Heightened expression of the cytotoxicity receptor NKG2D correlates with acute and chronic nephropathy after kidney transplantation.
The activating cytotoxicity receptor NKG2D binds to stress-regulated molecules encoded by the major histocompatibility complex class I chain-related (MIC) and UL-16-binding protein (ULBP)/retinoic acid early transcript (RAET) gene family. To assess whether acute allograft rejection leads to an induction of these inducible ligands and their receptor NKG2D, we examined the mRNA profiles in kidney transplant biopsies. Expression levels were correlated with the incidence of acute rejection (aRx) episodes and chronic allograft nephropathy (CAN) proven by histology. Whereas MICA, ULBP1/3 and RAET1-E did not display heightened gene expression, elevated levels of NKG2D mRNA could be associated with aRx (p < 0.001). Immunohistology of kidney biopsies diagnosed with aRx revealed NKG2D+ cells in tubulointerstitial areas positive for CD8+ cells. Most importantly, elevated levels of NKG2D mRNA were associated with restricted long-term graft function assessed by the glomerular filtration rate at 6, 12 and 18 months posttransplantation. Induced NKG2D mRNA expression was still observable in biopsies diagnosed with CAN (p < 0.001), demonstrating a higher sensitivity and specificity compared to CD3, granzyme B and granulysin mRNA measurement. Significant elevated levels of NKG2D mRNA could be further detected in urine sediment prior to aRx, suggesting this receptor as a new candidate marker for the diagnosis of acute and chronic allograft rejection.


The proportion of unmet costs considering inpatients billing of selected hospitals, after 2014 Health System reform implementation in Isfahan Province.
Since 2013, in Iran's health care, the contribution of direct payments for health-care services was estimated more than 50 % of all expenditures. In May 2014, Iran's health-care reform was established to improve health services quality and reduce patients' out-of-pocket payments <10% in urban and 5% in rural areas. Therefore, the purpose of this study is to investigate unmet costs (those which are not covered either by the insurance companies nor the recent reform coverage mentioned in Sections 1.2.2 and 1.2.1, Article 6 of the Health Minister Reform Guideline) in the inpatient billings within the first 5 months from the reform implementation. This study was conducted as a cross-sectional research in the second half of 2014 on the selected hospitals in Isfahan Province. Data were collected by investigating 97,000 inpatients' billing records issued by 28 hospitals affiliated to Isfahan University of Medical Sciences using census method. Findings of the study showed that the average of unmet costs paid by the inpatients constituted 21.8% of the total billing costs in 28 hospitals, and the average unmet costs paid by each patient was 1,903,832 Rials. Considering the definition of unmet cost in the context of health-care reform guideline and hospitals' problems in providing some costly services, drugs, and medical equipment (that were not covered by insurance organizations and the reform scheme) within the obligations of the reform, it is necessary to review these obligations and further interact with insurance companies about expanding the coverage to some costly services required by the patients.


Buccal Alveolar Bone changes and upper first molar displacement after maxillary expansion with RME, Ni-Ti leaf springs expander and Tooth- Bone-borne Expander. A CBCT based analysis.
To evaluate the buccal alveolar bone changes and the upper first molar displacement in subjects treated with conventional rapid maxillary expansion (RME), Ni-Ti leaf springs expander (Leaf Expander) and Tooth-Bone-borne Expander (Hybrid Expander) using CBCT scans. The sample consisted of 52 children treated with RME (n=18), Leaf Expander (n= 17) and Hybrid Expander (n= 17). CBCTs were taken before and after maxillary expansion and the Horos software was used for the analysis. Descriptive statistics and paired t-test were used to assess changes between the pre-treatment and post-treatment measurements. ANOVA test and Tukey's post hoc test with Bonferroni correction was used for between groups comparison. The Hybrid Expander during preadolescence showed few advantages over the use of tooth-anchored expanders. An expansion approach with mini-screws is not preferable during early mixed dentition to a conventional approach. The differences in dental tipping values were clinically insignificant and the reduction in cortical bone thickness remained less than 1 mm. When possible, the use of second primary molars as anchorage should be preferred.


Growth acceleration and stem cell expansion in Dexter-type cultures by neutralization of TGF-beta.
Hematopoietic lineage-restricted stem cell growth has been shown to be significantly inhibited by the addition of exogenous transforming growth factor-beta (TGF-beta) to Dexter-type long-term murine bone-marrow cultures. In order to examine whether TGF-beta produced by these cells has a role in hematopoietic growth regulation, Dexter cultures have been treated with either 1D11.16, a monoclonal antibody that neutralizes the biological activity of TGF-beta types 1, 2, and 3, or with a control antibody. The composition and cellularity of the nonadherent cell populations in these cultures were assessed weekly. Treatment with anti-TGF-beta antibody resulted in a five- to 20-fold increase in nonadherent cells in the cultures when compared to either the control or untreated cultures by week 4. The majority of these cells were granulocyte/macrophage-lineage cells as assessed by histologic and flow-cytometric analysis. There was also a significant increase of megakaryocytes in cultures treated with anti-TGF-beta antibody. Stem-cell analysis, using a colony-forming unit-spleen (CFU-S) assay that combined both the adherent and nonadherent populations from either 4- or 6-week cultures, showed that there are an equivalent number of hematopoietic stem cells per 10(6) cells regardless of antibody treatment. Therefore, cultures treated with anti-TGF-beta antibody contained at least three times as many stem cells as the control cultures. Finally, kinetics studies show that the presence of anti-TGF-beta antibody is required from the onset of culture to produce these effects. These results suggest that TGF-beta is involved in normal growth regulation of bone-marrow hematopoietic cells. By addition of a neutralizing antibody, the normal TGF-beta negative growth signal is disrupted, allowing for expanded growth of several cell populations.


COVID-19 impact on timing of brachytherapy treatment and strategies for risk mitigation.
The purpose of this study was to highlight the importance of timely brachytherapy treatment for patients with gynecologic, breast, and prostate malignancies, and provide a framework for brachytherapy clinical practice and management in response to the COVID-19 pandemic. We review amassing evidence to help guide the management and timing of brachytherapy for gynecologic, breast, and prostate cancers. Where concrete data could not be found, peer-reviewed expert opinion is provided. There may be a significant negative impact on oncologic outcomes for patients with gynecologic malignancies who have a delay in the timely completion of therapy. Delay of prostate or breast cancer treatment may also impact oncologic outcomes. If a treatment delay is expected, endocrine therapy may be an appropriate temporizing measure before delivery of radiation therapy. The use of shorter brachytherapy fractionation schedules will help minimize patient exposure and conserve resources. Brachytherapy remains a critical treatment for patients and may shorten treatment time and exposure for some. Reduced patient exposure and resource utilization is important during COVID-19. Every effort should be made to ensure timely brachytherapy delivery for patients with gynecologic malignancies, and endocrine therapy may help temporize treatment delays for breast and prostate cancer patients. Physicians should continue to follow developing institutional, state, and federal guidelines/recommendations as challenges in delivering care during COVID-19 will continue to evolve.


American Academy of Pediatrics. The use of complementary and alternative medicine in pediatrics.
The American Academy of Pediatrics is dedicated to optimizing the well-being of children and advancing family-centered health care. Related to these goals, the American Academy of Pediatrics recognizes the increasing use of complementary and alternative medicine in children and, as a result, the need to provide information and support for pediatricians. From 2000 to 2002, the American Academy of Pediatrics convened and charged the Task Force on Complementary and Alternative Medicine to address issues related to the use of complementary and alternative medicine in children and to develop resources to educate physicians, patients, and families. One of these resources is this report describing complementary and alternative medicine services, current levels of utilization and financial expenditures, and associated legal and ethical considerations. The subject of complementary and alternative medicine is large and diverse, and consequently, an in-depth discussion of each method of complementary and alternative medicine is beyond the scope of this report. Instead, this report will define terms; describe epidemiology; outline common types of complementary and alternative medicine therapies; review medicolegal, ethical, and research implications; review education and training for complementary and alternative medicine providers; provide resources for learning more about complementary and alternative medicine; and suggest communication strategies to use when discussing complementary and alternative medicine with patients and families.


COPD Anno 2011: emphasis on bronch(iol)odilation.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and death worldwide. Although COPD is considered to be a preventable and treatable disease, there are concerns that COPD remains substantially underdiagnosed and undertreated. Even in mild disease, patients suffer from significant impairments in health status, which places a considerable burden on patients as well as society. Symptomatic patients are likely to progress to more advanced disease. To avoid breathlessness, they adapt and gradually reduce their activities, which, inevitably, leads to further deconditioning. As a consequence, a progressive deterioration in physical activity with increasing severity of COPD can be observed. Because physical activity is closely related to exacerbation rate, hospitalization, and mortality in patients with COPD, it is important to recognize the role of pharmaceutical interventions in enabling patients to stay physically active. Bronch(iol)odilation not only has important direct effects (symptom relief), but also exerts indirect effects on exercise capacity, exacerbation rate, health status, and mortality. In patients with COPD, the latter effects may be even more important than the direct effects. In this review the current view on causes and consequences of activity limitation in COPD is summarized. From this perspective, the rationale behind bronch(iol)odilator therapy as the cornerstone of treatment for patients with COPD will be discussed.


Increased Azithromycin Susceptibility of Multidrug-Resistant Gram-Negative Bacteria on RPMI-1640 Agar Assessed by Disk Diffusion Testing.
Increasing antibiotic resistances and a lack of new antibiotics render the treatment of Gram-negative bacterial infections increasingly difficult. Therefore, additional approaches are being investigated. Macrolides are not routinely used against Gram-negative bacteria due to lack of evidence of in vitro effectiveness. However, it has been shown that Pseudomonas spp. are susceptible to macrolides in liquid RPMI-1640 and clinical data suggest improvement in patients' outcomes. So far, these findings have been hardly applicable to the clinical setting due to lack of routine low-complexity antimicrobial susceptibility testing (AST) for macrolides. We therefore optimized and compared broth microdilution and disk diffusion AST. Multidrug-resistant Gram-negative bacteria (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa) were tested for azithromycin susceptibility by disk diffusion and broth microdilution in Mueller-Hinton and RPMI-1640 media. Azithromycin susceptibility of Enterobacteriaceae and a subgroup of P. aeruginosa increased significantly on RPMI-1640 agar compared to Mueller-Hinton agar. Further, a significant correlation (Kendall, τ, p) of zone diameters and minimal inhibitory concentrations (MICs) was found on RPMI-1640 agar for E. coli (-0.4279, 0.0051), E. cloacae (-0.3783, 0.0237) and P. aeruginosa (-0.6477, <0.0001). Performing routine disk diffusion AST on RPMI-1640 agar may lead to the identification of additional therapeutic possibilities for multidrug-resistant bacterial infections in the routine clinical diagnostic setting.


Direct electrochemical measurement of nitric oxide released from human platelets.
A porphyrinic microsensor has been used to investigate the release of nitric oxide (NO) from human platelets in whole blood and in washed platelet suspensions. Basal release of NO was not detectable. Aggregation of platelets by collagen (1-15 micrograms/ml) but not by thrombin (0.1 U/ml) resulted in a concentration-dependent release of NO. This release was prolonged and potentiated by L-arginine (100-1000 microM) and inhibited by NG-monomethyl-L-arginine (300 microM). These data support our previous findings that human platelets generate NO during aggregation.


Ultrafast Removal of Cadmium(II) by Green Cyclodextrin Metal-Organic-Framework-Based Nanoporous Carbon: Adsorption Mechanism and Application.
Water contaminated with heavy metals has been identified as a significant threat to human health. Therefore, the development of safe and rapid water-treatment techniques is necessary. We have synthesized an eco-friendly γ-cyclodextrin metal-organic framework (MOF)-based nanoporous carbon (γ-CD MOF-NPC) material, conducted a comprehensive characterization of it, and found its rapid and effective CdII -removal capacity. The γ-CD MOF-NPC could effectively sequester a majority of cadmium ions within one minute, and it still demonstrated excellent adsorption ability under various conditions, including different pH, adsorbent dosage, and coexistent ions. The maximum adsorption capacity was calculated to be 140.85 mg g-1 by means of the Langmuir model. The adsorption was primarily due to the effect of ion exchange of oxygen-containing functional groups, as determined by studying the ζ potential and Fourier transform infrared spectroscopy. Flow-through experiments further proved the rapid CdII -removal capacity and potential of the practical application of γ-CD MOF-NPC in water treatment according to the cytotoxic data.


Effects of acute voluntary loaded wheel running on BDNF expression in the rat hippocampus.
Voluntary loaded wheel running involves the use of a load during a voluntary running activity. A muscle-strength or power-type activity performed at a relatively high intensity and a short duration may cause fewer apparent metabolic adaptations but may still elicit muscle fiber hypertrophy. This study aimed to determine the effects of acute voluntary wheel running with an additional load on brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Ten-week old male Wistar rats were assigned randomly to a (1) sedentary (Control) group; (2) voluntary exercise with no load (No-load) group; or (3) voluntary exercise with an additional load (Load) group for 1-week (acute period). The expression of BDNF genes was quantified by real-time PCR. The average distance levels were not significantly different in the No-load and Load groups. However, the average work levels significantly increased in the Load group. The relative soleus weights were greater in the No-load group. Furthermore, loaded wheel running up-regulated the BDNF mRNA level compared with that in the Control group. The BDNF mRNA levels showed a positive correlation with workload levels (r=0.75), suggesting that the availability of multiple workload levels contributes to the BDNF-related benefits of loaded wheel running noted in this study. This novel approach yielded the first set of findings showing that acute voluntary loaded wheel running, which causes muscular adaptation, enhanced BDNF expression, suggesting a possible role of high-intensity short-term exercise in hippocampal BDNF activity.


A p-Type Zinc-Based Metal-Organic Framework.
An original concept for the property tuning of semiconductors is demonstrated by the synthesis of a p-type zinc oxide (ZnO)-like metal-organic framework (MOF), (ZnC2O3H2)n, which can be regarded as a possible alternative for ZnO, a natural n-type semiconductor. When small oxygen-rich organic linkers are introduced to the Zn-O system, oxygen vacancies and a deep valence-band maximum, the two obstacles for generating p-type behavior in ZnO, are restrained and raised, respectively. Further studies of this material on the doping and photoluminescence behaviors confirm its resemblance to metal oxides (MOs). This result answers the challenges of generating p-type behavior in an n-type-like system. This concept reveals that a new category of hybrid materials, with an embedded continuous metal-oxygen network, lies between the MOs and MOFs. It provides concrete support for the development of p-type hybrid semiconductors in the near future and, more importantly, the enrichment of tuning possibilities in inorganic semiconductors.


Feasibility of Biventricular Repair in Right Dominant Unbalanced Atrioventricular Septal Defect: A New Echocardiographic Metric to Refine Surgical Decision-Making.
Unbalanced forms of atrioventricular septal defect continue to be challenging and present poor surgical outcomes. Echocardiographic indicators such as atrioventricular valve index, right ventricle/left ventricle inflow angle, and size of the ventricular septal defect have been identified as relevant discriminators that may guide surgical strategy. Our purpose is to describe another metric to refine surgical decision-making. We outline a geometrical description of the anatomic features of atrioventricular septal defect and describe equations that help explain the interplay between the main echocardiographic variables. A new metric called "indexed ventricular septal defect" is defined as the size of the defect in relation to the valve diameter. We derive a final equation relating this index with the atrioventricular valve index and the right ventricle/left ventricle inflow angle. In the light of that equation, we discuss the interdependence of variables and employ data from a Congenital Heart Surgeons' Society study to set the limits of the new index. Combined use of indexed ventricular septal defect and atrioventricular valve index might help clarify surgical decision-making in patients with mild and moderate unbalance (modified atrioventricular valve index between 0.2 and 0.39). For indexed ventricular septal defect smaller than 0.2, biventricular repair may be recommended. Between 0.2 and 0.35, this strategy could probably be achieved depending on other factors. However, other strategies should be considered for those patients showing an indexed ventricular septal defect between 0.35 and 0.5. For values above 0.5 to 0.55, univentricular palliation might be a reasonable strategy.


Amphotericin B Resistant Apophysomyces elegans Causing Rhino-oculo-Cerebral Mucormycosis in an Immunocompetent Host.
Mucormycosis, an angioinvasive infection is caused by the ubiquitous filamentous fungi of the order Mucorales and class Mucormycetes. Reports of this disease are on the rise over the past few decades. Rhino-oculo-Cerebral presentation associated with uncontrolled diabetes is the predominant characteristic of this entity. We report here a case of rhinooculocerebral mucormycosis (ROCM) due to Apophysomyces elegans (A. elegans) in a 45-year-old diabetic lady with background illness of hypothyroidism and polyradiculoneuropathy. Though this condition is usually managed with surgical debridement of the affected tissue and medical therapy with Amphotericin B, the isolate recovered in our case was found to be resistant to Amphotericin B.


Transposition of ISHp608, member of an unusual family of bacterial insertion sequences.
ISHp608 from Helicobacter pylori is active in Escherichia coli and represents a recently recognised group of insertion sequences. Its transposase and organisation suggest that it transposes using a different mechanism to that of other known transposons. The IS was shown to excise as a circular form, which is accompanied by the formation of a resealed donor plasmid backbone. We also demonstrate that TnpA, which is less than half the length of other transposases, is responsible for this and for ISHp608 transposition. Transposition was shown to be site specific: both insertion and transposon excision require a conserved target, 5'TTAC. Deletion analysis suggested that potential secondary structures at the left and right ends are important for transposition. In vitro TnpA bound both ends, showed a strong preference for a specific single-stranded DNA and introduced a single-strand break on the same strand at each end. Although many of the characteristics of ISHp608 appear similar to rolling-circle transposons, there are differences suggesting that, overall, transposition occurs by a different mechanism. The results have permitted the formulation of several related models.


Study of the triplet periodicity phase shifts in genes.
The definition of a phase shift of triplet periodicity (TP) is introduced. The mathematical algorithm for detection of TP phase shift of nucleotide sequences has been developed. Gene sequences from Kegg-46 data bank were analyzed with a purpose of searching genes with a phase shift of TP. The presence of a phase shift of triplet periodicity has been shown for 318329 genes (approximately 10% from the number of genes in Kegg-46). We suppose that shifts of the TP phase may indicate the shifts of reading frame (RF) in genes. A relationship between the phase shifts of TP and the frame shifts in genes is discussed.


Wild flora of mine tailings: perspectives for use in phytoremediation of potentially toxic elements in a semi-arid region in Mexico.
The aim of this research was to identify wild plant species applicable for remediation of mine tailings in arid soils. Plants growing on two mine tailings were identified and evaluated for their potential use in phytoremediation based on the concentration of potentially toxic elements (PTEs) in roots and shoots, bioconcentration (BCF) and translocation factors (TF). Total, water-soluble and DTPA-extractable concentrations of Pb, Cd, Zn, Cu, Co and Ni in rhizospheric and bulk soil were determined. Twelve species can grow on mine tailings, accumulate PTEs concentrations above the commonly accepted phytotoxicity levels, and are suitable for establishing a vegetation cover on barren mine tailings in the Zimapan region. Pteridium sp. is suitable for Zn and Cd phytostabilization. Aster gymnocephalus is a potential phytoextractor for Zn, Cd, Pb and Cu; Gnaphalium sp. for Cu and Crotalaria pumila for Zn. The species play different roles according to the specific conditions where they are growing at one site behaving as a PTEs accumulator and at another as a stabilizer. For this reason and due to the lack of a unified approach for calculation and interpretation of bioaccumulation factors, only considering BCF and TF may be not practical in all cases.


Mycetoma in West Africa.
Mycetoma is a neglected disease, which is socioeconomically important, and with the possibility of permanent disability in infected persons if not treated early. This is especially true in resource-limited settings such as West Africa, where there is a lack of facilities and skilled personnel to make a definitive laboratory diagnosis. Countries in West Africa have similar climatic conditions to Sudan. The majority of patients seek medical care very late, when there is already bone involvement, resulting in amputations. This results in poor capture of the true burden of the problem in the literature. A review of the literature revealed about 2685 documented cases in West Africa from 1929 to 2020; from 15 out of 16 countries, Senegal accounted for 74.1% (1943) of cases in the subregion. The majority of lesions were found on the foot; however, other body parts were also reported. Rural dwellers accounted for most cases. Only 547 (20.4%) cases had identified isolates reported. Actinomycetoma accounted for 47.9% of cases, eumycetoma 39.7% and unidentified pathogens 12.4%. Actinomadura pelletieri was the predominant pathogen isolated (21.4%; 117 isolates). There is a dire need for capacity building, provision of facility and health education to raise awareness of this debilitating disease in West Africa.


A Self-Learning Discrete Jaya Algorithm for Multiobjective Energy-Efficient Distributed No-Idle Flow-Shop Scheduling Problem in Heterogeneous Factory System.
In this study, a self-learning discrete Jaya algorithm (SD-Jaya) is proposed to address the energy-efficient distributed no-idle flow-shop scheduling problem (FSP) in a heterogeneous factory system (HFS-EEDNIFSP) with the criteria of minimizing the total tardiness (TTD), total energy consumption (TEC), and factory load balancing (FLB). First, the mixed-integer programming model of HFS-EEDNIFSP is presented. An evaluation criterion of FLB combining the energy consumption and the completion time is introduced. Second, a self-learning operators selection strategy, in which the success rate of each operator is summarized as knowledge, is designed for guiding the selection of operators. Third, the energy-saving strategy is proposed for reducing the TEC. The energy-efficient no-idle FSP is transformed to be an energy-efficient permutation FSP to search the idle times. The speed of operations which adjacent are idle times is reduced. The effectiveness of SD-Jaya is tested on 60 benchmark instances. On the quality of the solution, the experimental results reveal that the efficacy of the SD-Jaya algorithm outperforms the other algorithms for addressing HFS-EEDNIFSP.


Using point-of-care CD34 enumeration to optimize PBSC collection conditions.
A PBSC graft containing 4-5 x 10(6) CD34(+) cells/kg is considered optimal in terms of durable engraftment. Tracking CD34 kinetics via point-of-care testing during PBSC mobilization could determine which (and when) patients will yield an optimal product. We evaluated whether microvolume fluorimetry (MVF) would be useful in optimizing PBSC mobilization/harvest and if it will shorten our standard 6 h collection. Absolute CD34 values were obtained using the IMAGN 2000 and STELLer CD34 assay (50 microL sample volume). Peripheral blood (PB) CD34 values from 30 patients undergoing PBSC mobilization were used to generate a PB CD34-based algorithm that would predict collection day/duration of apheresis. The algorithm was then used prospectively to collect PBSC products on 50 hematologic malignancy (HM) patients. Using the algorithm, patients were assigned to either a 6 (11-20 CD34/microL), 4 (21-49 CD34/microL) or 2 (> or = 50 CD34/microL) h collection. Patients with a CD34 value < or = 10/microL were re-tested. All patients (n = 43) predicted to mobilize reached the optimal CD34 (4-5 x 10(6)/kg) value with 1.0 apheresis procedure; seven patients had < or = 10/microL (nonmobilizers). The majority (75%) had apheresis charges decreased by 33-66%; 47% only required a 2 h procedure and 28% required 4 h. All patients demonstrated rapid trilineage engraftment. Absolute PB CD34 measurement using MVF offers a rapid and reliable approach to obtaining optimal PBSC products with minimal technical expertise. Although not a replacement for conventional flow cytometry, it meets the requirements for a point-of-care procedure.


Protection of retinal cells from ischemia by a novel gap junction inhibitor.
Retinal cells which become ischemic will pass apoptotic signal to adjacent cells, resulting in the spread of damage. This occurs through open gap junctions. A class of novel drugs, based on primaquine (PQ), was tested for binding to connexin 43 using simulated docking studies. A novel drug has been synthesized and tested for inhibition of gap junction activity using R28 neuro-retinal cells in culture. Four drugs were initially compared to mefloquine, a known gap junction inhibitor. The drug with optimal inhibitory activity, PQ1, was tested for inhibition and was found to inhibit dye transfer by 70% at 10 microM. Retinal ischemia was produced in R28 cells using cobalt chloride as a chemical agent. This resulted in activation of caspase-3 which was prevented by PQ1, the gap junction inhibitor. Results demonstrate that novel gap junction inhibitors may provide a means to prevent retinal damage during ischemia.


Life cycle assessment of edible insects (Protaetia brevitarsis seulensis larvae) as a future protein and fat source.
Because it is important to develop new sustainable sources of edible protein, insects have been recommended as a new protein source. This study applied Life Cycle Assessment (LCA) to investigate the environmental impact of small-scale edible insect production unit in South Korea. IMPACT 2002 + was applied as the baseline impact assessment (IA) methodology. The CML-IA baseline, EDIP 2003, EDP 2013, ILCD 2011 Midpoint, and ReCiPe midpoint IA methodologies were also used for LCIA methodology sensitivity analysis. The protein, fat contents, and fatty acid profile of the investigated insect (Protaetia brevitarsis seulensis larvae) were analyzed to determine its potential food application. The results revealed that the studied edible insect production system has beneficial environmental effects on various impact categories (ICs), i.e., land occupation, mineral extraction, aquatic and terrestrial ecotoxicity, due to utilization of bio-waste to feed insects. This food production system can mitigate the negative environmental effects of those ICs, but has negative environmental impact on some other ICs such as global warming potential. By managing the consumption of various inputs, edible insects can become an environmentally efficient food production system for human nutrition.


Should we use central venous saturation to guide management in high-risk surgical patients?
Measurements of central venous oxygen saturation (ScvO2) have been successfully used to guide haemodynamic therapy in critical care. The efficacy of this approach in the treatment of severe sepsis and septic shock has stimulated interest in the use of ScvO2 to guide management in patients undergoing major surgery. The physiological basis of ScvO2 measurement is complex. A number of outstanding issues will need to be resolved before incorporating ScvO2 measurement into routine practice. First, it is not yet clear which value of ScvO2 should be targeted. Second, there is some uncertainty as to which interventions are the most effective for achieving the desired value of ScvO2 or how long this value should be maintained. The study by The Collaborative Study Group on Perioperative ScvO2 Monitoring published in this edition of Critical Care may help provide answers to some of these questions. Our understanding of ScvO2 measurement remains limited, however, and the routine use of peri-operative ScvO2-guided goal-directed therapy cannot be recommended until a large randomised trial has confirmed the value of this approach.


[Stress-buffering effects of perceived social supports from family members and friends: a comparison of college students and middle-aged adults].
This study investigated perceived social support, emotional as well as instrumental, from family members and friends, and examined their stress-buffering effects on depression in college students and middle-aged adults in Japan. For both samples, family members were relatively more important sources of instrumental support, whereas friends were primarily perceived as emotional support providers. No gender differences were found for the middle-aged adults, but as in previous studies, women in the college sample perceived more support for them than men. A series of hierarchical regression analyses with support by stress interaction terms revealed distinctive patterns of support effects on depression for men and women of each sample. Characteristics of perceived social support in each sample were described, and overall results suggested that it is essential in social support research to take the meanings of supportive relationship into consideration, in the context of social and developmental factors of the samples under study.


Dextran as a Resorbable Coating Material for Flexible Neural Probes.
In the quest for chronically reliable and bio-tolerable brain interfaces there has been a steady evolution towards the use of highly flexible, polymer-based electrode arrays. The reduced mechanical mismatch between implant and brain tissue has shown to reduce the evoked immune response, which in turn has a positive effect on signal stability and noise. Unfortunately, the low stiffness of the implants also has practical repercussions, making surgical insertion extremely difficult. In this work we explore the use of dextran as a coating material that temporarily stiffens the implant, preventing buckling during insertion. The mechanical properties of dextran coated neural probes are characterized, as well as the different parameters which influence the dissolution rate. Tuning parameters, such as coating thickness and molecular weight of the used dextran, allows customization of the stiffness and dissolution time to precisely match the user's needs. Finally, the immunological response to the coated electrodes was analyzed by performing a histological examination after four months of in vivo testing. The results indicated that a very limited amount of glial scar tissue was formed. Neurons have also infiltrated the area that was initially occupied by the dissolving dextran coating. There was no noticeable drop in neuron density around the site of implantation, confirming the suitability of the coating as a temporary aid during implantation of highly flexible polymer-based neural probes.


Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms.
To compare the preoperative and postoperative health-related quality of life (QOL) and psychological state of patients with asymptomatic unruptured intracranial aneurysms (ICAs) who underwent elective surgery. Out of 67 patients who underwent neck clipping of ICAs, we assessed the QOL of 61 patients using Short Form-36 (SF-36); their psychological state was rated on the Hospital Anxiety and Depression Scale (HADS) before, 3 months, and 1 and 3 years after treatment. The preoperative mean scores for each of the eight SF-36 domains except bodily pain were significantly lower in the study population than in the reference population. 14 (20.9%) patients experienced surgical complications defined as neurological deterioration and/or abnormal CT findings within 30 days of the operation. Despite some complications, the QOL of all operated patients returned to the mean level of the reference population 3 years after treatment. At 3 months after surgery, the scores for psychosocial activities and general health perception were transiently below the preoperative levels. According to the HADS, the patients experienced mild anxiety before the operation; it disappeared by the third postoperative month. Preoperatively, patients with unruptured ICAs reported a significantly decreased QOL. It further declined transiently after elective surgery, but it returned to the mean level recorded for the reference population within 3 years. Our findings suggest that these patients derived significant QOL benefits from their surgery. Hence subjective QOL issues should be considered in deciding whether treatment-related risks and their natural history, such as their potential rupture, warrant surgery of asymptomatic unruptured ICAs.


Increased production of prostacyclin (PGI2) by vascular intimal smooth muscle cells from atherosclerotic rabbit aorta.
In vitro PGI2 synthesis by aortic strips obtained from thoracic aorta of rabbits fed a high cholesterol diet was examined and compared with that of control rabbits fed a normal diet. In this report, the amounts of PGI2 produced were shown as 6-keto-PGF1 alpha per microgram of aortic tissue DNA instead of per mg wet weight. We also investigated PGI2 synthesis by cultured smooth muscle cells (SMC) obtained from atherosclerotic intima. Basal PGI2 production by aortic strips from atherosclerotic rabbit aorta was significantly augmented compared with that of controls. Arachidonic acid (AA)-induced PGI2 production by atherosclerotic aorta was also significantly higher than that of controls. PGI2 producing capacities of intimal and medial layers, separated from atherosclerotic aorta, were examined and the intimal layer was found to elicit a significantly greater PGI2 production than the medial layer. Furthermore, cultured intimal SMC obtained from atherosclerotic rabbit aorta produced a greater amount of PGI2 than medial SMC from normal rabbit aorta at various cultured conditions. These results suggest that the possibility of enhanced PGI2 production by atherosclerotic aorta may well be considered as a defence mechanism of the vessel wall against damaging stimuli.


Continuous low-level heat wrap therapy provides more efficacy than Ibuprofen and acetaminophen for acute low back pain.
A prospective, randomized, single (investigator) blind, comparative efficacy trial was conducted. To compare the efficacy of continuous low-level heat wrap therapy (40 C, 8 hours/day) with that of ibuprofen (1200 mg/day) and acetaminophen (4000 mg/day) in subjects with acute nonspecific low back pain. The efficacy of topical heat methods, as compared with oral analgesic treatment of low back pain, has not been established. Subjects (n = 371) were randomly assigned to heat wrap (n = 113), acetaminophen (n = 113), or ibuprofen (n = 106) for efficacy evaluation, or to oral placebo (n = 20) or unheated back wrap (n = 19) for blinding. Outcome measures included pain relief, muscle stiffness, lateral trunk flexibility, and disability. Efficacy was measured over two treatment days and two follow-up days. Day 1 pain relief for the heat wrap (mean, 2) was higher than for ibuprofen (mean, 1.51; P = 0.0007) or acetaminophen (mean, 1.32; P = 0.0001). Extended mean pain relief (Days 3 to 4) for the heat wrap (mean, 2.61) also was higher than for ibuprofen (mean, 1.68; P = 0.0001) or acetaminophen (mean, 1.95; P = 0.0009). Lateral trunk flexibility was improved with the heat wrap (mean change, 4.28 cm) during treatment (P </= 0.009 vs acetaminophen [mean change, 2.93 cm], P </= 0.001 vs ibuprofen [mean change, 2.51 cm]). The results were similar on Day 4. Day 1 reduction in muscle stiffness with the heat wrap (mean, 16.3) was greater than with acetaminophen (mean, 10.5; P = 0.001). Disability was reduced with the heat wrap (mean, 4.9), as compared with ibuprofen (mean, 2.7; P = 0.01) and acetaminophen (mean, 2.9; P = 0.0007), on Day 4. None of the adverse events were serious. The highest rate (10.4%) was reported in the ibuprofen group. Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain.


Predictors of development of diabetes mellitus in patients with coronary artery disease taking antihypertensive medications (findings from the INternational VErapamil SR-Trandolapril STudy [INVEST]).
Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, beta blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p <0.01). Characteristics associated with risk for newly diagnosed DM included United States residence, left ventricular hypertrophy, previous stroke/transient ischemic attack, Hispanic ethnicity, coronary revascularization, hypercholesterolemia, greater body mass index, and higher follow-up systolic BP. Addition of trandolapril to verapamil SR decreased DM risk and addition of hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings associated with more severe vascular disease and Hispanic ethnicity identify a group at high risk for developing DM, whereas lower on-treatment BP and treatment with verapamil SR-trandolapril attenuated this risk.


GABPB1-AS1 Promotes the Development of Osteosarcoma by Targeting SP1 and Activating the Wnt/β-Catenin Pathway.
In this study, the role of GABPB1-AS1 in osteosarcoma (OS) was analyzed. The expression of GABPB1-AS1 in different OS cell lines U2OS, HOS, MG63, and hFOB1.19 was detected. SiRNA GABPB1-AS1 was transfected with U2OS and HOS cell lines. The effects of GABPB1-AS1 silencing on proliferation, clonal formation, and migration of U2OS and HOS were detected by CCK-8 method, plate cloning method, and Transwell chamber. Western blot analysis was used to detect the protein levels of SP1, Wnt, β-catenin, c-Myc, and SOX2 in osteosarcoma cells. The binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells was detected by a dual-luciferase reporter gene assay. Results showed that GABPB1-AS1 was higher in OS cells than that in hFOB1.19. Silencing GABPB1-AS1 inhibited the proliferation, clonal formation, migration, and epithelial-mesenchymal transformation of U2OS and HOS. There was a binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells. GABPB1-AS1 mediated osteosarcoma cells via the SP1/Wnt/β-catenin signaling pathway. This study suggested that GABPB1-AS1 plays a carcinogenic role in OS through the SP1/Wnt/β-catenin signaling pathway through competitive binding and inhibition of miR-199a-3p.


[Lucien-Henri-Armand Coullon, called Pascalon, pharmacist, poet and humorist (1860-1940?)].
Under the pseudonym of Pascalon, L.-H.-A. Coullon published several compilations of poems. The authors present the most important of these anthologies, Les Refrains de l'officine, as well as the personality of their creator. By means of this example they draw up a definition of "pharmaceutical humor".


Not only for Christmas: Prophylactic oral application of trans-cinnamaldehyde alleviates acute murine campylobacteriosis.
The prevalence of Campylobacter jejuni infections is increasing worldwide and responsible for significant morbidities and socioeconomic expenses. The rise in antimicrobial resistance of C. jejuni underscores the urge for evaluating antibiotics-independent compounds as therapeutic and preventive treatment options of human campylobacteriosis. Given its well-known anti-microbial and immune-modulatory properties we here surveyed the disease-modifying effects of trans-cinnamaldehyde pretreatment in experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally challenged with trans-cinnamaldehyde starting 7 days prior C. jejuni infection. Whereas gastrointestinal colonization properties of the enteropathogens remained unaffected, trans-cinnamaldehyde pretreatment did not only improve clinical signs in infected mice, but also alleviated colonic epithelial cell apoptosis on day 6 post-infection. Furthermore, trans-cinnamaldehyde application resulted in less pronounced T cell responses in the colon that were accompanied by dampened proinflammatory mediator secretion in distinct intestinal compartments. Notably, the immune-modulatory effects of trans-cinnamaldehyde were not restricted to the intestinal tract but could also be observed in extra-intestinal organs such as the liver and kidneys. In conclusion, our preclinical placebo-controlled intervention study provides first evidence that due to its immune-modulatory effects, trans-cinnamaldehyde constitutes a promising prophylactic option to alleviate campylobacteriosis.


Kirenol Inhibits the Function and Inflammation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis in vitro and in vivo.
Kirenol is a diterpenoid extracted from the Chinese herbal medicine Siegesbeckiae. Siegesbeckiae has been used to treat Rheumatoid arthritis (RA) in China for several centuries. RA is characterized by the proliferation of synoviocytes in inflamed synovia, as well as by their expression of inflammatory cytokines. In the present study, we found that Kirenol inhibited the migration, invasion, and proinflammatory of IL-6 secretion of RA-associated synovial fibroblasts (FLS) at a concentration of 100-200 μg/ml in vitro. Proinflammatory cytokines production and synovium hyperplasia and cartilage erosion were also inhibited in a collagen-induced arthritis (CIA) mouse model upon Kirenol treatment. Together, our results thus confirm that Kirenol has potent therapeutic efficacy in RA owing to its ability to suppress negative FLS activities.


Electronic notebooks in the post-america invents act world.
The enactment of the America Invents Acts (AIA) lit a fire under the feet of the patent community in 2013 when the United States instituted a "first-to-file" system. At first glance, many believed that these new laws greatly reduced the need to be diligent in keeping laboratory notebooks. However, it is still imperative to maintain laboratory notebooks, especially in view of some of the potential pitfalls associated with electronic notebooks and their use in a court of law in this post-AIA world.


Occupational Therapy Management of a Moderate COVID-19 Disease Process in a Skilled Nursing Facility: A Case Report.
Older adults living in skilled nursing facilities (SNFs) and long-term care facilities are particularly susceptible to the coronavirus disease 2019 virus and face unique challenges during their rehabilitation process. This case report highlights the disease and rehabilitation course of an older adult who received all of his medical and rehabilitative treatment while residing in a SNF. The occupational therapy evaluation and intervention processes, as well as the client's response to intervention, are described. The client's positive outcomes are linked directly to occupational therapy's ability to incorporate medical, physical, and psychosocial aspects into part of the interdisciplinary model of care in a SNF.


A histopathological diagnosis of mesenteric cystic lymphangioma, clinically misdiagnosed as simple mesenteric cyst - case report.
Abdominal cystic lymphangiomas are relatively rare congenital malformations, predominantly found in the pediatric age group. They are usually found in the head and neck of affected children. Lymphangioma of the small-bowel mesentery is rare, having been reported for less than 1% of all lymphangiomas. The gross and histopathological findings may resemble benign multicystic mesothelioma and lymphangiomyoma. The immunohistochemical study for factor VIII-related antigen, D2-40, calretinin and human melanoma black-45 (HMB-45) is essential for diagnosis. Factor VIII-related antigen and D2-40 are positive in lymphangioma but negative in benign multicystic mesothelioma. HMB-45 shows positivity in the smooth-muscle cells around the lymphatic spaces of the lymphangiomyoma. This report describes a case of a large mesenteric lymphatic cyst identified in the neonatal period. Early diagnosis was possible due to the prenatal imagistic methods. Fetal ultrasound identified in the 17th week of gestational life an abdominal tumor that increased with fetal growth. The anatomopathological differential diagnosis and modalities of treatment are also discussed.


Allowing patients to decide.
...allowing physicians to withhold life support and resuscitation because they feel it is futile, no matter how beneficent their intentions, would be an unwarranted step backwards toward the type of paternalism modern American society has turned away from. If we agree that all professional ethics must, in some way, be responsive to the society that profession serves, then in these most critical situations, the final decision must rest with the patient.


Identification of microRNA that represses IRS-1 expression in liver.
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs have recently been implicated in glucose metabolism, but the roles of miRNAs in insulin-resistant conditions, such as obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3' untranslated region (3' UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3' UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.


Multiple roles for basement membrane proteins in cancer progression and EMT.
Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is the principal reason for increased mortality. The epithelial-mesenchymal transition (EMT) of the basement membrane (BM) allows cells of epithelial phenotype to transform into a mesenchymal-like (quasi-mesenchymal) phenotype and metastasize via the lymphovascular system through a metastatic cascade by intravasation and extravasation. This helps in the progression of carcinoma from the primary site to distant organs. Collagen, laminin, and integrin are the prime components of BM and help in tumor cell metastasis, which makes them ideal cancer drug targets. Further, recent studies have shown that collagen, laminin, and integrin can be used as a biomarker for metastatic cells. In this review, we have summarized the current knowledge of such therapeutics, which are either currently in preclinical or clinical stages and could be promising cancer therapeutics. DATA AVAILABILITY: Not applicable.


Rapidly dissolving repaglinide powders produced by the ultra-rapid freezing process.
The objective of the study was to produce rapidly dissolving formulations of the poorly water-soluble drug repaglinide using an innovative new technology, ultra-rapid freezing (URF), and to investigate the influence of excipient type on repaglinide stability. Repaglinide compositions containing different types and levels of excipients and different drug potencies (50%-86%) were produced by the URF technology. Repaglinide/excipient solutions were frozen on a cryogenic substrate, collected, and lyophilized to form a dry powder. Surfactants, including sodium dodecyl sulfate, and alkalizing agents such as diethanolamine (DEA) and tromethamine (TRIS) were incorporated into the compositions. Forced degradation of repaglinide was conducted under stressed conditions (eg, elevated temperature, exposure to peroxide) to determine the stability of the drug in such environments. The solubility of repaglinide increased as a function of increasing pH; therefore, incorporation of an alkalizing agent into the URF formulations increased the drug's solubility. Drug instability resulted when the drug was exposed to pH values above 9.0. URF formulations containing alkalizing agents showed no degradation or spontaneous recrystallization in the formulation, indicating that increased stability was afforded by processing. URF processing created nanostructured drug/excipient particles with higher dissolution rates than were achieved for unprocessed drug. Alkalizing agents such as TRIS and DEA, present at levels of 25% to 33% wt/wt in the formulations, did not cause degradation of the drug when processed using URF. URF processing, therefore, yielded fast-dissolving formulations that were physically and chemically stable, resistant to alkali degradation or spontaneous recrystallization in the formulation.


Hemodynamic effects of oral contraceptives during exercise.
The effects of a combined oral contraceptive pill on female hemodynamics during exercise were studied in 14 young, healthy women. The increase in blood volume, stroke volume, and cardiac output during exercise was significantly greater during combined oral contraceptive therapy than when the patients were not taking the pill. The use of combined oral contraceptive pills may be advantageous to the physical fitness of female athletes.


Use of cyanide antidotes in burn patients with suspected inhalation injuries in North America: a cross-sectional survey.
This study aimed to assess the use of cyanide antidotes and the determine the opinion on empiric administration of hydroxocobalamin in North American burn patients with suspected smoke inhalation injuries. An online cross-sectional survey was sent to directors of 90 major burn centers in North America, which were listed on the American Burn Association Web site. A multiple-choice format was used to determine the percentage of patients tested for cyanide poisoning on admission, the current administration of a cyanide antidote based solely on clinical suspicion of poisoning, and the antidote used. To ascertain views on immediate administration of hydroxocobalamin before confirmation of cyanide poisoning an option was included to expand the response in written format. Twenty-nine of 90 burn directors (32%) completed the survey. For the population of interest, the majority of burn centers (59%) do not test for cyanide poisoning on admission and do not administer an antidote based solely on clinical suspicion of cyanide poisoning (58%). The most commonly available antidote is hydroxocobalamin (50%), followed by the cyanide antidote kit (29%). The opinion regarding instant administration of hydroxocobalamin when inhalation injury is suspected is mixed: 31% support its empiric use, 17% do not, and the remaining 52% have varying degrees of confidence in its utility. In North America, most patients burnt in closed-space fires with inhalation injuries are neither tested for cyanide poisoning in a timely manner nor empirically treated with a cyanide antidote. Although studies have shown the safety and efficacy of empiric and immediate administration of hydroxocobalamin, most centers are not willing to do so.


In vitro screening of probiotic characteristics of some italian products.
Six commercial probiotic products produced and marketed Italy (containing Lactobacillus GG, Lactobacillus casei DG, Lactobacillus reuteri, Bacillus clausii spores, Bifidobacterium longum and Saccharomyces boulardii) were assayed for their stability during storage, acid, base and bile tolerance and adherence to human intestinal cells. Results indicate that storage, even at conditions established by manufacturers, affects the microbial content of products based on B. longum and partially of that containing L. casei GG . Differences in acid and bile tolerance were found for the products, S. boulardii being better able to survive acid and bile than bacteria. Vegetative cells of B. clausii and B. longum were more susceptible than lactobacilli to low pH values, while fewer differences were found for bile tolerance. Lactobacilli and only partially B. longum, were able to adhere to Caco-2 cells, while S. boulardii and B. clausii showed reduced adherence to human intestinal cells. In conclusion, the products did not completely fulfill all probiotic attributes.


Fcgamma receptor IIIA polymorphism in Korean patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complex, which is cleared by Fcgamma receptors. Genotype analysis was done to investigate whether the FcgammaRIIIA-176F/V polymorphism is a risk factor for SLE in Koreans. We genotyped 145 Korean SLE patients and 75 control subjects for FcgammaRIIIA-176F/ V. After amplifying a 1.7-kb fragment containing the Fcgamma/RIIIA-176F/V polymorphic site using two FcgammaRIIIA gene-specific primers, we performed a nested polymerase chain reaction (PCR) for allele-specific genotyping at position 559 in FcgammaRIIIA. FcgammaRIIIA genotype or allele distribution was not significantly different between lupus patients and controls, and also between lupus nephritis patients and healthy controls. Neither creatinine clearance, 24 h urine proteinuria, number of American College of Rheumatology (ACR) criteria, nor the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index was different according to the genotype. In conclusion, FcgammaRIIIA-176F/V polymorphism is not associated with SLE in Koreans.


Using Tablet-Based Assessment to Characterize Speech for Individuals with Dementia and Mild Cognitive Impairment: Preliminary Results.
Early detection of dementia as well as improvement in diagnosis coverage has been increasingly important. Previous studies involved extracting speech features during neuropsychological assessments by humans, such as medical pro- fessionals, and succeeded in detecting patients with dementia and mild cognitive impairment (MCI). Enabling such assessment in an automated fashion by using computer devices would extend the range of application. In this study, we developed a tablet-based application for neuropsychological assessments and collected speech data from 44 Japanese native speakers including healthy controls (HCs) and those with MCI and dementia. We first extracted acoustic and phonetic features and showed that several features exhibited significant difference between HC vs. MCI and HC vs. dementia. We then constructed classification models by using these features and demonstrated that these models could differentiate MCI and dementia from HC with up to 82.4 and 92.6% accuracy, respectively.


Thrombotic thrombocytopenic purpura in a patient treated with imatinib mesylate: true association or mere coincidence?
Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic hemolytic anemia, is a relatively rare disorder. The majority of cases have no defined causes. TTP has been reported in association with many drugs, but not with imatinib mesylate. We report a 22-year-old African-American woman who developed idiopathic hypereosinophilic syndrome. She was treated with imatinib mesylate and subsequently developed microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. TTP was diagnosed. A kidney biopsy was performed and was diagnostic of thrombotic microangiopathy. The patient was treated with plasma exchange and hemodialysis. Her eosinophilia resolved, but she remained dialysis dependent. To our knowledge, this is the first case report of the possible association between imatinib mesylate and TTP.


Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes.
We studied the pharmacokinetics and clinical outcome of a new once-daily intravenous area under the curve-targeted dosing scheme for busulfan based on body surface area. Eighteen children undergoing busulfan-based conditioning for allogeneic stem cell transplantation were enrolled. The age of the children ranged from 0.5 to 16 years. For all children, the starting dose was 80 mg/m. Unlimited dose adjustment was allowed to reach the target area under the curve (3800 micromol/l . min). This target area under the curve was determined on the basis of a previous study in our hospital. Pharmacokinetic studies were performed after the first dose. The median area under the curve on day 1 was 2616 (range 1781-5040) micromol/l . min at a dose of 80 mg/m. This resulted in a median dose increment to 114 (range 62-168) mg/m to reach the target area under the curve. In only one patient, the dose was decreased. Donor engraftment was established in 14 out of 18 patients (78%). Two of the four patients were successfully retransplanted. Relapse occurred in two patients (one died, one received additional treatment). Fourteen patients survived with a median follow-up of 1.6 years (1.0-2.2 years). The disease-free survival was 66% (12 of 18 patients). Despite the high systemic peak levels, there was no new unexpected or unusual toxicity. Moderate veno-occlusive disease was seen in one patient only. We conclude that intravenous busulfan in children administered once daily is safe, convenient and feasible, and can be dosed surface-based, independent of age. There was very limited (liver) toxicity, but the rejection rate was relative high, which can be probably overcome by a higher exposure to busulfan. Future investigations should be aimed at further optimizing the target area under the curve of intravenous busulfan for specific patient groups.


Does stress affect bleeding in hemophilia? A review of the literature.
Many bleeding episodes in hemophilia are thought to be related to ambient stress. The evidence in support of this hypothesis comes from a variety of anecdotal and clinical reports. Whether or not stress leads to bleeding has had little direct study in a prospective way, however, and methodological problems affect most of the studies in this field. This paper examines the evidence in support of this hypothesis and suggests ways to improve research relating stress to bleeding.


Extrinsic bronchial obstruction caused by scoliosis.
A case report. To emphasize the importance of monitoring the breathing capacity in patients with moderate to severe scoliosis, even in adulthood. Diseases that disturb the structure of the chest wall affect the function of the respiratory pump. Restrictive respiratory pattern is caused by severe scoliosis. However, scoliosis may provoke obstructive changes due to compression of the airways. It can be a direct compression because of imprinting of vertebral bodies, or an indirect one, due to rotation forces. METHODS.: We have collected data from the patients' clinical history and have reviewed similar published cases. a white female, with frequent respiratory tract infections during her childhood. She was diagnosed as having 55° right T5-T11 scoliosis. At age of 26, an increase of her pulmonary symptoms appeared with difficulty to expel mucus and medium efforts dyspnea. A computed axial tomographic scan showed T8 vertebral body pushing against the right intermediate bronchus. A bronchoscopy found a decrease in the bronchial area, with near contact between the walls. Lung function test: 41% forced vital capacity (FVC), 43% forced expiratory volume in 1 second (FEV1), and 91 FEV1/FVC1. The patient underwent surgical correction using rods and pedicle screws; she had improvement of symptoms, image tests, and pulmonary function (70% FVC, 71% FEV1, and 101 FEV1/FVC). Increased frequency and severity of respiratory tract infections, difficulty in expelling mucus and dyspnea are warning signs of compromised airways. Spirometry tests and image tests such as computed axial tomography and bronchoscopy are essential for diagnosis. Surgical approach may be the treatment of choice.


Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women.
Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women. This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented. Current psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0). These results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.


ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities.
In the last decade, numerous markers and strategies for Down syndrome screening have been developed. Algorithms that combine ultrasound and serum markers in the first and second trimesters have been evaluated. Furthermore, the practice of using age cutoffs to determine whether women should be offered screening or invasive diagnostic testing has been challenged. The purpose of this document is to 1) present and evaluate the best available evidence for the use of ultrasonographic and serum markers for selected aneuploidy screening in pregnancy and 2) offer practical recommendations for implementing Down syndrome screening in practice.


Effect of Neighborhood Sanitation Coverage on Fecal Contamination of the Household Environment in Rural Bangladesh.
Enteric pathogens can be transmitted within the household and the surrounding neighborhood. The objective of this study was to understand the effect of neighborhood-level sanitation coverage on contamination of the household environment with levels of fecal indicator bacteria in rural Bangladesh. We conducted spot-check observations of sanitation facilities in neighboring households (NHs) within a 20-m radius of target households with children aged 6-24 months. Sanitation facilities were defined as improved (a private pit latrine with a slab or better) or unimproved. Fecal coliforms (FCs) on children's hands and sentinel toy balls were measured and used as indicators of household-level fecal contamination. We visited 1,784 NHs surrounding 428 target households. On average, sentinel toy balls had 2.11(standard deviation [SD] = 1.37) log10 colony-forming units (CFUs) of FCs/toy ball and children's hands had 2.23 (SD = 1.15) log10 CFU of FCs/two hands. Access to 100% private improved sanitation coverage in the neighborhood was associated with a small and statistically insignificant difference in contamination of sentinel toy balls (difference in means = -0.13 log10 CFU/toy ball; 95% confidence intervals [CI]: -0.64, 0.39; P = 0.63) and children's hands (difference in means = -0.11 log10 CFU/two hands; 95% CI: -0.53, 0.32; P = 0.62). Improved sanitation coverage in the neighborhood had limited measurable effect on FCs in the target household environment. Other factors such as access to improved sanitation in the household, absence of cow dung, presence of appropriate water drainage, and optimal handwashing practice may be more important in reducing FCs in the household environment.


Flexible working time systems--the process of design and implementation.
Examples of the design and implementation processes of flexible working time systems are derived from a counselling project in North Rhine-Westphalia, Germany. The practical cases shown represent a diversity of variable or flexible working time systems according to different branches and different anticipated aims to reach with flexibility. For companies flexibility should improve or at least consolidate their economic situation, and for employees flexibility should result in a beneficial effect on health, family and social life. Three examples of counselling practice are reported in this paper, each case representing a different approach to flexibility in working time. To avoid overtime an industrial production plant expanded the weekly operating time without increasing the employees working time. For this purpose shifts off had to be planned. To provide a continuous service one department of a service company changed from duty on call to regular shifts on weekends. Responsibility in handling the new working times was assigned to the team. In an old people's home working times were designed according to the irregular demands throughout the day, in combining full and part-time jobs adequately.


Prevention of leakage of low-melting-point metals from styrofoam molds.
Leakage of low-melting-point metals from the underside of polystyrene molds can be prevented by applying a silicone caulking material to the bottom of the mold and pressing the mold on a metal plate before pouring.


Implementing a guideline for the request of chest and abdominal x-rays in nontrauma pathologic conditions in an ED.
The purpose of this study is to evaluate the impact of implementing a guideline for the request of chest and abdominal x-ray to reduce unnecessary examinations in nontraumatic pathologic conditions. We selected most common chief complaints in nontrauma pathologic conditions at emergency department (ED) and reviewed the available literature to determine the effectiveness of chest and abdominal x-rays for each one. We developed a guideline for the request of x-rays according to the chief complaints, including modulating factors derived from initial clinical evaluation. Guideline implementation was achieved through a multifaceted educational intervention. To evaluate its impact, both in the absolute number and in the adequateness of x-ray requests, we compared data obtained from patients coming to the ED at 2 different time points, October 2004 (preimplementation) and October 2005 (postimplementation). In the preimplementation period, 52.7% of the patients underwent chest x-rays and 28.0% abdominal x-rays, whereas in the postimplementation period, the proportions decreased to 41.8% and 13.5%, respectively (P<.001 in both cases). The adequateness of x-ray requests improved, as shown by a reduction in the number of inappropriate x-ray examinations (absolute error reduction of 9.2%; 95% confidence interval, 7.7-10.8, and relative error reduction of 59.8%; 95% confidence interval, 49.7-69.8). In our ED, implementing a specifically designed guideline for the request of chest and abdominal x-ray examinations in nontraumatic pathologic conditions reduced the absolute number of requests and the rate of inappropriate requests.


Respiratory variation of extrahepatic bile duct diameter during ultrasonography.
The attachments and adjacent structures of the extrahepatic bile duct may not move uniformly throughout the respiratory cycle, potentially affecting the diameter of the common bile duct. This study was performed to evaluate possible respiratory variation in extrahepatic bile duct diameter. Thirty consecutive subjects with maximal anteroposterior common bile duct diameter of 5 mm or greater were studied. Inspiratory increase in ductal diameter exceeding 1 mm was noted in 11 subjects (37%), eight without biliary obstruction. Awareness of this normal phenomenon may avert sonographic misdiagnosis of common bile duct obstruction, particularly during fatty-meal sonography.


Multidisciplinary European low dose initiative: an update of the MELODI program.
This paper provides an update and summary on the organization of European research in the field of low dose risk and radiation protection. To address declining resources and competence in radiation protection and related research across European countries, a High Level and Expert Group (HLEG) was established in 2007. The HLEG identified key policy and scientific questions to be addressed through a strategic research agenda for low dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). Dr Bill Morgan closely followed the European low dose programme and chaired the international Advisory Boards of DoReMi Network of Excellence and the MELODI platform. The MELODI research platform is dedicated to low dose ionizing radiation risk. In 2010, MELODI was founded as a registered association with 15 members. As of September 2016, the association´s membership increased to 46. A major activity of MELODI is the establishment and updating of a long-term Strategic Research Agenda (SRA) for research on low dose risk in Europe. The SRA is intended to guide the priorities for national and European research programmes and the preparation of competitive calls at the European level. A key priority for radiation protection research is to improve health risk estimates for exposures corresponding to the dose limits for occupational exposures and to reference levels for the exposure of the population in emergency situations.


Insights into the mechanism of electrocatalytic hydrogen evolution mediated by Fe2(S2C3H6)(CO)6: the simplest functional model of the Fe-hydrogenase active site.
The di-iron complex Fe2(S2C3H6)(CO)6 (a), one of the simplest functional models of the Fe-hydrogenases active site, is able to electrocatalyze proton reduction. In the present study, the H2 evolving path catalyzed by a has been characterized using density functional theory. It is showed that, in the early stages of the catalytic cycle, a neutral mu-H adduct is formed; monoelectron reduction and subsequent protonation can give rise to a diprotonated neutral species (a-muH-SH), which is characterized by a mu-H group, a protonated sulfur atom, and a CO group bridging the two iron centers, in agreement with experimental IR data indicating the formation of a long-lived mu7-CO species. H2 release from a-muH-SH, and its less stable isomer a-H2 is kinetically unfavorable, while the corresponding monoanionic compounds (a-muH-SH- and a-H2-) are more reactive in terms of dihydrogen evolution, in agreement with experimental data. The key species involved in electrocatalysis have structural features different from the hypothetical intermediates recently proposed to be involved in the enzymatic process, an observation that is possibly correlated with the reduced catalytic efficiency of the biomimetic di-iron assembly.


[Dynamic observation of intestinal epithelial stem cells of small intestine during the injured-repaired progress induced by 5-FU].
To investigate the dynamic changes of intestinal epithelial stem cells during the injured-repaired progress induced by 5-FU. Fifty adult C57BL/6J mice were enrolled in this study, 40 of them were intraperitoneally injected with 5-FU (30 mg per kg of body weigh) for five days, and 10 of them intraperitoneally injected with PBS as control. At day 1, 3, 5, 7 after treatment, the mice were killed and middle intestine was taken. Pathology was examined by HE staining. Musashi-1 (msi-1) expression was detected by immunohistochemical technique. The percentage of Rho low staining cells was detected by flow cytometry. After treatment with 5-FU, the intestinal mucosa was damaged. The Rho low staining cells were increasing, and at day 1 after treatment, the percentage of Rho low staining cells reached the highest level (P<0.01). The number of cells expressing msi-1 did not change significantly (P>0.05), but the percentage of positive msi-1 cells increased significantly (P<0.01). There was positive correlation between the percentage of Rhodamine 123 low staining cells and positive msi-1 cells in each group (r=0.867, P<0.01). The Rho low staining cells may contain rich intestinal epithelial stem cells. The intestinal epithelial stem cells expressing msi-1 can regenerate the damage of intestinal mucosa induced by 5-FU.


Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor.
Interactions of anandamide (N-arachidonylethanolamide), an endogenous compound for cannabinoid receptors, with the receptors for 5-hydroxytryptamine (5-HT), benzodiazepine, and gamma-aminobutyric acid(A) (GABA[A]) receptors in bovine synaptic membrane were examined. Anandamide decreased the 5-HT receptor bindings at concentrations of 1-100 microM, although it did not cause any change in benzodiazepine or GABA(A) receptor bindings. A high concentration of anandamide, 100 microM, significantly decrease both [3H]5-HT and [3H]ketanserin bindings. The present study revealed that the pharmacological activity of anandamide might be partially mediated through the 5-HT receptor.


FTIR spectroscopy of the all-trans form of Anabaena sensory rhodopsin at 77 K: hydrogen bond of a water between the Schiff base and Asp75.
Anabaena sensory rhodopsin (ASR) is an archaeal-type rhodopsin found in eubacteria, and is believed to function as a photosensor interacting with a 14 kDa soluble protein. Most of the residues in the retinal binding pocket are similar in ASR except proline 206, where the corresponding amino acid in other archaeal-type rhodopsins is highly conserved aspartate that constitutes the counterion complex of the positively charged protonated Schiff base. The recently determined X-ray crystallographic structure of ASR revealed a water molecule between the Schiff base and Asp75 [Vogeley, L., Sineshchekov, O. A., Trivedi, V. D., Sasaki, J., Spudich, J. L., and Luecke, H. (2004) Science 306, 1390-1393], as well as the case for bacteriorhodopsin (BR), a typical transport rhodopsin working as a proton pump. In this study, we applied low-temperature Fourier transform infrared (FTIR) spectroscopy to the all-trans form of ASR at 77 K, and compared the local structure around the chromophore and their structural changes upon retinal photoisomerization with those of BR. The K intermediate minus ASR difference spectra were essentially similar to those for BR, indicating that photoisomerization yields formation of the distorted 13-cis form. In contrast, little amide I bands were observed for ASR. The presence of the proline-specific vibrational bands suggests that peptide backbone alterations are limited to the Pro206 moiety in the K state of ASR. The N-D stretching of the Schiff base is presumably located at 2163 (-) and 2125 (-) cm(-)(1) in ASR, suggesting that the hydrogen bonding strength of the Schiff base in ASR is similar to that in BR. A remarkable difference between ASR and BR was revealed from water bands. Although ASR possesses a bridged water molecule like BR, the O-D stretching of water molecules was observed only in the >2500 cm(-)(1) region for ASR. We interpreted that the weak hydrogen bond of the bridged water between the Schiff base and Asp75 originates from their geometry. Since ASR does not pump protons, our result supports the working hypothesis that the existence of strongly hydrogen bonded water molecules is essential for proton pumping activity in archaeal rhodopsins.


Factors determining spontaneous histamine release from human basophils purified with Percoll gradients and Dynabeads.
Identification of factors influencing histamine release from purified and cultured basophil leukocytes is important for proper interpretation of results obtained on histamine release. This paper describes factors that influence spontaneous histamine secretion from human basophil leukocytes purified on Percoll gradients, followed by negative selection with Dynabeads. Anti-IgE and recombinant human interleukin-3 were used as model stimulants, and the purified basophil leukocytes were stimulated for 10 min and 6 h. The effect of the following conditions was examined: Percoll temperature, cell-suspension density, and serum in the media. The results showed that low Percoll temperature, high cell-suspension density, and the presence of serum in the media decreased spontaneous histamine release and increased maximal net histamine release upon stimulation.


Effects of LATCH versus Available Seatbelt Installation of Rear Facing Child Restraint Systems on Head Injury Criteria for 6 Month Old Infants in Rear End Collisions.
The Lower Anchor and Tethers for CHildren (LATCH) system was introduced in vehicles made after September 1, 2002 and intended to make installation of rear and forward-facing child safety seats easier. Due to the lack of rear impact testing of RFCRS required per the Federal Motor Vehicle Safety Standards (FMVSS), the purpose of this study was to explore the effects, if any, of installation method of RFCRS on the performance of commonly purchased makes and models of RFCRS. Specifically, we hypothesize that in a 48 km/h (29.8 MPH) rear-end collision, installation of RFCRS using the LATCH system will result in higher Head Injury Criteria (HIC) values when compared to using the available lap/shoulder seatbelt (Emergency Locking Retractor - ELR or Automatic Locking Retractor - ALR). The test matrix included 36 rear impact sled tests conducted using 3 installation methods on 3 models of RFCRS: the Graco SnugRide® with and without the base, the Britax Chaperone with base-mounted anti-rebound bar, and the Evenflo Tribute®, a model of convertible rearward/forward facing restraint system used in the rearward facing mode. The seats were installed using the LATCH system, ELR lap/shoulder belts, or ALR lap/shoulder belts in seating positions 4 and 6 on a vehicle buck mounted to the sled test base. The infant seat and 6 month old CRABI anthropometric test device (ATD) installation methods were in accordance with standards set forth in the National Highway Traffic Safety Administration's (NHTSA) FMVSS No. 213, Child Restraint Systems. All tests were conducted on pneumatic controlled acceleration sled (HYGE, Inc., PA, USA) at 48 km/h. Installation of infant seat type RFCRS using the LATCH system resulted in higher HIC15 values when compared to using the available lap/shoulder seatbelt (ELR or ALR). The mean HIC15 values were most severe when infant seat type RFCRS were installed using LATCH (Graco SnugRide® HIC15 = 394 and Britax Chaperone HIC15 = 133) compared to using either ELR lap/shoulder belts (Graco SnugRide® HIC15 = 218 and Britax Chaperone HIC15 = 65) or ALR lap/shoulder belts (Graco SnugRide® HIC15 = 194 and Britax Chaperone HIC15 = 78). The installation method did not result in a statistically significant difference in HIC for the convertible type RFCRS (Evenflo Tribute®). In many of the tests, the ATD's head struck the seatback in which the RFCRS was installed. These head strikes resulted in the higher HIC15 scores recorded throughout the testing. The results of this study suggest that LATCH does not offer equal protection to lap/shoulder belts from head injuries in rear impacts when used with infant seat type RFCRS.


GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis.
Although previous studies have identified many extracellular guidance molecules and intracellular signaling proteins that regulate axonal outgrowth and extension, most were conducted in the context of unidirectional neurite growth, in which the guidance cues either attract or repel growth cones. Very few studies addressed how intracellular signaling molecules differentially specify bidirectional outgrowth. Here, using the bipolar PLM neurons in Caenorhabditis elegans, we show that the guanine nucleotide exchange factors (GEFs) UNC-73/Trio and TIAM-1 promote anterior and posterior neurite extension, respectively. The Rac subfamily GTPases act downstream of the GEFs; CED-10/Rac1 is activated by TIAM-1, whereas CED-10 and MIG-2/RhoG act redundantly downstream of UNC-73. Moreover, these two pathways antagonize each other and thus regulate the directional bias of neuritogenesis. Our study suggests that directional specificity of neurite extension is conferred through the intracellular activation of distinct GEFs and Rac GTPases.


Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.
In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.


Caregiver Burden in Adults With Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is a chronic condition that has a relapsing and remitting disease course. There is high degree of inpatient and outpatient health care utilization by IBD patients along with a great deal of psychosocial stress associated with the condition. Patients frequently rely on family, friends, and other informal caregivers to provide medical, instrumental, and emotional support. The role of caregiving for adult IBD patients can lead to significant caregiver burden. At present, there are limited data on the existence of caregiver burden in adult IBD patients. Moreover, there are no specific measures for evaluating caregiver burden and there are no interventions targeting caregiver burden in adults with IBD. This review outlines the limited available data on caregiver burden in IBD, explores caregiver burden in other chronic conditions, and proposes applications of these data for creating screening and assessment tools and interventions for caregiver burden in IBD.


Immature and advanced patterns of T cell receptor gene rearrangement among lymphocytes in splenic culture.
Bulk populations and 39 hybridomas from splenic Con A cultures were analyzed for rearrangements among TCR genes: alpha, beta, gamma, and delta. Patterns were categorized to reveal general rules governing gene rearrangement within the activated adult peripheral population. Many patterns of gene rearrangement were consistent with previous studies of T cell lines. Additional points of interest were the following: 1) A large proportion of Con A-stimulated splenic cells bore no TCR gene rearrangements. 2) One splenic hybridoma exhibited an unusual gene pattern, with rearrangements, at alpha and beta, but not J gamma 1 or J gamma 2 loci. 3) Multiple gamma rearrangements were noted other than V1.2-J2 and V2-J1. 4) One hybridoma exhibited TCR gene rearrangements typical of day 14 to 15 fetal thymocytes, as well as rearrangements at immunoglobulin gene loci. 5) Among hybridomas with J alpha rearrangements, homologous chromosomes exhibited rearrangements at similar positions along the J alpha locus.


Design of a retarding potential grid system for a neutral particle analyzer.
The ion energy distribution in a magnetically confined plasma can be inferred from charge exchange neutral particles. On the Madison Symmetric Torus (MST), deuterium neutrals are measured by the Florida A&M University compact neutral particle analyzer (CNPA) and the advanced neutral particle analyzer (ANPA). The CNPA energy range covers the bulk deuterium ions to the beginning of the fast ion tail (0.34-5.2 keV) with high-energy resolution (25 channels) while the ANPA covers the vast majority of the fast ion tail distribution (∼10-45 keV) with low energy resolution (10 channels). Though the ANPA has provided insight into fast ion energization in MST plasma, more can be gained by increasing the energy resolution in that energy range. To utilize the energy resolution of the CNPA, fast ions can be retarded by an electric potential well, enabling their detection by the diagnostic. The ion energy distribution can be measured with arbitrary resolution by combining data from many similar MST discharges with different energy ranges on the CNPA, providing further insight into ion energization and fast ion dynamics on MST.


The role of systemic cytotoxic therapy for prostate cancer.
Prostate cancer is among the most common types of cancer and cause of cancer-related deaths among men in the USA and Europe. Despite improvements in early detection and treatment for localized disease, many patients still present with advanced disease, or attempted curative local therapy fails. Although hormone therapy is successful initially in the vast majority of patients, most develop hormone-refractory prostate cancer (HRPC) after 18-24 months. In the past, the use of chemotherapy in the management of prostate cancer has been limited, but recent evidence of its efficacy in HRPC has prompted further research to determine if it could have a more extensive role in the treatment of this disease. Data from several studies have highlighted the possible beneficial effects of incorporating chemotherapeutic agents in treatment regimens for HRPC, showing evidence of a survival advantage. One of the goals of research now is to determine optimal management strategies for different patient populations with prostate cancer. Preliminary data suggest that further improvements in efficacy might be achieved with multi-agent chemotherapy or by treating patients earlier in the disease process.


The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases to affect humans, regardless of whether patients receive multimodal therapy (including surgery, radiotherapy, and chemotherapy). This resistance to intervention is currently considered to be caused by the desmoplastic change of the extracellular matrix (ECM) in PDAC tissues, which is characterized by the accumulation of cancer-associated fibroblasts, collagen, proteoglycan, and hyaluronan. Among these ECM components, hyaluronan has attracted interest because various studies have indicated that hyaluronan-rich PDAC is correlated with the progressive properties of cancer cells, both in experimental and clinical settings. Hence, the reduction of hyaluronan in cancer tissue may represent a novel therapeutic approach for PDAC. 4-methylumbelliferone (4-MU) is a derivative of coumarin that was reported to suppress the synthesis of hyaluronan in cultured human skin fibroblasts in 1995. As an additional study, our group firstly reported that 4-MU reduced the hyaluronan synthesis of mouse melanoma cells and exerted anti-cancer activity. Subsequently, we have showed that 4-MU inhibited liver metastasis in mice inoculated with human pancreatic cancer cells. Thereafter, 4-MU has been accepted as an effective agent for hyaluronan research and is expected to have clinical applications. This review provides an overview of the interaction between PDAC and hyaluronan, the properties of 4-MU as a suppressor of the synthesis of hyaluronan, and the perspectives of PDAC treatment targeting hyaluronan.


Hepatitis prevention project in the Korean American community in Killeen, Texas.
Educational efforts related to viral hepatitis have the potential to increase awareness and identify chronically infected individuals and can lead to successful vaccination strategies. However, in underserved semirural communities, such as the Korean American community in Killeen, Texas, these outreach activities are lacking. The GanYum ("hepatitis" in Korean) Prevention Project aimed to evaluate thoughts/behaviors, assess vulnerability, and educate Korean Americans on hepatitis B and C. Two outreach events were held at a Korean church and a Korean market (O'Mart) to provide education, screening, and outreach about viral hepatitis. Ninety-six patients were screened at two events. Five patients were found to be positive for hepatitis B surface antigen and were referred to their primary care physicians and the liver clinic at Scott & White Healthcare in Temple, Texas. Fifty-one patients (53%) were found to be immune to hepatitis B, and 40 patients (42%) were hepatitis B vulnerable. We demonstrated that the prevalence of chronic hepatitis B in Koreans in our study is similar to the previously documented prevalence (5%). Our educational efforts were successful in changing perceptions regarding the modes of transmission and exacerbating factors of chronic viral hepatitis and encouraged participants to seek care for their liver diseases, if needed. We found that both venues (the church and Korean market) were appropriate to screen and educate participants; churches seemed to have a more engaged audience.


RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase.
Methods that allow the specific silencing of a desired gene are invaluable tools for research. One of these is based on RNA interference (RNAi), a process by which double-stranded RNA (dsRNA) specifically suppresses the expression of a target mRNA. Recently, it has been reported that RNAi also works in mammalian cells if small interfering RNAs (siRNAs) are used to avoid activation of the interferon system by long dsRNA. Thus, RNAi could become a major tool for reverse genetics in mammalian systems. However, the high cost and the limited availability of the short synthetic RNAs and the lack of certainty that a designed siRNA will work present major drawbacks of the siRNA technology. Here we present an alternative method to obtain cheap and large amounts of siRNAs using T7 RNA polymerase. With multiple transfection procedures, including calcium phosphate co-precipitation, we demonstrate silencing of both exogenous and endogenous genes.


Selective inhibition of Ras interaction with its particular effector by synthetic peptides corresponding to the Ras effector region.
Ras proteins possess multiple downstream effectors of distinct structures. We and others demonstrated that Ha-Ras carrying certain effector region mutations could interact differentially with its effectors, implying that significant differences exist in their Ras recognition mechanisms. Here, by employing the fluorescence polarization method, we measured the activity of effector region synthetic peptides bearing various amino acid substitutions to inhibit association of Ras with the effectors human Raf-1 and Schizosaccharomyces pombe Byr2. The effect of these peptides on association with another effector Saccharomyces cerevisiae adenylyl cyclase was also examined by measuring inhibition of the Ras-dependent adenylyl cyclase activity. The peptide corresponding to the residues 17-44 competitively inhibited Ras association with all the three effectors at the Ki values of 1 approximately 10 microM, and the inhibition was considerably attenuated by the D38A mutation. The peptide with the D38N mutation inhibited association of Ha-Ras with Byr2 but not with the others, whereas that with the P34G mutation inhibited association of Ha-Ras with Raf-1 and Byr2 but not with adenylyl cyclase. Thus, the specificity observed with the whole Ras protein was retained in the effector region peptide. These results suggest that the effector region residues constitute a major determinant for differential recognition of the effector molecules, raising a possibility for selective inhibition of a particular Ras function.


Developing grasshopper neurons show variable levels of guanylyl cyclase activity on arrival at their targets.
The ability of certain grasshopper neurons to respond to exogenously applied donors of nitric oxide (NO) by producing cyclic GMP (cGMP) depends on their developmental state. ODQ, a selective blocker of NO-sensitive guanylyl cyclase, blocks cGMP production at 10(-5) M, thus confirming the nature of the response. Experiments in which the distal axon is separated from its proximal stump before application of an NO donor show that guanylyl cyclase is distributed uniformly throughout the neuron. In the locust abdomen, where segments are formed sequentially, the pattern of guanylyl cyclase up-regulation is predictable and sequential from anterior to posterior. There are two patterns of innervation by cGMP-expressing motor neurons. In the first, typified by muscle 187, an innervating neuron begins to be NO responsive on arrival at its muscle and continues to be so over most of the remainder of embryonic development, including the formation of motor end plates. In the second, typified by a neuron innervating muscle 191, the neuron extends well along the muscle, apparently laying down a number of sites of contact with it, before it becomes NO responsive. In both patterns, however, NO responsiveness marks the neuron's transition from growth cone elongation to the production of lateral branches. Individual muscles receive innervation from multiple motor neurons, some of which express transient NO sensitivity during development and others which do not. With the exception of the leg motor neuron SETi, the first motor neuron to reach any muscle is usually not NO responsive. We suggest that cGMP plays a role in, or reflects, the early stages of communication between a target and specific innervating neurons.