Influenza A virus protein PA-X suppresses host Ankrd17-mediated immune responses.
Influenza A virus (IAV) PA-X is a critical ribonuclease protein involved in host cell shutoff but its role in modulating the host immune response to IAV infection remains to be addressed. In this study, host cellular proteins that directly interact with PA-X were screened to investigate the biological function of PA-X in the pathogenesis of IAV infection. The protein ankyrin repeat domain 17 (Ankrd17), a positive regulator of inflammatory responses via the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling pathway, was identified as a specific PA-X binding partner that preferred PA-X to the PA protein. The N-terminal ankyrin repeats of Ankrd17 are the key domain for the interaction with PA-X rather than PA, which is required for the function of Ankrd17 in elevating the host immune response. Using Ankrd17 knockout and overexpression, we confirmed that PA-X significantly affected the Ankrd17-mediated response to infection in host cells. Our data therefore reveal a novel function for PA-X in the regulation of innate immune pathways via the interaction between PA-X and Ankrd17.


Peritoneal metastasis of a brainstem anaplastic ganglioglioma in a 2-year-old boy: case report and literature review.
Anaplastic gangliogliomas (AGG) are rare tumors of the central nervous system (CNS) that commonly affect children and young adults, with an unusual infratentorial presentation, which is related to hydrocephalus and a worse prognosis. We report a case of a brainstem AGG in a 2-year-old boy who underwent a ventriculoperitoneal shunting (VPS) and later presented peritoneal metastasis. We also reviewed the related literature. Even though rare, disease dissemination through VPS should be sought in patients with CNS tumors and VPS who develop new abdominal symptoms. The early diagnosis and intervention may minimize morbidity and improve quality of life of such patients.


Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory
Disrupting maladaptive memories may provide a novel form of treatment for neuropsychiatric disorders, but little is known about the neurochemical mechanisms underlying the induction of lability, or destabilization, of a retrieved consolidated memory. Destabilization has been theoretically linked to the violation of expectations during memory retrieval, which, in turn, has been suggested to correlate with prediction error (PE). It is well-established that PE correlates with dopaminergic signaling in limbic forebrain structures that are critical for emotional learning. The basolateral amygdala is a key neural substrate for the reconsolidation of pavlovian reward-related memories, but the involvement of dopaminergic mechanisms in inducing lability of amygdala-dependent memories has not been investigated. Therefore, we tested the hypothesis that dopaminergic signaling within the basolateral amygdala is required for the destabilization of appetitive pavlovian memories by investigating the effects dopaminergic and protein synthesis manipulations on appetitive memory reconsolidation in rats. Intra-amygdala administration of either the D1-selective dopamine receptor antagonist SCH23390 or the D2-selective dopamine receptor antagonist raclopride prevented memory destabilization at retrieval, thereby protecting the memory from the effects of an amnestic agent, the protein synthesis inhibitor anisomycin. These data show that dopaminergic transmission within the basolateral amygdala is required for memory labilization during appetitive memory reconsolidation.


Myocardial non-esterified fatty acids during normoxia and ischemia in Langendorff and working rat hearts.
In isolated perfused rat hearts, the tissue levels of non-esterified fatty acids (NEFA) decreased during normoxic perfusion for 60 min in the working heart but not in the Langendorff heart. The levels of both saturated and unsaturated NEFA increased during ischemia for 20 min in the working heart but not in the Langendorff heart, although unsaturated NEFA increased in the Langendorff heart when the ischemic period was 40 min. Arachidonic and linoleic acids were the NEFA that accumulated most prominently.


Relation between ionised calcium and pH in infants with acute acid-base disturbances.
Plasma ionised calcium, [Ca2+], and pH were negatively correlated in 21 infants with disturbed acid-base homeostasis. The slopes of the individual regression lines indicated a mean decrease in [Ca2+] of 42% per pH increase. (Mean delta log[Ca2+]/delta pH = -0.184, SEM = 0.050, p less than 0.001). The value was not significantly different from the relation between [Ca2+] and pH in vitro, when whole blood or plasma was equilibrated with CO2-air mixtures. pH and [Ca2+] must be measured and considered together to allow a proper interpretation of the result.


Carbon and silver nanoparticles in the fight against the filariasis vector Culex quinquefasciatus: genotoxicity and impact on behavioral traits of non-target aquatic organisms.
Mosquito-borne diseases represent a deadly threat for millions of people worldwide. The Culex genus, with special reference to Culex quinquefasciatus, comprises the most common vectors of filariasis across urban and semi-urban areas of Asia. In recent years, important efforts have been conducted to propose green-synthesized nanoparticles as a valuable alternative to synthetic insecticides. However, the mosquitocidal potential of carbon nanoparticles has been scarcely investigated. In this study, the larvicidal and pupicidal activity of carbon nanoparticle (CNP) and silver nanoparticle (AgNP) was tested against Cx. quinquefasciatus. UV-Vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, and Raman analysis confirmed the rapid and cheap synthesis of carbon and silver nanoparticles. In laboratory assays, LC50 (lethal concentration that kills 50 % of the exposed organisms) values ranged from 8.752 ppm (first-instar larvae) to 18.676 ppm (pupae) for silver nanoparticles and from 6.373 ppm (first-instar larvae) to 14.849 ppm (pupae) for carbon nanoparticles. The predation efficiency of the water bug Lethocerus indicus after a single treatment with low doses of silver and carbon nanoparticles was not reduced. Moderate evidence of genotoxic effects induced by exposure to carbon nanoparticles was found on non-target goldfish, Carassius auratus. Lastly, the plant extract used for silver nanosynthesis was tested for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Overall, our results pointed out that AgNP and CNP can be a candidate for effective tools to reduce larval and pupal populations of filariasis vectors, with reduced genotoxicity and impact on behavioral traits of other aquatic organisms sharing the same ecological niche of Cx. quinquefasciatus.


[Preventive oral and dental care in radiotherapy patients].
An overview is presented of the preventive measures that can be taken with regard to the various side effects of radiotherapy of the head-and-neck region. Xerostomia, mucositis, radiation caries, trismus and osteoradionecrosis are to some extent preventable.


Spatial imagery in deductive reasoning: a functional MRI study.
Various cognitive theories aim to explain human deductive reasoning: (1) mental logic theories claim syntactic language-based proofs of derivation, (2) the mental model theory proposes cognitive processes of constructing and manipulating spatially organized mental models, and (3) imagery theories postulate that such abilities are based on visual mental images. To explore the neural substrates of human deductive reasoning, we examined BOLD (blood oxygen level dependent) contrasts of twelve healthy participants during relational and conditional reasoning with whole-brain functional magnetic resonance imaging (fMRI). The results indicate that, in the absence of any correlated visual input, reasoning activated an occipitoparietal-frontal network, including parts of the prefrontal cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association cortex (BA 19). In the discussion, we first focus on the activated occipito-parietal pathway that is well known to be involved in spatial perception and spatial working memory. Second, we briefly relate the activation in the prefrontal cortical areas and in the anterior cingulate gyrus to other imaging studies on higher cognitive functions. Finally, we draw some general conclusions and argue that reasoners envisage and inspect spatially organized mental models to solve deductive inference problems.


Role of Nitric oxide in the renal and systemic vasodilatory responses to platelet-activating factor in the rat, in vivo.
Chemical mediator(s) involved in the renal vasodilatory and systemic hypotensive effects of platelet-activating factor (PAF) remain unresolved. Because nitric oxide (NO) and PAF have many similar cardiovascular actions, we examined whether endogenous NO contributes to the renal and systemic actions of PAF. PAF was administered into the renal arterial or systemic venous circulation of anesthetized rats. The change in renal blood flow (RBF) and/or mean arterial blood pressure (MAP) was recorded in the absence and presence of NO synthase inhibition. Transient exposure of the renal vacsular bed to intrarenal PAF boluses (1-10 ng kg(-1)) resulted in an immediate increase in RBF that was partially inhibited by the intrarenal administration of a NO synthase inhibitor, whereas the ensuing rapid fall in MAP was unaffected by NO synthase blockade. A sustained exposure to intrarenal PAF infusion (2.5 ng min(-1) kg(-1)) in intrarenal NO synthase inhibitor-treated rats (hypertensive with vasoconstricted kidneys) had no effect on RBF and MAP, which was in contrast to the increase in RBF and modest fall in MAP in control intrarenal vasopressin-treated rats (hypertensive with vasoconstricted kidneys). To dissociate the influence of systemic hypotension on the RBF response, rat kidneys were denervated and MAP elevated by a pressor agent whilst maintaining renal arterial blood pressure constant. Subsequent intrarenal PAF infusion at 2.5 and 10 ng min(-1) kg(-1) resulted in a substantial rise in RBF and modest fall in MAP, responses that were abolished by intrarenal NO synthase inhibition at the lower intrarenal PAF infusion or abolished/attenuated at the higher intrarenal PAF infusion. Additional experiments administered drugs intravenously to exclude the possibility that the modified MAP response by NO synthase inhibition was related to the drugs being administered into the kidney. Intravenous PAF boluses (0.1-1 microg kg(-1)) resulted in a transient fall in MAP that was independent of the NO pathway, whereas the systemic hypotension induced by intravenous PAF infusion (10 ng min(-1) kg(-1)) was greatly attenuated by NO synthase inhibition. NO has a major role in mediating the renal and peripheral vasodilatory responses induced by a sustained exposure to PAF in the rat, whereas NO's overall contribution was less or absent during transient PAF exposure.


The thresholding problem and variability in the EEG graph network parameters.
Graph thresholding is a frequently used practice of eliminating the weak connections in brain functional connectivity graphs. The main aim of the procedure is to delete the spurious connections in the data. However, the choice of the threshold is arbitrary, and the effect of the threshold choice is not fully understood. Here we present the description of the changes in the global measures of a functional connectivity graph depending on the different proportional thresholds based on the 146 resting-state EEG recordings. The dynamics is presented in five different synchronization measures (wPLI, ImCoh, Coherence, ciPLV, PPC) in sensors and source spaces. The analysis shows significant changes in the graph's global connectivity measures as a function of the chosen threshold which may influence the outcome of the study. The choice of the threshold could lead to different study conclusions; thus it is necessary to improve the reasoning behind the choice of the different analytic options and consider the adoption of different analytic approaches. We also proposed some ways of improving the procedure of thresholding in functional connectivity research.


Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant.
S-adenosyl-L-methionine (SAMe), a putative antidepressant, is a naturally occurring substance whose mechanism of action is still a matter of speculation. It has been recently postulated that SAMe may increase the dopaminergic tone in depressed patients. Since dopamine inhibits both thyrotropin (TSH) and prolactin secretion, we investigated the effects of treatment with SAMe on the TSH and prolactin response to thyrotropin-releasing-hormone (TRH) stimulation in 7 depressed outpatient women (mean age: 46.1 +/- 7.2 years) and 10 depressed outpatient men (mean age: 38.0 +/- 10.0 years) participating in a six-week open study of oral SAMe in the treatment of major depression. At the end of the study, there was a significant reduction after treatment with SAMe in the response of both prolactin and TSH to TRH stimulation in the group of depressed men compared to pre-treatment values. On the other hand, in the group of depressed women, the posttreatment prolactin response to TRH did not appear to change when compared to pre-treatment and the TSH response to TRH challenge tended even to augment slightly after treatment with SAMe. Our results, at least in depressed men, seem to support the hypothesis of a stimulating effect of SAMe on the dopaminergic system.


Quantification of Carnosine-Aldehyde Adducts in Human Urine.
Lipid peroxidation generates several reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde. One major pathwayof aldehydes detoxification is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smokers young adults. Standard adducts were prepared and isolated by HPLC. The results showed the presence of a new product from the reaction of CAR with ACR. This new adduct was completely characterized by HPLC/MS-MSn, 1H RMN, COSY and HSQC. The new HPLC/MS/MS methodology employing stable isotope-labeled internal standards (CAR-HHEd5 and CAR-HNEd11) was developed for adducts quantification. This methodology permits quantification of 10pmol CAR-HHE and 1pmol of CAR-ACR and CAR-HNE. Accurate determinations in human urine sample were performed and showed 4.65±1.71 to CAR-ACR, 5.13±1.76 to CAR-HHE and 5.99±3.19nmol/mg creatinine to CAR-HNE. Our results indicate that carnosine pathways can be an important detoxification route of a, ß -unsaturated aldehydes. Moreover, carnosine adducts may be useful as redox stress indicator.


One-step fabrication of integrated disposable biosensor based on ADH/NAD+/meldola's blue/graphitized mesoporous carbons/chitosan nanobiocomposite for ethanol detection.
A novel strategy to simplify the dehydrogenase-based electrochemical biosensor fabrication through one-step drop-coating nanobiocomposite on a screen printed electrode (SPE) was developed. The nanobiocomposite was prepared by successively adding graphitized mesoporous carbons (GMCs), meldola's blue (MDB), alcohol dehydrogenase (ADH) and cofactor nicotinamide adenine dinucleotide (NAD(+)) in chitosan (CS) solution. MDB/GMCs/CS film was prepared. Cyclic voltammetry measurements demonstrated that MDB was strongly adsorbed on GMCs. After optimizing the concentration of MDB and the working potential, the MDB/GMCs/CS film presented a fast amperometric response (5s), excellent sensitivity (10.36 nA μM(-1)), wide linear range (10-410 μM) toward NADH and without any other interference signals (such as AA, UA, DA, H2O2 and metal ions). Furthermore, concentrations of ADH and NAD(+) in nanobiocomposite and the detection conditions (temperature and pH) were also optimized. The constructed disposable ethanol biosensor showed an excellent linear response ranged from 0.5 to 15 mM with high sensitivity (67.28 nA mM(-1)) and a low limit of detection (80 μM) and a remarkable long-term stability (40 days). The intra-batch and inter-batch variation coefficients were both less than 5% (n=5). The ethanol recovery test demonstrated that the proposed biosensor offered a remarkable and accurate method for ethanol detection in the real blood samples.


Predictable correction of tricuspid insufficiency by semicircular annuloplasty.
During surgical correction of multivalvular lesions, acquired tricuspid insufficiency is best treated by a semicircular annuloplasty technique. In order to achieve an individualized and accurate correction, the tricuspid annuloplasty suture is tied around an obturator, the dimensions of which are based upon Carpentier's tricuspid ring.


The effect of intracerebral ouabain administration on the composition of edema fluid isolated from cats with cold-induced brain edema.
Brain edema fluid was collected from cats with a freezing lesion in the left parietal cortex by the insertion into the brain of needles containing nylon wicks and connected to polyethylene tubes. The edema fluid samples which accumulated in the polyethylene tubes were regularly analyzed for Na+ and K+ content, colloid osmotic pressure, lactate dehydrogenase and creatine phosphokinase activity, and 99mTc-albumin radioactivity; the albumin tracer being introduced intravenously at the time of cold-injury. One series of cats received an intracerebral injection of ouabain solution, the control series an intracerebral injection of saline, at 100 min after the cold-injury. The ouabain injection was followed by an increase of K+ content, LDH and CPK activities but a decrease of Na+ concentration in the edema fluid, attributable to a concentration of solutes in the edema fluid as presumably water and Na+ were shifted into the cells and hence the extracellular space was reduced.


[Therapeutic test in trachoma: putting in place a study model and preliminary results].
This study, performed in Atar and Nouakchott, has tested a new proceeding for biological diagnostic of trachoma (Chlamydia trachomatis direct specimen test, SYVA Merieux microtrak), and has controlled the efficiency of different therapeutic schemes against trachoma. An experimental pattern for subsequent studies is proposed.


[Epidemiology of cutaneous leishmaniasis in five villages of Dogon country, Mali].
The epidemiology of the cutaneous leishmaniasis (CL) with Leishmania major is poorly documented in Mali. Following reports of CL in the tourist areas of the Dogon country (Bandiagara Escarpment), a joint French and Malian bio-clinical team conducted a field study from 16 to 27 January, 2010. The population of 5 villages has been examined by a dermato-infectiologist and cases were selected by visual inspection of skin lesions. Smears and biopsies (from the lesions) and venous blood were obtained from suspected cases of CL. Diagnosis was performed by light microscopy, in vitro cultures, serology and molecular biology. Fifty patients with skin lesions have been examined. Twenty-one have been suspected as CL. At least one sample was obtained from 18 patients. The lesions were predominantly old, more or less scarring and secondary infected. A skin smear was performed for 15 patients, a skin biopsy for 14 patients: smears and cultures were all negative. The PCR (Leishmania spp.) made on 14 biopsies was positive for 12 patients (86%). The low amount of amplified DNA obtained did not allow the sequencing and identification of the species of Leishmania. Western blot (WB) serology was positive in 11 cases out of 12 (92%). This investigation showed the presence of cutaneous leishmaniasis in Bandiagara. A further investigation is required during transmission period (September-October) to confirm the presence of Leishmania major epidemic in Dogon country.


DJR-1.2 of Caenorhabditis elegans is induced by DAF-16 in the dauer state.
Caenorhabditis elegans DJR-1.2, a homolog of human DJ-1, has recently been demonstrated to be a novel glyoxalase and protects worms against glyoxals. Here, we report that expression of DJR-1.2 is substantially increased during starvation as well as in the dauer stage. The induction of DJR-1.2 led to increased glyoxalase activity in the dauer state, thereby increasing protection against glyoxals. The induction is regulated by DAF-16, a transcriptional regulator implicated in oxidative stress and normal lifespan.


Fully automated imaging protocol independent system for pituitary adenoma segmentation: a convolutional neural network-based model on sparsely annotated MRI.
This study aims to develop a fully automated imaging protocol independent system for pituitary adenoma segmentation from magnetic resonance imaging (MRI) scans that can work without user interaction and evaluate its accuracy and utility for clinical applications. We trained two independent artificial neural networks on MRI scans of 394 patients. The scans were acquired according to various imaging protocols over the course of 11 years on 1.5T and 3T MRI systems. The segmentation model assigned a class label to each input pixel (pituitary adenoma, internal carotid artery, normal pituitary gland, background). The slice segmentation model classified slices as clinically relevant (structures of interest in slice) or irrelevant (anterior or posterior to sella turcica). We used MRI data of another 99 patients to evaluate the performance of the model during training. We validated the model on a prospective cohort of 28 patients, Dice coefficients of 0.910, 0.719, and 0.240 for tumour, internal carotid artery, and normal gland labels, respectively, were achieved. The slice selection model achieved 82.5% accuracy, 88.7% sensitivity, 76.7% specificity, and an AUC of 0.904. A human expert rated 71.4% of the segmentation results as accurate, 21.4% as slightly inaccurate, and 7.1% as coarsely inaccurate. Our model achieved good results comparable with recent works of other authors on the largest dataset to date and generalized well for various imaging protocols. We discussed future clinical applications, and their considerations. Models and frameworks for clinical use have yet to be developed and evaluated.


Electroencephalography characteristics to predict one-year outcomes in pediatric anti-NMDA receptor encephalitis.
Electrographic characteristics (extreme delta brush, posterior dominant rhythm and slow waves) may predict outcomes in anti-NMDA receptor encephalitis (NMDARE). However, whether changes in EEG sleep architecture predict outcomes are unknown. We examine electrophysiological characteristics including sleep architecture in a pediatric NMDARE population and correlate with outcomes at one year. Retrospective chart and EEG review was performed in pediatric NMDARE patients at a single center. Patients with first EEGs available within 48 h of admission, prior to treatment, and one-year follow-up data were included. EEGs were independently reviewed by two epileptologists, and a third when disagreement occurred. Clinical outcomes included modified Rankin scale (mRS) at one year. Nine patients (6 females) (range 1.9-16.7 years) were included. Five of nine patients had loss of posterior dominant rhythm (PDR) and three of nine patients had absent sleep architecture. Loss of PDR correlated with a worse mRS score at one year (2.8 versus 0.5, p = 0.038). Loss of PDR and loss of sleep architecture was associated with increased inpatient rehabilitation stay and in higher number of immunotherapy treatments administered. In multivariate analysis, absence of sleep architecture (p = 0.028), absence of PDR (p = 0.041), and epileptiform discharges (p = 0.041) were predictors of mRS at one year. Loss of normal PDR, absence of sleep architecture, and epileptiform discharges are associated with worse outcomes at one year which has not been reported before. EEG characteristics may help prognosticate in NMDARE. Larger studies are needed to confirm these findings.


Extended deep vein and inferior vena cava thrombosis in a 15-year-old boy: successful lysis with recombinant tissue-type plasminogen activator 2 weeks after onset of symptoms.
We present the case of a 15-year-old boy with thrombosis of the inferior vena cava, the femoral, inguinal, and renal veins of unknown origin. Although the thrombosis was 2 weeks old, thrombolytic therapy with recombinant tissue-type plasminogen activator (maximum dosage: 0.4 mg/kg/h) was started as this appeared to be the only change to re-establish normal kidney function. After 1 week, treatment was discontinued because of generalized bleeding. At this time, the infrarenal inferior vena cava was again patent with complete lysis of all other clots. Phlebography 3 months after lysis documented an abnormal renal vein, a tubular, subhepatical stenosis of the inferior vena cava and a large collateral vessel between the inferior vena cava and the azygos vein.


Survey data on home gardeners and urban gardening practice in Pune, India.
The role of home gardens as productive green spaces in emerging megacities has so far been neglected when addressing pathways for sustainable urban development. This data article provides quantitative data from a questionnaire survey on gardening practice among home gardeners in Pune, one of the fastest growing cities in India and the Asian-Pacific region. Data include growing decisions and food production, fertilization, treatment of pests or irrigation as well as the cultural and recreational use of the garden. The survey also covered sociodemographic background information on the respondents and their gardening motivations. The data were used for a research article to build indicators for economic, environmental and socio-cultural sustainability dimensions of urban agriculture and analyze gardeners' characteristics that lead to increased sustainability outcomes entitled "Home Gardening Practice in Pune (India), the Role of Communities, Urban Environment and the Contribution to Urban Sustainability"[1]. The data and questionnaire are provided at the Open Research Data repository at the Leibniz-Centre for Agricultural Landscape Research (ZALF), Germany (https://doi.org/10.4228/ZALF.DK.109). The data offer an empirical baseline to conduct studies on the interrelationships of gardeners' motivations, gardening practice and the value and outcomes of home gardening in an accelerated urbanization process.


A comparison between polymeric microsphere and bacterial vectors for macrophage P388D1 gene delivery.
The purpose of this study was to compare bacterial and polymeric gene delivery devices for the ability to deliver plasmid DNA to a murine macrophage P388D1 cell line. An 85:15 ratio of poly(lactic-co-glycolic acid) (PLGA) and poly(beta-amino ester) polymers were formulated into microspheres that physically entrapped plasmid DNA encoding for the firefly luciferase reporter gene; whereas, the same plasmid was biologically transformed into a strain of Escherichia coli engineered to produce recombinant listeriolysin O. The two delivery devices were then tested for gene delivery and dosage effects using a macrophage cell line with both assays taking advantage of a 96-well high throughput format to quantify and compare each vector type. Gene delivery was comparable for both vectors at higher vector dosages while lower dosages showed an improved delivery for the microsphere vectors. Delivery efficiency (defined as luciferase measurement/mg cellular protein/ng DNA delivered) was 881 luminescence mg(-1) ng(-1) for polymeric microspheres compared to 171 luminescence mg(-1) ng(-1) for the bacterial vectors. A first head-to-head comparison between polymeric and bacterial gene delivery vectors shows a delivery advantage for polymeric microspheres that must also be evaluated in light of vector production, storage, and future potential.


Differential effects of lidocaine on defibrillation threshold with monophasic versus biphasic shock waveforms.
Defibrillation waveforms and antiarrhythmic drugs have disparate effects on myocardial excitability and refractoriness, making it likely that antiarrhythmic drugs will interact with one waveform differently than with another. The aim of the present study was to determine if the increase in defibrillation threshold (DFT) induced by lidocaine is similar for electrical shocks with monophasic and biphasic waveforms. Twenty-six pentobarbital-anesthetized farm-raised pigs were instrumented with pacing catheters and epicardial defibrillation electrodes. Each pig was assigned to one of four groups: (1) monophasic shock waveform and placebo (5% dextrose in water [D5W]) (n = 7), (2) monophasic shock waveform and lidocaine (n = 7), (3) biphasic shock waveform and placebo (D5W) (n = 5), or (4) biphasic shock waveform and lidocaine (n = 7). DFT was measured at baseline and subsequently during treatment (D5W or lidocaine). In the monophasic waveform groups, DFT increased from baseline in response to lidocaine by 92% (P < .0001), whereas DFT values in response to D5W did not change. In the biphasic waveform groups, DFT values did not change from baseline in response to lidocaine (P = NS), whereas DFT values from baseline in response to D5W significantly decreased by 29% (P = .04). In the monophasic waveform groups, the change in DFT from baseline in response to lidocaine was significantly different than the change from baseline in response to D5W (92 +/- 29% versus -0.5 +/- 29%, respectively) (P < .0002). In the biphasic waveform groups, however, the change in DFT from baseline in response to lidocaine was similar to the change from baseline in response to D5W (-5.66 +/- 15% versus -29 +/- 17%, respectively) (P = .48). Furthermore, the change in DFT from baseline in response to lidocaine differed significantly between monophasic and biphasic waveform groups (92 +/- 29% versus -5.66 +/- 15%) (P < .0002), whereas the change from baseline in response to D5W did not differ between monophasic and biphasic waveforms (-0.5 +/- 29% versus -29 +/- 17%) (P = .34). Compared with placebo groups, DFT values increased during lidocaine treatment to a much greater degree in the monophasic waveform group than in the biphasic waveform group receiving lidocaine. These data support our hypothesis that antiarrhythmic drugs can affect the defibrillation efficacy of monophasic waveforms differently than that of biphasic waveforms.


Maximum length sequence applied to the measurement of brainstem auditory evoked responses.
An evoked response may be assumed to consist of synchronous electrical activities of groups of neurons in response to a stimulus. Unfortunately, this response is usually weak and often masked by the background EEG activity generated spontaneously by the brain. In order to extract the embedded evoked response we have employed the theory of maximum length sequence, assuming only a temporal linearity of the system from which measurements are taken. The technique has been applied successfully with the aid of a microcomputer. The system also supports the same measurement by a conventional averaging technique. The results of the two are compared, indicating the advantages of the maximum length technique: improved signal-to-noise ratio, repeatability and speed.


Incidence of early complications requiring treatment plan changes after vitreoretinal surgery: a single-center study in South Korea.
Information regarding incidence of treatment plan changes may be useful when discussing postoperative treatment plans for patients. Moreover, it may help establish a standardized postoperative treatment plan. This study aimed to evaluate the incidence of early complications requiring treatment plan changes in patients following vitreoretinal surgery and investigate its risk factors. This single-center retrospective study included 465 patients who had undergone vitreoretinal surgery. The reasons, incidence, and timing of treatment plan changes within 14 days of surgery were identified. Potential factors associated with the changes, such as patient demographics, surgeon's experience, diagnoses, and type of surgery were also analyzed. The treatment plan was changed in 76 patients (16.3%) at a mean of 4.0 ± 3.2 days after vitreoretinal surgery. The reasons for the plan changes were increased intraocular pressure (IIOP) in 66(86.8%), intraocular inflammation in 2(2.6%), corneal edema in 3(3.9%), leakage from the sclerotomy wound in 3(3.9%) patients, and combined IIOP and intraocular inflammation in 2(2.6%). The date of discharge was postponed because of treatment plan changes in 17 patients (22.4%). The incidence of plan changes was higher in patients who underwent gas or oil tamponade (P < 0.001) and those who underwent surgery performed by less experienced surgeons (P = 0.034). Treatment plan was changed in 16.3% of patients after vitreoretinal surgery. The risk of treatment plan changes was associated with the surgeon's experience in vitreoretinal surgery and the type of surgery. These results should be considered when establishing standardized care plans for patients who require vitreoretinal surgery.


Nephrotic syndrome and focal glomerular sclerosis in aging man.
Focal glomerular sclerosis (FGS) with the nephrotic syndrome is a disecades. Less than 2% of reported patients are older than 60 years of age, and to our knowledge no patients over 70 years of age have been described. The present report documents with renal biopsies the occurrence of FGS and the nephrotic syndrome in 4 patients with an average age of 70 years, 3 being septuagenarians. We suggest that FGS in these patients may represent a disease of senescence, and that FGS in younger patients may result from accelerated glomerulotubular senescence.


Pancreatic cancer in chronic pancreatitis.
Data exists to indicate a definite association between chronic pancreatitis and pancreatic cancer. The strength of this association varies between various causes of pancreatitis, with hereditary and tropical pancreatitis more likely to result in malignancy. Pathogenesis may involve genetic factors, diabetes, smoking and alcohol consumption. Clinically a significant overlap exists between the two conditions, with histology difficult to obtain and interpret in this setting. Biomarkers like CA19-9 and others may be useful, as is a variety of newer imaging modalities. Treatment needs to be individualised as surgery offers the only chance of cure, albeit in but a few.


Rhabdomyosarcoma of the breast.
The aim of this study was to describe the first imaging studies of a primary embryonal rhabdomyosarcoma of the breast in an adult woman. This 45-year-old woman was seen for investigation of a palpable mass in the left breast. Examinations included mammography, Doppler ultrasound, and MRI. The diagnosis was made after surgical biopsy. Treatment consisted in neoadjuvant chemotherapy, followed by quadrantectomy and interstitial curietherapy. Imaging studies were performed both prior to and during therapy (i.e., after three then after six courses of chemotherapy). Imaging findings were correlated with histopathological findings. Mammography was not very contributive as the breasts were dense, particularly in the external left quadrants. On ultrasound, the mass had a tissue density and sharp contours; the mass was not highly vascularized on Doppler. MRI revealed a mass that enhanced markedly on both early and late contrast-enhanced T1-weighted sequences and was hyperintense on T2-weighted sequences. MRI appeared to be the best technique for the evaluation of the residual tissue. Rhabdomyosarcoma is a rare tumor in adults; to our knowledge, this is the first report describing the imaging features and value of MRI for the work-up and follow-up of mammary rhabdomyosarcoma.


Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols.
Although abundant data are available on the toxicity of bisphenol-A (2,2-bis (4-hydroxydiphenyl)propane; BPA), little is known about the toxicities of the structurally similar compounds, namely bisphenols (BPs). A variety of BPs were examined for their acute toxicity against Daphnia magna, mutagenicity, and estrogenic activity using the Daphtoxkit (Creasel Ltd.), the umu test system, and the yeast two-hybrid system, respectively, in comparison with BPA. BPA was moderately toxic to D. magna (48-h EC50 was 10 mg/l) according to the current U.S. EPA acute toxicity evaluation standard, and it was weakly estrogenic with 5 orders of magnitude lower activity than that of the natural estrogen 17 beta-estradiol in the yeast screen, while no mutagenicity was observed. All seven BPs tested here showed moderate to slight acute toxicity, no mutagenicity, and weak estrogenic activity as well as BPA. Some of the BPs showed considerably higher estrogenic activity than BPA, and others exhibited much lower activity. Among the tested BPs, two compounds, i.e., bisphenol-S (bis(4-hydroxydiphenyl)sulfone) and bis(4-hydroxyphenyl)sulfide, have never been reported for their estrogenic activity previously.


Effect of providing drug utilization review information on tricyclic antidepressant prescription in the elderly.
Tricyclic antidepressants are known as potentially inappropriate medications in the elderly. A notification issued in July 2015 in South Korea recommended caution while prescribing tricyclic antidepressants to the elderly. Further, since October 2015, the nationwide computerized drug utilization review monitoring system provides a pop-up window, on a real-time basis, whenever tricyclic antidepressants are prescribed to elderly outpatients. Therefore, we evaluated whether providing drug utilization review information was effective in reducing tricyclic antidepressant prescription to elderly outpatients. We used the Health Insurance Review and Assessment Service-Adult Patient Sample data from 2014 to 2016. Data related to the prescription of tricyclic antidepressants to outpatients aged 65 years or more were extracted. We determined the number of prescriptions per day per 100,000 elderly patients in each month, compared the average number of prescriptions before and after the drug utilization review information was provided, and evaluated the changes in the number of prescriptions by using an interrupted time series analysis. The average number of tricyclic antidepressant prescriptions per day per 100,000 elderly patients decreased from 76.6 (75.5 to 77.6) to 65.7 (64.5 to 66.9), a 14.2% reduction after the provision of drug utilization review information started. Following initiation of provision of drug utilization review information, there was an immediate drop of 9.2 tricyclic antidepressant prescriptions per day per 100,000 elderly patients, whereas there was no statistically significant change in trends. Providing the drug utilization review information on tricyclic antidepressant prescription for the elderly contributed to the reduction in tricyclic antidepressant prescriptions.


Production methods for heparosan, a precursor of heparin and heparan sulfate.
Heparin and heparan sulfate belong to the glycosaminoglycan family. Heparin which is known as a powerful anticoagulant has been also described to have potential in therapeutic applications such as in the treatment against cancer and prevention of virus infections. Heparan sulfate, an analog of heparin, which is not used for medical purposes yet, was reported to have the same pharmaceutical potential as heparin. Both heparin and heparan sulfate share a common precursor molecule known as heparosan. Heparosan determines the polymer chain length and the sugar unit backbone composition, which are determinant structural parameters for the biological activity of heparin and heparan sulfate. In this review we give an overview of the different methods used to synthesize heparosan, and we highlight the pro and cons of each method in respect to the synthesis of bioengineered heparin-like molecules. Advancements in the field of the synthesis of bioengineered heparin are also reported.


A novel therapeutic approach for the treatment of central sleep apnea: The remedē® system.
Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē® System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA.


Neural net based MRAC for a class of nonlinear plants.
A neural net based state feedback model reference adaptive control scheme is presented for a class of nonlinear plants. The proposed scheme employs a time varying pseudo-linear state feedback control, where the state feedback gain being generated from the output of artificial neural networks. The plant need not be in a feedback linearizable form. Both regulation and tracking control have been considered. Global stability of the scheme has been proved through Lyapunov theory. The extension of the scheme to MIMO plants is also included. Simulation studies have been conducted on an industrial robot to validate and illustrate the proposed method.


[Distribution volume and elimination of triamterene and its active metabolites in the rabbit (author's transl)].
In rabbits the volumes of distribution of triamterene (TA) and its metabolites hydroxytriamterene (OH-TA) and hydroxytriamterene sulfuric acid ester (OH-TA-ester) were determined after i.v. administration of the agents. Both TA as well as its metabolites distribute in at least 2 compartments, OH-TA exhibiting by far the greatest volume of distribution, followed by TA and then by OH-TA-ester. TA and its phase-II-metabolite are eliminated at practically equal rate, whereas the elimination of OH-TA is relatively slow.


Complementary roles for the amygdala and hippocampus during different phases of appetitive information processing.
Evidence collected from rodent models of memory storage suggests that rapid forms of learning engage the involvement of multiple brain regions each of which may participate in a different component of information processing. The present study used temporary inactivation of the amygdala and hippocampus during different phases of information processing on a one-trial appetitive-conditioning task to examine how these two regions might participate in the storage of appetitive memories. Male Long Evans rats were chronically implanted into the amygdala or dorsal hippocampus and food deprived. Rats were trained on a radial maze conditioned cue preference task where training occurred in one 40-min session and testing took place 24 h later. The amygdala or hippocampus was inactivated separately with muscimol (50 ng/microl) injected immediately before or after training, or immediately before testing. Saline-injected rats displayed a conditioned preference by spending more time in the arm that previously contained food than in the arm that did not contain food. Muscimol injected into the amygdala before training or testing blocked the conditioned preference. Muscimol injected into the hippocampus immediately after training blocked the conditioned preference. These results suggest that the processing of memories may require multiple contributions from separate brain systems for at least short-term (24 h) storage. The resulting output from each system may converge on a similar downstream target to influence behavior.


Metamaterial Absorber for Electromagnetic Waves in Periodic Water Droplets.
Perfect metamaterial absorber (PMA) can intercept electromagnetic wave harmful for body in Wi-Fi, cell phones and home appliances that we are daily using and provide stealth function that military fighter, tank and warship can avoid radar detection. We reported new concept of water droplet-based PMA absorbing perfectly electromagnetic wave with water, an eco-friendly material which is very plentiful on the earth. If arranging water droplets with particular height and diameter on material surface through the wettability of material surface, meta-properties absorbing electromagnetic wave perfectly in GHz wide-band were shown. It was possible to control absorption ratio and absorption wavelength band of electromagnetic wave according to the shape of water droplet-height and diameter- and apply to various flexible and/or transparent substrates such as plastic, glass and paper. In addition, this research examined how electromagnetic wave can be well absorbed in water droplets with low electrical conductivity unlike metal-based metamaterials inquiring highly electrical conductivity. Those results are judged to lead broad applications to variously civilian and military products in the future by providing perfect absorber of broadband in all products including transparent and bendable materials.


Pseudoaneurysm after sutureless repair of left ventricular free wall rupture: Sequential magnetic resonance imaging demonstration.
Sutureless repair is an effective procedure for acute left ventricular free wall rupture; however, it may be complicated with a left ventricular pseudoaneurysm during the late postoperative period. We present a case of a large ventricular pseudoaneurysm that occurred after the sutureless repair of an inferior myocardial infarction with oozing left ventricular free wall rupture. The patient underwent aneurysmectomy successfully. Serial magnetic resonance imaging (MRI) indicated that the necrotic left ventricular wall, which was covered by Teflon felt, had ruptured and developed a pseudoaneurysm. Therefore, after simple gluing for a left ventricular free wall rupture, patients should undergo careful follow-up evaluation for potential pseudoaneurysm. Moreover, early detection by MRI and prompt surgical repair of the complication are important in patients with left ventricular free wall rupture.


Conflict and exchange rate valuation: Evidence from the Russia-Ukraine conflict.
The Russian-Ukraine conflict is decisive in determining the course of contemporary global politics. The war has a spillover effect, with potentially considerable direct and indirect consequences on economic activity. Therefore, the study evaluates the causal impact of the Russian-Ukraine conflict on the exchange rate of Russia. The results explore that the conflict has a negative effect on the exchange rate and observed rapid depreciation. The outcomes show a rapid divergence from counterfactual predictions, and the actual exchange rate is consistently lower than would have been expected in the absence of conflict. The point-wise causal effect displays an estimate of the exchange rate depreciation following the conflict. In relative terms, the response variable decrease, suggesting that currency depreciation is observed during the intervention period. The counterfactual prediction provides a robust technique for evaluating the size of shocks and can be used as a reference to estimate the genuine impact of the conflict in various ways.


Broad neutralization against SARS-CoV-2 variants induced by ancestral and B.1.351 AS03-Adjuvanted recombinant Plant-Derived Virus-Like particle vaccines.
Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted hundreds of millions of people in a worldwide pandemic. Several safe and effective COVID-19 vaccines are now available. However, the rapid emergence of variants and risk of viral escape from vaccine-induced immunity emphasize the need to develop broadly protective vaccines. A recombinant plant-derived virus-like particle vaccine for the ancestral COVID-19 (CoVLP) recently authorized by Canadian Health Authorities and a modified CoVLP.B1351 targeting the B.1.351 variant (both formulated with the adjuvant AS03) were assessed in homologous and heterologous prime-boost regimen in mice. Both strategies induced strong and broadly cross-reactive neutralizing antibody (NAb) responses against several Variants of Concern (VOCs), including B.1.351/Beta, B.1.1.7/Alpha, P.1/Gamma, B.1.617.2/Delta and B.1.1.529/Omicron strains. The neutralizing antibody (NAb) response was robust with both primary vaccination strategies and tended to be higher for almost all VOCs following the heterologous prime-boost regimen.


Efficacy of postoperative antibiotic injection in and around ventriculoperitoneal shunt in reduction of shunt infection: A randomized controlled trial.
Infection is a common complication of ventriculoperitoneal (VP) shunt surgery. The incidence of shunt infection is still high despite routine administration of perioperative antibiotics. A lower incidence of shunt infection was observed when antibiotic-impregnated shunts (AIS) were used to treat hydrocephalus and a rapid cure was reported in cases of ventriculitis when antibiotics were injected into external ventricular drain (EVD). That is why we theorized that postoperative prophylactic injection of antibiotics in and around the shunt hardware would reduce the incidence of shunt infection. A randomized controlled clinical trial where 60 patients up to one year old, diagnosed with congenital hydrocephalus and submitted to VP shunt insertion, were randomly assigned to one of 3 groups. The treatment groups received the conventional perioperative antibiotics in addition to vancomycin and gentamicin injection in the reservoir and around the peritoneal catheter either once (group A) or twice (group B), while the control group (C) received only the conventional perioperative antibiotics. Cases were followed-up for up to 1 year. The majority of patients were less than 1 month old. The follow-up period ranged from 2 to 12 months with a mean of 8.9 months. The mean duration of onset of infection after surgery was 30 days. Prematurity (p=0.00236), age less than one month (p<0.0001) and duration of surgery of 90 min or more (p<0.00001) were significant risk factors for postoperative shunt infection. Significantly more cases of shunt infection occurred within one month after surgery (p=0.021). The control group had significantly more cases of postoperative shunt infection than the treatment groups (p=0.0042). In congenital hydrocephalus patients submitted to VP shunt insertion, injection of prophylactic vancomycin and gentamicin in and around the shunt hardware significantly reduced the incidence of postoperative shunt infection.


The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia.
Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 muCi of iodinated LPS ((125)I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). (125)I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-alpha, IL-1beta and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1beta was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.


Effects of acute stimulation through contacts placed on the motor cortex for chronic stimulation.
We tried to determine which neural elements were activated in awake subjects by stimulation through contacts placed chronically on the motor cortex. We recorded the motor effects of stimulation through 4 disc contacts placed in the subdural space over the motor cortex in 9 patients undergoing chronic stimulation for the control of pain or for the control of the rigidity of multiple system atrophy. Single stimuli could elicit short latency motor evoked potentials or facilitate active motoneurons in the contralateral limbs. The responsible neural elements had a short chronaxie (the pulse duration necessary to reach threshold with a stimulus intensity twice that required to reach threshold at the longest pulse duration used) and refractory period implying that they were myelinated axons. The facilitation was larger with cathodal than with anodal monopolar stimulation. The short latency facilitation in response to the second of two stimuli was greater at condition test intervals of 2-5 ms. This enhancement could be demonstrated with conditioning stimuli subthreshold for the excitation of active motoneurons suggesting that it arose, in part, at the level of the cortex. Single cortical stimuli could result in inhibition of voluntarily activated motoneurons. The inhibition was larger with cathodal than anodal monopolar stimulation. The responsible neural elements also had a short chronaxie and refractory period. Stimulation in awake subjects through contacts placed chronically over the motor cortex appears to activate axons in the cortex, which excite both corticospinal neurons and inhibitory neurons.


Diel variation in fig volatiles across syconium development: making sense of scents.
Plants produce volatile organic compounds (VOCs) in a variety of contexts that include response to abiotic and biotic stresses, attraction of pollinators and parasitoids, and repulsion of herbivores. Some of these VOCs may also exhibit diel variation in emission. In Ficus racemosa, we examined variation in VOCs released by fig syconia throughout syconium development and between day and night. Syconia are globular enclosed inflorescences that serve as developing nurseries for pollinating and parasitic fig wasps. Syconia are attacked by gallers early in their development, serviced by pollinators in mid phase, and are attractive to parasitoids in response to the development of gallers at later stages. VOC bouquets of the different development phases of the syconium were distinctive, as were their day and night VOC profiles. VOCs such as α-muurolene were characteristic of the pollen-receptive diurnal phase, and may serve to attract the diurnally-active pollinating wasps. Diel patterns of release of volatiles could not be correlated with their predicted volatility as determined by Henry's law constants at ambient temperatures. Therefore, factors other than Henry's law constant such as stomatal conductance or VOC synthesis must explain diel variation in VOC emission. A novel use of weighted gene co-expression network analysis (WGCNA) on the volatilome resulted in seven distinct modules of co-emitted VOCs that could be interpreted on the basis of syconium ecology. Some modules were characterized by the response of fig syconia to early galling by parasitic wasps and consisted largely of green leaf volatiles (GLVs). Other modules, that could be characterized by a combination of syconia response to oviposition and tissue feeding by larvae of herbivorous galler pollinators as well as of parasitized wasps, consisted largely of putative herbivore-induced plant volatiles (HIPVs). We demonstrated the usefulness of WGCNA analysis of the volatilome in making sense of the scents produced by the syconia at different stages and diel phases of their development.


Methodological framework for Life Cycle Assessment of sustainable aviation (SA) systems.
A comprehensive framework is proposed for Life Cycle Assessment (LCA) in the field of commercial aviation (passengers and cargo), capable to ensure transparency and comparability when evaluating the overall environmental performances of four emerging aviation systems, i.e., biofuels, electrofuels, electric, and hydrogen. The projected global revenue passenger kilometer (RPK) and is suggested as the functional unit for two timeframes representing near-term (2035) and long-term (2045), and for two segments, namely domestic and international. To solve the difficulty of comparing liquid fuels and electric aviation, the framework proposes a methodology to translate projected RPK into energy requirements for each of the studied sustainable aviation systems. Generic system boundaries are defined with their key activities for all four systems, with the biofuel system being sub-divided into two categories to distinguish whether it stems from residual or land-dependent biomass. The activities are grouped in seven categories: (i) conventional (fossil-based) kerosene activity, (ii) conversion processes from feedstock supply (to fuel or energy production for aircraft operation), (iii) counterfactual uses of constrained resources and displacement effects associated to co-products management, (iv) aircraft manufacture, (v) aircraft operation, (vi) additional infrastructure needed, and (vii) end-of-life management (aircraft and batteries). Considering applying regulations, the framework also includes a methodology to handle: (i) hybridization (the use of more than one source of energy/propulsion system to power an aircraft), (ii) the mass penalty affecting the number of carried passengers in some of the systems, and (iii) impacts stemming from non-CO2 tailpipe emissions - aspects that are currently neglected in most LCA studies. The proposed framework builds upon the most recent knowledge in the field; however, some choices are dependent on upcoming scientific advances concerning e.g., tailpipe emissions at high altitude and their environmental impacts, new aircraft configuration, etc., and are subject to significant uncertainties. Overall, this framework provides a guideline for LCA practitioners addressing new energy sources for future aviation.


Proteolytic activation of protein kinase C in the extracts of cells treated for a short time with phorbol ester.
A 10 min treatment of human neutrophils with phorbol 12-myristate 13-acetate (PMA) has been reported to induce accumulation of the proteolytically activated Ca2+/phospholipid-independent catalytic fragment of protein kinase C in the cytosol of intact cells [(1986) J. Biol. Chem. 261, 4101-4105]. We investigated the proteolytic conversion of protein kinase C to Ca2+/phospholipid-independent form in the cytosol and membrane fractions of pig neutrophils. The activity of protein kinase C was measured with its specific oligopeptide substrate Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide designed previously. In our experiments the short-term treatment of neutrophils with PMA did not induce the accumulation of the proteolytically activated form of protein kinase C in the cytosol of intact cells. However, treatment of cells with PMA enhanced the limited proteolysis of protein kinase C during the preparation of cell extracts.


Dynamic functional network connectivity reveals the brain functional alterations in lung cancer patients after chemotherapy.
This study aimed to investigate alterations of brain functional network connectivity (FNC) in lung cancer patients after chemotherapy and explore links between these FNC differences and cognitive impairment. Twenty-two lung cancer patients receiving chemotherapy and 26 healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and neuropsychological testing. Group independent component analysis (GICA) was applied to rs-fMRI data to extract whole-brain resting state networks (RSNs). Static and dynamic FNC (dFNC) were constructed to reveal RSNs connectivity alterations between lung cancer patients and HCs group, and the correlations between the group differences in RSNs and cognitive performance were analyzed. Our findings revealed that chemotherapeutics can produce widespread connectivity abnormalities in RSNs, mainly focused on default mode network (DMN) and executive control network. Furthermore, the dFNC analysis help identify network configurations of each state and capture more chemotherapy-induced disorders of interactions between and within RSNs, which mainly includes sensorimotor network, attentional network and auditory network. In addition, after chemotherapy, the lung cancer patients spend shorter mean dwell time (MDT) in state 2. The decreased dFNC between DMN [independent component 5 (IC5)] and DMN (IC6) in the lung cancer patients after chemotherapy in state 4 was negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r=-0.447, p=0.042). The dFNC analysis enrich our understanding of the neural mechanisms underlying the chemobrain, and suggested that the temporal dynamics of FNC could be a potential effective method to detect cognitive changes in lung cancer patients receiving chemotherapy.


Logistic regression model can reduce unnecessary artificial liver support in hepatitis B virus-associated acute-on-chronic liver failure: decision curve analysis.
Several models have been proposed to predict the short-term outcome of acute-on-chronic liver failure (ACLF) after treatment. We aimed to determine whether better decisions for artificial liver support system (ALSS) treatment could be made with a model than without, through decision curve analysis (DCA). The medical profiles of a cohort of 232 patients with hepatitis B virus (HBV)-associated ACLF were retrospectively analyzed to explore the role of plasma prothrombin activity (PTA), model for end-stage liver disease (MELD) and logistic regression model (LRM) in identifying patients who could benefit from ALSS. The accuracy and reliability of PTA, MELD and LRM were evaluated with previously reported cutoffs. DCA was performed to evaluate the clinical role of these models in predicting the treatment outcome. With the cut-off value of 0.2, LRM had sensitivity of 92.6 %, specificity of 42.3 % and an area under the receiving operating characteristic curve (AUC) of 0.68, which showed superior discrimination over PTA and MELD. DCA revealed that the LRM-guided ALSS treatment was superior over other strategies including "treating all" and MELD-guided therapy, for the midrange threshold probabilities of 16 to 64 %. The use of LRM-guided ALSS treatment could increase both the accuracy and efficiency of this procedure, allowing the avoidance of unnecessary ALSS.


Maximizing the utility of a single site randomized controlled psychotherapy trial.
There is increasing interest in including measures of biological mechanisms as mediators and moderators of treatment outcome in randomized controlled trials (RCT's) of psychotherapy efficacy. However, examining biological mechanisms is often expensive and budget caps of most major funding agencies have remained stable in recent years. The goal of this manuscript is to describe how a psychotherapy efficacy trial is using a model of collaborative, affiliated grants to maximize resources and the potential knowledge to be gained from a single site RCT. Principal results and conclusions: The trial is an ongoing RCT comparing two psychotherapies for the treatment of concurrent posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) with a sample of treatment seeking veterans. Through collaboration with a team of investigators with independently-funded but affiliated grants, measures of select sleep, neurobiological, and genetic biomarkers were integrated into this single site RCT. This model has allowed us to pose research questions regarding the role of biological mechanisms, maximize the utility of recruitment, and be efficient in maximizing knowledge to be gained in a way that would not be possible solely on the funding of a single site RCT. Challenges of this model include high participant burden in regard to assessment and complicated coordinating procedures among studies. Strategies to address these challenges are described.


Developmental reprogramming by UV-B radiation in plants.
Plants are extremely plastic organisms with the ability to adapt and respond to the changing environmental conditions surrounding them. Sunlight is one of the main resources for plants, both as a primary energy source for photosynthesis and as a stimulus that regulates different aspects of their growth and development. UV-B comprises wavelengths that correspond to a high energy region of the solar spectrum capable of reaching the biosphere, influencing plant growth. It is currently believed that plants are able to acclimate when growing under the influence of this radiation and perceive it as a signal, without stress signs. Nonetheless, many UV-B induced changes are elicited after DNA damage occurs as a consequence of exposure. In this review we focus on the influence of UV-B on leaf, flower and root development and emphasize the limited understanding of the molecular mechanisms for most of this developmental processes affected by UV-B documented over the years of research in this area.


Erratum to: Model of Cation Transportation Mediated by High-Affinity Potassium Transporters (HKTs) in Higher Plants.
[This corrects the article DOI: 10.1186/s12575-014-0013-3.].


Posttraumatic Trigeminal Neuropathic Pain in Association with Dental Implant Surgery.
Posttraumatic trigeminal neuropathy in association with dental implant surgery is preventable, and this should be the emphasis for all clinicians considering this treatment for a patient. Once the nerve injury and posttraumatic neuropathy with or without pain ensues, there is very little the clinician can do to reverse it and the high pain and permanency of the neuropathy will have a significant functional and psychological impact on the patient. Immediate implant removal is required, and home check should be routine for all cases. International diagnostic criteria are available and should be implemented in everyday practice.


Endothelium-dependent vasoconstriction in isolated vessel grafts: a novel mechanism of vasospasm?
YC-1 (3-(5'-hydroxymethyl-2'furyl)-1-benzyl-indazole) is an allosteric activator of soluble guanylyl cyclase (sGC) and a vasodilator. This study describes a paradoxical action of YC-1 in isolated vessels of patients with coronary artery disease (CAD) that appears to trigger an endothelium-dependent vasoconstrictor pathway present in vessels with endothelial dysfunction. Effects of YC-1 on the tensions of isolated vessels were investigated in an organ bath. Vasoconstrictors released from the vessels were quantified through enzyme-linked immunosorbent assay. YC-1 elicited long-lasting constriction in saphenous veins and radial arteries from patients with CAD, but not in human umbilical veins. The half-maximal effective dose was 1.0 μmol/L. Constriction was attenuated by nifedipine (an L-type Ca(2+)-channel blocker), bosentan (an endothelin [ET](A)/ET(B) inhibitor), BQ-788 (N-[(cis-2,6-Dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D-norleucine; an ET(B) inhibitor), and by denuding, but not by ODQ (1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one; an inhibitor of sGC), BQ-123 (cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu); an ET(A) inhibitor), or phosphoramidon (an endothelin converting enzyme inhibitor). Indomethacin (an inhibitor of cyclooxygenase-1 and -2) and SQ29,548 ([1S-[1α,2α(Z),3α,4α]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid; a thromboxane receptor antagonist) suppressed YC-1-induced constriction, whereas DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; a cyclooxygenase-2 inhibitor) had no effect. Rings of saphenous vein released significantly more endothelin-1 in the presence than in the absence of YC-1. YC-1-induced vasoconstriction demonstrates the existence of an endothelium-dependent vasoconstrictor pathway in the blood vessels of patients with CAD that to date has been described only in animal models of hypertension. Patients with CAD who have elevated plasma levels of endothelin-1 are thus prone to endothelium-dependent vasoconstriction, which may also play a role in vasospasm in vascular grafts.


A versatile procedure for the closure of small skin defects.
The author describes a method for the primary, direct closure of wide skin lesions, combining the "lazy S," "crown," and the "H"-advancement flap techniques. The "lazy S" edges of the flaps permit the satisfactory use of adjacent surrounding skin with good aesthetic results, when the flaps alone would otherwise be placed under too much strain.


Numerical simulation of the influence of gravity and posture on cardiac performance.
A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.


An Acylsucrose-Producing Tomato Line Derived from the Wild Species Solanum pimpinellifolium Decreases Fitness of the Whitefly Trialeurodes vaporariorum.
A combination of biological control and host plant resistance would be desirable for optimally controlling the greenhouse whitefly, Trialeurodes vaporariorum in tomato crops. Whitefly settlement preference, oviposition, and survivorship were evaluated on ABL 10-4 and 'Moneymaker', two nearly-isogenic tomato lines with, and without, whitefly-resistance traits based on type IV leaf glandular trichomes derived from the tomato wild species Solanum pimpinellifolium, respectively. Significantly reduced preference of T. vaporariorum adult whiteflies for ABL 10-4 leaves was observed. Moreover, T. vaporariorum altered its abaxial-adaxial settling performance on leaves of ABL 10-4 plants. A significantly lower tendency to settle on abaxial leaf surface was observed in ABL 10-4 compared to Moneymaker plants. Furthermore, T. vaporariorum deposited fewer eggs and exhibited a significantly reduced egg to adult survivorship in ABL 10-4 than in Moneymaker plants. Therefore, reduced fitness and distorted performance were observed for T. vaporariorum on ABL 10-4 tomato plants supporting that type IV leaf glandular trichomes might protect them from this pest and, indirectly, from the viruses it transmits.


Open questions: how do engineered nanomaterials affect our cells?
Our cells have evolutionarily conserved mechanisms that battle foreign and toxic materials to maintain cellular homeostasis and viability. How do these cellular machineries respond to engineered nanomaterials?


Effects of fetal exposure to isoflurane on postnatal memory and learning in rats.
In a maternal fetal rat model, we investigated the behavioral and neurotoxic effects of fetal exposure to isoflurane. Pregnant rats at gestational day 21 were anesthetized with 1.3% isoflurane for 6h. Apoptosis was quantified in the hippocampus and cortex at 2 and 18h after exposure in the fetal brain and in the postnatal day 5 (P5) pup brain. Spatial memory and learning of the fetal exposed pups were examined with the Morris Water Maze at juvenile and adult ages. Rat fetal exposure to isoflurane at pregnancy day 21 through maternal anesthesia significantly decreased spontaneous apoptosis in the hippocampal CA1 region and in the retrosplenial cortex at 2h after exposure, but not at 18h or at P5. Fetal exposure to isoflurane did not impair subsequent juvenile or adult postnatal spatial reference memory and learning and, in fact, improved spatial memory in the juvenile rat. These results show that isoflurane exposure during late pregnancy is not neurotoxic to the fetal brain and does not impair memory and learning in the juvenile or adult rat.


[Stationary thromboprophylaxis in casualty surgery. Relevance of postoperative mobility and preexisting risk factors].
The presented thromboprophylactic concept includes weight bearing and ankle motion as well as breathing therapy and drug prophylaxis (antiphlogistics, analgesic drugs, heparin). Routinely performed ultrasound screening of the deep veins (legs and pelvis) before release showed a low DVT incidence of 2.5% in a prospective clinical observation of 841 inpatients. Obesity, venous insufficiency, and a history of previous thromboembolic events were associated with a significantly increased risk of thrombosis (relative risk 4.1, 4,9, and 5.8, respectively) The duration of immobilization also had a relevant influence indicating that early postoperative physiotherapy in traumatology and orthopedic surgery has a widely underestimated thromboprophylactic effect.


Thermomechanical stability of sclera after glyceraldehyde crosslinking.
Recently, glyceraldehyde-induced crosslinking was proposed by us for the treatment of progressive myopia, increasing significantly the biomechanical rigidity of sclera. The aim of the present study was to investigate the changes in thermo-mechanical stability after scleral glyceraldehyde crosslinking, allowing a better evaluation of the efficacy of crosslinking. One hundred and twenty six porcine eyes were retrieved from the local abattoir. Using hot saline solution, the threshold shrinkage temperature (Ts) was determined for both equatorial scleral strips and whole eye globes incubated with glyceraldehyde for 4 days. Untreated control samples and specimens crosslinked with formaldehyde for 4 days were tested for comparison. In the globes, a small 6 mm limbus-parallel scleral strip was excised 5 mm behind the limbus to allow extrusion of the vitreous, facilitating heat-induced globe contraction. After heat exposure, the eyes were examined histologically by light microscopy. There was significant Maillard browning of the sclera after incubation with glyceraldehyde. The contraction temperature determined in the glyceraldehyde group was 78°C for both scleral strips and globes, in the formaldehyde group 88°C for scleral strips and 92°C for globes, and in non-crosslinked controls 62°C for scleral strips and 68°C for globes. Interestingly, the eye balls contracted in an implosion-like manner, leading to an abrupt reduction in eye volume by about one third. On light microscopy, scleral thickening, heat denaturation of collagen fibers, and loss of birefringence were noted. Scleral collagen crosslinking by glyceraldehyde proved very efficient in increasing the scleral thermomechanical stability by at least 10°C in Ts, stabilizing the eye shape and preventing the shrinkage of the eye in all dimensions. There is hope that, in a similar manner, glyceraldehyde crosslinking can stabilize the scleral collagen crosslinks and eye shape in myopia, stopping progression of scleral thinning and stretching.


Operation Shaddock--the Australian Defence Force response to the tsunami disaster in Papua New Guinea.
Operation Shaddock was the name given to the deployment of a major field medical unit of 58 Australian Defence Force medical and other personnel to Vanimo, in northwestern Papua New Guinea. Hundreds of victims of the tsunami disaster were treated and more than 200 surgical procedures performed in a 10-day mission.


The detection of Vaccinia virus confirms the high circulation of Orthopoxvirus in buffaloes living in geographical isolation, Marajó Island, Brazilian Amazon.
In Brazil, serologic evidence of Orthopoxvirus (OPV) circulation showed positivity around 20% in cattle, humans, monkeys and rodents. Although OPV seropositivity has been described in buffalo herds in southeastern Brazil, no Vaccinia virus (VACV) (member of genus OPV) outbreaks in buffalo herds have been described in this country. This study aimed to investigate the detection of anti-OPV antibodies and to study the OPV genome in Brazilian buffalo herds. Our results demonstrated a high OPV seropositivity in buffalo herds on Marajó Island and molecular data confirmed the circulation of VACV. The geographical isolation conditionmight be a sine qua non condition to explain our results.


Safety and clinical outcomes of outpatient parenteral antibiotic therapy for infective endocarditis in Christchurch, New Zealand: A retrospective cohort study.
We examined the safety and clinical outcomes of outpatient parenteral antibiotic therapy (OPAT) for patients with infective endocarditis (IE) in Christchurch, New Zealand. Demographic and clinical data were collected from all adult patients treated for IE over 5 years. Outcomes were stratified by receipt of at least partial OPAT vs entirely hospital-based parenteral therapy. There were 172 episodes of IE between 2014 and 2018. OPAT was administered in 115 cases (67%) for a median of 27 days after a median of 12 days of inpatient treatment. In the OPAT cohort, viridans group streptococci were the commonest causative pathogens (35%) followed by Staphylococcus aureus (25%) and Enterococcus faecalis (11%). There were six (5%) antibiotic-related adverse events and 26 (23%) readmissions in the OPAT treatment group. Mortality in OPAT patients was 6% (7/115) at 6 months and 10% (11/114) at 1 year and for patients receiving wholly inpatient parenteral therapy was 56% (31/56) and 58% (33/56), respectively. Three patients (3%) in the OPAT group had a relapse of IE during the 1-year follow-up period. OPAT can be used safely in patients with IE, even in selected cases with complicated or difficult-to-treat infections.


Reduced thermotolerance in aged cells results from a loss of an hsp72-mediated control of JNK signaling pathway.
Aged organisms exhibit a greatly decreased ability to induce the major heat shock protein, Hsp72, in response to stresses, a phenomenon that can also be observed in cell cultures (Heydari AR, Takahashi R, Gutsmann A, You S and Richardson A (1994) Hsp70 and aging. Experientia 50: 1092-1098). Hsp72 was shown to protect cells from a variety of stresses. The protective function of Hsp72 has been commonly ascribed to its chaperoning ability. However, recently we showed that Hsp72 protects cells from heat shock by suppression of a stress-kinase JNK, an essential component of the heat-induced apoptotic pathway (Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI and Sherman MY (1997) Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem 272: 18033-18037). Here we demonstrate that because of the diminished inducibility of Hsp72 in aged cells, Hsp72-mediated control of JNK signaling pathway is compromised. This results in increased rate of apoptotic cell death following heat shock. We show that forced expression of Hsp72 in aged cells from an adenovirus-based vector completely suppresses activation of JNK by heat shock and consequently protects from heat-induced apoptosis. We also demonstrate for the first time that it is possible to restore endogenous expression of Hsp72 in aged cells. This can be achieved by treatment with the proteasome inhibitor MG132. Induction of Hsp72 in aged cells under these conditions leads to suppression of JNK activation by a heat shock and restoration of thermotolerance manifested in a lower rate of apoptosis.


The Burden on Carers with Multiple Sclerosis.
The family members of patients with multiple sclerosis (MS) are called to become carers, playing a vital and difficult role in supporting the patients in their daily life. The aim of this study was to investigate the extent of the multidimensional burden on the carers of multiple sclerosis. Data were collected from 111 carers with MS patients. The survey was conducted in Patras General Hospital. According to the research findings, the multidimensional burden of carers is proportional to the severity of the patient's condition. In particular, the majority of patients were in a good kinetic state, so the carers examined felt gentle with a moderate burden. On both scales, Zarit and BAKAS, it was observed that the age of the caregiver, the type of care he provides, and the patient's dependence on him increase the feeling of the burden. Positive results from care improve the caregiver's relationship with the patient, his self-esteem, and his ability to cope with stress. According to the F-COPES scale, it is observed that the relationship between the caregiver and the patient is responsible for accepting the problem; the greater the caregiver's age, the higher the percentage of those seeking help from doctors, social services. The burden on carers is indisputable; support from family members, social and economic support, and education may mitigate the burden of care.


Immobilization of Horseradish Peroxidase for Phenol Degradation.
The use of enzymes to degrade environmental pollutants has received wide attention as an emerging green approach. Horseradish peroxidase (HRP) can efficiently catalyze the degradation of phenol in the environment; however, free HRP exhibits poor stability and temperature sensitivity and is easily deactivated, which limit its practical applications. In this study, to improve their thermal stability, HRP enzymes were immobilized on mesoporous molecular sieves (Al-MCM-41). Specifically, Al-MCM-41(W) and Al-MCM-41(H) were prepared by modifying the mesoporous molecular sieve Al-MCM-41 with glutaraldehyde and epichlorohydrin, respectively, and used as carriers to immobilize HRP on their surface, by covalent linkage, to form the immobilized enzymes HRP@Al-MCM-41(W) and HRP@Al-MCM-41(H). Notably, the maximum reaction rate of HRP@Al-MCM-41(H) was increased from 2.886 × 105 (free enzyme) to 5.896 × 105 U/min-1, and its half-life at 50 °C was increased from 745.17 to 1968.02 min; the thermal stability of the immobilized enzyme was also significantly improved. In addition, we elucidated the mechanism of phenol degradation by HRP, which provides a basis for the application of this enzyme to phenol degradation.


Dieting attempts modify the association between quality of diet and obesity.
Evidence on the nature of the relationship between obesity and the quality of diet remains controversial. Likewise, the possible effect of dieting attempts on this association is poorly understood. This study investigates the possible modifying effect of dieting attempts on the association between the quality of diet and obesity. The authors hypothesize that among dieters the association may be biased. The study was based on a Finnish cohort, including 5910 men and women aged 30 to 99 years, with information on diet and body mass index (BMI). Using data from a food frequency questionnaire (FFQ), an Alternate Healthy Eating Index (AHEI) applicable to the Finnish regimen was formed. Obesity was defined as a BMI ≥30 kg/m2. Information on dieting attempts was collected using a questionnaire. The statistical analyses were based on linear and logistic regression. We found a positive association between the quality of the diet and obesity, the relative odds of obesity between the highest and lowest quintiles of AHEI being 1.48 (95% CI, 1.20-1.82) after adjustment for confounding factors. However, in the interaction analysis of dieting attempts and AHEI, no association was observed in non-dieters (OR, 0.92; 95% CI, 0.69-1.24) but among dieters a slightly elevated risk was found (OR, 1.40; 95% CI, 0.98-1.98). We found no association between a high quality diet and obesity among non-dieters, but a tendency for a positive association in dieters. Dieting thus seems to modify the association between diet and obesity, which should be further studied using a longitudinal design.


Evaluation of the Roche prototype 454 HIV-1 ultradeep sequencing drug resistance assay in a routine diagnostic laboratory.
Studies have shown that low-frequency resistance mutations can influence treatment outcome. However, the lack of a standardized high-throughput assay has precluded their detection in clinical settings. To evaluate the performance of the Roche prototype 454 UDS HIV-1 drug resistance assay (UDS assay) in a routine diagnostic laboratory. 50 plasma samples, previously characterized by population sequencing and that had shown ≥1 resistance associated mutation (RAM), were retrospectively tested by the UDS assay, including 18 B and 32 non-B subtypes; viral loads between 114-1,806,407 cp/ml; drug-naive (n=27) and drug-experienced (n=23) individuals. The UDS assay was successful for 37/50 (74%) samples. It detected all RAMs found by population sequencing at frequencies above 20%. In addition, 39 low-frequency RAMs were exclusively detected by the UDS assay at frequencies below 20% in both drug-naïve (19/26, 73%) and drug-experienced (9/18, 50%) individuals. UDS results would lead to changes from susceptible to resistant to efavirenz (EFV) in one drug-naive individual with suboptimal response to an EFV-containing regimen and from susceptible to resistance to lamivudine (3TC) in one drug naïve subject who subsequently failed a 3TC-containing regimen and in a treatment experienced subject who had failed a 3TC-containing regimen. The UDS assay performed well across a wide range of subtypes and viral loads; it showed perfect agreement with population sequencing for all RAMs analyzed. In addition, the UDS assay detected additional mutations at frequencies below 20% which correlate with patients' treatment history and had in some cases important prognostic implications.


Circulating fluorocytes at the first attack of acute intermittent porphyria: a missing link in the pathogenesis.
Acute intermittent porphyria (AIP) is an autosomal dominant disorder of the haem biosynthesis resulting from a partial deficiency of hydroxymethylbilane synthase (HMBS) with incomplete penetrance. By conventional means, it is able to identify asymptomatic mutation carrier by molecular diagnosis, but one cannot reliably predict an acute porphyric attack. The presence of fluorescent red cells (fluorocytes) in AIP is probably under-recognized since AIP is a hepatic porphyria and not associated with photosensitivity. We used an automatic image acquisition platform to detect the circulating fluorocytes at 700 nm emission in a diabetic AIP patient during acute attack. We screened the patient and her family members for the mutation on HMBS, urine porphobilinogen and circulating fluorocytes. The patient was heterozygous for a disease-causing mutation on HMBS and several bright circulating fluorocytes were detected. We showed evidence that protoporphyrin contributed to the erythrocyte auto-fluorescence. Interestingly, asymptomatic mutation carriers with increased urine porphobilinogen did not have circulating fluorocytes. All mutation-negative family members revealed no circulating fluorocytes. Sudden decrease in plasma glucose concentration might invoke acute attack of AIP and appearance of circulatory fluorocytes. Potential of detecting fluorocytes as screening test or for predicting an acute attack of AIP in diabetes is worth investigating.


Relations between physical activity and behavioral and perceptual correlates among midwestern college students.
Given the inconsistent findings in the literature, the authors' purpose in this study was to examine the associations between physical activity and behavioral and perceptional correlates, such as binge drinking, cigarette smoking, fruit or vegetable consumption, and weight perceptions, among midwestern college students. The authors invited a convenience sample of 1,200 undergraduate college students enrolled in the 2004-2005 academic year in 4 different midwestern universities to participate in a survey. Of the 1,163 students who participated in the survey, a total of 1,134 usable surveys were received (response rate of 94.5%). Hierarchical multiple logistic regression analyses indicated that smoking, perceived weight, and consumption of fruit were independent predictors of physical activity when controlling for other variables. Physical activity promotion requires tailored approaches that are dependent on the target segment of the college student populations.


Confocal imaging and timing of secretion of matrix proteins by osteoblasts derived from avian long bone.
Primary osteoblasts derived from avian long bone have been evaluated in terms of spatial and temporal expression of known osteoblastic marker proteins during the early phases of cell culture. Confocal imaging of matrix proteins revealed that osteocalcin, bone sialoprotein, osteopontin, and osteonectin were restricted to the cell interior at day 4 of culture; secretion and deposition into the extra-cellular matrix of bone sialoprotein and osteopontin was evident at 8 and 12 days of culture. Osteocalcin and osteonectin were not deposited in the matrix within the timeframe of the study. Total collagen levels produced and alkaline phosphatase activity were substantial by day 4 of culture, and increased from that point 4.0- and 5.5-fold, respectively, by culture day 12. The expression of type I collagen, PTHrP receptor, osteopontin, bone sialoprotein and osteocalcin was followed by Northern blot analysis. Type I collagen and osteopontin mRNA were expressed at constant levels throughout the culture period. Over the 12 days of culture both PTH/PTHrP receptor and bone sialoprotein mRNA expression were found to increase by 2.3- and 2.5-fold, respectively. In contrast, the expression of osteocalcin message decreased by 2.5-fold by day 8 of culture.


Disruption of the p53-p53r2 DNA repair system in ulcerative colitis contributes to colon tumorigenesis.
With ulcerative colitis (UC)-associated tumorigenesis, p53 gene alteration is considered to be a key event. To clarify whether the p53-checkpoint is operating in foci of inflammation and that its disruption is a feature of UC-associated neoplasms, the present immunohistochemical study was conducted. Since accumulation of butyric acid with active UC is associated with apoptosis, effects of in vitro exposure of newly established UC-cancer derived cell lines to organic acids were also assessed. The regulatory subunit of ribonucleotide reductase, p53R2, was found to be localized with p53 in situ, and levels of p53, phospho-p53, p53R2 and inducible nitric oxide synthase were significantly intercorrelated. However, p53R2 expression was clearly reduced with progression through UC-associated dysplasia to carcinoma, demonstrating an inverse relation with p53 overexpression. In vitro treatment with butyrate or propionic acid, but not succinic acid, elicited a positive response in the p53-p53R2 system. Moreover, p53-dependent DNA repair, investigated by radioactive nucleotide incorporation, was induced by butyric acid and inhibited by short-interfering p53 and p53R2 RNAs. Therefore, it was concluded that the p53-p53R2-dependent DNA repair system is constitutively stimulated by butyric acid, which accumulates in UC inflammatory lesions. Since failure of the p53-G(1) checkpoint may cause dysfunction of repair under the influence of butyrate, gene alterations may increase and spread through the genome, leading to tumorigenesis.


Neurogenic mediators in control of pulpal blood flow.
In view of recent findings, classical nerve-released transmitters that modulate pulpal blood flow share their roles with novel vasoactive peptides. Noradrenaline coexists with neuropeptide Y in sympathetic nerves in the pulp and both substances contribute to a vasoconstriction. Vasoactive intestinal peptide has vasodilator effects and its presence in nerves in the pulp may represent a parasympathetic influence on pulpal vessels. Sensory nerves in the pulp contain a number of peptides which have vasodilatory effects. They are released and cause rapid increase in blood flow when the tooth is reached by an intense stimulus. A population of sensory nerves may thus play a role in instant defense reactions in the pulp.


Pseudoxanthoma elasticum: report of a case without any mutations in 5 exons of the MRP6 gene.
Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder of connective tissue. We describe a patient with PXE who does not have mutations in exons 16, 24, 27, 28, and 30 of the MRP6 gene.


[Variants of microsurgical autologous transplantation of composite skin flaps from the external surface of the hip].
Topographic anatomical investigations have established the possibility to make a new complex skin flap on the lateral surface of the femur on the branches of the second perforating artery and vein. The authors propose methods of making a transplant in this field on two vascular pedicles with anastomoses in one of them--a larger one and two separate flaps: a skin-fat and a muscular flaps on a single feeding pedicle. The experimental findings were confirmed by successful clinical observations.


Increasing Incidence of Thoracic Aortic Aneurysm Repair in Germany in the Endovascular Era: Secondary Data Analysis of the Nationwide German DRG Microdata.
Nationwide population based data on epidemiology and surgical treatment of descending thoracic aortic (DTA) aneurysms are not available for Germany. The aim was to assess the in hospital incidence, and to report outcomes of patients who received surgical treatment. Data were acquired by analysing the diagnosis related group (DRG) statistics of the German Federal Statistical Office. All inpatient cases of ruptured (rDTA aneurysm, ICD Code I71.1) or non-ruptured DTA aneurysm (nrDTA aneurysm; I71.2) who received thoracic endovascular (TEVAR; OPS procedure code 5-38a.7/70/8/80) or open aortic repair (OAR; OPS 5-384.3) between 2005 and 2014 were included. To adjust for sex, age, medical risk (Elixhauser comorbidity score), type of procedure, and type of admission, a multilevel multivariable regression model with robust error variance was applied. The primary outcome was in hospital mortality; secondary outcomes were organ complications. A volume outcome analysis was performed. A total of 48,098 cases of DTA aneurysm (5,848, 12.2% rDTA aneurysm) were identified. The average age was 69 ± 12 years. 65.2% were male. Frequent comorbidities were hypertension (74.9%), peripheral artery disease (including abdominal aortic aneurysm, 42.6%), other heart diseases (41.6%), coronary heart disease (26.2%), and renal failure (22.5%). Surgical treatment was received by 4969 patients (10.3%): 4057 TEVAR (81.6%) and 912 OAR (18.4%) procedures. Mortality for rDTA aneurysm was 42.9% (OAR) and 22.3% (TEVAR). It was 10.5% and 3.7% for DTA aneurysm, respectively. Rupture, increasing age, and higher comorbidity score were significantly associated with higher mortality (RR 6.66, 5.33-8.25; 1.28, 1.17-1.40; and 1.06, 1.05-1.08, respectively). Endovascular treatment was associated with lower mortality (RR 0.31, 0.23-0.41). Hospital volume was not significantly associated with in hospital mortality. Eighty per cent of patients treated surgically for a DTA aneurysm receive endovascular therapy, with low peri-operative mortality in non-ruptured cases. Elective endovascular repair should be considered for individuals at a high risk of rupture who are fit for surgery. Open repair, increased age, and a high comorbidity score are associated with higher mortality.