UV-cured, flexible, and transparent nanocomposite coating with remarkable oxygen barrier.
A polymer-layered silicate nanocomposite coating is prepared by combining a novel synthetic lithium-hectorite and an UV-curable, cationic polyurethane. Oxygen transmission measurements clearly indicate the supremacy of the lithium-hectorite as compared to a standard montmorillonite. In addition, a very high degree of optical transparency of the nanocomposite coating is achieved, rendering this material highly interesting for flexible packaging and encapsulation applications.


[Combination therapy of advanced choriocarcinoma--an analysis of 60 patients].
From Jan. 1973 to Dec. 1984, 60 patients with advanced choriocarcinoma were treated in our hospital. 34 of them were stage IIIB and 26 stage IV. There were 36 patients with lobulated pulmonary metastases and 13 with brain metastases. The 4-drug chemotherapy (methotrexate or fluorouracil, kengsengmycin, vincristine and nitrogen mustard) was used as the main treatment, supplemented by surgery or irradiation. In those with lobulated pulmonary metastatic foci and lesions in the brain, the 4-drug chemotherapy was used before, during or after split course irradiation. Generally, radiation with a total dose of 4,000 rad (2,000 rad/12 D, interval of 4 weeks, 2,000 rad/12 D) was given after 3-4 courses of chemotherapy. The 1, 3 and 5 year survival rates were 85.7%, 78.6% and 79.4%, respectively. Lobulated pulmonary lesions as treated with 4-drug chemotherapy plus split course irradiation gave a 3 year survival rate of 88.0% (22/25). 7 of 8 with brain metastases treated by the same modality gave complete remission. 5 have survived for more than 3 years. In this series, the combination therapy of advanced choriocarcinoma, role of irradiation for this tumor and individualization in treatment are discussed. The authors believe that the 4-drug chemotherapy for advanced choriocarcinoma is superior to the other regiment and, when combined with split course irradiation is very effective in lobulated pulmonary and brain metastases.


High-resolution CT of the normal and abnormal fallopian canal.
A two-part anatomic and clinical high-resolution computed tomographic (HRCT) study of the fallopian canal was conducted. From the correlation of HRCT images of eight specimen temporal bones with their corresponding anatomic sectional images, it was evident that the full length of the fallopian canal can be accurately visualized. An axial section demonstrates the labyrinthine segment, geniculate ganglion fossa, and proximal part of the tympanic segment, whereas a Stenver projection is used for the tympanic segment, second knee, and mastoid segment. In clinical studies axial sections simultaneously visualized the proximal parts of the fallopian canal in 82% of 28 cases, whereas Stenver projections simultaneously visualized the distal parts in 75% of 16 cases of acute facial nerve palsy. Twenty-one patients with intratemporal facial nerve palsy and six patients with congenital atresia of the external auditory canal were also examined. HRCT was highly accurate in detecting and defining neoplastic, inflammatory, and congenital lesions of the fallopian canal. A lower rate of detection was recorded for traumatic lesions.


Hazards and risks in oncology: radiation oncology.
Adverse effects and hazards which have their origin from radiation using conventional techniques like 3-D conformal radiotherapy and total radiation doses are well known. However little is known about the sprectum of especially late toxicity after radiation using new technologies like intensity modulated radiotherapy (IMRT) combined with novel target volume and dose concepts. Since IMRT allows for selective protection of the large salivary glands this technique improves the intermediate term quality of life and is the standard of care despite many details need further prospective evaluation. Combining cytotoxic drugs and radiotherapy yield improved survival in well-defined high risk patients. However morbidity and mortality of these protocols are high and deserve special expertise and supportive therapy. EGF-receptor antibodies have gained well defined indications, albeit specific toxicities in combination with irradiation deserve prospective studies and special attention.


[Variations of plasma levels of testosterone and delta 4-androstenedione in growing Hubbard cockerels].
Variations in the plasma concentrations of testosterone (T) and delta 4-androstenedione (delta 4) levels were measured by radioimmunoassay in individual young Hubbard Chickens from the age of 16 days until 100 days. Plasma testosterone was low and remained relatively stable between days 16 and 63 (0.10 to 0.30 ng/ml), but increased then rapidly (0.32 +/- 0.07 ng/ml on day 65 vs. 1.49 +/- 0.27 ng/ml on day 100). During the same period delta 4 levels increased too (0.23 +/- 0.06 ng/ml on day 65 vs. 0.75 +/- 0.18 ng/ml on day 100). During the first weeks of life, delta 4-androstenedione prevailed over testosterone. The [delta 4]/[T] ratio reached a maximum between days 30 and 40 and was then reversed to negative values. Results are discussed in relation to those obtained for Chicken from other stocks.


Activation of Pseudomonas aeruginosa elastase in Pseudomonas putida by triggering dissociation of the propeptide-enzyme complex.
The propeptide of Pseudomonas aeruginosa elastase functions both as an intramolecular chaperone required for the folding of the enzyme and as an inhibitor that prevents activity of the enzyme before its secretion into the extracellular medium. Since expression of the lasB gene, which encodes elastase, in Pseudomonas putida did not result in extracellular elastase activity, it has been suggested that the enzyme is not recognized by the Xcp secretion machinery of the heterologous host. Here, it is demonstrated that the proenzyme is normally processed in P. putida and that it is indeed not actively secreted by the Xcp machinery. Nevertheless, substantial amounts of the enzyme were detected in the extracellular medium. Co-immunoprecipitations revealed that the extracellular enzyme was associated with the propeptide, which explains the lack of enzymic activity. Since the propeptide-enzyme complex in P. putida apparently does not dissociate spontaneously, it is concluded that a host-specific factor is required to induce this event. Mutants were selected which showed extracellular elastase activity. Two mutations, located within the lasB gene, were further characterized. These mutations, resulting in the substitution of Ala and Thr at positions -15 and -153, respectively, of the propeptide (where position +1 is defined as the first residue of the mature enzyme) destabilized the propeptide-enzyme complex. It is concluded that Ala-15 and Thr-153 are required for the inhibitor function, but not for the chaperone function of the propeptide.


Bimetallic TiO2 Nanoparticles for Lignin-Based Model Compounds Valorization by Integrating an Optocatalytic Flow-Microreactor.
The challenge of improving the activity of TiO2 by modifying it with metals and using it for targeted applications in microreactor environments is an active area of research. Recently, microreactors have emerged as successful candidates for many photocatalytic reactions, especially for the selective oxidation process. The current work introduces ultrasound-assisted catalyst deposition on the inner walls of a perfluoro-alkoxy alkane (PFA) microtube under mild conditions. We report Cu-Au/TiO2 and Fe-Au/TiO2 nanoparticles synthesized using the sol-gel method. The obtained photocatalysts were thoroughly characterized by UV-Vis diffuse-reflectance spectroscopy (DRS), high-resolution scanning electron microscopy (HR-SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and N2 physisorption. The photocatalytic activity under UV (375 nm) and visible light (515 nm) was estimated by the oxidation of lignin-based model aromatic alcohols in batch and fluoropolymer-based flow systems. The bimetallic catalyst exhibited improved photocatalytic selective oxidation. Herein, four aromatic alcohols were individually investigated and compared. In our experiments, the alcohols containing hydroxy and methoxy groups (coniferyl and vanillin alcohol) showed high conversion (93% and 52%, respectively) with 8% and 17% selectivity towards their respective aldehydes, with the formation of other side products. The results offer an insight into ligand-to-metal charge transfer (LMCT) complex formation, which was found to be the main reason for the activity of synthesized catalysts under visible light.


Effect of Nickel and Cobalt on Methanogenic Enrichment Cultures and Role of Biogenic Sulfide in Metal Toxicity Attenuation.
Metals play an important role in microbial metabolism by acting as cofactors for many enzymes. Supplementation of biological processes with metals may result in improved performance, but high metal concentrations are often toxic to microorganisms. In this work, methanogenic enrichment cultures growing on H2/CO2 or acetate were supplemented with trace concentrations of nickel (Ni) and cobalt (Co), but no significant increase in methane production was observed in most of the tested conditions. However, high concentrations of these metals were detrimental to methanogenic activity of the cultures. Cumulative methane production (after 6 days of incubation) from H2/CO2 was 40% lower in the presence of 8 mM of Ni or 30 mM of Co, compared to controls without metal supplementation. When acetate was used as substrate, cumulative methane production was also reduced: by 18% with 8 mM of Ni and by 53% with 30 mM of Co (after 6 days of incubation). Metal precipitation with sulfide was further tested as a possible method to alleviate metal toxicity. Anaerobic sludge was incubated with Co (30 mM) and Ni (8 mM) in the presence of sulfate or sulfide. The addition of sulfide helped to mitigate the toxic effect of the metals. Methane production from H2/CO2 was negatively affected in the presence of sulfate, possibly due to competition of hydrogenotrophic methanogens by sulfate-reducing bacteria. However, in the enrichment cultures growing on acetate, biogenically produced sulfide had a positive effect and more methane was produced in these incubations than in similar assays without sulfate addition. The outcome of competition between methanogens and sulfate-reducing bacteria is a determinant factor for the success of using biogenic sulfide as detoxification method.


Primary pericardial angiosarcoma: case report and review of treatment options.
A primary cardiac angiosarcoma is a rare type of soft-tissue sarcoma with a high mortality rate. This report describes a young woman who presented with chest pain and worsening shortness of breath over the course of a year. She was diagnosed with and treated for latent tuberculosis and autoimmune pericarditis over the last year, however, her condition kept worsening. Further workup revealed a large pericardial and right atrial mass associated with multiple lung nodules. The biopsy from the lung mass showed angiosarcoma, and she was diagnosed with primary metastatic angiosarcoma of the pericardium. She was treated with doxorubicin and Ifosfamide (AIM-75 regimen), which led to a partial response. However, soon after completion of six cycles, the tumour progressed rapidly, leading to cardio-respiratory failure. In this report, we will discuss the clinical challenges and treatment options (surgical and medical) that are available for treating patients with angiosarcoma of the heart.


High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial.
The aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting. The IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence. At 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not. High non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET.


Carcinogenicity studies in animals relevant to the use of anabolic agents in animal production.
It has long been known that certain estrogens and testosterone may increase, or sometime decrease, the incidence of neoplasmas in laboratory animals. They probably act by switching-on inappropriate genetic information or switching-off appropriate genetic information contained in nucleic acids. For instance, they may switch-on in adult animals information which is relevant only to a certain stage of embryogenesis or they may facilitate the expression of oncogenic viruses which would otherwise lay harmlessly dormant. The situation is rendered complex because an effect on one endocrine gland leads to effects on others so that factors which favour tumour development may result indirectly from administration of an anabolic or other hormonal agent. Two kinds of neoplasm are now known to be associated with human exposure to anabolic agents: vaginal adenocarcinoma and liver-cell tumours. Tumours of both kinds are among the spectrum of neoplasms that has been seen in laboratory animals exposed to agents of the same kind. In both animals and man there is evidence that tumours arising in response to anabolic agents are sometimes, initially at least, hormone-dependent. The evidence that 17beta-estradiol, diethylstilbestrol, chlormadinone, and testosterone are carcinogenic for laboratory animals is briefly reviewed and the reader's attention is directed towards the 1974 IARC Monograph on the evaluation of sex hormones for carcinogenic risk to man where the same evidence is reviewed more extensively. The significance for man of the results of studies on laboratory animals is discussed with special reference to the use of anabolic agents in meat production. Non-residue uses are to be preferred, as are naturally-occurring agents as opposed to compounds which do not occur in nature. More information is needed concerning the possible effects of prolonged exposure to very low doses of anabolic agents.


[Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients].
Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to different markers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohistochemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) were analyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significant increase in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with noncaspase dependent apoptotic death process, without being able to rule out death by necrosis. Key words: Drug resistant temporal lobe epilepsy. Apoptosis. Necrosis. Neuronal loss. Neurología 2008;23(9):555-565.


Mineralocorticoid receptor actions in cardiovascular development and disease.
Mineralocorticoid receptors (MRs) are transcriptional regulators that mediate the diverse physiological and pathophysiological actions of corticosteroid hormones across many tissues. In the kidney aldosterone control of sodium/water resorption via DNA-binding actions of the MR is established. MRs also regulate tissues not involved in electrolyte homeostasis such as the heart, adipose tissue, brain, and inflammatory cells where the MRs can respond to both aldosterone and cortisol. The pathology of inappropriate MR activation in non-epithelial tissues are well-described, and steroidal antagonists of the MR have been clinically beneficial in the management of heart failure and blood pressure for decades. However, the role of cortisol-dependent MR activation in the physiological setting is less well defined. Like other steroid hormone receptors, the MR also regulates non-DNA-binding pathways including MAPK pathways and G protein coupled receptors to provide diversity to MR signaling. Whether nonDNA binding pathways are more relevant for MR activation in non-epithelial, versus epithelial, tissues remain unclear. This review will focus on molecular regulation of ligand-dependent MR activation and the physiology and pathophysiology of MR actions in the heart with a focus on the cardiomyocyte and provide a discussion of relevant genomic and non-genomic MR pathways and potential new transcriptional partners for the MR and their relevance for health and disease. Understanding MR actions in the heart will provide new insights into cell-selective mechanisms that underpin the therapeutic benefits of MRAs, and are a critical step towards developing next-generation tissue selective MR modulators with improved safety profiles.


Efficacy of duloxetine in patients with fibromyalgia: pooled analysis of 4 placebo-controlled clinical trials.
To investigate the efficacy of duloxetine in the treatment of pain and improvement in functional impairment and quality of life in patients with fibromyalgia from a pooled analysis of 4 placebo-controlled, double-blind, randomized trials. Patients were eligible for inclusion in the studies if they were at least 18 years of age, met criteria for fibromyalgia as defined by the American College of Rheumatology, and had specified minimum pain severity scores. Across all studies, 797 patients received duloxetine 60-120 mg/d and 535 patients received placebo. Pain was assessed by the Brief Pain Inventory (BPI) 24-hour average pain severity score; other efficacy measures included the Clinical Global Impressions-Severity of Illness scale (CGI-S), Patient Global Impressions-Improvement scale (PGI-I), 17-item Hamilton Depression Rating Scale (HDRS-17), Fibromyalgia Impact Questionnaire (FIQ) total score, BPI pain interference items, Sheehan Disability Scale (SDS), and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) mental and physical components. Changes from baseline to endpoint (last observation carried forward) for most of the above efficacy measures were analyzed using an analysis-of-covariance model. After 12 weeks of treatment, pain was significantly reduced in patients treated with duloxetine (P < .001) compared with placebo. In addition, duloxetine was superior to placebo in improving CGI-S (P < .001); PGI-I (P < .001); FIQ total (P < .001); HDRS-17 total (P = .003); SDS global functioning (P < .001), work/school (P = .018), and family life (P < .001); SF-36 mental (P < .001) and physical (P = .026) component; and BPI pain interference (P < .001) scores. Treatment-by-subgroup interactions were not significant for sex (P = .320), age (P = .362), or race (P = .180). This pooled analysis provides evidence that 12 weeks of treatment with duloxetine 60-120 mg/d effectively improves fibromyalgia symptoms and may offer benefits beyond pain relief.


A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression.
Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75NTR). Thus, modulating p75NTR signaling is considered a promising therapeutic strategy for AD. Accordingly, our laboratory has developed small molecule p75NTR ligands that increase survival signaling and inhibit amyloid-β-induced degenerative signaling in in vitro studies. Previous work found that a lead p75NTR ligand, LM11A-31, prevents degeneration of cholinergic neurites when given to an AD mouse model in the early stages of disease pathology. To extend its potential clinical applications, we sought to determine whether LM11A-31 could reverse cholinergic neurite atrophy when treatment begins in AD mouse models having mid- to late stages of pathology. Reversing pathology may have particular clinical relevance as most AD studies involve patients that are at an advanced pathological stage. In this study, LM11A-31 (50 or 75 mg/kg) was administered orally to two AD mouse models, Thy-1 hAPPLond/Swe (APPL/S) and Tg2576, at age ranges during which marked AD-like pathology manifests. In mid-stage male APPL/S mice, LM11A-31 administered for 3 months starting at 6-8 months of age prevented and/or reversed atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites. Importantly, a 1 month LM11A-31 treatment given to male APPL/S mice (12-13 months old) with late-stage pathology reversed the degeneration of cholinergic neurites in basal forebrain, ameliorated cortical dystrophic neurites, and normalized increased basal forebrain levels of p75NTR. Similar results were seen in female Tg2576 mice. These findings suggest that LM11A-31 can reduce and/or reverse fundamental AD pathologies in late-stage AD mice. Thus, targeting p75NTR is a promising approach to reducing AD-related degenerative processes that have progressed beyond early stages.


FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein.
Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG). Indeed, FABP1 bound ECs with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA-containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists. The physiological impact was examined with liver from wild-type (WT) versus FABP1 gene-ablated (LKO) male mice. As shown by liquid chromatography and mass spectrometry, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD and DAGL) or a decreased level of EC degradative enzyme (FAAH) but correlated with complete loss of FABP1, a decreased level of SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and a decreased level of degradative enzymes (NAAA and MAGL). These data indicated that FABP1 not only is the most prominent endocannabinoid and cannabinoid binding protein but also impacts hepatic endocannabinoid levels.


Counting in the dark: non-intrusive laser scanning for population counting and identifying roosting bats.
Population surveys and species recognition for roosting bats are either based on capture, sight or optical-mechanical count methods. However, these methods are intrusive, are tedious and, at best, provide only statistical estimations. Here, we demonstrated the successful use of a terrestrial Light Detection and Ranging (LIDAR) laser scanner for remotely identifying and determining the exact population of roosting bats in caves. LIDAR accurately captured the 3D features of the roosting bats and their spatial distribution patterns in minimal light. The high-resolution model of the cave enabled an exact count of the visibly differentiated Hipposideros larvatus and their roosting pattern within the 3D topology of the cave. We anticipate that the development of LIDAR will open up new research possibilities by allowing researchers to study roosting behaviour within the topographical context of a cave's internal surface, thus facilitating rigorous quantitative characterisations of cave roosting behaviour.


[Antituberculosis chemoprophylaxis in children]
OBJECTIVE: To present a review of the indications of antituberculosis chemoprophylaxis in childhood, based on Brazilian official rules of the National Program for the Control of Tuberculosis of the Ministry of Health and the new tendencies pointed by the Brazilian Consensus on Tuberculosis. METHODS: Articles on the theme were selected from Medline and publications of the Ministry of Health. RESULTS: The chemoprophylaxis is an effective and safe form of prevention of tuberculosis in childhood. It does not conflict with the BCG vaccination program, because it aims at avoiding that tuberculosis infection develops into disease. CONCLUSIONS: International proposals an recent national tendencies recommend the expansion of chemoprophylaxis indications in childhood. Thus measures that expand its use in our country are needed.


Death investigation systems and disease surveillance.
Medico-legal death investigation systems have the potential to play an important role in disease surveillance. While these systems are in place to serve a public function, the degree to which they are independent of central government can vary depending on jurisdiction. How these systems use this independence may present problems for public health initiatives, as it allows death investigators to decline to participate in government-led surveillance regardless of how critical the studies may be to public health and safety. A recent illustration of this problem in the UK is examined, as well as general lessons for removing impediments to death investigation systems participating in public health research.


Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target.
Abdominal aortic aneurysms (AAA) are a major cause of death. Currently, the mainstay of treatment for AAA is surgical repair and there are no FDA approved medical therapies for AAA. Much research is in progress to discover new medical therapies for AAA. The pathophysiology of AAA is understood to be a complex interplay of inflammatory and proteolytic processes that degenerate the aneurysm wall. Arterial calcification, which is observed in AAA but to a lesser extent than in arterial occlusive disease, occurs in a highly regulated manner in a similar process as mineral deposition in bone. Osteoblasts-like cells are responsible for mineral deposition in atherosclerotic plaques. Recently, osteoclast-like cells - the catabolic counterpart to osteoblasts - were discovered in atherosclerotic plaques. Additionally, osteoclast-like cells are present in the wall of AAA but not in healthy aortas. Osteoclast-like cells secrete matrix metalloproteinases (MMP) - proteases implicated in arterial aneurysm wall degeneration - and may contribute to the degredation of the aneurysm wall. Inhibiting osteoclast-like cells may prevent aneurysm progression by reducing tissue levels of MMPs. In this review, we discuss the pathophysiology of AAA formation and the current role of medical therapy in treatment of AAA. Furthermore, we highlight the emerging hypothesis that osteoclasts play a key role in the development of AAA and discuss therapies to inhibit osteoclastogenesis in AAA.


Purkinje cell cytoplasmic antibody type 1 (anti-Yo) autoimmunity in a child with Down syndrome.
Purkinje cell cytoplasmic antibody type 1 (PCA-1)-IgG (or anti-Yo) is characteristically detected in women with gynecological or breast adenocarcinoma. We describe 2 unique scenarios occurring in 1 patient: PCA-1 paraneoplastic autoimmunity in a child, and a paraneoplastic neurological disorder in the context of Down syndrome. A child with Down syndrome and a history of adrenocortical carcinoma resected at age 1 year presented at age 7 years with cerebellar ataxia of subacute onset. Paraneoplastic serological and cerebrospinal fluid evaluations revealed PCA-1. Serological and biochemical studies also supported a diagnosis of subclinical autoimmune hypothyroidism. Extensive serum, urine, and radiological testing did not reveal a new or recurrent neoplasm. Neurological improvements after standard immunotherapy were lacking. Solid organ neoplasms are uncommon among patients with Down syndrome, but organ-specific autoimmune diseases are common. In our patient, Down syndrome-related impaired T regulatory lymphocyte function (previously reported) may have resulted in both enhanced immunity against an undetected solid neoplasm and paraneoplastic neurological (PCA-1) autoimmunity.


The combination measles, mumps, rubella and varicella vaccine in healthy children.
A clinical trial was conducted to compare the combination measles, mumps, rubella, varicella vaccine (MMRV) and the standard measles, mumps, rubella vaccine and subsequent varicella vaccine (MMR + V) in 15 to 17 month old healthy children. Both the MMRV and MMR + V schedules stimulated virtually 100% seroconversion for all component viruses. Mean antibody titers were similar for each virus component in the two vaccine groups. Clinical reactivity post immunization was also similar with 25-29% morbilliform rashes, 12-25% mild papulovesicular (varicella) rashes, and 12.5-18% temperature elevations above 101 degrees F. Antibodies to measles, mumps, and rubella viruses were persistent in 8/10 originally seronegative MMRV vaccinees and 5/5 MMR + V recipients tested. On MMRV recipient had a household exposure to chickenpox during the year postvaccination that resulted in a subclinical boost in varicella antibody titer. Two children in the MMR + V group had close varicella exposures: one developed mild varicella (20 lesions). There were no known exposures to natural measles, mumps, or rubella. Three of four MMRV vaccinees with low titer antibody to varicella prior to immunization had greater than four-fold rises in antibodies. The combination measles, mumps, rubella, varicella vaccine is an immunogenic, safe and cost effective approach to varicella immunization of healthy children.


Predicting crossover generation in DNA shuffling.
We introduce a quantitative framework for assessing the generation of crossovers in DNA shuffling experiments. The approach uses free energy calculations and complete sequence information to model the annealing process. Statistics obtained for the annealing events then are combined with a reassembly algorithm to infer crossover allocation in the reassembled sequences. The fraction of reassembled sequences containing zero, one, two, or more crossovers and the probability that a given nucleotide position in a reassembled sequence is the site of a crossover event are estimated. Comparisons of the predictions against experimental data for five example systems demonstrate good agreement despite the fact that no adjustable parameters are used. An in silico case study of a set of 12 subtilases examines the effect of fragmentation length, annealing temperature, sequence identity and number of shuffled sequences on the number, type, and distribution of crossovers. A computational verification of crossover aggregation in regions of near-perfect sequence identity and the presence of synergistic reassembly in family DNA shuffling is obtained.


Pharmacokinetic Behaviour of Enrofloxacin after Single Intramuscular Dosage in American Black Vultures (Coragyps atratus).
The aim of the study was to investigate the intramuscular pharmacokinetics of enrofloxacin in black vultures (Coragyps atratus). The pharmacokinetics of a single intramuscular dose (10 mg/kg) of enrofloxacin was studied in six vultures. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high-performance liquid chromatography (HPLCuv). Pharmacokinetic parameters were estimated using non-compartmental and compartmental analysis. After intramuscular administration, enrofloxacin showed a rapid and complete absorption, reaching a Cmax value of 3.26 ± 0.23 μg/mL at 1.75 ± 0.53 h. A long terminal half-life of 19.58 h has been observed. Using previously published MIC values to perform a PK/PD analysis, cumulative fraction responses obtained after Monte Carlo simulation for AUC/MIC > 30, 50 and 125 were 72.93%, 72.34% and 30.86% for E. coli and 89.29%, 88.89% and 58.57% for Mycoplasma synoviae, respectively. Cumulative fraction responses obtained for Cmax/MIC index were 33.93% and 40.18% for E. coli and M. synoviae, respectively. The intramuscular administration of 10 mg/kg could be appropriate to treat infectious diseases caused by gram-positive bacteria with MIC value lower than 1 µg/mL; however, although enrofloxacin showed a slow elimination in black vultures, plasma concentrations were insufficient to reach the gram-negative stablished breakpoints.


Small artery structural alterations of patients with microvascular angina (syndrome X).
1. There is increasing evidence that a substantial number of patients who suffer from angina have normal epicardial arteries (Syndrome X), and it has been suggested that these individuals have a generalized disorder of small vessels not confined to the intramyocardial vasculature. 2. Small arteries were therefore obtained from biopsies of skin and subcutaneous fat from nine normotensive patients with Syndrome X and nine matched control subjects. Vessels were dissected and mounted as ring preparations in a myograph for morphological and functional assessment. 3. Morphological measurements revealed a significant increase in media thickness/lumen diameter ratio in arteries from patients with Syndrome X. Contractile responses to U46619 were similar in arteries from patients and control subjects. Endothelium-dependent relaxation induced with acetylcholine and bradykinin was greater in arteries from patients although differences were not statistically significant. Endothelium-independent relaxation induced by forskolin and sodium nitroprusside was not different. 4. In conclusion, these data demonstrate that subcutaneous small arteries from patients with Syndrome X are characterized by increased media thickness/lumen diameter ratios, although contractile responses were normal. Additionally, endothelium-dependent relaxation was not impaired in arteries from these patients. Thus, no significant functional abnormalities were associated with the observed structural differences.


The role of surgery for haematologic neoplasms of bone.
We report on 205 patients with haematologic neoplasms of bone treated from 1985 to 2009. There were 77 patients with primary bone lymphoma, 77 with myeloma and 51 with plasmacytoma. All patients had medical treatments; 43 patients had wide and 162 intralesional surgery. Mean follow-up was 5 years (median, 3.5 years); 11 patients were lost to followup. At the latest examination, 99 patients were alive without disease, 20 were alive with disease and 75 were dead of disease; 13 patients (6.7%) had local recurrence; 12 patients (24%) with plasmacytoma developed myeloma. Survival to death was significantly higher after wide resection for lymphoma and plasmacytoma, but not for myeloma. Survival to local recurrence was not statistically different between wide and intralesional surgery for any haematologic neoplasm. Surgical complications including aseptic loosening, infection, neurological deficits and breakage of implants occurred in 21 patients (11%).


Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).
Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses. Herein we report data from a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC. Group E in CheckMate 370 was a single-arm cohort designed to evaluate the safety of first-line nivolumab (240 mg every 2 weeks) plus crizotinib (250 mg twice daily) in patients with ALK translocation-positive NSCLC. The primary endpoint of safety would be met if ≤20% of patients discontinued treatment due to treatment-related adverse events by week 17. Objective response rate was a secondary endpoint. A planned safety review occurred in November 2016; the data cutoff was May 26, 2017. Of the first 13 patients treated with nivolumab plus crizotinib, 5 (38%) developed severe hepatic toxicities leading to the discontinuation of the combination. Of these, two patients died and the presence of severe hepatic toxicities may have contributed to death. Enrollment was closed and combination treatment discontinued due to observed grade ≥3 hepatic toxicities. Five patients (38%) had a partial response. These findings do not support further evaluation of nivolumab 240 mg every 2 weeks plus crizotinib 250 mg twice daily.


Genome-Wide Association Study Reveals the Genetic Architecture of Stripe Rust Resistance at the Adult Plant Stage in Chinese Endemic Wheat.
Chinese endemic wheat, comprising Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum), Yunnan hulled wheat (T. aestivum ssp. yunnanense), and Xinjiang rice wheat (T. petropavlovskyi), are genetically and morphologically unique. To examine the adult plant resistance to stripe rust among Chinese endemic wheat germplasms, a panel of 213 accessions was inoculated with mixed virulent races of wheat stripe rust (Puccinia striiformis f. sp. tritici) in four different field environments. Four traits associated with stripe rust resistance, infection type, final disease severity, disease index, and area under the disease progress curve, were used to evaluate the accessions. The phenotypic datasets were used for 55K single-nucleotide polymorphism (SNP) array-based genome-wide association studies to identify effective resistance loci. Eighty-nine accessions with stable resistance were identified in at least three of the four environments by phenotypic evaluation. Eleven markers located on chromosomes 1A, 2B, 5A, 5D, 7B, and 7D by the genome-wide association studies analysis showed significant associations with at least two resistance-associated traits in two of the environments. These loci, corresponding to seven genomic regions based on linkage disequilibrium decay distance, explained 9.3 to 26.0% of the total phenotypic variation. Five quantitative trait loci (QTLs) on chromosomes 1A, 2B, 7B, and 7D overlapped or were in close proximity to previously reported QTLs based on the consensus and physical maps using the reference sequence of bread wheat (IWGSC RefSeq v1.0). The other two QTLs were potential novel QTLs given their physical positions. Haplotype variants of QTL QYr.sicau-2BS showed subspecies-specific inheritance of the stripe rust resistance locus. Resistant loci among Chinese endemic wheat germplasms could be introduced into common wheat cultivars, and the high-confidence SNP markers will aid in marker-assisted selection in breeding for stripe rust disease resistance.


Control of Bovine Viral Diarrhea.
Bovine viral diarrhea (BVD) is one of the most important infectious diseases of cattle with respect to animal health and economic impact. Its stealthy nature, prolonged transient infections, and the presence of persistently infected (PI) animals as efficient reservoirs were responsible for its ubiquitous presence in cattle populations worldwide. Whereas it was initially thought that the infection was impossible to control, effective systematic control strategies have emerged over the last 25 years. The common denominators of all successful control programs were systematic control, removal of PI animals, movement controls for infected herds, strict biosecurity, and surveillance. Scandinavian countries, Austria, and Switzerland successfully implemented these control programs without using vaccination. Vaccination as an optional and additional control tool was used by e.g., Germany, Belgium, Ireland, and Scotland. The economic benefits of BVD control programs had been assessed in different studies.


Improved recognition of error related potentials through the use of brain connectivity features.
Brain error processing plays a key role in goal-directed behavior and learning in human brain. Directed transfer function (DTF) on EEG signal brings unique features for discrimination between correct and error cases in brain-computer interface (BCI) system. We describe the first application of brain connectivity features for recognizing error-related signals in non-invasive BCI. EEG signal were recorded from 16 human subjects when they monitored stimuli moving in either correct or erroneous direction. Classification performance using waveform features, brain connectivity features and their combination were compared. The result of combined features yielded highest classification accuracy, 0:85. In addition, we also show that brain connectivity at theta band around 200 ms after stimuli carry highly discriminant information between error and correct trials. This paper provides evidence that the use of connectivity features improve the performance of an EEG based BCI.


PICOT binding to chromatin-associated EED negatively regulates cyclin D2 expression by increasing H3K27me3 at the CCND2 gene promoter.
Protein kinase C (PKC)-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3 (Grx3; Glrx3)) is a ubiquitous protein that can interact with the embryonic ectoderm development (EED) protein via each of its two C-terminal PICOT/Grx homology domains. Since EED is a Polycomb-Group protein and a core component of the polycomb repressive complex 2 (PRC2), we tested the involvement of PICOT in the regulation of PRC2-mediated H3 lysine 27 trimethylation (H3K27me3), transcription and translation of selected PRC2 target genes. A fraction of the cellular PICOT protein was found in the nuclei of leukemia cell lines, where it was associated with the chromatin. In addition, PICOT coimmunoprecipitated with chromatin-residing EED derived from Jurkat and COS-7 cell nuclei. PICOT knockdown led to a reduced H3K27me3 mark and a decrease in EED and EZH2 at the CCND2 gene promoter. In agreement, PICOT-deficient T cells exhibited a significant increase in CCND2 mRNA and protein expression. Since elevated expression levels of PICOT were reported in several different tumors and correlated in the current studies with decreased transcription and translation of the CCND2 gene, we tested whether this opposite correlation exists in human cancers. Data from the Cancer Genome Atlas (TCGA) database indicated statistically significant negative correlation between PICOT and CCND2 in eight different human tumors where the highest correlation was in lung (p = 8.67E-10) and pancreatic (p = 1.06E-5) adenocarcinoma. Furthermore, high expression of PICOT and low expression of CCND2 correlated with poor patient survival in five different types of human tumors. The results suggest that PICOT binding to chromatin-associated EED modulates the H3K27me3 level at the CCND2 gene promoter which may be one of the potential mechanisms for regulation of cyclin D2 expression in tumors. These findings also indicate that a low PICOT/CCND2 expression ratio might serve as a good predictor of patient survival in selected human cancers.


IL-10+CD19+ regulatory B cells induce CD4+Foxp3+regulatory T cells in serum of cervical cancer patients.
Increase of regulatory T cells (Tregs) in the tumour microenvironment predicts worse survival of patients with various types of cancer. Recently, B cells play a significant role in the maintenance of Treg cells. However, the relevance of regulatory B cells (Bregs) to tumour immunity in humans remains elusive. Flow cytometry analysis was used to detect the Bregs and Tregs. Double staining results illustrated that the proportion of Bregs and Tregs were prominently higher in cervical cancer than normal tissues. Increase of Bregs and Tregs in cervical cancer microenvironment was associated with poor survival. Furthermore, Bregs cocultured with cervical cancer cell lines increased and induced Tregs. To sum up, the increased expression of Bregs contributes to the differentiation of CD4+ T cells into Tregs in the cervical cancer.


The silver lining of a viral agent: increasing seed yield and harvest index in Arabidopsis by ectopic expression of the potato leaf roll virus movement protein.
Ectopic expression of viral movement proteins (MPs) has previously been shown to alter plasmodesmata (PD) function and carbon partitioning in transgenic plants, giving rise to the view of PD being dynamic and highly regulated structures that allow resource allocation to be adapted to environmental and developmental needs. However, most work has been restricted to solanaceous species and the potential use of MP expression to improve biomass and yield parameters has not been addressed in detail. Here we demonstrate that MP-mediated modification of PD function can substantially alter assimilate allocation, biomass production, and reproductive growth in Arabidopsis (Arabidopsis thaliana). These effects were achieved by constitutive expression of the potato leaf roll virus 17-kD MP (MP17) fused to green fluorescent protein (GFP) in different Arabidopsis ecotypes. The resulting transgenic plants were analyzed for PD localization of the MP17:GFP fusion protein and different lines with low to high expression levels were selected for further analysis. Low-level accumulation of MP17 resulted in enhanced sucrose efflux from source leaves and a considerably increased vegetative biomass production. In contrast, high MP17 levels impaired sucrose export, resulting in source leaf-specific carbohydrate accumulation and a strongly reduced vegetative growth. Surprisingly, later during development the MP17-mediated inhibition of resource allocation was reversed, and final seed yield increased in average up to 30% in different transgenic lines as compared to wild-type plants. This resulted in a strongly improved harvest index. The release of the assimilate export block was paralleled by a reduced PD binding of MP17 in senescing leaves, indicating major structural changes of PD during leaf senescence.


Contemporary diversity of β-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups.
Escherichia coli (328 isolates), Klebsiella pneumoniae (296), Klebsiella oxytoca (44), and Proteus mirabilis (33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-β-lactamase (ESBL) phenotypes were evaluated for the presence of β-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for K. pneumoniae (16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112 K. pneumoniae strains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried blaCTX-M. SHV genes encoding ESBL activity were detected among 176 isolates. Other β-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried ≥2 β-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ml) were the most active agents tested. Overall, meropenem (MIC50, ≤0.06 μg/ml), ceftazidime-avibactam (MIC50, 0.12 to 0.5 μg/ml), and tigecycline (MIC50, 0.12 to 2 μg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all β-lactams tested. The diversity and increasing prevalence of β-lactamase-producing Enterobacteriaceae have been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals.


Armadillo motifs involved in vesicular transport.
Armadillo (ARM) repeat proteins function in various cellular processes including vesicular transport and membrane tethering. They contain an imperfect repeating sequence motif that forms a conserved three-dimensional structure. Recently, structural and functional insight into tethering mediated by the ARM-repeat protein p115 has been provided. Here we describe the p115 ARM-motifs for reasons of clarity and nomenclature and show that both sequence and structure are highly conserved among ARM-repeat proteins. We argue that there is no need to invoke repeat types other than ARM repeats for a proper description of the structure of the p115 globular head region. Additionally, we propose to define a new subfamily of ARM-like proteins and show lack of evidence that the ARM motifs found in p115 are present in other long coiled-coil tethering factors of the golgin family.


Neurogenic plasma leakage in mouse airways.
1. This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microvascular plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. 2. Single bolus intravenous injections of capsaicin (0.5 and 1 micromol kg(-1), i.v.) or substance P (1, 10 and 37 nmol kg(-10, i.v.) failed to induce significant leakage in the trachea, assessed as extravasation of Evans blue dye, but did induce leakage in the urinary bladder and skin. 3. Pretreatment with captopril (2.5 mg kg(-1), i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg(-1), i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline leakage of Evans blue in the absence of any exogenous inflammatory mediator. The increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg kg(-1), i.v.). 4. After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg(-1), i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg(-1), i.v.). 5. Experiments using Monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi, although the labelled vessels were less numerous in mice than in comparably treated rats. Blood vessels of the pulmonary circulation were not labelled. 6. We conclude that neurogenic inflammation can occur in airways of pathogen-free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmonary microvasculature.


[Cephalosporin C production by solid state fermentation with rice grains].
The purpose of the present study was to investigate the production of cephalosporin C in solid state fermentation with rice as a basal substrate. Among the various grains as basal substrates tested, rice was the best one and the worst one was soyflour . Among the varieties of rice examined, Tsailai rice was the best. The proposed best formula for the fermentation medium on the basis of 10 g rice grain consists the following % of the ingredients, 0.65, peptone, 0.65, ammonium sulfate, 0.26, inositol, 1.3 (v/w), trace element solution, 0.65 calcium carbonate, 0.65 calcium sulfate, 0.065, potasium sulfate, 1.3, sucrose, 0.13, DL-methionine and 2.6, methyl oleate. Of the strains of C. acremonium used, strain M8650 -R-3 was superior to strain ATCC 14553. The optimum inoculum density was 2.8 X 10(8) spores of C. acremonium M8650 -R-3 per g substrate. The initial moisture content of the medium at 49-51%, the water activity at 0.985, and the fermentation temperature at 25 degrees C were found as the optimun . After 7 days of fermentation, the maximum yield of cephalosporin C was 6420 micrograms per g substrate and the total cephalosporin C equivalent potency was 11,000 micrograms per g substrate.


Genetic differences in BCG-induced resistance to Schistosoma mansoni are not controlled by genes within the major histocompatibility complex of the mouse.
Induction of nonspecific resistance to Schistosoma mansoni infection after the i.v. injection of viable BCG was investigated in outbred mice and a panel of inbred and H-2 congenic strains. Significant protection was induced in CF1, A/J, C57BL/6, C57BL/10, DBA/2, C57BR, and SJL mice. BALB/c mice were not protected whereas CBA and C3H mice expressed intermediate degrees of protection. Expression of the protective phenomenon is not controlled by genes within the MHC as shown by the marked differences in response between BALB/c and DBA/2 (H-2d) as well as between C57BR and C3H (H-2k) mice. H-2 congenic strains with C57BL/10 background (B10.A and B10.D2) were high responders. BALB.B10 mice carrying the high responder (B10) MHC on the nonresponder (BALB/c) background were not protected. The degree of splenic hypertrophy did not correlate with the expression of nonspecific resistance. These results demonstrate that, in addition to controlling specific immune responses, genetic differences influence the nonspecific protective phenomena related to BCG administration as well.


Ageism in Nursing.
Stereotypes of older adults and assumptions of old age as a time of dependency and vulnerability affect not only how older adults are perceived and treated by society, but how they are treated by members of the nursing profession as well. When nurses display ageist attitudes, it can be harmful to older patients both physically and emotionally. In this review article the author describes some of the literature related to ageism in nursing, discusses how ageism can affect the quality of the care that is provided to older adult patients, and explains theories that may help explain ageism in nursing.


Contrast media in cardiovascular magnetic resonance.
Among the available imaging techniques, Magnetic Resonance Imaging (MRI) is gaining an increasing role in the cardiologic setting because its specific properties such as the use of non ionising energies, the natural strong contrast between different tissues, the absence of spatial limitations, the good spatial and temporal resolution, the reduced operator dependency. To further improve the images quality and the histopathologic characterisation of tissues the use of contrast media (molecules containing gadolinium, manganese, iron, dysprosium ions) has been proposed both in the experimental and in the clinical settings. Among these ions gadolinium, which having 7 odd electrons in the external orbit has a strong magnetic momentum, is the most used. Gadolinium by itself is extremely toxic but once it is linked with a chelanting agent such as DTPA (Dietilen-Triamin-Penta-Acetic acid) the resulting complex shows a very low toxicity. The number of Gadolinium based compound is growing together with the use of contrast agents in MRI. These contrast agents are routinely used to perform Magnetic Resonance Angiography (MRA) and to a better definition of several cardiac diseases such as the presence of a intra- or paracardiac mass, the evaluation of myocardial perfusion and the evaluation of viability. Both the latter applications have relevant clinical implications. In fact the assessment of myocardial perfusion is one of the most used approach for detecting inducible myocardial ischemia due to major coronary artery disease or to assess the presence of a microvascular disease. The presence and the extent of viable myocardium is deeply modifying the clinical decision making as this viable tissue can recruit a normal function spontaneously or after revascularisation. Furthermore, the extent of viable myocardium has a strong correlation with negative prognosis. Clinical events are also time related to the detection of viable tissue. These evidences imply that the diagnostic procedure needs the highest level of accuracy. Either in the case of myocardial perfusion and in that of myocardial viability the advantages of MRI with respect to the others techniques are the use of non ionising radiations, the superior spatial resolution, an overall cost/benefit favourable ratio which explains the growing interest among cardiologists toward this new diagnostic tool.


Thermal hydrogen-atom transfer from methane: the role of radicals and spin states in oxo-cluster chemistry.
Hydrogen-atom transfer (HAT), as one of the fundamental reactions in chemistry, is investigated with state-of-the-art gas-phase experiments in conjunction with computational studies. The focus of this Minireview concerns the role that the intrinsic properties of gaseous oxo-clusters play to permit HAT reactivity from saturated hydrocarbons at ambient conditions. In addition, mechanistic implications are discussed which pertain to heterogeneous catalysis. From these combined experimental/computational studies, the crucial role of unpaired spin density at the abstracting atom becomes clear, in distinct contrast to recent conclusions derived from solution-phase experiments.


Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells.
T-regulatory (Treg) cells suppress the immune response to maintain homeostasis. There are 2 main subsets of Treg cells: FOXP3 (forkhead box protein 3)-positive Treg cells, which do not produce high levels of effector cytokines, and type 1 Treg (Tr1) cells, which are FOXP3-negative and secrete interleukin (IL) 10. IL10 is an anti-inflammatory cytokine, so Tr1 cells might be used in the treatment of inflammatory bowel diseases. We aimed to develop methods to isolate and expand human Tr1 cells and define their functions. We obtained blood and colon biopsy samples from patients with Crohn's disease or ulcerative colitis or healthy individuals (controls). CD4+ T cells were isolated from blood samples and stimulated with anti-CD3 and anti-CD28 beads, and Tr1 cells were purified by using an IL10 cytokine-capture assay and cell sorting. FOXP3-positive Treg cells were sorted as CD4+CD25highCD127low cells from unstimulated cells. Tr1 and FOXP3-positive Treg cells were expanded, and phenotypes and gene expression profiles were compared. T cells in peripheral blood mononuclear cells from healthy donors were stimulated with anti-CD3 and anti-CD28 beads, and the suppressive abilities of Tr1 and FOXP3-positive Treg cells were measured. Human colon organoid cultures were established, cultured with supernatants from Tr1 or FOXP3-positive cells, and analyzed by immunofluorescence and flow cytometry. T84 cells (human colon adenocarcinoma epithelial cells) were incubated with supernatants from Tr1 or FOXP3-positive cells, and transepithelial electrical resistance was measured to determine epithelial cell barrier function. Phenotypes of Tr1 cells isolated from control individuals vs patients with Crohn's disease or ulcerative colitis did not differ significantly after expansion. Tr1 cells and FOXP3-positive Treg cells suppressed proliferation of effector T cells, but only Tr1 cells suppressed secretion of IL1B and tumor necrosis factor from myeloid cells. Tr1 cells, but not FOXP3-positive Treg cells, isolated from healthy individuals and patients with Crohn's disease or ulcerative colitis secreted IL22, which promoted barrier function of human intestinal epithelial cells. Tr1 cell culture supernatants promoted differentiation of mucin-producing goblet cells in intestinal organoid cultures. Human Tr1 cells suppress proliferation of effector T cells (adaptive immune response) and production of IL1B and TNF by myeloid cells (inmate immune response). They also secrete IL22 to promote barrier function. They might be developed as a cell-based therapy for intestinal inflammatory disorders.


Systemic effects of intratympanic dexamethasone therapy.
The study aimed to assess the possible systemic effects of intratympanic dexamethasone (IT-Dex) on the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and bone metabolism. A prospective cohort study including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg IT-Dex over a period of 10 days was carried out. Effects on plasma and salivary cortisol concentrations (basal and after low-dose (1 μg) ACTH stimulation), peripheral white blood cell count, and biomarkers for bone turnover were measured before (day 0) and after IT-Dex (day 16). Additional measurements for bone turnover were performed 5 months after therapy. Clinical information and medication with possible dexamethasone interaction were recorded. IT-Dex was well tolerated, and no effect was detected on the HPA axis (stimulated plasma and salivary cortisol concentration on day 0: 758±184 and 44.5±22.0 nmol/l; day 16: 718±154 and 39.8±12.4 nmol/l; P=0.58 and 0.24 respectively). Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1±10.5 and 23.6±8.8 μg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5±4.2, 10.3±3.4, and 12.6±5.06 μg/l); similarly, there was no difference in the peripheral white blood cell count (5.7×10(12)/l and 6.1×10(12)/l on days 0 and 16 respectively). IT-Dex therapy did not interfere with endogenous cortisol secretion or bone metabolism.


tRNA punctuation model of RNA processing in human mitochondria.
A 3'-end proximal segment of most of the putative mRNAs encoded in the heavy strand of HeLa cell mtDNA has been partially sequences and aligned with the DNA sequence. In all cases, the 3'-end nucleotide of the individual mRNA coding sequences has been found to be immediately contiguous to a tRNA gene or another mRNA coding sequence. These and previous results indicate that the heavy (H) strand sequences coding for the rRNA, poly(A)-containing RNA and tRNA species form a continuum extending over almost the entire length of this strand. We propose that the H strand is transcribed into a single polycistronic RNA molecule, which is processed later into mature species by precise endonucleolytic cleavages which occur, in most cases, immediately before and after a tRNA sequence.


[Helminthiasis in children--possible variants of symbiosis].
protozoal diseases and helminthiases are an essential part of infectious diseases. The massive spread of parasitic diseases had been identified in all regions of the world, including in children., number of suffering from parasitic infections exceeds 20 million and has a tendency to increase in Russia. The magnitude of damage to people's health, intestinal helminthiases are among the four leading causes of all diseases. under the supervision was a child with mixed-infestation of 7 helminths and parasites: enterobiosis + giardiasis, enterobiosis + ascariasis, ascariasis + trihotsefalez; enterobiosis giardiasis + toxocariasis. the case is of interest to clinicians and pediatricians in terms of diagnosis, because the helminthiasis was proceeded under the guise of somatic diseases associated with severe visceral injuries. Highlight helminthiasis on the stage of mixed-infestation among several helminths and parasites indicates a lack of pediatricians' alertness on parasitosis.


In Vitro and in Vivo Antitumor Effects of Plant-Derived Miliusanes and Their Induction of Cellular Senescence.
Our earliest phytochemical separation of Miliusa sinensis aided us in the isolation of a class of unique miliusanes, which were demonstrated as anticancer lead molecules. In the present study, we isolated 19 miliusanes (1-19), including 11 novel ones (5 and 10-19) from another Miliusa plant ( M. balansae), and synthesized additional derivatives to elucidate the structure-activity relationship of miliusanes. When extrapolated to various carcinoma xenograft mouse models, miliusol (1) and its derivatives 20, 26, and 27 (7.5-40 mg/kg) were demonstrated with tumor inhibitory efficacy comparable or even superior to the mainstay chemotherapeutics paclitaxel or fluorouracil. To gain a molecular insight into their anticancer mechanism, 1-3 (GI50 0.03-4.79) were administered to a wide spectrum of human cancer cell lines, including those with specific drug resistance. We further revealed that the antiproliferative properties of miliusanes in carcinoma cells were highly associated with the p21-dependent induction of cellular senescence.


A Sensitive, Portable Microfluidic Device for SARS-CoV-2 Detection from Self-Collected Saliva.
Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in December 2019, the spread of SARS-CoV2 infection has been escalating rapidly around the world. In order to provide more timely access to medical intervention, including diagnostic tests and medical treatment, the FDA authorized multiple test protocols for diagnostic tests from nasopharyngeal swab, saliva, urine, bronchoalveolar lavage and fecal samples. The traditional diagnostic tests for this novel coronavirus 2019 require standard processes of viral RNA isolation, reverse transcription of RNA to cDNA, then real-time quantitative PCR with the RNA templates extracted from the patient samples. Recently, many reports have demonstrated a direct detection of SARS-Co-V2 genomic material from saliva samples without any RNA isolation step. To make the rapid detection of SARS-Co-V2 infection more accessible, a point-of-care type device was developed for SARS-CoV-2 detection. Herein, we report a portable microfluidic-based integrated detection-analysis system for SARS-CoV-2 nucleic acids detection directly from saliva samples. The saliva cartridge is self-contained and capable of microfluidic evaluation of saliva, from heating, mixing with the primers to multiplex real-time quantitative polymerase chain reaction, detecting SARS-CoV-2 with different primer sets and internal control. The approach has a detection sensitivity of 1000 copies/mL of SARS-CoV-2 RNA or virus, with consistency and automation, from saliva sample-in to result-out.


Factors associated with off-label use of drug-eluting stents in patients with ST-elevation myocardial infarction.
Drug-eluting stents (DESs) are used in >80% of percutaneous coronary intervention (PCI) procedures; however, up to 2/3 are used for off-label indications. Factors associated with DES use in patients with ST-elevation myocardial infarction (STEMI) are not known in contemporary clinical practice. We analyzed temporal trends, geographic patterns, and sociodemographic factors associated with off-label use of DESs in patients undergoing primary PCI for STEMI from July 2004 to March 2006 in the National Cardiovascular Data Registry (NCDR). The main outcome of this study was receipt of any DES, and the candidate independent variables were sociodemographic, hospital, clinical, and procedural variables. We also analyzed temporal trends and geographic patterns for use of DESs. A total of 30,235 patients with STEMI underwent primary PCI with use of DESs (84%) or bare metal stents (16%). Adoption of DESs was rapid but varied widely as a function of geographic location. After adjusting for clinical and procedural variables, older age was associated with lower use (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.91 to 0.98), whereas white race (OR 1.14, 95% CI 1.03 to 1.27), commercial insurance (OR 1.22, 95% CI 1.11 to 1.34), and the west census region (OR 1.37, 95% CI 1.04 to 1.81) were associated with higher use of DESs. In conclusion, adoption of DESs was rapid in patients with STEMI, but geographic location and sociodemographic and hospital factors were associated with the use DESs.


Dialysis water and fluid purity: more than endotoxin.
The evolution of extracorporeal treatment of end-stage renal failure has enforced focus on the purity of dialysis fluid. A major challenge of high-flux haemodialysis (HD) and haemodiafiltration relates to the necessity for ultrapure dialysis fluid and for sterile non-pyrogenic substitution fluid. The present review focuses especially on the possible microbial contamination including, next to intact micro-organisms, a variety of microbial derivatives. It is pointed out that there are conditions (e.g. contamination by non-culturable micro-organisms or bacterial derivatives other than lipopolysaccharides) where the detection of biologically relevant contaminants can be missed when applying the recommended standard detection methods such as bacterial culture and limulus amoebocyte lysate test. Possible approaches for action upon positive sampling results, exceeding the levels recommended in the latest ISO 11663:2009, are described in detail and illustrated with flow charts. The issue of purity of dialysis fluids is highly relevant, since the chronic exposure of HD patients to low levels of cytokine-inducing microbial components can significantly contribute to the micro-inflammatory status of these patients.


Mouse Resistance Against Foot-and-Mouth Disease Virus Induced by Injections of Pyran.
Mouse resistance to foot-and-mouth disease virus (FMDV) was induced by intraperitoneal injections of pyran copolymer. A biphasic pattern of protection occurred with greatest resistance 4 and 48 hr after injection of this polyanion. Viremia was not detectable in pretreated mice challenge-exposed with FMDV. Incubation of virus with pyran did not alter viral infectivity in mice or tissue culture. Serum interferon was demonstrated 1 and 2 days after pyran administration.


40 dB gain all fiber bismuth-doped amplifier operating in the O-band.
In this Letter, we investigate and compare the gain and noise figure characteristics of bismuth (Bi)-doped fiber amplifiers configured in both single and double signal pass implementations. A maximum gain of 25 dB and a noise figure of 4 dB is measured at 1360 nm in the single pass configuration for -23 dBm input signal power, whereas in the double pass configuration the gain of the amplifier is improved significantly by 14 dB allowing us to achieve a gain of 39 dB with a noise figure of 5 dB. To the best of our knowledge, this is the highest gain reported to date using Bi-doped fiber as a gain medium. Furthermore, we also study the gain and noise figure dependency on pump power, signal power, and pump wavelength for the double pass amplifier configuration. We observed similar gain and noise figure performance in the double pass configuration to that of the single pass configuration but with the benefit of less pump power and a shorter length of the Bi-doped fiber.


HB-EGF promotes progenitor cell proliferation and sensory neuron regeneration in the zebrafish olfactory epithelium.
Maintenance and regeneration of the zebrafish olfactory epithelium (OE) are supported by two distinct progenitor cell populations that occupy spatially discrete stem cell niches and respond to different tissue conditions. Globose basal cells (GBCs) reside at the inner and peripheral margins of the sensory OE and are constitutively active to replace sporadically dying olfactory sensory neurons (OSNs). In contrast, horizontal basal cells (HBCs) are uniformly distributed across the sensory tissue and are selectively activated by acute injury conditions. Here we show that expression of the heparin-binding epidermal growth factor-like growth factor (HB-EGF) is strongly and transiently upregulated in response to OE injury and signals through the EGF receptor (EGFR), which is expressed by HBCs. Exogenous stimulation of the OE with recombinant HB-EGF promotes HBC expansion and OSN neurogenesis in a pattern that resembles the tissue response to injury. In contrast, pharmacological inhibition of HB-EGF membrane shedding, HB-EGF availability, and EGFR signaling strongly attenuate or delay injury-induced HBC activity and OSN restoration without affecting maintenance neurogenesis by GBCs. Thus, HB-EGF/EGFR signaling appears to be a critical component of the signaling network that controls HBC activity and, consequently, repair neurogenesis in the zebrafish OE.


Deletion of Glucocorticoid Receptors in Forebrain GABAergic Neurons Alters Acute Stress Responding and Passive Avoidance Behavior in Female Mice.
The glucocorticoid receptor (GR) is critically involved in regulation of stress responses [inhibition of the hypothalamic-pituitary-adrenal (HPA) axis], emotional behavior and cognition via interactions with forebrain corticolimbic circuity. Work to date has largely focused on GR actions in forebrain excitatory neurons; however, recent studies suggest a potential role mediated by interneurons. Here, we targeted GR deletion in forebrain GABAergic neurons, including the cortical interneurons, using a Dlx5/6-Cre driver line to test the role of forebrain interneuronal GR in HPA axis regulation and behavior. Our data indicate that GR deletion in GABAergic neurons causes elevated corticosterone stress responsiveness and decreased cross-over latencies in a passive avoidance task in females, but not males. Dlx5/6-Cre driven gene deletion caused loss of GR in interneurons in the prefrontal cortex (PFC) and hippocampus, but also in select diencephalic GABAergic neurons (including the reticular thalamic nucleus and dorsomedial hypothalamus). Our data suggest that GR signaling in interneurons is differentially important in females, which may have implications for GR-directed therapies for stress-related affective disease states.


Why are some people more fit than others? Correlates and determinants of cardiorespiratory fitness in adults: protocol for a systematic review.
Cardiorespiratory fitness (CRF) is a physical condition that is now well established as a predictor of numerous adverse health outcomes, independent of physical activity levels. In order to be able to improve CRF at the population level and to develop effective interventions and public health programmes, it is important to understand why some people are more fit than others. Therefore, the primary aim of the systematic review described in this protocol is to examine individual and interpersonal factors that are correlated with or determine CRF among adults. The review will focus on quantitative studies that investigate any personal and interpersonal correlates and/or determinants of objectively measured CRF among the general, non-symptomatic, non-institutionalized adult population (aged 18-65 years) worldwide. The databases MEDLINE, Embase, and Cochrane Library will be searched to identify all relevant published journal articles, and Google Scholar and Scopus will be searched for grey literature. Studies where CRF is not an outcome variable and experimental studies where participants specifically receive a fitness intervention that increases CRF will be excluded. For each study, data extracted will include, among other variables, study characteristics, methodology for selecting participants into the study as well as the participants' demographic characteristics, types of correlates and determinants of CRF investigated and their measurement methods, the objective measure of CRF used and its measurement method and validity, and the main reported results on the association between the correlates or determinants and CRF. In addition, observational studies will be assessed for methodological quality and risk of bias using a customized version of the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies by the National Heart, Lung, and Blood Institute. Experimental studies will be assessed using the 27-item Downs and Black "Checklist for Measuring Study Quality". The final results will be presented as a narrative synthesis of the main findings of all included studies. By consolidating and synthesizing the current research on possible individual and interpersonal correlates and determinants of CRF among adults worldwide, we aim to aid future public health actions, as well as identify gaps in our full understanding of what influences CRF. PROSPERO CRD42017055456 .


N,N-Diethyl-anilinium 5-(2,4-dinitro-phen-yl)-2,6-dioxo-1,2,3,6-tetra-hydro-pyrimidin-4-olate.
The asymmetric unit of the title mol-ecular salt, C10H16N(+)·C10H5N4O7(-) (trivial name: N,N-diethyl-anilinium 2,4-dinitro-phenyl-barbiturate), comprises two anion-cation units. In the anions, the dinitro-phenyl ring and the mean plane of the barbiturate ring [planar to within 0.011 (2) and 0.023 (2) Å in the two anions] are inclined to one another by 41.47 (9) and 45.12 (9)°. In the crystal, the anions are linked via strong N-H⋯O hydrogen bonds, forming chains propagating along [10-1]. Within the chains, adjacent inversion-related anionic barbiturate entities are joined through R2(2)(8) ring motifs. The cations are linked to the chains via N-H⋯O hydrogen bonds. The chains are linked via a number of C-H⋯O inter-actions, forming a three-dimensional structure.


High Seroprevalence Against Typhus Group and Spotted Fever Group Rickettsiae in Rural Indigenous Populations of Peninsular Malaysia.
Rickettsioses of the typhus group (TG) and spotted fever group (SFG) are emerging bacterial infections worldwide, especially in the tropics. Only a few studies on these pathogens and their respective clinical diseases have been conducted in Malaysia. Here, we performed a seroprevalence study among 544 healthy, afebrile indigenous people (Orang Asli) from peninsular Malaysia for TG and SFG rickettsioses in nine rural and peri-urban settlements. The study population encompassed children, adolescents, and adults. The overall seroprevalence of rickettsiosis in the Orang Asli was 48.5%, with 27.9% seroprevalence against TG rickettsiae and 20.6% seroprevalence against SFG rickettsiae. In 7.9% of the study participants, antibodies against both rickettsial groups were found. The highest seropositivity rates against TG and SRG rickettsiae were detected in young children and adults. Overall, there were no gender differences. Seroprevalences were similar among inhabitants of different settlements, except for two localities. More studies are needed to shed more light on the ecology and risk factors for TG and SFG rickettsioses in Malaysia.


Tubal pregnancy. Associated histopathology.
Endometrial histologic characteristics are of little value in predicting ectopic pregnancy. The growing tubal gestation does not have any unique characteristics as far as the maternal-fetal tissue interface is concerned. The placentation is relatively superficial, and the growth is intraluminal. Tubal rupture occurs as a result of progressive tubal distention with focal hemorrhagic necrosis. Persistence is a reflection of incomplete evacuation combined with the noncyclic shedding of the tubal epithelium. The evacuated implantation site and conservative surgical incisions are not directly related to the recurrence of ipsilateral tubal pregnancies. The most common histologic finding related to tubal pregnancy is that of prior tubal disease.


Factors influencing the filtration-bleb volume after Ex-PRESS® surgery.
The aim of this study was to investigate the factors influencing the volume of the filtration bleb after Ex-PRESS® surgery. This was a retrospective non-randomized study. After excluding patients who had undergone an additional glaucoma surgery, 99 glaucoma patients who underwent Ex-PRESS® surgeries and were followed up for >2 years were analyzed. We used anterior segment optical coherence tomography to measure the bleb volume, and compared the volume at 1 year with that at 2 years after surgery. We also examined potential influencing factors, including age, number of medications, central corneal thickness, type of glaucoma, preoperative intraocular pressure (IOP), postoperative IOP, reduction ratio of IOP, history of trabeculotomy, and operation method (Ex-PRESS® surgery only or simultaneous cataract surgery). Ex-PRESS® surgeries significantly decreased the IOP from 26.3±9.7 mmHg to 11.6±3.7 mmHg after 24 months (P<0.001). The success rate at 2 years was 81.2% (IOP ≥21 mmHg or ≥20% reduction from the baseline IOP). The results showed that age, postoperative IOP, glaucoma type, and simultaneous cataract surgeries influenced the filtration-bleb volume. Advanced age, higher postoperative IOP, pseudo-exfoliation glaucoma, and simultaneous cataract surgeries were all found to decrease the volume of the filtration bleb.


[Psychophysiologic interrelations in healthy subjects and alcoholics in remission].
Twenty male patients suffering from alcoholism (10 at the second and 10 at the third stage of disease) at the phase of a remission were subjected to electropolygraphic examination during night sleep and relaxed wakefulness. The mental state was examined by MIL and Spilberger's tests. A control group included 14 normal subjects in whom, additionally to the baseline examinations, the authors studied the effect of a single dose of ethanol taken before sleep on the nonspecific cerebral systems. The latter was associated with an increase in the deep stages of sleep and a reduction of the phase of rapid sleep as well as a decrease of the activation parameters. The electropolygraphic and psychological characteristics in patients with alcoholism of stage II and III showed no significant differences, yet both groups differed considerably from healthy subjects which was expressed in the intensified desynchronization of the cerebral bioelectrical activity in both sleep and wakefulness and in the presence of anxiety-depressive disorders. Hyperfunction of the ascending activating system of the brain seems to be responsible for the above psychophysiological changes.


Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle.
AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose transport in skeletal muscle. In muscles with different fiber type composition from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum brevis, and not at all in soleus muscles. Contraction increased both transport and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and contractions on glucose transport were partially additive despite a lower AMPK activity with AICAR compared with contraction alone. In EPI from fed rats, glucose transport responses were smaller than what was seen in fasted rats, and AICAR did not increase transport despite an increase in AMPK activity. AICAR and contraction activated both alpha(1)- and alpha(2)-isoforms of AMPK. Expression of both isoforms varied with fiber types, and alpha(2) was highly expressed in nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport.


Formation and reduction of a 'peroxy' intermediate of cytochrome c oxidase by hydrogen peroxide.
In the presence of micromolar concentrations of H2O2, ferric cytochrome c oxidase forms a stable complex characterized by an increased absorption intensity at 606-607 nm with a weaker absorption band in the 560-580 nm region. Higher (millimolar) concentrations of H2O2 result in an enzyme exhibiting a Soret band at 427 nm and an alpha-band of increased intensity in the 589-610 nm region. Addition of H2O2 to ferric cytochrome c oxidase in the presence of cyanide results in absorbance increases at 444nm and 605nm. These changes are not seen if H2O2 is added to the cyanide complex of the ferric enzyme. The results support the idea that direct reaction of H2O2 with ferric cytochrome a 3 produces a 'peroxy' intermediate that is susceptible to further reduction by H2O2 at higher peroxide concentrations. Electron flow through cytochrome a is not involved, and the final product of the reaction is the so-called 'pulsed' or 'oxygenated' ferric form of the enzyme.


Ultra-low price of generic agents in China may weaken patients' drug recognition and compliance.
Drug quantity purchase in China has reshaped the pattern of drug market with lower price of generic drugs and relatively higher price of original brand-name drugs. However, most Chinese people do not trust the safety and efficacy of the generic drugs that sold at a very low price. Ultra-low price of generic agents may weaken patients' drug recognition and compliance, and affect the implementation of drug quantity purchase policy.


The Shortening of MWNT-SPION Hybrids by Steam Treatment Improves Their Magnetic Resonance Imaging Properties In Vitro and In Vivo.
Carbon nanotubes (CNTs) have been advocated as promising nanocarriers in the biomedical field. Their high surface area and needle-like shape make these systems especially attractive for diagnostic and therapeutic applications. Biocompatibility, cell internalization, biodistribution, and pharmacokinetic profile have all been reported to be length dependent. In this study, further insights are gotten on the role that the length of CNTs plays when developing novel contrast agents for magnetic resonance imaging (MRI). Two samples of CNTs with different length distribution have been decorated with radio-labeled iron oxide nanoparticles. Despite characterization of the prepared hybrids reveals a similar degree of loading and size of the nanoparticles for both samples, the use of short CNTs is found to enhance the MRI properties of the developed contrast agents both in vitro and in vivo compared to their long counterparts.


Hypertension: Are Current Guidelines Inclusive of Sex and Gender?
Background: Hypertension (HTN) accounts for one in five deaths of American women. Major societies worldwide aim to make evidence-based recommendations for HTN management. Sex- or gender-based differences exist in epidemiology and management of HTN; in this study, we aimed to assess sex- and gender-based language in major society guidelines. Materials and Methods: We reviewed HTN guidelines from four societies: the American College of Cardiology (ACC), the American College of Emergency Physicians (ACEP), the European Society of Cardiology (ESC), and the Eighth Joint National Committee (JNC8). We quantified the sex- and gender-based medicine (SGBM) content by word count in each guideline as well as identified the gender of guideline authors. Results: Two of the four HTN guidelines (ACC, ESC) included SGBM content. Of these two guidelines, there were variations in the quantity and depth of content coverage. Pregnancy had the highest word count found in both guidelines (422 words in ACC and 1,523 words in ESC), which represented 2.45% and 3.04% of the total words in each guideline, respectively. There was minimal coverage, if any, of any other life periods. The number of women authors did not impact the SGBM content within a given guideline. Conclusions: Current HTN management guidelines do not provide optimal guidance on sex- and gender-based differences. Inclusion of sex, gender identity, hormone therapy, pregnancy and lactation status, menopause, and advanced age in future research will be critical to bridge the current evidence gap. Guideline writing committees should include diverse perspectives, including cisgender and transgender persons from diverse racial and ethnic backgrounds.


Pistillate flower development and pollen tube growth mode during the delayed fertilization stage in Corylus heterophylla Fisch.
Unlike most angiosperms, in which fertilization occurs within several days after pollination, fertilization in hazel (Corylus Spp.) is delayed by two to three and a half months. However, the female inflorescences or young fruits are too hard or lignified to be dissected according to regular paraffin sectioning technique. So, what the nature of development during the extended progamic phases of hazel remains unknown. The female inflorescence development and pollen tube growth mode during the delayed fertilization stage in hazel were investigated by improved paraffin sectioning and aniline blue staining of pollen tubes. The results showed ovaries and ovules of hazel were invisible at the time of blooming. Early ovary and ovule primordium began to form from 15 to 20 days after blooming, respectively. Integument and mature embryo sacs differentiated from the nucellus on 40th and 55th day after blooming, respectively. Pollen tubes were retarded in the bottom of the style or the pollen tube cavity (PTC, a specifical lignified cavity structure at the bottom of style for pollen tube to rest during progamic phase) for about 26 days. Then, the pollen tubes were observed to leave the PTC and began to enter the ovary. After that, a single pollen tube passed through the vicinity of the micropyle. Finally, pollen tubes turned a corner and penetrated the embryo sac through the tissue of the chalaza instead of micropyle on 52 and 55 days after blooming, respectively. The results of more in-depth information will be beneficial to better understanding of the delayed fertilization process in hazel.


Ultrastructural characteristics of the non-immune rosette-forming cell.
Non-immune rosette formation, where a non-sensitized lymphocyte is surrounded by three or more sheep red blood cells, is an in vitro technique which is thought to be specific in the identification of thymus-dependent (T) lymphocytes. Using the electron microscope and tissue culture techniques, we have studied the ultrastructure of the rosette-forming lymphocyte which has been stimulated by various cellular mitogens. Non-sensitized but stimulated lymphocytes, which form rosettes, have a morphology similar to that of previously identified T cells, adding further credence to the concept that non-sensitized rosette-forming cells represent a population of T cells. Changes in the binding pattern of the sheep red cell membrane to the lymphocyte have been identified which may represent an early phase of cell 'activation'. This marker of activation offers a potential method of studying membrane responses in attempts to localize cellular defects involving the T lymphocyte. In addition, preliminary studies using fluorescein-labelled sheep red blood cell fragments suggest specific attachment of labelled membrane to the T lymphocyte, allowing rapid identification of T cells in smears or tissue preparations.


RANK Ligand Helps Immunity to Leishmania major by Skewing M2-Like Into M1 Macrophages.
Macrophages host Leishmania major infection, which causes cutaneous Leishmaniasis in humans. In the murine model, resistance to infection depends on the host immunity mediated by CD4 T-cell cytokines and macrophages. In association to other stimuli, the Th1 cytokine IFN-γ induces NO-mediated microbial killing by M1/classically-activated macrophages. By contrast, the Th2 cytokine IL-4 promotes M2/alternatively activated macrophages, which express arginase-1 and shelter infection. Other cytokines, such as RANKL, might also participate in the crosstalk between T cells and macrophages to restrict parasite infection. RANKL and its receptor RANK are known to play an essential role in bone remodeling, by inducing osteoclatogenesis. It has also been shown that RANKL stimulates antigen-presenting cells, such as DCs and macrophages, to enhance T cell responses. Here we investigated how RANKL directly modulates the effector macrophage phenotypes and immunity to L. major parasites. We found that inflammatory peritoneal macrophages from B6 mice express RANK and M2 features, such as CD301 (MGL) and CD206 (mannose receptor). Nonetheless, treatment with RANKL or IFN-γ induced macrophage differentiation into more mature F40/80hi macrophages able to produce IL-12 and TNF-α. In parallel, macrophages treated with RANKL, IFN-γ, or RANKL along with IFN-γ progressively downregulated the expression of the M2 hallmarks MGL, arginase-1, and CCL17. Moreover, a synergism between IFN-γ and RANKL enhanced inducible NO synthase (iNOS) expression and NO production by macrophages. These results are consistent with the idea that RANKL helps IFN-γ to induce a M2-like to M1 phenotype shift. Accordingly, concomitant treatment with RANKL and IFN-γ promoted macrophage-mediated immunity to L. major, by inducing NO and ROS-dependent parasite killing. Furthermore, by cooperating with IFN-γ, endogenous RANKL engages CD4 T-cell help toward L. major-infected macrophages to upregulate M1 and Th1 cytokine responses. Therefore, RANKL, in combination with IFN-γ, is a potential local therapeutic tool to improve immune responses in Leishmaniasis, by skewing M2-like into effector M1 macrophages.


[The postnatal development of the hemato-C-cellular system in the thyroid of rats sympathectomized with guanethidine].
We used ultrastructural morphometry to examine submicroscopical organization of spatial contacts between the C-cells and perifollicular hemocapillaries in the thyroid gland of 2-, 4-, 12-, 26-, and 52-week-old rats desympathized with guanetidine. We found that desympathization does not affect typology of ultrastructural elements of the hemato-C-cellular complex, and predominant coupling of the vascular pole of the C-cell with peripheral zone of endotheliocyte highly effective in terms of transport. Postnatal changes of certain parameters of the hemato-C-cellular system, however, undergo some statistically significant changes. Under experimental conditions, we observed the formation of hemato-C-cellular contacts simultaneously involving two C-cells.


Quantification of cigarette smoke particle deposition in vitro using a triplicate quartz crystal microbalance exposure chamber.
There are a variety of smoke exposure systems available to the tobacco industry and respiratory toxicology research groups, each with their own way of diluting/delivering smoke to cell cultures. Thus a simple technique to measure dose in vitro needs to be utilised. Dosimetry-assessment of dose-is a key element in linking the biological effects of smoke generated by various exposure systems. Microbalance technology is presented as a dosimetry tool and a way of measuring whole smoke dose. Described here is a new tool to quantify diluted smoke particulate deposition in vitro. The triplicate quartz crystal microbalance (QCM) chamber measured real-time deposition of smoke at a range of dilutions 1:5-1:400 (smoke:air). Mass was read in triplicate by 3 identical QCMs installed into one in vitro exposure chamber, each in the location in which a cell culture would be exposed to smoke at the air-liquid interface. This resulted in quantification of deposited particulate matter in the range 0.21-28.00 μ g/cm(2). Results demonstrated that the QCM could discriminate mass between dilutions and was able to give information of regional deposition where cell cultures would usually be exposed within the chamber. Our aim is to use the QCM to support the preclinical (in vitro) evaluation of tobacco products.