocytes and null cells. Mo3, as distinguished from Mo1 and Mo2, is weakly expressed by virgin peripheral blood monocytes but becomes well expressed if monocytes are cultured overnight at 37 degrees C. Mo4 is coexpressed by monocytes and platelets, while Plt-1 appears to be a platelet-specific antigen whose detection on monocytes reflects adherence of platelets to monocyte membranes. That Mo2-4 are true monocyte antigens is demonstrated by their resynthesis following protease treatment of monocytes (Mol expression is resistant to proteolytic digestion). During myeloid-monocyte differentiation, the Mo antigens are infrequently expressed by immature myeloid cells but are found at higher frequency on leukemic monocytic forms. Macrophages from cultured peripheral blood monocytes and HL-60 cells exposed to lymphokines or phorbol diester express Mo1-4, but noncirculating peritoneal macrophages lack Mo3. The Mo antigens are differentiation markers whose expression reflects membrane heterogeneity during myeloid-monocyte-macrophage maturation.


Community Organization and Empowerment of Women: The Mujeres Pescadoras del Manglar Cooperative in Oaxaca, Mexico.
Gender equity is still a challenge for the world, especially in those regions where sociocultural practices permeated by machismo, that is, male chauvinism, intersect with poverty and institutionalized racial discrimination. The creation of safe and feminized spaces where women can express themselves freely is crucial in the process of cultivating their awareness of their own positions, and the first step toward individual and collective empowerment. In this article the authors point out the direct and positive relationship between feminine cooperativism and women's empowerment, taking as a case study the Mujeres Pescadoras del Manglar cooperative in Oaxaca, Mexico, a group of women who, thanks to a social work program implemented by La Ventana civic association, has been able to gain empowerment and recognition at a personal and political level. Likewise, Mujeres Pescadoras del Manglar is an example of the national phenomenon of bolstering female employment in the fishing sector, which is on the rise thanks to the growing number of women's cooperatives, through which they can access the labor market, feminize new spaces, and achieve full empowerment for themselves, their families, and the society in which they live. The fieldwork was carried out from November 2018 to February 2019 in the community of El Zapotalito, Oaxaca. The methodology used consists of semistructured interviews, life stories, field diaries, and participant observation. This article showcases a positive example of social work empowering low-income women on the Chica coast of Oaxaca.


Microring structure for flexible polymer waveguide-based optical pressure sensing.
Flexible pressure sensors provide a promising platform for artificial smart skins, and photonic devices provide a new technique to fabricate pressure sensors. Here, we present a flexible waveguide-based optical pressure sensor based on a microring structure. The waveguide-based optical pressure sensor is based on a five-cascade microring array structure with a size of 1500 µm × 500 µm and uses the change in output power to linearly characterize the change in pressure acting on the device. The results show that the device has a sensing range of 0-60 kPa with a sensitivity of 23.14 µW/kPa, as well as the ability to detect pulse signals, swallowing, hand gestures, etc. The waveguide-based pressure sensors offer the advantages of good output linearity, high integration density and easy-to-build arrays.


Enhanced chirality by adding achiral molecules into the chiral system.
It is generally accepted that the doping of chiral materials with achiral molecules diminishes the chirality of the system. Here we report the opposite phenomenon. It was found that the structural chirality of smectic phases made of rodlike molecules, Sm-C(*) or Sm-C(*)(A) phases, measured as the reverse length of the helical pitch, is enhanced by adding small amount of achiral bent-shaped molecules. The effect is due to the chirality transfer between host and guest systems. Achiral bent-shaped molecules become structurally chiral due to the interactions with the chiral host that induces tilt and polar order of bent-shaped molecules. This induced chirality is then transferred back to the host.


Mechanisms of visual loss in corneal edema.
Although visual disability from corneal edema is a well-recognized clinical finding, it is not easily confirmed by routine visual assessment. A more reliable assessment of visual changes resulting from corneal edema of varying origins is achieved by measurement of changes in the contrast sensitivity function. The measurements can be sensitized by the presence of a glare source to allow a more accurate determination of the nature of the visual loss. Even in the absence of a measurable loss of visual acuity, corneal edema leads to diminished visual function. The magnitude and type of this loss is dependent on the origin of the edema and the site of the corneal response.


[Illnesses caused by amalgam?].
As side effects of dental amalgam have been mentioned allergy, oral lichen, electro-galvanism, amalgam tattoos of gingiva or oral mucosa, and undesirable esthetics. Patients with amalgam restorations show increased mercury levels in different body fluids compared to amalgam-free controls. An intoxication due to dental amalgam fillings, however, is not to be expected-despite equivocal statements in the literature. In contrast, recent studies revealed that dental amalgam contributes to mercury exposure less than assumed few years ago. Therefore, amalgam will stay an option as a restorative material in future. The removal of intact amalgam fillings in the intention of "detoxification" is not science-based. Successful caries prevention (e.g. due to the widespread use of fluoride) and the further development of esthetic restorative materials based on composite resins will limit the utilisation of amalgam. Thus, alternative materials have not been shown to have a lower rate of side effects (e.g. allergy) compared to amalgam.


Local delivery of a cancer-favoring oncolytic vaccinia virus via poly (lactic-co-glycolic acid) nanofiber for theranostic purposes.
Local delivery of viruses via nanomaterials has been demonstrated in the treatment of colon cancer. A cancer-favoring oncolytic vaccinia virus (CVV), which is an evolutionary cancer-favoring engineered vaccinia virus carrying the green fluorescent protein (GFP) gene, has antitumor efficacy in drug-resistant colon cancer and metastatic liver cells. Here, we present the antitumor efficacy of a CVV coated a poly lactic-co-glycolic acid (PLGA) nanofiber for local drug delivery in theranostic approaches. In vitro- and in vivo-based analyses using mouse colon carcinoma models confirmed the therapeutic efficacy of CVV-PLGA nanofibers through diagnostic localization of the tumors and reduced tumor burden as a result of enhanced apoptosis. We propose that the CVV-PLGA nanofiber may be used for theranostic purposes in cancer therapy.


Evolution and Ecology of Salmonella.
Over the past 120 to 160 million years, the genus Salmonella has evolved into a complex group of more than 2,300 genetically and phenotypically diverse serovars. Members of this genus are able to infect a wide diversity of vertebrate and invertebrate hosts; disease manifestations in humans range from gastroenteritis to typhoid fever. The evolution of the genus Salmonella and the divergence and radiation of particular lineages within this group have resulted from selection acting on new genetic variation generated by events such as the gain, loss, and/or rearrangement of genetic material. These types of genetic events have contributed to the speciation of Salmonella from its ancestral association with cold-blood animals to a pathogen of warm-blooded hosts. Moreover, adaptive radiation due to changes in gene content within S. enterica subspecies I has impacted host specificity and aided in the selection of host-restricted, host-adapted, and non-host-adapted serovars. In addition to the genetic diversity important for the wide phenotypic heterogeneity within the genus, a subset of core Salmonella-specific genes present in all Salmonella species and serovars has been identified that may contribute to the conserved aspects of the lifestyle of this microorganism, including the ability to survive in nutrient-poor nonhost environments such as soil and water. Whole-genome comparisons of isolates differing in host range and virulence will continue to elucidate the genetic mechanisms that have contributed to the evolution and diverse ecology of the genus Salmonella.


High-order time expansion path integral ground state.
The feasibility of path integral Monte Carlo ground state calculations with very few beads using a high-order short-time Green's function expansion is discussed. An explicit expression of the evolution operator which provides dramatic enhancements in the quality of ground-state wave functions is examined. The efficiency of the method makes possible to remove the trial wave function and thus obtain completely model-independent results still with a very small number of beads. If a single iteration of the method is used to improve a given model wave function, the result is invariably a shadow-type wave function, whose precise content is provided by the high-order algorithm employed.


Ramsay Hunt syndrome in a girl with acute lymphoblastic leukemia during maintenance therapy.
A 5-year-old girl with precursor B-cell acute lymphoblastic leukemia developed peripheral-type right facial palsy and very faint erythema on her right pinna during maintenance therapy. Acyclovir was started for possible zoster infection. The following day, vesicles appeared and a diagnosis of Ramsay Hunt syndrome was made. Prednisolone was started on day 5 after onset. Her facial palsy recovered within 6 months. Ramsay Hunt syndrome is a rare cause of facial palsy in patients with acute lymphoblastic leukemia, and this is the first case report. Preemptive therapy with acyclovir before the development of vesicles should help the patient recover from facial palsy.


Depression in adults with intellectual disability. Part 2: A pilot study.
To identify adults with intellectual disability (ID) with a depressive disorder referred to a tertiary consultation clinic for psychiatric assessment; to investigate common presenting features of depression in adults with ID; to assess the utility of visual analogue scale (VAS) measures of emotion/behaviour, the CORE measure of psychomotor disturbance, and substitutive diagnostic criteria in the assessment of depressive disorders in this patient group. Over a 6-month period 47 patients were seen for psychiatric evaluation. Patients in whom a diagnosis of depression was made were further assessed using: VAS measures of depression, irritability, verbal aggression, physical aggression, temper outbursts, regressed behaviour; CORE measure of psychomotor disturbance; and substitutive diagnostic criteria designed by the authors. Ten patients were found to have a depressive disorder. Substitutive criteria resulted in a greater rate of diagnosis than standard DSM-IV criteria. The VAS measure of irritability was highly scored for all 10 depressed patients. All 10 depressed patients were assigned to the melancholic subgroup according to CORE score. Standard assessment measures and diagnostic criteria may require modification to enhance their utility in this patient group. Melancholic features require further investigation.


Chemoradiation Improves Survival Compared With Chemotherapy Alone in Unresected Nonmetastatic Gastric Cancer.
Background: Limited data are available to guide management of patients with stage I-III gastric cancer not undergoing potentially curative surgical resection. We compared survival outcomes associated with chemotherapy alone versus chemoradiation (CRT) in the treatment of nonmetastatic gastric cancer. Methods: Patients with gastric adenocarcinoma from 2004 to 2015 were identified using the National Cancer Database. Patients were excluded if they had surgery, metastatic disease, or T0, Tis, or T1a disease. Logistic regression was used to evaluate predictors of CRT use. Cox proportional hazards modeling was performed to compare overall survival (OS) between chemotherapy alone and CRT in overall and propensity score-matched cohorts. Results: We identified 4,795 patients with stage I-III gastric adenocarcinoma who did not undergo surgery, at a median follow-up of 11.8 months. A total of 3,316 patients (69.2%) received chemotherapy alone and 1,479 patients (30.8%) received CRT. Predictors of increased CRT use were age ≥65 years (odds ratio [OR] 1.68; 95% CI, 1.43-1.99; P<.001), Charlson-Deyo comorbidity score ≥2 (OR, 1.46; 95% CI, 1.18-1.81), and treatment at a community facility (OR, 1.27; 95% CI, 1.07-1.51; P=.006). Patients receiving CRT had a 2-year OS rate of 28.3% compared with 21.5% among those receiving chemotherapy. Multivariate analysis showed that CRT was associated with improved OS (hazard ratio [HR], 0.82; 95% CI, 0.77-0.89; P<.001). After propensity score matching, a persistent survival benefit was observed (HR, 0.80; 95% CI, 0.74-0.88; P<.001). Conclusions: In patients with stage I-III gastric cancer not undergoing surgical resection, CRT was associated with improved survival compared with chemotherapy alone. However, only 30.8% of patients received CRT in this setting.


Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway.
Long-term deficiency of cobalamin or folate causes a demyelinating disease of the brain and spinal cord. A reduced supply of methyl groups has been implicated as its cause. To examine the mechanisms of demyelination in human beings, we have studied three children with sequential inborn errors of the methyl-transfer pathway. One child had abnormal methylfolate metabolism, one abnormal methylcobalamin metabolism, and one hypermethioninaemia probably caused by methionine adenosyltransferase deficiency. Magnetic resonance imaging of the brain and measurement of cerebrospinal-fluid concentrations of 5-methyltetrahydrofolate, methionine, and S-adenosylmethionine were carried out before and after 6-12 months of appropriate treatment. Each patient had abnormal myelination before treatment; the scans suggested demyelination. The only consistent biochemical abnormality in the cerebrospinal fluid was a low concentration of S-adenosylmethionine. Treatment led to substantial clinical improvement, apparent remyelination, and increases in cerebrospinal-fluid S-adenosylmethionine concentration into the normal range. Cerebrospinal-fluid concentrations of S-adenosylmethionine and methionine were significantly lower in eight other children with errors of the methyl-transfer pathway than in an age-matched reference population (mean [95% confidence interval] standard deviation score -1.81 [0.57], p less than 0.001 for S-adenosyl methionine and -1.82 [0.19], p less than 0.001 for methionine). The concentrations of these metabolites increased to within the reference range on treatment. We have shown that demyelination is associated with cerebrospinal-fluid S-adenosylmethionine deficiency and that restoration of S-adenosylmethionine is associated with remyelination.


The COVID-19 Vaccines: A Description of Adverse Events of Reactions Reported in Kansas.
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and has spread rapidly throughout the world since its discovery in 2019. Three vaccines (Pfizer-BioNTech, Moderna/NIAID/BARDA, and Johnson & Johnson's Janssen) have been developed for use in the U.S. to aid in the fight against this virus, but have been scrutinized intensely for their efficacy and safety. It is important to understand and interpret the adverse events or reactions (AERs) associated with these vaccines in an objective and analytical manner. The goal of this descriptive study was to provide a resource outlining AERs associated with the three available vaccines in Kansas. Reports were obtained from the Vaccine Adverse Event Reporting System (VAERS), representing AERs observed in Kansas from December 11, 2020 to May 13, 2021. All data were screened and coded, and descriptive statistics were used to describe AERs based on vaccine manufacturer, patient age and biological sex, and reported deaths. Only 0.00068% of COVID-19 vaccine doses given in Kansas were associated with an AER (1,445/2,120,350). There were 4,297 individual AERs reported, and the most common were fatigue/tiredness (266; 6.2%), tingling/itching (251; 5.9%), fever (226; 5.3%), hives (223; 5.2%), and muscle/joint pain (209; 4.9%). Only 0.002% of COVID-19 vaccine doses in Kansas were associated with a death (38/2,120,350). The majority of VAERS reports were by females (1,139; 78.8%) and those aged 30 to 39 years (297; 20.6%). No reported AERs were unexpected compared to national data, and no VAERs report provided a causal relationship between vaccine administration and death. Vaccines are, and will continue to be, essential tools to fight COVID-19 in the quest to reach herd immunity. Providing a resource of potential AERs could aid in individual decisions to receive a vaccine and may help in the control of COVID-19. Future studies may include describing reported AERs for children under age 12 as the vaccines become available for those age groups, as well as reporting AERs for those who have received the vaccine after our study time period.


Does treating pain with alcohol affect drinking reduction among women with HIV enrolled in a clinical trial of naltrexone?
Many women living with HIV (WLWH) experience pain. Alcohol use with the intent to treat pain could lead to hazardous drinking and difficulty in reducing drinking. Naltrexone acts on opioid receptors important for pain regulation and is an approved treatment for alcohol use disorder. In this secondary analysis of a randomized double-blind placebo-controlled naltrexone clinical trial, the goals were to (1) compare alcohol reduction between women who drank to treat pain and those who did not and (2) examine differences in alcohol reduction by both drinking intention and treatment arm. Women living with HIV (N = 194, mean age 48.3 years, 83% non-Hispanic Black, 11% Hispanic) with hazardous drinking (>7 drinks/week) were randomized to receive daily treatment with naltrexone 50 mg or placebo for 4 months. Study visits occurred at baseline and 2, 4, and 7 months (posttreatment). The number of drinks/week was measured using the Timeline Follow Back. Use of alcohol to treat pain was self-reported. Participants were categorized as using alcohol to treat pain or not and in the naltrexone or placebo group. Chi-square, t-test, MANOVA, and sequential mixed effects models were used to determine group differences in demographic factors, mean/drinks per week, and percent change in mean drinks/week at baseline and each follow-up visit. There was a consistent decrease in drinking throughout the study. There was not a significant difference in mean drinks/week at any point in the study between women who used alcohol to treat pain and those who did not. When considering treatment arm, at 2 months only those who did not use alcohol to treat pain in the naltrexone group had a significantly lower mean drinks/week than the other groups (p = 0.007); all groups had similar decreases in drinking from 4 months onward. In the naltrexone group, WLWH who drank to treat pain reduced their alcohol consumption more slowly than WLWH who did not drink to treat pain. Replication of these findings would suggest that alcohol treatment guidelines should address pain as a factor in drinking outcomes.


Increasing referral of at-risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center.
Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals. A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling. A total of 34,851 patients were screened during the study period, and 1246 (4%) patients were found to be eligible for referral; 245 of these patients made a genetic counseling appointment, and 142 patients received genetic counseling. Forty patients (28%) had a personal history of breast cancer but were not previously tested. Following counseling, 105 patients were tested for BRCA1/2. Eight patients (8%) tested positive for a pathogenic mutation and nine (9%) had a variant of unknown significance. Although they tested negative, many patients met the criteria to add breast magnetic resonance imaging to their screening due to greater than 20% lifetime breast cancer risk based on their family cancer history. This study led to improved clinical risk management in 67% of the patients who underwent genetic counseling. This study shows that large-scale screening of patients for HBOC syndromes at time of breast imaging is practical and highly feasible. The screening tool identified women with actionable BRCA1/2 mutations and mutation-negative but high-risk women, leading to significant changes in their risk management; these women would otherwise have been missed. Hereditary breast and ovarian cancer (HBOC) caused by pathogenic mutations in breast cancer genes (BRCA1/BRCA2) increase an individual's lifetime risk of getting HBOC. Identifying these high-risk individuals and using proven preventive clinical risk management strategies can significantly reduce their lifetime risk of HBOC. Using an innovative family cancer history questionnaire, 34,000 women were screened at a community breast imaging center, and genetic counseling and testing were provided to eligible women from the screening. Several women at high risk for HBOC were identified and this led to positive clinical risk management changes. These women would have been missed if not for intervention.


Characterization of Two Human Skeletal Calsequestrin Mutants Implicated in Malignant Hyperthermia and Vacuolar Aggregate Myopathy.
Calsequestrin 1 is the principal Ca(2+) storage protein of the sarcoplasmic reticulum of skeletal muscle. Its inheritable D244G mutation causes a myopathy with vacuolar aggregates, whereas its M87T "variant" is weakly associated with malignant hyperthermia. We characterized the consequences of these mutations with studies of the human proteins in vitro. Equilibrium dialysis and turbidity measurements showed that D244G and, to a lesser extent, M87T partially lose Ca(2+) binding exhibited by wild type calsequestrin 1 at high Ca(2+) concentrations. D244G aggregates abruptly and abnormally, a property that fully explains the protein inclusions that characterize its phenotype. D244G crystallized in low Ca(2+) concentrations lacks two Ca(2+) ions normally present in wild type that weakens the hydrophobic core of Domain II. D244G crystallized in high Ca(2+) concentrations regains its missing ions and Domain II order but shows a novel dimeric interaction. The M87T mutation causes a major shift of the α-helix bearing the mutated residue, significantly weakening the back-to-back interface essential for tetramerization. D244G exhibited the more severe structural and biophysical property changes, which matches the different pathophysiological impacts of these mutations.


Mammary tuberculosis in the young: a case report and literature review.
Tuberculosis (TB) of the breast is a rare condition with few cases reported outside of Asia. Its presence in juveniles is even more uncommon. Despite this, it is often easily treatable. The diagnosis of mammary TB should always be considered in an atypical presentation, and especially in those with high risk demographics. We present the case of a 16 year old girl with TB of the breast and review the literature currently available.


Polygenic prediction across populations is influenced by ancestry, genetic architecture, and methodology.
Polygenic risk scores (PRSs) developed from multi-ancestry genome-wide association studies (GWASs), PRSmulti, hold promise for improving PRS accuracy and generalizability across populations. To establish best practices for leveraging the increasing diversity of genomic studies, we investigated how various factors affect the performance of PRSmulti compared with PRSs constructed from single-ancestry GWASs (PRSsingle). Through extensive simulations and empirical analyses, we showed that PRSmulti overall outperformed PRSsingle in understudied populations, except when the understudied population represented a small proportion of the multi-ancestry GWAS. Furthermore, integrating PRSs based on local ancestry-informed GWASs and large-scale, European-based PRSs improved predictive performance in understudied African populations, especially for less polygenic traits with large-effect ancestry-enriched variants. Our work highlights the importance of diversifying genomic studies to achieve equitable PRS performance across ancestral populations and provides guidance for developing PRSs from multiple studies.


Methodological Challenges in Conducting Research with Refugee Women.
The purpose of this pilot study was to evaluate the acceptability and feasibility of a 10-week community-based, culturally tailored mental health intervention, called Healthy Sudanese Families, with 12 South Sudanese refugee women living in a metropolitan area of the Midwestern United States. This mixed-methods study used the Dinka and Arabic versions of the Hopkins Symptoms Checklist-25 to measure indicators of anxiety and depression and a final focus group to evaluate the women's responses to the intervention. The women found the mental health intervention acceptable and relevant. Methodological challenges encountered in cross-cultural research with refugees are discussed.


Identification of two major ammonia-releasing reactions involved in secondary natto fermentation.
Natto is a traditional Japanese food made from soybeans fermented by strains of Bacillus subtilis natto. It gives off a strong ammonia smell during secondary fermentation, and the biochemical basis for this ammonia production was investigated in this study. When natto was fermented by strain r22, ammonia production was shown to involve degradation of soybean proteins releasing amino acids, and only the glutamate contained in the natto obviously decreased, while the other amino acids increased during secondary fermentation. Strain r22 has two active glutamate dehydrogenase genes, rocG and gudB, and inactivating both genes reduced ammonia production by half, indicating that deamination of glutamate was one of the major ammonia-releasing reactions. In addition, urease encoded by ureABC was found to degrade urea during secondary fermentation. A triple mutant lacking rocG, gudB, and ureC exhibited minimal ammonia production, suggesting that the degradation of urea might be a further ammonia-releasing reaction.


A method to minimise the fading effects of LiF:Mg,Ti (TLD-600 and TLD-700) using a pre-heat technique.
Passive integrating dosemeters [thermoluminescent dosimeter (TLD) and optically stimulated luminescence (OSL)] are the only legally permitted individual dosemeters for occupational external radiation exposure monitoring in Korea. Also its maximum issuing cycle does not exceed 3 months, and the Korean regulations require personal dosemeters for official assessment of external radiation exposure to be issued by an approved or rather an accredited dosimetry service according to ISO/IEC 17025. KHNP (Korea Hydro & Nuclear Power, LTD), a unique operating company of nuclear power plants (NPPs) in Korea, currently has a plan to extend a TLD issuing cycle from 1 to 3 months under the authors' fading error criteria, ±10%. The authors have performed a feasibility study that minimises post-irradiation fading effects within their maximum reading cycle employing pre-heating technique. They repeatedly performed irradiation/reading a bare TLD chip to determine optimum pre-heating conditions by analysing each glow curve. The optimum reading conditions within the maximum reading cycle of 3 months were decided: a pre-heating temperature of 165°C, a pre-heating time of 9 s, a heating rate of 25°C s(-1), a reading temperature of 300°C and an acquisition time of 10 s. The fading result of TLD-600 and TLD-700 carried by newly developed time temperature profile (TTP) showed a much smaller fading effect than that of current TTP. The result showed that the fading error due to a developed TTP resulted in a ∼5% signal loss, whereas a current TTP caused a ∼15% loss. The authors also carried out a legal performance test on newly developed TTP to confirm its possibility as an official dosemeter. The legal performance tests that applied the developed TTP satisfied the criteria for all the test categories.


PTEN Inhibition in Human Disease Therapy.
The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs.


Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas.
A consecutive series of 143 unselected adult patients with histologically proved World Health Organization grade II gliomas was reviewed to assess the prognostic value of growth rates of mean tumor diameters on successive magnetic resonance images before treatment. There is an inverse correlation between growth rates and survival (p < 0.001; median survival at 5.16 years for a growth rate of 8mm/year or more; median survival >15.0 years for a growth rate <8mm/year). Thus, individual magnetic resonance imaging tumor growth rates should be incorporated in the planning of the initial therapeutic strategy of grade II gliomas.


IL-10 plays an important role in the homeostatic regulation of the autoreactive repertoire in naive mice.
We have previously shown that naive SJL (H-2(s)) mice, which are highly susceptible to myelin proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), have a very high frequency (1/20,000 CD4 T cells) of PLP(139-151)-reactive T cells in the naive repertoire. In this study, we examine the function of this endogenous PLP(139-151)-reactive repertoire in vivo and find that this repertoire encompasses the precursors of pathogenic T cells. Because SJL mice do not develop spontaneous EAE, we have explored the mechanisms that keep this autopathogenic repertoire in check and prevent the development of spontaneous autoimmunity. We crossed IL-4 and IL-10 deficiency onto the SJL background and analyzed the roles of these two immunoregulatory cytokines in regulating the size and effector function of the endogenous PLP(139-151)-reactive repertoire and development of autoimmune disease. We find that IL-10 is important in the homeostatic regulation of the endogenous PLP(139-151)-reactive repertoire in that it both limits the size of the repertoire and prevents development of effector autoaggressive T cells. SJL IL-10(-/-) mice with high numbers of PLP(139-151)-specific precursors in the repertoire did not develop spontaneous EAE, but when they were injected with pertussis toxin, they showed atypical clinical signs of EAE with small numbers of typical mononuclear cell infiltrates predominantly in the meninges. EAE could be inhibited by prior tolerization of the mice with soluble PLP(139-151) peptide. These findings indicate that IL-10 may contribute to the regulation of the endogenous autoimmune repertoire.


Are reframing strategies more effective than empathy in processing trauma reports? A pilot study.
Listening to trauma reports can lead to the development of symptoms associated with secondary traumatization. This is particularly relevant for psychotherapists in practice, where psychologists need to estabilish effective strategies for processing and coping with such emotionally challenging events. This explorative study investigated adaptive reframing strategies for future therapists listening to trauma stories compared to feeling empathy for the client. In a mixed design, 42 postgraduate psychology students were randomly instructed to objectively distance themselves, reappraise, or feel empathetic while watching a video of a presumed trauma patient reporting a single violent act. An overall ANOVA did not reveal a difference between the reframing groups and the empathy group (between subjects manipulated) in their skin conductance level and heart rate variability during the video, as well as their change in state depression and state anxiety over the three measurements (before the video, after the video, and 2 days later). Nevertheless, an explorative t-test showed a significantly weaker rise in state depression and state anxiety from before the video to after the video in the reframing groups compared to the empathy group. This supports the suggestion that reframing strategies can be discussed as a protective factor against health issues such as secondary traumatization in therapists and should be examined in further studies in more detail.


Opportunities for Cancer Health Care Disparities and Care Delivery Research: An Analysis of the NCI Health Care Delivery Research Program Portfolio.
Cancer health care disparities are complex, involve patient, clinician and health care system factors, and are defined as adverse differences in cancer outcomes. This analysis describes NCI's Healthcare Delivery Research Program's (HDRP) portfolio of disparities-focused research and identifies future research opportunities. Grants through HDRP (fiscal years 2012 to 2016) focused on detecting, understanding, and/or intervening on disparities in or among health disparity populations were reviewed by co-authors. Forty-eight funded grants were identified, coded, and characterized. Descriptive analyses are reported. Most studies focused on racial/ethnic minorities and socioeconomically disadvantaged groups. Colorectal, breast, and cervical cancers were most frequently examined. Almost 40% of studies addressed the intervening phase of the disparities research continuum. Few studies focused on clinician-level factors or involved the community in the research design. A sustained disparities research emphasis is essential to addressing the determinants of and cancer burden among health disparity populations across the cancer care continuum.