Simultaneous multiple organ emboli in a patient with solid organ malignancy: a case report.
Thrombosis is a dangerous complication of cancer. At least 20% of cancer patients are diagnosed with a venous thrombotic event and 1% with an intra-arterial thrombotic event. Here, we present a patient that developed separate thrombi that occurred simultaneously in both the venous and arterial circulation. An 80-year-old woman with a history of recently diagnosed squamous cell lung cancer presented to our institution with an out of hospital cardiac arrest. On arrival, she was found to have an inferior ST-elevation myocardial infarction on electrocardiogram and on examination was found to have right-sided neurological deficits. Computed tomography head and aortogram showed an acute ischaemic stroke and bilateral segmental pulmonary emboli. Coronary angiogram showed thrombotic occlusion distal to the right coronary artery, and the patient underwent aspiration thrombectomy with thrombolysis in myocardial infarction 3 flow established at the end of the procedure. The patient was then transferred to interventional radiology where she had successful clot retrieval of the cerebral thrombus. The patient progressed well and had full neurological recovery 72 h post-presentation. Subsequent transoesophageal echocardiography showed no evidence of a patent foramen ovale or other intracardiac shunt. The patient was prescribed long-term anticoagulant with Clexane. There was suspicion for a deep vein thrombosis with subsequent embolization to the lungs and paradoxical embolization through an intracardiac shunt. However, no such defect was detected and it appears that the patient did develop thrombi in the arterial and venous system separately. This case highlights the prothrombotic state of malignancy, with the patient suffering from multiple separate life-threatening thrombi.


Mechanism-independent method for predicting response to multidrug combinations in bacteria.
Drugs are commonly used in combinations larger than two for treating bacterial infection. However, it is generally impossible to infer directly from the effects of individual drugs the net effect of a multidrug combination. Here we develop a mechanism-independent method for predicting the microbial growth response to combinations of more than two drugs. Performing experiments in both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, we demonstrate that for a wide range of drugs, the bacterial responses to drug pairs are sufficient to infer the effects of larger drug combinations. To experimentally establish the broad applicability of the method, we use drug combinations comprising protein synthesis inhibitors (macrolides, aminoglycosides, tetracyclines, lincosamides, and chloramphenicol), DNA synthesis inhibitors (fluoroquinolones and quinolones), folic acid synthesis inhibitors (sulfonamides and diaminopyrimidines), cell wall synthesis inhibitors, polypeptide antibiotics, preservatives, and analgesics. Moreover, we show that the microbial responses to these drug combinations can be predicted using a simple formula that should be widely applicable in pharmacology. These findings offer a powerful, readily accessible method for the rational design of candidate therapies using combinations of more than two drugs. In addition, the accurate predictions of this framework raise the question of whether the multidrug response in bacteria obeys statistical, rather than chemical, laws for combinations larger than two.


Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate: Data from the Efficacy of Nitric Oxide in Stroke Randomised Controlled Trial.
Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke. Clinical Trial Registration Clinical Trial Registration-URL: http://www.controlled-trials.com . Unique identifier: ISRCTN99414122.


A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene.
Macrothrombocytopenias are the most important subgroup of inherited thrombocytopenias. This subgroup is particularly heterogeneous because the affected genes are involved in various functions such as cell signaling, cytoskeleton organization, and gene expression. Herein we describe the clinical and hematological features of a consanguineous family with a severe autosomal recessive macrothrombocytopenia associated with a thrombocytopathy inducing a bleeding tendency in the homozygous mutated patients. Platelet activation and cytoskeleton reorganization were impaired in these homozygous patients. Exome sequencing identified a c.222C>G mutation (missense p.74Ile>Met) in PRKACG, a gene encoding the γ-catalytic subunit of the cyclic adenosine monophosphate-dependent protein kinase, the mutated allele cosegregating with the macrothrombocytopenia. We demonstrate that the p.74Ile>Met PRKACG mutation is associated with a marked defect in proplatelet formation and a low level in filamin A in megakaryocytes (MKs). The defect in proplatelet formation was rescued in vitro by lentiviral vector-mediated overexpression of wild-type PRKACG in patient MKs. We thus conclude that PRKACG is a new central actor in platelet biogenesis and a new gene involved in inherited thrombocytopenia with giant platelets associated with a thrombocytopathy.


Radiotelemetric comparison of two antacids using the Heidelberg capsule.
The acid neutralizing capacity of a new antacid, almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax) has been compared with that of a popular mixture of aluminium-magnesium hydroxide codried gel, aluminium hydroxide and calcium carbonate (antacid A) using a transistorized telemetric technique (Heidelberg capsule) in 10 healthy volunteers following a double-blind crossover design. After placement of the radio transmitter capsule in the stomach a standard bicarbonate alkali test was made followed by the antacid under study. From the pH versus time curves obtained it was clearly shown that both antacid A and Almax produced a rapid (less than 1 min) neutralization of gastric acid (greater than pH 3) and that there were no significant differences between the two in terms of duration of effect (mean values of 48.35 and 54.65 min, respectively) and area under the pH versus time curves (mean values of 166.9 and 197.2 mm2, respectively). The maximum pH reached with Almax (mean 8.3) was, however, significantly (p less than 0.05) higher than that reached with antacid A (mean 7.6) although these maximum values were only transient. A calculation of antacid capacity relative to the bicarbonate alkali test control in each subject showed that Almax (5.75) had an apparently greater capacity than antacid A (3.33) but the individual variations were too great to allow statistical confirmation of this difference.


Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells.
Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.


Photocontrolled chiroptical switch based on the self-assembly of azobenzene-bridged bis-tryptophan enantiomers.
Chirality dynamic tuning plays fundamental roles in chemistry, material science and biological system. Herein, a pair of azobenzene-bridged bis-tryptophan enantiomers (Azo-di-d/l-Trp) were designed and synthesized via simple reactions. With the fuel of glucono-δ-lactone (GdL), releasing protons during its hydrolysis, the alkaline solution of Azo-di-d/l-Trp gradually self-assembled into contrast chiral helical structures and displayed magnitude and mirror image of circular dichroism (CD) signals. While the chiral helices converted to CD silent nanoparticles when the azobenzene moiety isomerized from trans- to cis-form under UV irradiation. More importantly, this chiroptical switch, displaying reversible interconversion between chiral amplification and silent, can be smartly controlled via photoirradiation at various wavelengths.


High performance, waveguide integrated Ge photodetectors.
Photonic systems based on complementary metal oxide semiconductor (CMOS) technology require the integration of passive and active photonic devices. The integration of waveguides and photodetector is one of the most important technologies. We report a Ge p-i-n photodetector that is monolithically integrated with silicon oxynitride and silicon nitride waveguides. All processes and materials are CMOS compatible and can be implemented in the current integrated circuit process technology. The small size of the devices results in low absolute dark current. The waveguidecoupled Ge devices show high efficiency (~90%) over a wide range of wavelengths well beyond the direct band gap of Ge, resulting in a responsivity of 1.08 A/W for 1550 nm light. The device speed of 7.2 GHz at 1V reverse bias is strongly affected by the capacitance of the probe pads. The high-performance of the devices at low voltage ( </= 1V) facilitates the integration with CMOS circuits.


Ranolazine terminates atrial flutter and fibrillation in a canine model.
Ranolazine has been shown to have antiarrhythmic properties. We tested the hypothesis that intravenous ranolazine would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model. In 6 dogs with sterile pericarditis, we performed electrophysiological measurements of the atrial effective refractory period (AERP) and conduction time (CT) while pacing from the right atrial appendage, Bachmann bundle, and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms before and after the administration of ranolazine. In 13 induced episodes of AFL (n = 9) and AF (n = 4), ranolazine was administered intravenously as a 3.2 mg/kg bolus, followed by a maintenance infusion of 0.17 mg/(kg·min). Six episodes (4 AFL and 2 AF) were induced in the open-chest state to perform simultaneous, multisite (486 electrodes), epicardial mapping of the arrhythmia and its termination. Ranolazine terminated 7 of 9 AFL and 3 of 4 AF episodes. Ranolazine significantly prolonged the AFL CL by a mean of 43 ms (P < .001) and the AF CL by a mean of 34 ms (P < .01). The AERP was prolonged (P < .05 overall), and the atrial capture threshold increased minimally (P < .01 for all). Ranolazine prolonged CTs (P < .01 overall). During open-chest, multisite mapping, block in the region of slow conduction in the reentrant circuit terminated AFL and interruption of the regular driver terminated AF. Ranolazine terminated AFL/AF in our canine sterile pericarditis model by interrupting the regular driver. Ranolazine was found to significantly prolong the AERP, CT, and tachycardia CLs.


Intracerebral transplantation of carotid body in rats with transient middle cerebral artery occlusion.
Recent laboratory and clinical studies demonstrate therapeutic efficacy of intracerebral transplantation of carotid body (CB) in Parkinson's disease, possibly through secretion of neurotrophic factors. Here, we examined the role of CB in experimental stroke. In the first experiment, we hypothesized that removal of CB would exacerbate cerebral infarction and stroke-related behavioral deficits. Eight-week-old, male Sprague-Dawley rats were randomly divided into two groups: stroke with intact CB and stroke with surgically removed CB. We used the stroke model of temporary middle cerebral artery occlusion. The ipsilateral CB was removed in animals assigned to treatment group exposed to stroke with surgically removed CB. Behavioral tests, using the elevated body swing test, were conducted at days 1-3 after surgery. Cerebral infarction was visualized by TTC staining on day 3 post-surgery. The data revealed no significant differences in behavioral deficits and infarct volumes between the two groups. In the second experiment, CB cell suspension grafts or control adult tissue grafts were intracerebally transplanted into the ischemic penumbra immediately (within 1 h) after stroke surgery. The results revealed significant reduction of behavioral deficits and infarct volumes, accompanied by increased levels of neurotrophic factors, as detected by ELISA, in transplanted ischemic striatum collected from CB-grafted stroke animals. These observations suggest that surgical resection of CB in the periphery did not alter stroke pathology; however, CB when made available in the CNS, via intracerebral transplantation, could protect against stroke possibly through the synergistic release of neurotrophic factors. The present study extends the use of CB as efficacious graft source for transplantation.


[Adherence to the Ongoing Education Program for family doctors in a southeastern Brazilian state].
Ongoing Health Education is a strategy for transformation of health practices, though the adherence of professionals is one of the challenges facing its implementation. Thus, the objective of this study was to investigate the factors associated with adherence of family doctors to the Ongoing Education Program in a southeastern Brazilian state from the perception of supervisors. It is a cross-sectional and quantitative study with the use of online questionnaires. Data were analyzed using the chi-square test with ongoing correction to determine the association between structure, topics, activities and difficulties of the supervisors working in Ongoing Health Education, difficulties of the physicians in Primary Health Care (PHC) and poor and good adherence to the program. Excellent medical participation was statistically related to the adequacy of physical space (p = 0.001), a multidisciplinary approach (p = 0.035) and epidemiological aspects (p = 0.043). Low adherence was associated with the inadequacy of the physical structure, difficulty understanding the methodology, less time in a supervisory position, multiple workdays, among others. A good adherence to Ongoing Health Education is a possibility for collective reconstruction of the everyday work of physicians in Primary Health Care.


N-(3-oxododecanoyl)-homoserine lactone regulates osteoblast apoptosis and differentiation by mediating intracellular calcium.
Pseudomonas aeruginosa (P. aeruginosa) is associated with periapical periodontitis. The lesions are characterized by a disorder in osteoblast metabolism. Quorum sensing molecular N-(3-oxododecanoyl)-homoserine lactone (AHL) is secreted by P. aeruginosa and governs the expression of numerous virulence factors. AHL can trigger intracellular calcium ([Ca2+]i) fluctuations in many host cells. However, it is unclear whether AHL can regulate osteoblast metabolism by affecting [Ca2+]i changes or its spatial correlation. We explored AHL-induced apoptosis and differentiation in pre-osteoblastic MC3T3-E1 cells and evaluated [Ca2+]i mobilization using several extraction methods. The spatial distribution pattern of [Ca2+]i among cells was investigated by Moran's I, an index of spatial autocorrelation. We found that 30 μM and 50 μM AHL triggered opposing osteoblast fates. At 50 μM, AHL inhibited osteoblast differentiation by promoting mitochondrial-dependent apoptosis and negatively regulating osteogenic marker genes, including Runx2, Osterix, bone sialoprotein (Bsp), and osteocalcin (OCN). In contrast, prolonged treatment with 30 μM AHL promoted osteoblast differentiation concomitantly with cell apoptosis. The elevation of [Ca2+]i levels in osteoblasts treated with 50 μM AHL was spatially autocorrelated, while no such phenomenon was observed in 30 μM AHL-treated osteoblasts. The blocking of cell-to-cell spatial autocorrelation in the osteoblasts provoked by 50 μM AHL significantly inhibited apoptosis and partially restored differentiation. Our observations suggest that AHL affects the fate of osteoblasts (apoptosis and differentiation) by affecting the spatial correlation of [Ca2+]i changes. Thus, AHL acts as a double-edged sword for osteoblast function.


Comparative Analysis of Different Tube Models for Linear Rheology of Monodisperse Linear Entangled Polymers.
The aim of the present paper is to analyse the differences between tube-based models which are widely used for predicting the linear viscoelasticity of monodisperse linear polymers, in comparison to a large set of experimental data. The following models are examined: Milner-McLeish, Likhtman-McLeish, the Hierarchical model proposed by the group of Larson, the BoB model of Das and Read, and the TMA model proposed by the group of van Ruymbeke. This comparison allows us to highlight and discuss important questions related to the relaxation of entangled polymers, such as the importance of the contour-length fluctuations (CLF) process and how it affects the reptation mechanism, or the contribution of the constraint release (CR) process on the motion of the chains. In particular, it allows us to point out important approximations, inherent in some models, which result in an overestimation of the effect of CLF on the reptation time. On the contrary, by validating the TMA model against experimental data, we show that this effect is underestimated in TMA. Therefore, in order to obtain accurate predictions, a novel modification to the TMA model is proposed. Our current work is a continuation of earlier research (Shchetnikava et al., 2014), where a similar analysis is performed on well-defined star polymers.


Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products.
Tobacco smoke contains a large number of compounds in the form of metals, volatile gases and insoluble particles, as well as nicotine, a highly addictive alkaloid. Marijuana is the most widely used illicit drug of abuse in the world, with a significant increase in the USA due to the increasing number of states that allow medical and recreational use. Of the over 70 phytocannabinoids in marijuana, Δ9-tetrahydrocannabinol (Δ9THC), cannabidiol (CBD) and cannibinol are the three main constituents. Both marijuana and tobacco smoking induce cytochrome P450 (CYP) 1A2 through activation of the aromatic hydrocarbon receptor, and the induction effect between the two products is additive. Smoking cessation is associated with rapid downregulation of CYP1A enzymes. On the basis of the estimated half-life of CYP1A2, dose reduction of CYP1A drugs may be necessary as early as the first few days after smoking cessation to prevent toxicity, especially for drugs with a narrow therapeutic index. Nicotine is a substrate of CYP2A6, which is induced by oestrogen, resulting in lower concentrations of nicotine in females than in males, especially in females taking oral contraceptives. The significant effects of CYP3A4 inducers and inhibitors on the pharmacokinetics of Δ9THC/CBD oromucosal spray suggest that CYP3A4 is the primary enzyme responsible for the metabolism of Δ9THC and CBD. Limited data also suggest that CBD may significantly inhibit CYP2C19. With the increasing use of marijuana and cannabis products, clinical studies are needed in order to determine the effects of other drugs on pharmacokinetics and pharmacodynamics.


A census of students with disabilities and the support provided at the University of Aix-Marseille.
Access to the college cycle for students with disabilities and their employability have become a priority for universities. The Handicap Mission manages it within the Aix-Marseille University (AMU). Few studies have focused on the students with disabilities' insertion/integration within the universities and on the compensations. The objective of this study is to analyze within the AMU the students with disabilities census and characteristics, and the Handicap Mission's operating. The census was conducted using a self-administered questionnaire (Handi need card: university curriculum, deficiencies, technical and social help, adjustments appealed for at the university). It was performed by the staff at the AMU's Mission Handicap Department/Office. If supporting measures seem to be necessary, the interdisciplinary team (comprised of representatives of the University teaching, Administrative and Technical staff, Mission Handicap staff, Preventive Medicine staff, and partners from associations involved in assisting people with disabilities) then defines and sets up suitable means of assistance. The Handicap Mission improves students with disabilities insertion, defines necessary adjustments, and promotes research on disability. A total of 551 students with disabilities were identified, 304 in law and human sciences. In all, 141 deficiencies encountered related to language disorders, among which 105 were not defined by the students ('Other' in the questionnaire). In all, 519 SWD benefited from extra time when sitting exams and 40 were helped to take notes by others students. Compensations and Handicap Mission improve the monitoring and the link between high school and university for the students with disabilities, promote their exam success, and support them in their working life.


Associations between breast milk viral load, mastitis, exclusive breast-feeding, and postnatal transmission of HIV.
. Exclusive breast-feeding is protective against postnatal transmission of human immunodeficiency virus (HIV), compared with mixed breast-feeding. Accordingly, exclusive breast-feeding for 6 months is the World Health Organization's recommendation to HIV-infected mothers for whom exclusive replacement feeding is not acceptable, feasible, affordable, safe, or sustainable. The mechanism of exclusive breast-feeding protection is unknown but is hypothesized to be mediated through reduced mastitis. We compared breast milk and plasma specimens of exclusive breast-feeding and mixed breast-feeding HIV- positive mothers archived from the ZVITAMBO trial in which mixed breast-feeding was associated with a 2-fold increased risk of postnatal transmission at 18 months. Plasma HIV load, breast milk HIV load and sodium/potassium ratio were measured as a proxy for subclinical mastitis. Mixed breast-feeding was not associated with mastitis or breast milk HIV load. Mastitis was associated with breast milk HIV load, and this effect increased with increasing maternal plasma HIV load; mastitis was associated with postnatal transmission only when maternal plasma HIV load was high (>3.7 log(10) copies/mL). Initiation of breast-feeding within an hour of delivery was associated with exclusive breast-feeding (adjusted odds ratio, 1.62; 95% confidence interval, 1.02-2.58). Exclusive breast-feeding is associated with reduced postnatal transmission of HIV from mother to child, but this protection is not mediated by reduced mastitis or breast milk HIV load. The deleterious effect of mastitis increases as the mother's plasma HIV load increases.


Comparative study of biological characteristics of the causal agents of zoonotic and anthroponotic cutaneous leishmaniasis in the USSR.
A comparative study was made of the virulence of Leishmania tropica major and L. tropica minor, the causal agents of the zoonotic and anthroponotic forms of cutaneous leishmaniasis, from the USSR and their antigenic characteristics were compared with those of other Leishmania species (L. donovani, L. adleri, and promastigotes from Turkmenian reptiles). The virulence of strains of L. t. major was slightly higher than that of strains of L. t. minor. However, the difference in virulence gradually levelled out in successive multiple passages of the strains in hamsters. A comparative serological study of L. t. major and L. t. minor revealed clear antigenic differences between them. The differences between L. t. major, L. t. minor and L. donovani were shown to be equal in degree.


Activation and inactivation of methanol: 2-mercaptoethanesulfonic acid methyltransferase from Methanosarcina barkeri.
Methanol is converted to methane by crude extracts of Methanosarcina barkeri. The first reaction involved in this process, is catalyzed by methanol:2-mercaptoethanesulfonic acid methyltransferase (EC 2.1.1.-). The methyltransferase has an optimum at pH 6.5 and is not inhibited by 2-bromoethanesulfonic acid. Pyridoxal-5'-phosphate acts as an inhibitor (Ki = 0.30 mM). The methyltransferase was tested in the presence of 2-bromoethanesulfonic acid, which inhibits the conversion of 2-(methylthio)ethanesulfonic acid to methane. The reaction is subject to activation and inactivation. Inactivation is brought about by the presence of oxygen, flavin mononucleotide, flavin adenine dinucleotide, and 2-(methylthio)ethanesulfonic acid, the product of the reaction. Activation of the system requires the presence of ATP and Mg2+ and of hydrogen. Hydrogen can be replaced by enzymatic systems, such as pyruvate dehydrogenase, which deliver free hydrogen.


Structural diversity in the coordination compounds of cobalt, nickel and copper with N-alkylglycinates: crystallographic and ESR study in the solid state.
Reactions of N-methylglycine (HMeGly), N-ethylglycine-hydrochloride (H2EtGlyCl) and N-propylglycine-hydrochloride (H2PrGlyCl) with cobalt(ii), nickel(ii) and copper(ii) ions in aqueous solutions resulted in ten new coordination compounds [Co(MeGly)2(H2O)2] (1), [{Co(MeGly)2}2(μ-OH)2]·2H2O (1d), [Cu(MeGly)2(H2O)2] (2α), [Co(EtGly)2(H2O)2] (3), [Ni(EtGly)2(H2O)2] (4), [Cu(μ-EtGly)2] n (5p), [Co(PrGly)2(H2O)2] (6), [Ni(PrGly)2(H2O)2] (7), and two polymorphs of [Cu(PrGly)2(H2O)2] (8α and 8β). Compounds were characterized by single-crystal and powder X-ray diffraction, infrared spectroscopy, thermal analysis and X-band electron spin resonance (ESR) spectroscopy. These studies revealed a wide range of structural types including monomeric, dimeric and polymeric architectures, as well as different polymorphs. In all monomeric compounds, except 2α, and in the coordination polymer 5p hydrogen bonds interconnect the molecules into 2D layers with the alkyl chain pointing outward of the layer. In 2α and in the dimeric compound 1d hydrogen bonds link the molecules into 3D structures. 1d with cobalt(iii), and 4 and 7 with nickel(ii) are ESR silent. The ESR spectra of 1, 3 and 6 are characteristic for paramagnetic high-spin cobalt(ii). The ESR spectra of all copper(ii) coordination compounds show that the unpaired copper electron is located in the d x 2-y 2 orbital, being in agreement with the elongated octahedral geometry.


Fishing for data and sorting the catch: assessing the data quality, completeness and fitness for use of data in marine biogeographic databases.
Being able to assess the quality and level of completeness of data has become indispensable in marine biodiversity research, especially when dealing with large databases that typically compile data from a variety of sources. Very few integrated databases offer quality flags on the level of the individual record, making it hard for users to easily extract the data that are fit for their specific purposes. This article describes the different steps that were developed to analyse the quality and completeness of the distribution records within the European and international Ocean Biogeographic Information Systems (EurOBIS and OBIS). Records are checked on data format, completeness and validity of information, quality and detail of the used taxonomy and geographic indications and whether or not the record is a putative outlier. The corresponding quality control (QC) flags will not only help users with their data selection, they will also help the data management team and the data custodians to identify possible gaps and errors in the submitted data, providing scope to improve data quality. The results of these quality control procedures are as of now available on both the EurOBIS and OBIS databases. Through the Biology portal of the European Marine Observation and Data Network (EMODnet Biology), a subset of EurOBIS records--passing a specific combination of these QC steps--is offered to the users. In the future, EMODnet Biology will offer a wide range of filter options through its portal, allowing users to make specific selections themselves. Through LifeWatch, users can already upload their own data and check them against a selection of the here described quality control procedures. Database URL: www.eurobis.org (www.iobis.org; www.emodnet-biology.eu/).


Adsorption enhancement of nitrogen gas by atomically heterogeneous nanospace of boron nitride.
In this study, porous boron nitride (p-BN) with hexagonal phase boron nitride (h-BN) pore walls was synthesized using high-temperature calcination. Negligible variation in pore-wall structure can be observed in powder X-ray diffraction (XRD) profiles and infrared (IR) spectra. However, a highly stable p-BN with a stable pore structure even at 973 K under the oxidative conditions is obtained when synthesized at higher than 1573 K under nitrogen gas flow. For p-BN, this stability is obtained by generating h-BN microcrystals. Nitrogen adsorption-desorption isotherms at 77 K provide type-IV features and typical adsorption-desorption hysteresis, which suggests micropore and mesopore formation. Moreover, adsorption-desorption isotherms of Ar at 87 K are measured and compared with those of nitrogen. The relative adsorbed amount of nitrogen (i.e., the amount of nitrogen normalized by that of Ar at each relative pressure or adsorption potential value) on p-BN is considerably larger than that on microporous carbon at low-pressure regions, which suggests the existence of strong adsorption sites on the p-BN surface. In fact, the relative number of adsorbed nitrogen molecules to that of Ar on p-BN is, at most, 150%-200% larger than that on microporous carbon for the same adsorption potential state. Furthermore, additional adsorption enhancement to nitrogen between P/P 0 = 10-5 and 10-3 can be observed for p-BN treated at 1673 K, which suggests the uniformly adsorbed layer formation of nitrogen molecules in the vicinity of a basal planar surface. Thus, unlike typical nanoporous sp2 carbons, p-BN materials have the potential to enhance adsorption for certain gas species because of their unique surface state.


Atmospheric evolution of sulfur emissions from Kı̅lauea: real-time measurements of oxidation, dilution, and neutralization within a volcanic plume.
The high atmospheric concentrations of toxic gases, particulate matter, and acids in the areas immediately surrounding volcanoes can have negative impacts on human and ecological health. To better understand the atmospheric fate of volcanogenic emissions in the near field (in the first few hours after emission), we have carried out real-time measurements of key chemical components of the volcanic plume from Kı̅lauea on the Island of Hawai'i. Measurements were made at two locations, one ∼ 3 km north-northeast of the vent and the other 31 km to the southwest, with sampling at each site spanning a range of meteorological conditions and volcanic influence. Instrumentation included a sulfur dioxide monitor and an Aerosol Chemical Speciation Monitor, allowing for a measurement of the partitioning between the two major sulfur species (gas-phase SO2 and particulate sulfate) every 5 min. During trade wind conditions, which sent the plume toward the southwest site, sulfur partitioning exhibited a clear diurnal pattern, indicating photochemical oxidation of SO2 to sulfate; this enabled the quantitative determination of plume age (5 h) and instantaneous SO2 oxidation rate (2.4 × 10(-6) s(-1) at solar noon). Under stagnant conditions near the crater, the extent of SO2 oxidation was substantially higher, suggesting faster oxidation. The particles within the plume were extremely acidic, with pH values (controlled largely by ambient relative humidity) as low as -0.8 and strong acidity (controlled largely by absolute sulfate levels) up to 2200 nmol/m(3). The high variability of sulfur partitioning and particle composition underscores the chemically dynamic nature of volcanic plumes, which may have important implications for human and ecological health.


[From materia medica to rational pharmacotherapy].
An introductory part concerned with historical developments in the fields of veterinary pharmacotherapy, pharmacology and toxicology is followed by a discussion of a number of aspects of the enforcement of the draft bill of the Veterinary Drugs Act. Among other things, attention is paid to the veterinary use of drugs registered for use by human individuals (supplementary registration), the position of particular species of animal (supplementary registration), pesticides effective against ectoparasites, non-allopathic drugs and criteria to be adopted in channelling. Improving education on veterinary drugs and their use is advocated. More and better instruction on pharmacotherapy during the second stage of vocational training than that provided for currently would appear to be urgently required. This also holds good for post-graduate education which should possibly be made compulsory.


Graphene specimen support technique for low voltage STEM imaging.
The scanning transmission electron microscopy (STEM) mode of today's field emission scanning electron microscopes enables sub-nanometer resolution imaging. Graphene is a single-atom thick, electrically conductive material, making it an excellent specimen support for the low voltage STEM imaging of nanometer-sized objects such as viruses. Here we present low voltage STEM images of bacteriophage T4 recorded on highly cleaned graphene films. The results show that ultrathin graphene support films markedly improve image signal at low accelerating voltages. Staining with a low atomic number methylamine vanadate stain combined with the graphene support film enables the clear visualization of the fine structure of the T4 tail by the low voltage STEM technique. Despite the advantages of graphene support films, difficulties are often encountered in placing hydrophilic biological samples on hydrophobic graphene electron microscopy grids. We employed a spin sedimentation sample loading method to overcome this problem.


Effect of oxprenolol on catecholamines and plasma renin activity: acute response to frusemide in hypertensive patients.
1. Catecholamine plasma concentrations and urinary excretion were measured together with plasma renin activity in ten patients with essential hypertension and in five normal control subjects before and after a frusemide challenge. 2. The same procedure was repeated in the same subjects 3--4 days later after pretreatment with oxprenolol. 3. Noradrenaline plasma concentrations and urinary excretion increased significantly after frusemide in all cases, returning to normal values at 30 and 60 min. Adrenaline plasma concentrations and urinary excretion were unchanged. 4. Plasma renin activity increased significantly in seven patients with hypertension and normal renin basal values, remaining unchanged in three hypertensive patients with low-renin basal values. 5. Oxprenolol suppressed the response of noradrenaline and plasma renin activity to frusemide in all cases.


Cost-effectiveness of influenza control measures: a dynamic transmission model-based analysis.
We investigated the cost-effectiveness of different influenza control strategies in a school setting in Taiwan. A susceptible-exposure-infected-recovery (SEIR) model was used to simulate influenza transmission and we used a basic reproduction number (R 0)-asymptomatic proportion (θ) control scheme to develop a cost-effectiveness model. Based on our dynamic transmission model and economic evaluation, this study indicated that the optimal cost-effective strategy for all modelling scenarios was a combination of natural ventilation and respiratory masking. The estimated costs were US$10/year per person in winter for one kindergarten student. The cost for hand washing was estimated to be US$32/year per person, which was much lower than that of isolation (US$55/year per person) and vaccination (US$86/year per person) in containing seasonal influenza. Transmission model-based, cost-effectiveness analysis can be a useful tool for providing insight into the impacts of economic factors and health benefits on certain strategies for controlling seasonal influenza.


Synthesis and the thermal and catalytic dehydrogenation reactions of amine-thioboranes.
A series of trimethylamine-thioborane adducts, Me(3)N·BH(2)SR (R = tBu [2a], nBu [2b], iPr [2c], Ph [2d], C(6)F(5) [2e]) have been prepared and characterized. Attempts to access secondary and primary amine adducts of thioboranes via amine-exchange reactions involving these species proved unsuccessful, with the thiolate moiety shown to be vulnerable to displacement by free amine. However, treatment of the arylthioboranes, [BH(2)-SPh](3) (9) and C(6)F(5)SBH(2)·SMe(2) (10) with Me(2)NH and iPr(2)NH successfully yielded the adducts Me(2)NH·BH(2)SR (R = Ph [11a], C(6)F(5) [12a]) and iPr(2)NH·BH(2)SR (R = Ph [11b], C(6)F(5) [12b]) in high yield. These adducts were also shown to be accessible via thermally induced hydrothiolation of the aminoboranes Me(2)N═BH(2), derived from the cyclic dimer [Me(2)N-BH(2)](2) (13), and iPr(2)N═BH(2) (14), respectively. Attempts to prepare the aliphatic thiolate substituted adducts R(2)NH·BH(2)SR' (R = Me, iPr; R' = tBu, nBu, iPr) via this method, however, proved unsuccessful, with the temperatures required to facilitate hydrothiolation also inducing thermal dehydrogenation of the amine-thioborane products to form aminothioboranes, R(2)N═BH(SR'). Thermal and catalytic dehydrogenation of the targeted amine-thioboranes, 11a/11b and 12a/12b were also investigated. Adducts 11b and 12b were cleanly dehydrogenated to yield iPr(2)N═BH(SPh) (22) and iPr(2)N═BH(SC(6)F(5)) (23), respectively, at 100 °C (18 h, toluene), with dehydrogenation also possible at 20 °C (42 h, toluene) with a 2 mol % loading of [Rh(μ-Cl)cod](2) in the case of the former species. Similar studies with adduct 11a evidenced a competitive elimination of H(2) and HSPh upon thermolysis, and other complex reactivity under catalytic conditions, whereas the fluorinated analogue 12a was found to be resistant to dehydrogenation.


Mitochondrial ascorbic acid is responsible for enhanced susceptibility of U937 cells to the toxic effects of peroxynitrite.
Otherwise nontoxic levels of peroxynitrite promote toxicity in U937 cells pre-exposed to low micromolar concentrations of l-ascorbic acid (AA). This event was associated with the mitochondrial accumulation of the vitamin and with the early formation of secondary reactive oxygen species and DNA single-strand breaks. The same concentrations of peroxynitrite, however, failed to elicit detectable effects in cells pre-exposed to dehydroascorbic acid (DHA), in which mitochondrial accumulation of vitamin C did not occur despite the identical cytosolic levels. Coherently, oxidation of extracellular AA failed to affect the intracellular concentration of the vitamin, but nevertheless prevented its mitochondrial localization as well as the enhanced response to peroxynitrite. Furthermore, in cells postincubated in vitamin C-free medium, time-dependent loss of mitochondrial AA was paralleled by a progressive decline of susceptibility to peroxynitrite, under the same conditions in which cells retained about half of the initial AA. Using different experimental approaches, we finally showed that the enhancing effects of AA are mediated by events associated with peroxynitrite-dependent superoxide/H2 O2 formation in the mitochondrial respiratory chain. Collectively, these results indicate that mitochondria actively take up vitamin C as AA and respond to otherwise inactive concentrations of peroxynitrite with the mitochondrial formation of secondary species responsible for DNA damage and toxicity. DHA preloading, while leading to the accumulation of identical levels of vitamin C, fails to produce these effects because of the poor mitochondrial accumulation of the vitamin.


Spiroplasma symbiont of the pea aphid, Acyrthosiphon pisum (Insecta: Homoptera).
From a laboratory strain of the pea aphid, Acyrthosiphon pisum, we discovered a previously unknown facultative endosymbiotic bacterium. Molecular phylogenetic analysis based on 16S ribosomal DNA revealed that the bacterium is a member of the genus Spiroplasma. The Spiroplasma organism showed stable vertical transmission through successive generations of the host. Injection of hemolymph from infected insects into uninfected insects established a stable infection in the recipients. The Spiroplasma symbiont exhibited negative effects on growth, reproduction, and longevity of the host, particularly in older adults. Of 58 clonal strains of A. pisum established from natural populations in central Japan, 4 strains possessed the Spiroplasma organism.


Strengthening asthma education to enhance disease control.
This article focuses on reducing the barriers to effectively applying what is known about asthma patient education. One barrier to effective asthma control in individuals and populations is failure to recognize the range of influences on patients trying to manage their disease, including actions of family, clinicians, friends and neighbors, work or school mates, and significant people and organizations in the wider social environment. Another deterrent is failing to assist patients in developing their self-regulation skills. Other barriers are the lack of attention to the patients' asthma management goals (as opposed to clinical objectives) and overlooking signs that indicate follow-up education is needed. Five actions taken by health-care professionals could significantly enhance the effectiveness of asthma education: (1) make messages to patients and core skills taught consistent with national asthma guidelines; (2) focus on developing the patient's ability to self-regulate; (3) develop comprehensive plans for treatment and education that assign clinicians to appropriate educative roles; (4) use clinician communication techniques demonstrated to enhance asthma management by patients; and (5) ensure that all providers of education are themselves trained to achieve actions 1 to 4.


Evolutionary search for (M©B16)Q (M = Sc-Ni; Q = 0/-1) clusters: bowl/boat vs. tubular shape.
Herein, using universal structure predictor: evolutionary xtallography (USPEX) method, followed by density functional theory (DFT) calculations, we performed global searches for the most stable structures of (M©B16)Q (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni; Q = 0, -1) clusters. It was found that the obtained ground-state structures of (M©B16)Q clusters exhibited a distinct structural evolution as M changed from V to Ni: from bowl-shaped, to boat-shaped, to an M-centered tubular structure named wheel-shaped, to drum-shaped (the metal atom was adsorbed on top of the cross section of the B16 species). Our analysis shows that hyper-coordination and the size of the metal atom are two competing factors determining the relative stability and topological properties of the (M©B16)0/-1 clusters, resulting in unprecedented structures for Sc, Ti, and Ni-doped clusters. The calculated binding energies for these new configurations are even larger than those of the previously synthesized B16-1, (Mn©B16)-1, and (Co©B16)-1 clusters, indicating their very good stability and possible experimental synthesis. A net charge transfer from the metal atom to the boron moiety occurs for all clusters, indicating that electrostatic interactions play an important role in the stability of these materials. Finally, the Sc©M16 and Ti©B16 clusters exhibit not only excellent thermal stability but also large first hyper-polarizability. Hence, they are expected to be potential innovative candidates for excellent electro-optical materials.


Solution structure of the antiapoptotic protein bcl-2.
The structures of two isoforms of Bcl-2 that differ by two amino acids have been determined by NMR spectroscopy. Because wild-type Bcl-2 behaved poorly in solution, the structures were determined by using Bcl-2/Bcl-x(L) chimeras in which part of the putative unstructured loop of Bcl-2 was replaced with a shortened loop from Bcl-x(L). These chimeric proteins have a low pI compared with the wild-type protein and are soluble. The structures of the two Bcl-2 isoforms consist of 6 alpha-helices with a hydrophobic groove on the surface similar to that observed for the homologous protein, Bcl-x(L). Comparison of the Bcl-2 structures to that of Bcl-x(L) shows that although the overall fold is the same, there are differences in the structural topology and electrostatic potential of the binding groove. Although the structures of the two isoforms of Bcl-2 are virtually identical, differences were observed in the ability of the proteins to bind to a 25-residue peptide from the proapoptotic Bad protein and a 16-residue peptide from the proapoptotic Bak protein. These results suggest that there are subtle differences in the hydrophobic binding groove in Bcl-2 that may translate into differences in antiapoptotic activity for the two isoforms.


Short communication: behavioral and physiological indicators of sensitivity or chronic pain following tail docking.
Docking the tails of dairy cattle causes mild to moderate behavior changes and physiological indicators of acute pain, but no studies have investigated the possibility that tail docking may lead to chronic pain. In human amputees, an incidence of increased limb surface temperature is associated with phantom limb pain, a central nervous system representation that survives peripheral loss. The objectives of this study were to assess indicators of sensitivity or chronic pain in heifers by using behavioral indicators and thermography. We tested 14 Holstein heifers, 7 docked and 7 intact, from a previous neonatal tail-docking experiment. All 14 animals were videotaped during a test sequence of alternating cold (-9 degrees C), hot (54 degrees C), and neutral packs applied to the underside of the tail. Packs were placed approximately 30.5 cm from the tail head on all animals. A thermal image of the tail was taken using infrared imagery prior to and after temperature sensitivity testing. Docked heifers tended to have greater changes in surface temperatures following the test sequence than did nondocked heifers. In docked heifers, temperatures on the underside of the tail were higher than those at the tip of the tail, both prior to and following the test sequence. Docked heifers also showed substantially higher stomping activity following application of the cold pack. Shifting increased in intact heifers after application of the hot pack, but shifting of the docked heifers did not change. Greater changes were observed in the tail surface temperatures of the docked heifers following temperature manipulation, similar to human amputees who are experiencing phantom limb pain, indicating that similar mechanisms are present in the stump of the docked tail. The behaviors of docked heifers indicated changes in their sensitivity to heat and cold.


Standardized Olea europaea L. leaf extract exhibits protective activity in carbon tetrachloride-induced acute liver injury in rats: the insight into potential mechanisms.
The protective activity of dry olive leaf extract (DOLE) in carbon tetrachloride (CCl4)-induced liver damage and possible mechanisms involved in this protection were investigated in rats. Acute CCl4 intoxication resulted in a massive hepatic necrosis, in increased serum transaminases, and in a perturbation of oxidative stress parameters in liver tissue [malondyaldehide, glutathione (GSH), catalase]. CCl4 did not affect the expression of caspase-3 and cytochrome c as markers of apoptosis; however, CCl4 increased the AMP-activated protein kinase (AMPK) activity and the expression of autophagy-related protein LC3II and decreased the expression of p62 protein. The pre-treatment with DOLE significantly improved serum markers of liver damage, liver catalase activity, and GSH concentration, suggesting that antioxidative mechanism is responsible for hepatoprotection. Oral administration of DOLE did not influence LC3II conversion and p62 degradation in liver, but AMPK activity was significantly decreased, suggesting the energy balance perturbation as an additional potential mechanism of DOLE hepatoprotective effect.


Phosphorylase ratio and susceptibility to malignant hyperthermia.
The ratio of muscle phosphorylase a to total phosphorylase, expressed as a percent, was determined in vastus lateralis muscle of 26 patients to examine the efficacy of this parameter as a method for screening for susceptibility to malignant hyperthermia (MH). As standard screening, all patients also had muscle contracture responses determined to 2% halothane and 0.25-32 mM caffeine at 37 degrees C. Each drug was given separately and not combined. Nine patients were susceptible to MH, based upon caffeine threshold of 2 mM or less (seven patients) or a rapidly developing contracture tension to halothane of more than 400 mg (seven patients, including five with positive caffeine responses). Mean phosphorylase ratio in these nine patients was 14.5 +/- 2.0% (mean, SEM). In the 17 nonsusceptible patients mean phosphorylase ratio (12.4 +/- 1.9%) was not significantly different. The range of phosphorylase ratios in susceptible patients was 6.5-26% while 13 nonsusceptible patients had ratios greater than 6% and up to 29%. The unacceptably high number of false-positive responses in nonsusceptible patients precludes the use of phosphorylase ratio as a definitive diagnostic test.


Cryoprotectant treatment tests on three morphologically diverse marine dinoflagellates and the cryopreservation of Breviolum sp. (Symbiodiniaceae).
Dinoflagellates are among the most diverse group of microalgae. Many dinoflagellate species have been isolated and cultured, and these are used for scientific, industrial, pharmaceutical, and agricultural applications. Maintaining cultures is time-consuming, expensive, and there is a risk of contamination or genetic drift. Cryopreservation offers an efficient means for their long-term preservation. Cryopreservation of larger dinoflagellate species is challenging and to date there has been only limited success. In this study, we explored the effect of cryoprotectant agents (CPAs) and freezing methods on three species: Vulcanodinium rugosum, Alexandrium pacificum and Breviolum sp. A total of 12 CPAs were assessed at concentrations between 5 and 15%, as well as in combination with dimethyl sulfoxide (DMSO) and other non-penetrating CPAs. Two freezing techniques were employed: rapid freezing and controlled-rate freezing. Breviolum sp. was successfully cryopreserved using 15% DMSO. Despite exploring different CPAs and optimizing the freezing techniques, we were unable to successfully cryopreserve V. rugosum and A. pacificum. For Breviolum sp. there was higher cell viability (45.4 ± 2.2%) when using the controlled-rate freezing compared to the rapid freezing technique (10.0 ± 2.8%). This optimized cryopreservation protocol will be of benefit for the cryopreservation of other species from the family Symbiodiniaceae.


Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.
We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.


Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus.
Antigen-ginding lymphocytes capable of binding native DNA (DNA-ABC) were identified in the peripheral blood of normal controls and patients with systemic lupus erythematosus (SLE) by autoradiography with 125I-nDNA. 12 patients with active SLE had 404 +/- 273 (mean +/- SD) DNA-ABC/105 lymphocytes, while 7 inactive SLE patients and 13 normals had 120 +/- 48 and 48 +/- 36, respectively. All three groups were significantly different from one another (p less than 0.01). No significant correlation was detected between the quantity of anti-native DNA (nDNA) antibody and number of DNA-ABC; however, most patients with large amounts of anti-nDNA antibody had both active disease and large numbers of DNA-ABC. Numbers of DNA-ABC and lymphocytes with surface immunoglobulin (Ig) did not change significantly after an 18-h incubation at 37degreeC. After depletion of B-lymphocytes by passage over bead columns coated with a complex of IgG and anti-IgG, the great majority of DNA-ABC were removed in both normal subjects and SLE patients. Labeling lymphocytes sequentially with 125I-nDNA, followed by an indirect fluorescence technique for identification of surface Ig, indicated that the great mahority of radiolabeled cells had surface Ig by fluorescence microscopy in four normals (average 93%) and five patients with active SLF (average 82%). The predominance of nDNA-sensitive B-lymphocytes in the peripheral blood of both normals and SLE patients is consistent with the concept that the induction of the anti-nDNA antibody response is due to the stimulation of preexisting nDNA-specific B lymphocytes by mechanisms other than those necessarily involving participation of nDNA-specific T lymphocytes.


Primary Plasma Cell Leukemia: Identity Card 2016.
Primary plasma cell leukemia (PPCL) is an aggressive and rare variant of multiple myeloma (MM), characterized by peculiar adverse clinical and biological features. Though the poor outcome of PPCL has been slightly improved by novel treatments during the last 10 years, due to the limited number of available studies in this uncommon disease, optimal therapy remains a classic unmet clinical need. Anyway, in the real-life practice, induction with a bortezomib-based three-drug combination, including dexamethasone and, possibly, lenalidomide, or, alternatively, thalidomide, cyclophosphamide, or doxorubicin, is a reasonable first-line option. This approach may be particularly advisable for patients with adverse cytogenetics, hyperleucocytosis, and rapidly progressive disease, in whom a fast response is required, or for those with suboptimal renal function, where, however, lenalidomide should be used with caution until renal activity is restored. In younger subjects, leukemia/lymphoma-like more intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone or continue-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide, may be also combined with bortezomib +/- thalidomide. Treatment must be started immediately after a diagnosis of PPCL is made to avoid the risk of irreversible disease complications and, in such a context, the prevention of tumor lysis syndrome is mandatory. In patients eligible for autologous stem cell transplantation (AuSCT), other alkylating agents, in particular melphalan, should be initially avoided in order to allow adequate collections of CD34+ peripheral blood stem cells (PBSC). A combination of lenalidomide and dexamethasone may be a valuable alternative option to manage older or unfit patients or those with slower disease evolution or with signs of neuropathy, contraindicating the use of bortezomib. Patients not suitable for transplant procedures should continue the treatment, if a response occurs and if tolerated, considering the possibility of a prolonged maintenance therapy. AuSCT should be pursued in all eligible patients less than 65 years old who achieve a significant response after a short course of induction treatment. PBSC collection should reach a threshold of at least 5 × 10(6) CD34+ PBSC/kg using cyclophosphamide plus G-CSF and adding the mobilizing agent plerixafor, if necessary. High-dose melphalan (HDM) (200 or 140 mg/m(2), according to age and renal function) remains the preferable conditioning regimen. A second AuSCT should be always considered, even in patients achieving complete response (CR) after the first AuSCT, as the short progression-free survival (PFS) generally seen in PPCL suggests the persistence of a relevant burden of residual disease; this provides a strong rationale for the use of post-transplantation therapies in PPCL to improve depth of response, to maintain remission, and, possibly, to increase survival, though consolidation and/or maintenance strategies with novel agents, whose efficacy has been well demonstrated in MM, have not been still extensively evaluated in PPCL. The search of a suitable donor should start as soon as possible and an allogeneic stem cell transplant (AlloSCT) with a myeloablative conditioning (MAC) regimen discussed with younger patients responsive to induction therapy and with poor prognostic parameters at diagnosis. A sequence of AuSCT followed by reduced intensity conditioning (RIC) or non-myeloablative (NMA) AlloSCT may be considered in selected cases. Salvage therapies for relapsed/refractory disease, especially using new drugs not employed at diagnosis, are sometimes effective in the short term, but a rapid relapse is still generally the rule; AlloSCT in relapsed and eligible patients with sensitive disease after salvage treatments is, therefore, recommended.


Changes in hormone sensitivity in the ventral prostate of aging Sprague-Dawley rats.
The adult rat ventral prostate, which has been used extensively as a model for hormone-dependent prostate cancer, is composed of hormone-dependent columnar secretory epithelial cells and a mixture of hormone-independent cuboidal epithelial cells, basal epithelial cells, and stromal cells. Androgen ablation causes the gland to regress due to the selective loss of the secretory luminal epithelial cells that undergo apoptosis. Most, if not all, of the studies examining the induction of apoptosis and the mechanism of regression have used young adult males at around 3 months of age. Prostate cancer, however, is a disease of older males, and we have therefore investigated whether age-related changes in hormone sensitivity and apoptosis occur in the ventral prostate of aged animals (12 months old) compared to young animals (3 months old). We have observed distinct differences in the morphology of the prostate between young and old rats prior to castration and a significant slowing in the rate of regression after castration in older animals. These changes are accompanied by changes in lipofuscin accumulation and levels of the antioxidant enzymes catalase and manganese (Mn) superoxide dismutase in the gland.


Landscape of two-proton radioactivity.
Ground-state two-proton (2p) radioactivity is a decay mode found in isotopes of elements with even atomic numbers located beyond the two-proton drip line. So far, this exotic process has been experimentally observed in a few light- and medium-mass nuclides with Z≤30. In this study, using state-of-the-art nuclear density functional theory, we globally analyze 2p radioactivity and for the first time identify 2p-decay candidates in elements heavier than strontium. We predict a few cases where the competition between 2p emission and α decay may be observed. In nuclei above lead, the α-decay mode is found to be dominating and no measurable candidates for the 2p radioactivity are expected.


Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis.
The use of bone marrow-derived mesenchymal stem cells (MSCs) has shown promise in cell-based cartilage regeneration. A yet-unsolved problem, however, is the unwanted up-regulation of markers of hypertrophy, such as alkaline phosphatase (AP) and type X collagen, during in vitro chondrogenesis and the formation of unstable calcifying cartilage at heterotopic sites. In contrast, articular chondrocytes produce stable, nonmineralizing cartilage. The aim of this study was to address whether coculture of MSCs with human articular chondrocytes (HACs) can suppress the undesired hypertrophy in differentiating MSCs. MSCs were differentiated in chondrogenic medium that had or had not been conditioned by parallel culture with HAC pellets, or MSCs were mixed in the same pellet with the HACs (1:1 or 1:2 ratio) and cultured for 6 weeks. Following in vitro differentiation, the pellets were transplanted into SCID mice. The gene expression ratio of COL10A1 to COL2A1 and of Indian hedgehog (IHH) to COL2A1 was significantly reduced by differentiation in HAC-conditioned medium, and less type X collagen protein was deposited relative to type II collagen. AP activity was significantly lower (P < 0.05) in the cells that had been differentiated in conditioned medium, and transplants showed significantly reduced calcification in vivo. In mixed HAC/MSC pellets, suppression of AP was dose-dependent, and in vivo calcification was fully inhibited. Chondrocytes secreted parathyroid hormone-related protein (PTHrP) throughout the culture period, whereas PTHrP was down-regulated in favor of IHH up-regulation in control MSCs after 2-3 weeks of chondrogenesis. The main inhibitory effects seen with HAC-conditioned medium were reproducible by PTHrP supplementation of unconditioned medium. HAC-derived soluble factors and direct coculture are potent means of improving chondrogenesis and suppressing the hypertrophic development of MSCs. PTHrP is an important candidate soluble factor involved in this effect.


Copper-Catalyzed Enantioselective Domino Arylation/Semipinacol Rearrangement of Allylic Alcohols with Diaryliodonium Salts.
A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols was developed. In the presence of a catalytic amount of an in situ generated chiral copper-bisoxazoline complex, reaction of allylic alcohols with diaryliodonium salts afforded spirocycloalkanones in high yields with high diastereo- and enantioselectivities. A two-point binding model engaging the carbon-carbon double bond and the proximal hydroxyl group was proposed to be responsible for the highly efficient chirality transfer.


Nucleotide sequence of the Rhodospirillum rubrum atp operon.
The nucleotide sequence was determined of a 8775-base-pair region of DNA cloned from the photosynthetic non-sulphur bacterium Rhodospirillum rubrum. It contains a cluster of five genes encoding F1-ATPase subunits. The genes are arranged in the same order as F1 genes in the Escherichia coli unc operon. However, as in the related organism Rhodopseudomonas blastica, neither genes for components of F0, the membrane sector of ATP synthase, nor a homologue of the E. coli uncI gene are associated with this locus, as they are in E. coli.


Does inequality in self-assessed health predict inequality in survival by income? Evidence from Swedish data.
This paper empirically addresses two questions using a large, individual-level Swedish data set which links mortality data to health survey data. The first question is whether there is an effect of an individual's self-assessed health (SAH) on his subsequent survival probability and if this effect differs by socioeconomic factors. Our results indicate that the effect of SAH on mortality risk declines with age-probably because of adjustment towards 'milder' overall health evaluations at higher ages-but does not seem to differ by indicators of socioeconomic status (SES) like income or education. This finding suggests that there is no systematic adjustment of SAH by SES and therefore that any measured income-related inequality in SAH is unlikely to be biased by reporting error. The second question is: how much of the income-related inequality in mortality can be explained by income-related inequality in SAH? Using a decomposition method, we find that inequality in SAH accounts for only about 10% of mortality inequality if interactions are not allowed for, but its contribution is increased to about 28% if account is taken of the reporting tendencies by age. In other words, omitting the interaction between age and SAH leads to a substantial underestimation of the partial contribution of SAH inequality by income. These results suggest that the often observed inequalities in SAH by income do have predictive power for the-less often observed-inequalities in survival by income.


Ab initio quantum chemical investigation of intramolecular magnetic interaction in some diradical derivatives of imino nitroxide and nitronyl nitroxide.
The magnetic properties of the monoradicals 2-(4-phenyl acetylene)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidozolyl-oxyl (1) and 2-(4-phenyl acetylene)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl-3-oxide (2) and the diradicals 2,2'-(1,2-ethynediyldi-4,1-phenylene)bis[4,4,5,5-tetramethyl-4,5-dihydro-1H-imidozolyl-oxyl] (3), 2,2'-(1,2-ethynediyldi-4,1 3,1-phenylene)bis[4,4,5,5-tetramethyl-4,5-dihydro-1H-imidozolyl-oxyl] (4), and 2,2'-(1,2-ethynediyldi-4,1 3,1-phenylene)bis[4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl-3-oxide] (5) are investigated by ab initio quantum chemical methods. The rule of spin alternation in the unrestricted Hartree-Fock (UHF) method clearly shows that the radical sites are antiferromagnetically coupled in 3 and ferromagnetically coupled in 4 and 5, which is consistent with a previous experiment. The molecular geometries are optimized at Hartree-Fock levels. This is followed by single-point calculations using the density functional (UB3LYP) treatment and the multiconfigurational complete active space self-consistent field (CASSCF) methodology. Magnetic exchange coupling constants are determined from the broken-symmetry approach. The calculated J values, -3.60 cm(-1) for 3, 0.16 cm(-1) for 4, and 0.67 cm(-1) for 5, are in excellent agreement with the observed values. Because of the very large size of the diradicals 3-5, the CASSCF (10,10) calculations cannot yield realistic J values. Nevertheless, the CASSCF calculations support the antiferromagnetic nature of the magnetic coupling in 3 and the ferromagnetic nature of the coupling in 4 and 5. The existence of an intramolecular magnetic coupling in 3-5 is also confirmed through computations of the isotropic hyperfine coupling constants for monoradicals 1 and 2 as well as diradicals 3-5.


Biomechanical mechanism of Tai-Chi gait for preventing falls: A pilot study.
Tai-Chi (TC) practice has been increasingly used to prevent falls in older adults. However, the biomechanical mechanisms underlying the effects of TC practice on fall risk among older adults remain unanswered. The objective of this pilot study was to examine how TC gait biomechanically impacts the human body in terms of dynamic gait stability and lower limb muscle strength in comparison with regular walking gait. Ten healthy adults performed five trials of TC gait following three to seven trials of regular walking. Full body kinematics and kinetics were collected, and then dynamic gait stability and lower limb joint moments were determined. During TC gait, individuals were less stable, moved more slowly and experienced a larger mediolateral movement in comparison with regular walking gait. The peak moment at the ankle joint on the sagittal and transverse planes, at the knee joint on all three planes, and at the hip joint on the frontal plane was significantly different when performing TC gait than during regular gait. The results indicate that TC gait challenges body balance and requires more muscle strength of the lower limb joints compared to regular walking gait. To cope with these challenges, the body could develop neuromuscular control strategies to maintain body balance and thus reduce the risk of falls. The findings and methodology in this study could provide preliminary guidance for identifying optimal TC forms in order to maximize the effects of TC-based fall prevention interventions among various populations with elevated risk of falls.


Serological evidence of persistence of Japanese encephalitis virus activity in Bihar, India.
A total of 64 sera samples from ducks, 212 from 245 fowls, 1 from 16 sparrows and 5 from human were examined for HI and CF antibodies to Japanese encephalitis (JE), West Nile (NW), Dengue-2 (DN-2), and Chikungunya (CHIK) viruses. The results were compared with those obtained earlier while examining pigs' sera from the same area. The results revealed that ducks, fowls and peridomestic sparrows possessed antibodies to JEV. JEV activity in ducks and fowls was significantly higher compared to its activity in pigs in the same area reported earlier indicating persistence of its activity.


Racial and ethnic disparities in the quality of primary care for children.
Healthy People 2010 calls for greater access to high-quality primary care as a means to reduce racial and ethnic disparities in children' health. Disparities in primary care quality have rarely been studied for children, and the few studies that have been conducted among adults are not readily applicable to children because of the different health care needs of the 2 populations. This study compared the quality of primary care experienced specifically by children of different racial and ethnic groups. We used a random cross-sectional community sample of children. Parents were questioned via structured telephone interview with the Primary Care Assessment Tool about a selected child's primary care experiences. Responses were compared across racial and ethnic groups, with white children as the reference group. The sample consisted of parents of 413 elementary school children, ages 5 to 12 years, enrolled in 1 school district spanning 3 suburban cities in San Bernardino County, California. We measured cardinal features of primary care quality including first-contact care (accessibility and utilization), longitudinality (strength of affiliation and interpersonal relationship), comprehensiveness (services offered and received), and coordination of care. After controlling for family demographics, socioeconomic status, and health system characteristics, minority children experienced poorer quality of primary care across most domains of care compared with white children. Asian Americans reported the lowest quality of care across most domains, but particularly in first-contact utilization, interpersonal relationship, and comprehensiveness of services received. Racial and ethnic disparities in quality persist in many aspects of primary care delivery. The findings suggested that these disparities are not simply reflections of ability to pay, health disparities, sociodemographics, or racial variations in expectations for care. The findings in this study that parents of minority children, in particular Asian Americans, report lower quality of primary care is consistent with previous research among adults but had not been demonstrated previously for children.


Agricultural land management options following large-scale environmental contamination.
The recent events at the Fukushima Daiichi nuclear power plant, in Japan, have raised questions about the accumulation of radionuclides in soils, the transfer in the food chain, and the possibility for restricted land use in the foreseeable future. This article summarizes what is generally understood about the application of agricultural countermeasures as a land management option to reduce the transfer of radionuclides in the food chain and to facilitate the return of potentially affected soils to agricultural practices in the vicinity of the Fukushima plant.


Bile duct ligation promotes covalent drug-protein adduct formation in plasma but not in liver of rats given zomepirac.
Acyl glucuronides are reactive electrophilic metabolites of carboxylate drugs, capable of undergoing hydrolysis, rearrangement and covalent binding reactions with proteins in vivo. Such covalent drug-protein adducts may be prerequisites for certain idiosyncratic immune and toxic responses in susceptible individuals. The present study examined the effect of experimental cholestasis on the extent and pattern of formation of protein adducts in plasma and liver of rats given the non-steroidal antiinflammatory drug (NSAID) zomepirac (ZP). Groups of intact, bile-exteriorized and bile duct-ligated rats given a 50 mg/kg i.v. dose of ZP were studied for 24 hr. In intact rats, only 1.4% of the dose was recovered as the sum of ZP, ZP acyl glucuronide (ZAG) and its rearrangement isomers (iso-ZAG) in urine in 24 hr. In bile-exteriorized animals, 0.5% of the dose was recovered in urine in 24 hr, with 31.6% of the dose being recovered in bile (2.7% as ZP, 20.0% as ZAG and 8.9% as iso-ZAG). In the bile duct-ligated group, recovery of dose in 24 hr urine totalled 17.5% (1.7% as ZP, 6.7% as ZAG and 9.1% as iso-ZAG). ZAG and iso-ZAG were measurable in plasma only in the bile duct-ligated group, and covalent binding of ZP to plasma proteins was much higher (5-6 fold) than in intact or bile-exteriorized rats. Total adduct concentrations in liver were not significantly different among the three groups. Immunoblotting using a polyclonal ZP antiserum confirmed that serum albumin was a major target protein in plasma. The major ZP-modified bands in the livers of intact and bile-exteriorized rats were at about 110, 140 and 200 kDa. However, the bands at 110 and 140 kDa were much lower in the livers of bile duct-ligated rats. The results show that about 30% of ZP doses are normally excreted as ZAG and its isomers in bile, with only minor excretion in urine. Bile duct ligation shunts the glucuronide into blood (and urine), strongly promoting adduct formation with plasma proteins, and alters the pattern but not the total quantity of drug-modified proteins formed in the liver.


Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.
To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.


Sequential Inward Bending of Arterial Bifurcations is Associated with Intracranial Aneurysm Formation.
To investigate the association between vascular morphology and the development of intracranial aneurysms (IAs), the morphological changes of intracranial arteries after IA induction were examined using a rodent model. The vascular morphology of the circle of Willis in rats was visualized at 1 week and at 3 months after IA induction using 7-T magnetic resonance imaging. The following 2 angle parameters were defined: the angle between the parent artery and the daughter arteries (PD angle), and the widening of the daughter arteries (DD angle). The correlations of the angle parameters with IA size and with the number of macrophages infiltrated in the IA wall by immunohistochemistry were examined. Magnetic resonance imaging showed bending of the arteries over time around the predilection site for IAs. The PD angle increased significantly 1 week after IA induction (P < 0.05) and correlated with IA size (P < 0.01). The DD angle did not increase after 1 week, but increased 3 months after IA induction (P < 0.01). The PD angle 1 week after surgery also correlated with the number of infiltrated macrophages in aneurysmal walls (P = 0.01). Sequential inward bending of arterial bifurcations occurred after IA induction in the rat model. The degree of arterial bending correlated with IA development and inflammation in the IA wall, suggesting that the vascular morphology may be strongly associated with IA development through a proinflammatory mechanism.


Brain Criticality EEG analysis for tracking neurodevelopment from Childhood to Adolescence.
The brain criticality hypothesis suggests that neural networks and multiple aspects of brain activity self-organize into a critical state, and criticality marks the transition between ordered and disordered states. This hypothesis is appealing from computer science perspective because neural networks at criticality exhibit optimal processing and computing properties while having implications in clinical applications to neurological disorders. In this paper, we introduced brain criticality analysis to track neurodevelopment from childhood to adolescence using the electroencephalogram (EEG) data of 662 subjects aged 5 to 16 years from the Child Mind Institute. We computed brain criticality from long-range temporal correlation (LRTC) using detrended fluctuation analysis (DFA). We also compared the brain criticality analysis with standard EEG power analysis. The results showed a statistically significant increase in brain criticality from childhood to adolescence in the alpha band. A decreasing trend was observed in theta band from EEG power analysis, but a much higher variance was observed compared to the brain criticality analysis. However, the significant results were only observed in some EEG channels, and not observed if the analysis were performed separately with eyes-open and eyes-close condition. Nonetheless, the results suggest that brain criticality may serve as a biomarker of brain development and maturation, but further research is needed to improve brain criticality algorithms and EEG analysis methods.Clinical Relevance- The brain criticality analysis may be used to characterize and predict neurodevelopment in early childhood.


Biosynthesis of unusual moth pheromone components involves two different pathways in the navel orangeworm, Amyelois transitella.
The sex pheromone of the navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), consists of two different types of components, one type including (11Z,13Z)-11,13-hexadecadienal (11Z,13Z-16:Ald) with a terminal functional group containing oxygen, similar to the majority of moth pheromones reported, and another type including the unusual long-chain pentaenes, (3Z,6Z,9Z,12Z,15Z)-3,6,9,12,15-tricosapentaene (3Z,6Z,9Z,12Z,15Z-23:H) and (3Z,6Z,9Z,12Z,15Z)- 3,6,9,12,15-pentacosapentaene (3Z,6Z,9Z,12Z,15Z-25:H). After decapitation of females, the titer of 11Z,13Z-16:Ald in the pheromone gland decreased significantly, whereas the titer of the pentaenes remained unchanged. Injection of a pheromone biosynthesis activating peptide (PBAN) into the abdomens of decapitated females restored the titer of 11Z,13Z-16:Ald and even increased it above that in intact females, whereas the titer of the pentaenes in the pheromone gland was not affected by PBAN injection. In addition to common fatty acids, two likely precursors of 11Z,13Z-16:Ald, i.e., (Z)-11-hexadecenoic and (11Z,13Z)-11,13-hexadecadienoic acid, as well as traces of (Z)-6-hexadecenoic acid, were found in gland extracts. In addition, pheromone gland lipids contained (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid, which also was found in extracts of the rest of the abdomen. Deuterium-labeled fatty acids, (16,16,16-D(3))-hexadecanoic acid and (Z)-[13,13,14,14,15,15,16,16,16-D(9)]-11-hexadecenoic acid, were incorporated into 11Z,13Z-16:Ald after topical application to the sex pheromone gland coupled with abdominal injection of PBAN. Deuterium label was incorporated into the C(23) and C(25) pentaenes after injection of (9Z,12Z,15Z)- [17,17,18,18,18-D(5)]-9,12,15-octadecatrienoic acid into 1-2 d old female pupae. These labeling results, in conjunction with the composition of fatty acid intermediates found in pheromone gland extracts, support different pathways leading to the two pheromone components. 11Z,13Z-16:Ald is probably produced in the pheromone gland by Delta11 desaturation of palmitic acid to 11Z-16:Acid followed by a second desaturation to form 11Z,13Z-16:Acid and subsequent reduction and oxidation. The production of 3Z,6Z,9Z,12Z,15Z-23:H and 3Z,6Z,9Z,12Z,15Z-25:H may take place outside the pheromone gland, and appears to start from linolenic acid, which is elongated and desaturated to form (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid, followed by two or three further elongation steps and finally reductive decarboxylation.


Epidemiological study of adolescent idiopathic scoliosis in Eastern China.
Previous epidemiological studies of adole-scent idiopathic scoliosis in mainland China have had diverse results. The aim of this cross-sectional study was to determine the epidemiology of adolescent idiopathic scoliosis based on a representative sample city, Wuxi, in eastern China. Primary and secondary school students aged 10-16 years were enrolled in the study. Physical examination and Adam's forward bending test, combined with scoliometer measurements were performed at school-based screening. Students with an angle of trunk inclination of 5° or more were referred for whole-spine X-ray. The threshold for confirmed diagnosis was a Cobb angle of 10° or more. A total of 79,122 students were screened. The overall prevalence of adolescent idiopathic scoliosis in Wuxi City was estimated as 2.4%. Girls had a higher prevalence in each age subgroup compared with boys. Higher prevalence was found in individuals with lower body mass index. Mild and moderate curves were the most common types in our study. The prevalence of adolescent idiopathic scoliosis in this region was slightly higher. Medical resources should be considered for children with lower body mass index and high risk of scoliotic progression. Measurement with a scoliometer would be suitable for mild-to-moderate scoliotic deformities, while alternative methods should be developed for those with severe deformities or higher body mass index.


Transcatheter Edge-to-Edge Repair for Tricuspid Regurgitation-A Systematic Review and Meta-Analysis.
Transcatheter edge-to-edge repair (TEER) has emerged as a widely accepted procedure for tricuspid regurgitation (TR) as gauged by echocardiographic parameters and clinical outcomes. Our study aims to assess TR severity and other echocardiographic outcomes in patients undergoing TEER with TriClip, MitraClip, and PASCAL devices. A literature search of 5 databases was performed until 1st June 2023. Randomized controlled trials (RCTs) or observational studies with moderate to severe (grade III-V) TR patients undergoing isolated TEER were considered eligible. Echocardiographic, and quality of life determining outcomes such as improvement in TR severity grade ≥3, New York Heart Association (NYHA) class ≥3, procedural success, 6-minute walking distance (6MWD), and adverse outcomes were analyzed. Grade assessment was performed and studies were assessed for risk of bias and publication bias. We included 15 studies (14 observational and 1 RCT) in our paper. Analysis revealed a substantial reduction in TR volume (P < 0.00001), TR grading (P < 0.00001), tricuspid annular diameter (P < 0.00001), proximal isovelocity surface area radius (P < 0.00001), effective regurgitant orifice area (P < 0.00001), and improvement in NYHA class (P < 0.00001) at 30 days from baseline, postprocedurally. A significant increase in 6MWD at 1 year (P = 0.001) was also recorded. No significant differences in left ventricular ejection fraction (P = 0.87), fractional area change (P = 0.37), or tricuspid annular plane systolic excursion (P = 0.76) were observed. TEER procedural success was 97%. TEER produced a significant reduction in TR grade and volume, NYHA class, 6MWD, and showed prominent procedural success. Large scale RCTs comparing the TEER devices are needed to strengthen the present findings.


Self-Powered Coiled Carbon-Nanotube Yarn Sensor for Gastric Electronics.
The strong peristaltic contraction of the stomach facilitates mixing and emptying of ingested food, which occurs rhythmically at approximately 3 cycles/min (cpm) in humans. Generally, most patients with gastroparesis show gastric electrical dysrhythmia that is disrupted electrical signals controlling gastric contractions. For treatment of gastric electrical dysrhythmia, in vivo electrical impulses to the stomach via an implanted gastric stimulator have been known to restore these gastric deformations. Nevertheless, improved sensors to monitor gastric contractions are still needed in current gastric stimulators. Recently, we have developed a new technology converting mechanical motion to electrical energy by using stretch-induced capacitance changes of a coiled carbon-nanotube (CNT) yarn. For its potential use as a gastric deformation sensor, the performance of a coiled CNT yarn was evaluated in several biological fluids. For a sinusoidal stretch to 30%, the peak-to-peak open-circuit voltage (OCV) was consistently generated at frequencies below 0.1 Hz. This sinusoidal variation in OCV augmented as the strain increased from 10 to 30%. In an in vitro artificial gastric system, the OCV was approximately linearly proportional to the balloon volume, which can monitor periodic deformations of the balloon at 2, 3, and 4 cpm as shown for human gastric deformations. Moreover, stretchy coiled yarns generate the peak electrical voltage and power when deformed. The present study shows that a self-powered CNT yarn sensor can not only monitor the changes in frequency and amplitude of volumetric change but also generate electrical power by periodic deformations of the balloon. Therefore, it seems possible to automatically deliver accurate electrical impulses according to real-time evaluation of a patient's gastric deformation based on information on the frequency, amplitude, and rate of the OCV from CNT yarn.


Perspectives of colorectal cancer screening in Germany 2009.
Adequate screening methods can decrease colorectal cancer (CRC) mortality. The guaiac test for fecal occult-blood (FOBT) is part of the German CRC Screening Program since 1970 and has evidence level Ia. In randomized multicenter-studies FOBT has an average sensitivity of 24% and decreases CRC mortality up to 30%. Immunological tests for human haemoglobin (iFOBT) show better performance characteristics than guaiac FOBT, with augmented sensitivity and specificity. However, the single tests show wide differences in diagnostic performance and iFOBT is not yet covered by insurance companies although it should replace the guaiac test for CRC screening. Visual colonoscopy, which was introduced to the German National Cancer Screening Program in 2002, is the gold standard for the diagnosis of colorectal neoplasia. From 2003 to 2007 more than 2.8 million examinations have been documented in Germany. The prevalence of adenomas is around 20% and of CRC about 0.7% to 1.0% of the screenings. Seventy percent of the carcinomas detected during screening are in an early stage (UICC I and II). Furthermore, screening colonoscopy is a cost saving procedure with a low complication rate (0.25% overall). Insurance companies save 216€ for each screening colonoscopy mainly by prevention of neoplasia due to polypectomy. In Germany, virtual colonography by computed tomography (CT) or magnetic resonance imaging still lacks standardization of the hard and software. In experienced centres the sensitivity for CRC and large polyps of CT colonography is comparable to colonoscopy but in meta-analyses the ranking is lower. New technologies like computer-aided colonoscopies with sheath or double balloon techniques are coming up as well as capsule colonoscopy, which sensitivity for large polyps is about 70%. Advised by his physician, the patient can choose his most acceptable examination method from this whole set of screening tools.


A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function.
k-turns are commonly-occurring motifs that introduce sharp kinks into duplex RNA, thereby facilitating tertiary contacts. Both the folding and conformation of k-turns are determined by their local sequence. k-turns fall into two conformational classes, called N3 and N1, that differ in the pattern of hydrogen bonding in the core. We show here that this is determined by the basepair adjacent to the critical G•A pairs. We determined crystal structures of a series of Kt-7 variants in which this 3b,3n position has been systematically varied, showing that this leads to a switch in the conformation. We have previously shown that the 3b,3n position also determines the folding characteristics of the k-turn, i.e. whether or not the k-turn can fold in the presence of metal ions alone. We have analyzed the distribution of 3b,3n sequences from four classes of k-turns from ribosomes, riboswitches and U4 snRNA, finding a strong conservation of properties for a given k-turn type. We thus demonstrate a strong association between biological function, 3b,3n sequence and k-turn folding and conformation. This has strong predictive power, and can be applied to the modeling of large RNA architectures.


Prescription drug use among older adults in Italy: a country-wide perspective.
In Italy, prescription drug costs represent approximately 17% of total public health expenditures. Older adults commonly use multiple drugs and, for this reason, this population is responsible for a large portion of drug-related costs. In 2012, public expenditure for pharmaceuticals in primary care exceeded 11 billion Euros (approximately 15.2 billion US $), and older adults aged 65 or older accounted for more than 60% of these costs. Recently, increased attention has been focused on studies aimed at monitoring drug use and evaluating the appropriateness of drug prescribing in older adults. In this article, we examined studies that assessed these issues in different settings at a national level. Specifically, results of surveys of prescription drug use in primary care (OsMED), hospital (GIFA, CRIME, and REPOSI) and long-term care (ULISSE and SHELTER) settings are reviewed. Overall, these studies showed that the quality of drug prescribing in older patients is far from optimal. This leads to an increased risk of negative health outcomes and increased health care costs. Data from these studies are valuable, not only to monitor drug use, but also to target interventions aimed at improving the quality of prescribing. Translating the findings of clinical research and monitoring programs will be challenging, but it will lead to quantifiable improvements in the quality of drug prescribing at a national level.


Spouse Psychological Well-Being: A Keystone to Military Family Health.
Understanding predictors of military spouse psychosocial vulnerability informs efforts to assess, identify, and support at-risk spouses and families. In this analysis we test the effects of family stress and strain on military spouse psychological health, using a sample of female civilian spouses (n=161). Regression findings confirm expectations of the significant contribution of family stressors, strain, and resources in explaining variation in spouses' psychological health, controlling for deployment and socioeconomic factors. Identifying the effects of family stress on military spouse psychological health supports the need for family-centered interventions and prevention programs.


Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes.
1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 microM TB produced concentration-dependent increases in CYP1A2, CYP2B6 and CYP3A4 mRNA levels, whereas treatment with BHT increased CYP2B6 and CYP3A4 mRNA levels. CYP1A2, CYP2B6 and CYP3A4 mRNA levels were induced around 48-, 21- and 9-fold, respectively, by 200 microM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 microM BHT. 3. In contrast, the treatment of human hepatocytes for 72 h with PG and CC had little or no effect on CYP mRNA levels. 4. The treatment of human hepatocytes with TB also induced CYP1A-dependent 7-ethoxyresorufin O-deethylase activity, whereas BHT induced CYP3A-dependent testosterone 6beta-hydroxylase activity. 5. In summary, the results demonstrate that TB is a mixed inducer of CYP forms in human hepatocytes inducing CYP1A, CYP2B and CYP3A forms, whereas BHT is an inducer of CYP2B and CYP3A forms.


Resistance of the insulinotropic action of alpha-D-glucose and beta-L-glucose pentaacetates to cholera and pertussis toxins.
The pentaacetate esters of alpha-D-glucose and beta-L-glucose were recently reported to stimulate insulin release. The possible participation of G-protein-coupled receptors to the insulinotropic action of these esters was investigated in rat pancreatic islets either preincubated with cholera toxin or obtained from animals injected with pertussis toxin. Neither procedure affected adversely the secretory response to the esters in islets incubated in the presence of L-leucine. Thus, in both situations, alpha-D-glucose pentaacetate and, to a lesser extent, beta-L-glucose pentaacetate augmented insulin release evoked by the branched-chain amino acid, whilst beta-L-galactose pentaacetate failed to do so. These findings suggest that G-proteins sensitive to either cholera or pertussis toxins are not involved in one of the two modalities by which these esters are thought to stimulate insulin secretion, namely that independent of the catabolic fate of their hexose moieties.


Serum cortisol and adrenocorticotrophic hormone (ACTH) in infants receiving topical and subconjunctival corticosteroids following cataract surgery.
Cushingoid features are occasionally encountered in infants after pediatric cataract surgery. The aim of this study is to evaluate whether the use of topical glucocorticoids (GCs) following congenital cataract surgery can result in endogenous adrenal suppression and/or systemic side effects similar to those seen with systemic steroids. A prospective study was performed on 20 infants with bilateral congenital cataract. All infants received a single subconjunctival betamethasone injection of 1 mg at the end of surgery in addition to topical dexamethasone eye drops 1 mg/ml for 6 weeks. All infants had anthropometric measurements and blood pressure measurements, serum cortisol, and ACTH level measurements before surgery and 2 months after. In addition, the total administered glucocorticoid adjusted per weight was calculated. The mean age of the infants was 4.93 ± 2.58 months. Thirteen were males (65%). The total administered glucocorticoid dose was 18.7 mg and the mean cumulative dexamethasone equivalent dose administered was 2.75 ± 1.31 mg/kg. There was a statistically significant increase in the adjusted weight percentile for age (P = 0.009). Both the systolic and diastolic blood pressure were significantly elevated (P = 0.005 and P = 0.025 respectively). There was a statistically significant reduction in both the morning and afternoon serum ACTH levels (P = 0.023 and P = 0.014). The reduction in serum cortisol levels was statistically non-significant. Topical steroids following pediatric cataract surgery can result in both subclinical and clinical changes in the hypothalamic-pituitary-adrenal axis that can be easily overlooked and need careful attention and follow-up.