The role of glycogen synthase kinase 3 in the early stages of Alzheimers' disease.
There are two different types of Alzheimers' disease, familiar Alzheimers' disease (FAD) and Sporadic Alzheimers' disease (SAD), and the origin of the disease could be different in both familial and sporadic cases. In terms of FAD, mutations in three different genes are likely to promote the onset of the disease whereas for SAD, different risk factors might be involved. Nevertheless, downstream of the initial causes of the disease some common factors may be involved. In this review, rather than the differences, we have focused on some of the common features shared by Alzheimers' patients, irrespective of the origin of their disorder. Among these common features, at the molecular level, the activation of the protein kinase GSK3 may be relevant.


Comparative evaluation of the effects of multiple autoclaving on cyclic fatigue resistance of three different rotary Ni-Ti instruments: An in vitro study.
The aim of this in vitro study was to evaluate comparatively the effects of multiple autoclaving on surface topography and cyclic fatigue of three different rotary nickel-titanium (Ni-Ti) instruments. Twenty-one files each of Twisted Files (TF), Revo-S, and RaCe were used in this study. They were grouped as group 1-TF, group 2-Revo-S, and group 3-RaCe. All the files were autoclaved and subjected for scanning electron microscopic analysis and cyclic fatigue analysis. Data were subjected to statistical analysis using one way analysis of variance (ANOVA) and post hoc Tukey's Kramer multiple comparison test. TF exhibited the highest cyclic fatigue resistance followed by Revo-S and RaCe. Scanning electron photomicrographs showed no obvious surface changes in the files after three autoclaving cycles. Within the limitation of this study, it can be concluded that Twisted Files was the most fatigue resistant compared to Revo-S and RaCe, and multiple autoclaving cycles did not have any significant alterations in the cyclic fatigue resistance of rotary Ni-Ti files.


Gold-Hybridized Zinc Oxide Nanorods as Real-Time Low-Cost NanoBiosensors for Detection of virulent DNA signature of HPV-16 in Cervical Carcinoma.
Detection of host integrated viral oncogenes are critical for early and point-of-care molecular diagnostics of virus-induced carcinoma. However, available diagnostic approaches are incapable of combining both cost-efficient medical diagnosis and high analytical performances. To circumvent this, we have developed an improved IDE-based nanobiosensor for biorecognition of HPV-16 infected cervical cancer cells through electrochemical impedance spectroscopy. The system is fabricated by coating gold (Au) doped zinc oxide (ZnO) nanorods interfaced with HPV-16 viral DNA bioreceptors on top of the Interdigitated Electrode (IDE) chips surface. Due to the concurrently improved sensitivity and biocompatibility of the designed nanohybrid film, Au decorated ZnO-Nanorod biosensors demonstrate exceptional detection of HPV-16 E6 oncogene, the cancer biomarker for HPV infected cervical cancers. This sensor displayed high levels of sensitivity by detecting as low as 1fM of viral E6 gene target. The sensor also exhibited a stable functional life span of more than 5 weeks, good reproducibility and high discriminatory properties against HPV-16. Sensor current responses are obtained from cultured cervical cancer cells which are close to clinical cancer samples. Hence, the developed sensor is an adaptable tool with high potential for clinical diagnosis especially useful for economically challenged countries/regions.


A Simplified Method to Assay Protein Carbonylation by Spectrophotometry.
Protein carbonylation is an irreversible oxidation process leading to a loss of function of carbonylated proteins. Carbonylation is largely considered as a hallmark of oxidative stress, the level of protein carbonylation being an indicator of the oxidative cellular status. The method described herein represents an adaptation to the commonly used 2,4-dinitrophenylhydrazine (DNPH)-based spectrophotometric method to monitor protein carbonylation level. The classical final sample precipitation was replaced by a gel filtration step avoiding the tedious and repetitive washings of the protein pellet to remove free DNPH while allowing optimal protein recovery.This improved protocol here implemented to assay protein carbonylation in plant leaves can potentially be used with any cellular extract.


Inhibition of Na+/Ca2+ exchange by amiloride acting from opposite sides of cardiac sarcolemma.
Amiloride inhibited the Na+Ca2+ exchange activity of cardiac sarcolemmal vesicles with similar affinities at the cis and trans sides of the membrane, estimated apparent Ki on both sides of the sarcolemma being similar. The extent of amiloride inhibition on Na+/Ca2+ exchange activity was decreased by alkaline pH only when the drug was acting from the external side of the vesicle sarcolemma, whereas when vesicles were preincubated with the drug at different pH values, amiloride appeared to act as a weak permeant base, being a more effective inhibitor at alkaline pH values. In fact, a rise in the pH of the preincubation medium may favour the entry and consequently the effect of the drug on the exchanger. The pH dependence of the inhibition of Na+/Ca2+ exchange activity by either extravesicular or intravesicular amiloride was consistent with the hypothesis that in both cases the protonated drug was the active form. Evidence is presented that the pattern of interaction of amiloride on the Na+/Ca2+ exchange system strictly depended on the sidedness of drug action. In fact, while Na+ protected against inhibition by amiloride when it was acting on the same side of the vesicle membrane as the drug, it synergically interacted with amiloride to inhibit exchange activity when it was acting on the opposite side of the sarcolemma as the drug. Furthermore, only extravesicular amiloride removed the stimulation of Na+/Ca2+ exchange activity in Ca2+-treated vesicles.


Effects of different levels of ergot in concentrate on the health and performance of male calves.
A number of studies dealing with the effects of ergot and ergot alkaloids on the health and performance of poultry and pigs were reported in the past, but only a few studies and field reports are available for ruminants. Therefore, a dose-response study was carried out with calves since young animals are considered to be especially sensitive to ergot.A total of 35 male Holstein calves were randomly assigned to three feeding groups after one month of feeding milk replacer. The mean initial live weight of the calves was 49.4±5.7 kg. One control group was fed an ergot-free concentrate (n=12), one group an ergot proportion of 1000 mg/kg in the concentrate (n=ll), and another group was fed a concentrate containing 5000 mg/kg ergot (n=12). Hay, grass silage and water were available forad libitum consumption, whereas the daily concentrate portion was restricted to 2 kg. Live weight, health parameters and feed intake were monitored over the experimental period of 84 days. In addition, blood samples were taken from theVena jugularis at the beginning and at the end of the experiment and analysed for ergot alkaloids and liver parameters.Total dry matter intake, live weight gain and feed-to-gain ratio were not significantly influenced by increasing ergot proportions when the whole experimental period was considered, although there was a trend for an ergot-related decrease in concentrate intake during the first 6 weeks of the experiment. After this period of time, it seemed that calves got used to the presence of ergot in the concentrate and were able to adjust their intake to the level of the control group. Moreover, health and liver parameters, such as total bilirubin, aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transpeptidase and creatine kinase in the serum were not significantly influenced by dietary treatments. Concentrations of the individual ergot alkaloids in serum were lower than the detection limits of the applied HPLC-method.In conclusion, it can be assumed that an ergot contamination of the concentrate up to 5000 mg/kg resulted in a transient depression of concentrate intake by the calves. However, no significant effects on health and performance could be detected when the entire test period of 84 days was considered.


Immunohistochemical localization of taurine in various tissues of the mouse.
The localization of taurine was investigated in several tissues of the mouse. Immunohistochemical methods using a polyclonal antibody for taurine derived from rabbits was used in these studies. This method was used since it is a simple procedure and the results are clear and reliable. Tissues were fixed with paraformaldehyde, embedded in paraffin and treated in a microwave oven before using an avidin-biotin-complex method (ABC method). Control staining was accomplished by employing absorption staining using various amino acids: taurine, arginine, cysteine, hypotaurine and others. For purposes of comparison, radioautography (RAG) with 3H-taurine was performed to confirm the reliability of the immunohistochemical staining compared with the localization of the 3H-taurine incorporation in endothelial cells of the blood vessels of several tissues. In this investigation, immunoreactivity was broadly observed in many tissues: Purkinje cells of the cerebellum, glia cells of brain tissue, cardiac muscle cells, matrices of the bone, mucus granules of goblet cells of the intestines, and brown adipose cells of the fetus. Although the meaning of this widespread localization of taurine can not be explained completely, we surmise that taurine may have a different function in each of the tissues. In addition, taurine reactivity was observed in cell nuclei which was evidence of the presence of taurine in the nuclei.


Prenatal diagnosis of periventricular hemorrhage by fetal brain magnetic resonance imaging.
Following the incidental diagnosis of triventricular hydrocephalus in a fetus 34 weeks after the mother's last menstrual period, during an uneventful pregnancy, 1.5-T brain magnetic resonance (MR) was carried out. A subependymal hemorrhage, which had not been revealed by transabdominal ultrasound, was found; this finding was confirmed by neonatal brain ultrasound and MR. Fetal MR allowed identification of the hemorrhage as the cause of the hydrocephalus and also established its time of occurrence. Unexplained hydrocephalus should be included among the indications for fetal MR.


Covalent binding of arachidonic acid metabolites to human platelet proteins. Identification of prostaglandin H synthase as one of the modified substrates.
The covalent modification of proteins by metabolites of arachidonic acid (AA) was investigated in human platelets. Following incubation of washed human platelets with radiolabeled AA, ethanol precipitation of the proteins, and lipid extraction by organic solvents, a small fraction of the radioactivity added (0.3%) was tightly bound to the protein pellet. A dozen labeled protein bands were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Exhaustive hydrolysis of platelet proteins by proteases released an amphipathic radiolabeled material which had a chromatographic behavior similar to that of a known peptidolipid, leukotriene C4. These findings suggest a covalent nature for the observed binding. This binding was specific for AA since palmitate, myristate, or linoleate did not bind to a significant extent. It involved products of both cyclooxygenase and lipoxygenase pathways: it was indeed inhibited to a greater extent by eicosatetraynoic acid than by indomethacin. The protein-associated radioactivity was increased by the thromboxane synthase inhibitor dazoxiben. Indomethacin completely abolished this increase in binding, which could not be reproduced by exogenous prostaglandin (PG) E2, F2 alpha, or D2, and might thus involve PGG2 and/or PGH2. Diamide, an agent known to inhibit the reduction of 12-hydroperoxyeicosatetraenoic acid in platelets, produced an increase of the covalent binding, which was abolished by eicosatetraynoic acid but not by indomethacin: this suggests that the lipoxygenase product bound was 12-hydroperoxyeicosatetraenoic acid or a by-product. Dazoxiben and diamide produced distinct patterns of protein labeling after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One labeled band had a Mr of 70,000 as the PGH synthase monomer. Addition of AA at 17 microM enhanced the labeling of this band, while 100 microM was inhibitory. Labeling of this band was also induced by thrombin in prelabeled platelets. Two monoclonal antibodies against PGH synthase caused immune precipitation of a 70-kDa labeled protein in homogenates of [3H]AA-labeled platelets. PGH synthase, purified from ram seminal vesicles, was covalently modified after incubation with [3H]AA: this labeling was almost completely abolished by indomethacin. As much as 40% of platelet PGH synthase was covalently modified after incubation with 17 microM AA. It can be concluded that in intact platelets PGH synthase is covalently modified by an eicosanoid following incubation with exogenous AA or after AA mobilization from phospholipids by thrombin.


False-positive ultrasonography in agenesis of the gallbladder: a pitfall in the laparoscopic cholecystectomy approach.
We report a case of agenesis of the gallbladder in a 15-year-old girl incorrectly diagnosed as cholelithiasis on preoperative sonography and suspected at laparoscopic surgery. The diagnosis of agenesis was confirmed at open surgery with intraoperative sonography, intraoperative cholangiography, and postoperative radioisotope scan. Difficulties in preoperative diagnosis and the management during laparoscopic and open surgery are discussed.


Is daily use of sunscreens of benefit in the U.K.?
There is an increasingly widespread belief that year-round use of topical agents containing ultraviolet (UV)-absorbing ingredients is an important factor in reducing the chronic degenerative cutaneous changes associated with sun exposure. To evaluate the benefit of using sunscreens during different periods of the year for people living in the U.K. An analysis was made of typical solar UV exposure at different times of the year in relation to different topical sunscreen practices. It was shown that using sun protection products during the six summer months (April-September) can reduce the lifetime (70 years) UV exposure of a person by an equivalent of almost 40 years unprotected exposure. However, virtually no benefit is gained from using UV protective products from October to March in the U.K. CONCLUSIONS; As their use is not without cost and the risk of adverse effects, topical products containing UV filters are best avoided during October to March in the U.K.


Co-activation of both 5-HT1A and 5-HT7 receptors induced attenuation of glutamatergic synaptic transmission in the rat visual cortex.
It has been suggested that functional interactions between the 5-HT receptor subtypes may modulate glutamatergic synaptic transmission. In this study, we used whole-cell patch-clamp recordings to test the role of 5-HT receptors in mediating the AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We found that the AMPA receptor-mediated component of mEPSCs could be inhibited by exogenously applied 5-HT. 5-HT significantly reduced the glutamatergic mEPSC amplitude and increased the inter-event interval of glutamatergic mEPSCs. Bath application of 5-CT or 8-OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist) mimicked 5-HT in its effect on mEPSCs. Additionally, a selective antagonist for the 5-HT7 receptor, SB-269970, displayed no influence on the inhibition of glutamatergic synaptic transmission by 5-CT or 8-OH-DPAT. Similar results were obtained by exogenously applied WAY-100135, the selective 5-HT1A receptor antagonist. However, the inhibition of glutamatergic synaptic transmission by 5-CT or 8-OH-DPAT was completely blocked by co-application of WAY-100135 and SB-269970. Altogether, our results indicated that 5-HT suppressed glutamatergic synaptic transmission by co-activation of synaptic 5-HT1A receptors and 5-HT7 receptors in layer II/III pyramidal neurons of the rat visual cortex.


[A new catheter system for percutaneous transluminal angioplasty (PTA) of carotid artery stenoses].
A new catheter system for the dilatation treatment of carotid artery stenoses was developed consisting of a dilatation catheter with a second lumen for simultaneous carotid artery perfusion. This catheter system was efficient in dilating experimental carotid artery stenoses in dogs.


Adrenoleukomyeloneuropathy presenting as cerebellar ataxia in a young child: a probable variant of adrenoleukodystrophy.
A child aged 5 years 7 months was diagnosed as suffering from adrenoleukomyeloneuropathy (ALMN). The first sign was ataxia, and high intensity lesions were observed in the cerebellar hemispheres on T2-weighted brain MRI. His condition progressed rapidly to a vegetative state in 1 year. When aged 7 years 3 months adrenal insufficiency supervened and his skin turned dark. Rectal biopsy revealed linear cytoplasmic inclusions in macrophages in the rectal membrane. At the age of 8 years 2 months, an analysis of very long-chain fatty acids of sphingomycin in plasma led to the final diagnosis. At the age of 10 years, cerebellar and cerebral atrophy were prominent and diffuse high intensity lesions were noted in the cerebellum and cerebrum. An onset below 9 years of age has not previously been documented in ALMN.


Depression, sensation seeking, and maternal smoking as predictors of adolescent cigarette smoking.
The purpose of this study was to examine maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicated that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (beta = 0.29, p < 0.001 and beta = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (beta = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (beta = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use.


Correction of severe lower extremity deformity with digital hexapod external fixator based on CT data.
Our goal was to examine the therapeutic effect of a self-designed digital six-axis external fixator technique for the correction of severe lower extremity deformities. Between January 2017 and December 2020, our institution employed self-developed digital hexapod external fixator technology (QSF), based on CT data, to gradually correct 28 severe tibial deformities, and 15 femurs underwent osteotomy and internal fixation. The mean patient age was 32.6 ± 14.3 years, and the mean follow-up duration was 27.4 ± 16.1 months. We also recoded and analyzed the values of preoperative and final follow-up MAD, mFTA, MPTA, LLD, mLDFA, LEFS, KSS, and functional score. The QSF adjustment duration was 21.4 ± 10.8 days, and the healing duration of the tibial osteotomy site was 17.6 ± 7.0 weeks. The preoperative MAD, mFTA, and MPTA were 54.1 ± 26.2 mm, 167.7 ± 15.7°, and 75.2 ± 12.0°, respectively. At the last follow-up, the MAD was 8.2 ± 9.9 mm, mFTA was 177.6 ± 3.4°, and MPTA was 87.6 ± 2.4°. Based on these data, we achieved significant improvement post operation. The preoperative LLD and mLDFA values were 13.8 ± 18 mm and 83.7 ± 10.8°, respectively, and the values were 7.6 ± 7.6 mm and 87.8 ± 2.6°, respectively, at the last follow-up. This indicated no significant difference in these values before and after the operation. Finally, the LEFS, KSS, and functional scores improved from preoperative 51.6 ± 11.2, 68.5 ± 11.7, and 67.8 ± 11.2 to postoperative 72.3 ± 6.1, 92.9 ± 3.4, and 94.2 ± 6.3, respectively. Based on our analyses, the QSF technique accurately corrected severe multiplanar tibial deformities in adults. When combined with femoral osteotomy, satisfactory lower extremity alignment was obtained while correcting for femoral deformity. This technology has the advantages of simple operation, reliable fixation, less trauma, and less complications.


The number of frog sciatic axons increases continually during body growth.
Frog sciatic nerves show a continuing addition of new myelinated and nonmyelinated fibers with body growth. Along with increases in fiber number there are also marked changes in axon calibers and in the relative thickness of the myelin sheaths. Our data show that frog nerves, as opposed to mammalian nerves, are composed of fibers of different ages, stages of growth and stages of myelination.


Fatty acid supplementation into warming solutions improves pregnancy outcomes after single vitrified-warmed cleavage stage embryo transfers.
This study aimed to examine the embryonic development of human 4-cell stage embryos after warming with fatty acids (FAs) and to assess the pregnancy outcomes after single vitrified-warmed cleavage stage embryo transfers (SVCTs). Experimental study: A total of 217 discarded, vitrified human 4-cell stage embryos donated for research by consenting couples were used. The embryos were warmed using the fatty acid (FA)-supplemented solutions (FA group) or nonsupplemented solutions (control group). The developmental rate, morphokinetics, and outgrowth competence were analyzed. Clinical study: The treatment records of women undergoing SVCT in natural cycles between April and September 2022 were retrospectively analyzed (April-June 2022, control group; July-September 2022, FA group). Experimental study: The rate of morphologically good blastocysts was significantly higher in the FA group than in the control group (p = 0.0302). The morphokinetics during cleavage, morula, and blastocyst stages were comparable between the groups. The outgrowth was significantly increased in the FA group (p = 0.0438). Clinical study: The rates of implantation, clinical pregnancy, and ongoing pregnancy after SVCTs were significantly increased in the FA group (p = 0.0223-0.0281). Fatty acid-supplemented warming solutions effectively improve embryo development to the blastocyst stage and pregnancy outcomes after SVCTs.


Directly observed versus self-administered antiretroviral therapies: preference of HIV-positive jailed inmates in San Francisco.
Directly observed therapy (DOT) of antiretroviral (ARV) medications has beneficial effects on HIV treatment for incarcerated inmates but has been associated with limited continuation after release and inadvertent disclosure of HIV status. Guided self-administered therapy (g-SAT) may be a preferred method of ARV delivery and may encourage medication-taking behavior. We surveyed the preference of 102 HIV-positive jailed inmates at the San Francisco City and County Jails regarding receiving ARVs via DOT versus g-SAT while incarcerated. Participants overwhelmingly preferred g-SAT over DOT.


Dendritic Morphology Affects the Velocity and Amplitude of Back-propagating Action Potentials.
The back-propagating action potential (bpAP) is crucial for neuronal signal integration and synaptic plasticity in dendritic trees. Its properties (velocity and amplitude) can be affected by dendritic morphology. Due to limited spatial resolution, it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology, such as the dendrite diameter and branching pattern, using patch-clamp recording. By taking advantage of Optopatch, an all-optical electrophysiological method, we made detailed recordings of the real-time propagation of bpAPs in dendritic trees. We found that the velocity of bpAPs was not uniform in a single dendrite, and the bpAP velocity differed among distinct dendrites of the same neuron. The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated. In addition, when bpAPs passed through a dendritic branch point, their velocity decreased significantly. Similar to velocity, the amplitude of bpAPs was also positively correlated with dendritic diameter, and the attenuation patterns of bpAPs differed among different dendrites. Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results. These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs. The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology. These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology, to further illuminate the role of bpAPs in neuronal communication.


Extra dural hematoma following a high voltage electrocution accident: A case report.
Electrification accidents is a serious pathology due to the passage of an electric current through the body. The clinical manifestation is mainly represented by skin lesions with burners of different degrees however all the tissues of the body can be affected. The cerebral manifestation is a rare entity described in the literature. In this paper, we report the case of a patient with an electrocution accident manifested by an extradural hematoma who has not encountered a similar case described in the literature. We therefore present this case which poses a poorly understood pathophysiological problem.


Physicochemical Properties of a Bi-aromatic Heterocyclic-Azo/BSA Hybrid System at the Air-Water Interface.
The interaction of a heterocyclic azo compound with itself and with bovine serum albumin (BSA) is realized by probing the structural modifications in Langmuir (L) monolayers and Langmuir-Blodgett (LB) films. It was found from the pressure-area/molecule isotherms that the elastic, thermodynamic, and hysteretic properties of the pure azo L monolayer were strongly altered due to the variation of temperature and pH of subphase water. In addition to that, the modification of such properties of the azo L monolayer due to mixing with BSA was also studied. The incorporation of BSA within the azo molecular assembly reduced the elasticity of that assembly. Such reduction of in-plane elasticity of the pure azo monolayer can also be achieved by reducing the temperature and pH of subphase water without adding BSA. A reduction in area per molecule of the azo assembly at the air-water interface associated with the conformational change from horizontal to vertical orientation facilitating π-π interaction was observed with increase in temperature and pH of the subphase. Such parameters also affected the interactions between azo and BSA molecules within the azo/BSA binary system. The structures of pure azo and binary films can be determined after they are transferred to hydrophilic and hydrophobic Si surfaces using the LB technique. Their out-of-plane and in-plane structures, as extracted from two complementary surface sensitive techniques, X-ray reflectivity and atomic force microscopy, were found to be strongly dependent on mixing with BSA, subphase pH, temperature, and substrate nature.


Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study.
Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.


Rapid, quantitative adipose conversion of chicken fibroblasts by high concentrations of chicken serum or plasma.
Rapid, quantitative adipose conversion of chicken fibroblasts occurs when these cells are cultured in undiluted commercial chicken serum or plasma. Fresh serum and plasma acquire this property after ageing.


Carboxylated graphene oxide-chitosan spheres immobilize Cu2+ in soil and reduce its bioaccumulation in wheat plants.
Due to the strong interaction with pollutants and the huge adsorption capacity, graphene adsorbents are widely applied in water decontamination. However, graphene adsorbents are seldom used in soil remediation, because the adsorptive sites on graphene would be occupied by soil components. In this study, we prepared carboxylated graphene oxide-chitosan (GO-COOH/CS) spheres for the immobilization of Cu2+ from water and soil. The pores in GO-COOH/CS allowed the internal diffusion of Cu2+ solution, while they blocked the direct contact between the solid soil and the adsorptive sites on graphene sheets. Therefore, the high adsorption capacity of GO-COOH/CS spheres (78 mg/g) was largely retained for the soil Cu2+ fixation. The partition coefficient (PC) for Cu2+ adsorption onto GO-COOH/CS spheres was 4.2 mg/g/μM at Ce of 0.48 mg/L and qe of 31 mg/g, while the PC value decreased to 0.096 mg/g/μM at Ce of 91.4 mg/L and qe of 78 mg/g. At initial Cu2+ concentrations of 120 mg/L and lower, the fixation efficiencies were all higher than 99% and the corresponding free Cu2+ concentrations in leachates were lower than 1.0 mg/L. The Cu2+ fixation on GO-COOH/CS spheres largely reduced its bioaccumulation in wheat roots from 127.8 μg/g to 51.2 μg/g. The toxicity evaluations suggested that GO-COOH/CS spheres were of low toxicity to wheat seedlings and did not amplify the toxicity of Cu2+. The implications to the design of graphene adsorbents for soil remediation are discussed. Overall, our results collectively indicated that porous GO-COOH/CS spheres were high-performance adsorbents for the immobilization of Cu2+ to reduce Cu2+ bioaccumulation in plants.


Effects of the Linear Fragments of Beta-(1→3)-Glucans on Cytokine Production in vitro.
Beta-glucans, homopolysaccharides composed of 3,6-branching β-(1→3)-D-glucan chains, attract great interest as inducers of cytokine synthesis. In this work, we studied the ability of linear fragments of beta-glucan chains to activate cytokine synthesis. Synthetic nona-β-(1→3)-D-glucoside (SO) representing a linear fragment of beta-glucan chain, endotoxin (ED), and natural β-(1→3)-D-glucan (GL) were tested for their role as inducers of cytokines in whole peripheral blood cultures collected from 17 individuals. The concentrations of IL-12p70, IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF-α, and TNF-β were measured in the supernatants after 2, 24, and 48 h of cell culturing. SO, ED, and GL stimulated production of pro-inflammatory IFN-γ, IL-1β, IL-2, IL-6, IL-8, TNF-α and anti-inflammatory IL-10. The highest levels of biosynthesis after stimulation with SO were registered for IL-6, IL-8, and TNF-α. SO stimulated production of all cytokines (except IFN-γ) to a lesser extent than ED and GL. The IFN-γ/IL-10 (Th1/Th2) ratios after 24 and 48 h of culturing were 3.1 and 7.5 for SO; 0.03 and 0.1 for GL; and 0.06 and 0.2 for ED, respectively. The results indicate that linear fragments of beta-glucans cause a more pronounced shift of immune response towards the pro-inflammatory (Th1) type than beta-glucan itself.


Comparison of pulmonary artery catheter, echocardiography, and arterial waveform analysis monitoring in predicting the hemodynamic state during and after cardiac surgery.
The aim of this trial was to determine whether Flotrac Vigileo™ (FV™) provides a reliable representation of the hemodynamic state of a cardiac surgical patient population when compared to pulmonary artery catheter (PAC) and echocardiography in the peril-operative period. This was a prospective observational trial comparing perioperative hemodynamic states using transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), FV™ and PAC during and post cardiothoracic surgery. Tertiary regional hospital Intensive Care Unit (ICU). 50 consecutive adult cardiothoracic patients with written consent provided. Comparison of the perioperative hemodynamic states using echocardiography, FV™ and PAC was performed. Evaluation of the hemodynamic state (HDS) was performed using TEE, TTE, PAC and FV™ during and after cardiac surgery. Data were compared between the three hemodynamic assessment modalities. Predicted hemodynamic state. FV™ and PAC were shown to correlate poorly with TEE/TTE assessment of the hemodynamic state. Both PAC and FV™ showed significant discordance with echocardiographic assessment of the hemodynamic state. In this trial, FV™ and PAC were shown to agree poorly with TTE/TEE assessment of the HDS in an adult cardiothoracic population. Agreement between the FV™ and PAC was also poor. Caution is recommended in interpreting isolated hemodynamic monitoring data. All hemodynamic monitoring devices have inherent sources of error. Caution is advised in interpreting any single device or measurement as a gold standard. We suggest that hemodynamic measuring devices such as FV™/PAC may act as triggers for a global hemodynamic assessment including consideration of TTE/TEE.


Differential contributions of nitric oxide synthase isoforms at hippocampal formation to negative feedback regulation of penile erection in the rat.
We established previously that a novel negative feedback mechanism for the regulation of penile erection, which is triggered by ascending sensory inputs initiated by tumescence of the penis, exists in the hippocampal formation (HF). This study further evaluated the participation of nitric oxide (NO) and the contribution of nitric oxide synthase (NOS) isoforms at the HF in this process. Adult, male Sprague-Dawley rats that were anaesthetized and maintained with chloral hydrate were used, and intracavernous pressure (ICP) recorded from the corpus cavernosum of the penis was employed as our experimental index for penile erection. Microinjection bilaterally of a NO donor, S-nitroso-N-acetylpenicillamine (0.25 or 1 nmoles), or the NO precursor, L-arginine (1 or 5 nmoles), into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited a significant reduction in baseline ICP. Bilateral hippocampal application of a NO trapping agent, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (10 nmoles), significantly potentiated the elevation in ICP induced by intracavernous administration of papaverine (400 microg). Microinjection bilaterally into the HF of equimolar doses (0.5 or 2.5 pmoles) of two selective neuronal NOS inhibitors, 7-nitroindazole or N(omega)-propyl-L-arginine; or equimolar doses (50 or 250 pmoles) of two selective inducible NOS inhibitors, aminoguanidine or S-methylisothiourea, significantly enhanced the magnitude and/or duration of the papaverine-induced elevation in ICP. In contrast, hippocampal application of a potent endothelial NOS inhibitor, N5-(1-iminoethyl)-L-ornithine (18 or 92 nmoles), was ineffective. Neither of these inhibitors, furthermore, affected baseline ICP. These results suggest that NO generated via both neuronal and inducible NOS at the HF may participate in negative feedback regulation of penile erection.


Existing instruments for assessing physician communication skills: are they valid in a computerized setting?
This study aims to highlight the differences in physicians' scores on two communication assessment tools: the SEGUE and an EMR-specific communication skills checklist. The first tool ignores the presence of the EMR in the exam room and the second, though not formally validated, rather focuses on it. We use the Wilcoxon Signed Ranks Test to compare physicians' scores on each of the tools during 16 simulated medical encounters that were rated by two different raters. Results show a significant difference between physicians' scores on each tool (z=-3.519, p<0.05 for the first rater, and z=-3.521, p<0.05 for the second rater), while scores on the EMR-specific communication skills checklist were significantly and consistently lower. These results imply that current communication assessment tools that do not incorporate items that are relevant for communication tasks during EMR use may produce inaccurate results. We therefore suggest that a new instrument, possibly an extension of existing ones, should be developed and empirically validated.


Toxic effect of Cadmium found in eyeliner to the eye of a 21 year old Saudi woman: A case report.
To raise the issue of increased use of traditional medicine while the Tertiary care hospitals are available to provide the appropriate care for each clinical condition. Eyeliner (Kohl) is an Arabic word denoting a fine powder with a texture and appearance similar to mascara. It is usually worn on the lid margins or inside the conjunctival sac by Middle and Far Eastern and in East Africans populations for different purposes like beauty or religious and as a treatment for many eye diseases. We report a case of a lady who put traditional locally prepared eyeliner in her eye that resulted in severe corneal edema and faint scaring. On toxicology analysis it was discovered to contain toxic levels of Cadmium (Cd) and Lead (Pb). Cd is a heavy toxic metal like Pb but has never been reported as a component of eyeliners. The most likely possible cause of the corneal clinical picture in our case is due to the toxic effect of Cd found in the traditional eyeliner (Kohl) used in Saudi Arabia.


Preparation of pyrenebutyric acid bonded silica stationary phases for the application to the separation of fullerenes.
A novel immobilization method was proposed for the preparation of pyrenebutyric acid-bonded silica (PYB-silica) stationary phases. The pyrene moiety was grafted to silica gel through spacers of aminoalkyl silanes. The HPLC separation of C60, C70 and higher fullerenes on the new pyrenebutyric acid-bonded silica stationary phases was also studied. Based on the temperature effect, the intermolecular interaction between stationary phases and solutes and the retention mechanism were discussed. The results of column loading capacity test demonstrated the potential for the separation of fullerenes in large amounts on the PYB-silica stationary phases.


Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.
Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.


Risk of Rebleeding in Patients Suffering From Ruptured Brain Arteriovenous Malformations Undergoing Subacute Treatment: A Single-Center Series and Systematic Review of the Literature.
The optimal timing for treatment of ruptured brain arteriovenous malformation (BAVM) is still controversial. The present study aims to determine safety of subacute BAVM management in clinically stable patients by identifying the rate of rebleeding. Patients presenting from 2000 to 2018 with ruptured BAVM who were scheduled for BAVM treatment at least 4 weeks after initial hemorrhage were included in the present study. After neurological rehabilitation of the patient and decreased hemorrhage-induced brain swelling, subacute treatment for the ruptured BAVM was carried out. Primary outcome of the present series was defined as treatment failure resulting from rehemorrhage caused by the ruptured BAVM in patients previously labeled eligible for subacute BAVM treatment. Additionally, we performed a systematic review of the contemporary peer-reviewed literature concerning treatment strategy in patients with ruptured BAVM. Fifty-five patients suffering from ruptured BAVM were considered eligible for subacute BAVM treatment at our institution. No patient suffered from early rebleeding before definitive BAVM treatment in our institutional group. Our own patient data were then pooled with data from the literature, resulting in 166 patients suffering from ruptured BAVM who underwent subacute BAVM treatment. Of these, 1 patient (0.6%) suffered from rehemorrhage during the recovery period 130 days after initial BAVM rupture. The present series and systematic review revealed a rehemorrhage rate of 0.6% in patients suffering from ruptured BAVM who underwent subacute treatment. Therefore, subacute treatment of patients with ruptured BAVM seems safe after application of rigorous treatment algorithms to sort out patients with higher risk for rehemorrhage.


Continuous increase of the antimicrobial resistance among gram-negative pathogens causing bacteremia: a nationwide surveillance study by the Korean Network for Study on Infectious Diseases (KONSID).
Antimicrobial susceptibility data for all microorganisms isolated from blood culture were collected from 13 institutions in Korea from June to September 2011. Data were compared with our previous studies performed during 2006-2007 and 2008. The prevalence of MRSA in 2011 has rebounded to 63.7% after a slight decrease in 2008. Vancomycin-resistant Enterococcus faecium declined to 24.1%. The resistance rates of Acinetobacter baumannii to imipenem and meropenem increased from 25.4% and 28.8% to 55.4% and 37.5%, respectively. Ciprofloxacin resistance of Escherichia coli has increased from 23.9% to 30.8%. The resistance rate of Klebsiella pneumoniae to ciprofloxacin has increased from 17.7% to 26.5%. Extended spectrum beta-lactamase-producing E. coli and K. pneumoniae have also seen increased levels of resistance, from 8.6% to 18.4% and 13.6% to 28.5%, respectively. An overall increase in antimicrobial resistance among gram-negative pathogens has been observed. Continued surveillance and intervention to slow the propagation of resistance are necessary.


Development of healthy gluten-free crackers from white and brown tef (Eragrostis tef Zucc.) flours.
This study evaluated the effect of inclusion of two types of tef flours (white and brown) at different levels (25, 50 and 100 %, total flour) on the nutritional (proximal and mineral composition), in vitro bioactive (antioxidant capacity and starch digestibility) and sensory properties of rice-tef crackers. The aim was to formulate a gluten-free product with nutritional and healthy benefits, and acceptable for consumers. Results showed than crackers enriched with white tef had a significant (p ≤ 0.05) higher concentration of all the minerals tested, except for calcium and manganese, compared to brown tef. Iron content of white tef was almost twice that of brown tef, and copper and magnesium increased from 0.12 mg/100 g and 39.2 mg/100 g in control crackers to 0.56 mg/100 g and 197 mg/100 g in white tef crackers (WT 100%), respectively. Moreover, white tef flour and crackers showed significantly higher antioxidant activity than rice or brown tef counterparts. Formulation with tef flour significantly contributed to a reduction of the rapidly available glucose and rapidly digestible starch of crackers.


Photodistributed erythema multiforme.
Although the existence of photodistributed erythema multiforme has been recognized for years, few cases have been described to date. It is an uncommon, and probably underdiagnosed, skin disorder that can affect individuals of both sexes and all ages. It has been associated with drugs, reactivation of herpes simplex virus infection, and polymorphous light eruption. A diagnosis is made on the basis of history, physical examination, histology, and phototesting. The condition runs a benign, self-limiting course but patients may experience outbreaks for several years if the causative agent is not eliminated. It is treated symptomatically and patients are advised to avoid triggers and excessive sun exposure.


The effects of in vitro application of purified botulinum neurotoxin at mouse motor nerve terminals.
1. Purified botulinum neurotoxin type A (10 nM) was applied in vitro to mouse diaphragm muscles. Intracellular micro-electrode recordings were made continuously in single fibres. 2. This treatment reduced end-plate potential (e.p.p.) amplitudes with a time to half-maximal effect of about 75 min at 22-25 degrees C. E.p.p. rise-times remained fast and unaffected by the toxin. 3. Miniature end-plate potential (m.e.p.p.) frequency was reduced by the toxin to less than 5% of control frequency, and followed a similar time course to the block of e.p.p. amplitudes. The m.e.p.p. rise-time and coefficient of variation (c.v.) of m.e.p.p. amplitude distributions both increased, but the time course of these increases lagged significantly behind the change in frequency. 4. A population of slow rise-time m.e.p.p.s was present in controls at low frequency. This population was found to be unaffected by the toxin. 5. The above-detailed in vitro changes could be explained by the toxin acting by a single common mechanism to inhibit the release process underlying both fast rise-time m.e.p.p.s and e.p.p.s. A distinct release process, which leads to slow rise-time m.e.p.p.s, was unaffected by the toxin.


Prevention of Cardiac Surgery-Associated Acute Kidney Injury: A Review of Current Strategies.
Acute kidney injury is a common and often severe postoperative complication after cardiac surgery, and is associated with poor short-term and long-term outcomes. Numerous randomized controlled trials have been conducted to investigate various strategies for prevention of cardiac surgery-associated acute kidney injury. Unfortunately, most trials that have been conducted to date have been negative. However, encouraging results have been demonstrated with preoperative administration of corticosteroids, leukocyte filtration, and administration of inhaled nitric oxide intraoperatively, and implementation of a Kidney Disease: Improving Global Outcomes bundle of care approach postoperatively. These findings require validation in large, multicenter trials.


Early gallbladder carcinoma associated with primary sclerosing cholangitis and ulcerative colitis.
Patients troubled with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at high risk for cholangiocarcinoma, whereas cancer of the gallbladder (GBC) is rarely reported to develop in that population. A Japanese man aged 62 years with a 14-year history of PSC and UC had been found to have a protruding lesion of the gallbladder by screening sonography. The preoperative examination suggested the lesion to be GBC at an early stage. Pathology examination after cholecystectomy proved that the lesion was papillary adenocarcinoma localized in the mucosal layer. Although the prognosis of GBC is poor, the outcome of cholecystectomy against early GBC is relatively good. Early detection of the tumor is required for a better prognosis of patients with GBC. According to the review of the literature, PSC and UC patients are regarded as a high-risk group not only for cholangiocarcinoma but also GBC. It is advocated that clinicians perform repeated radiographic examinations including sonography for patients with PSC and UC even if the diseases are being controlled.


Pharmacokinetic aspects of digoxin in patients with terminal renal failure. IV. Clinical implications of own observations with a recent review of literature.
Digoxin dosage regimens for patients on chronic intermittent hemodialysis (CIH) were calculated from pharmacokinetic data of digoxin in these patients between the during hemodialyses. Especially when a maximal digitalisation is not necessary an administration of 0.125 mg digoxin only on days without hemodialysis will be adequate. The regimens should be considered as a suitable starting-point in therapy as individual differences in bioavailability, apparent volume of distribution. clearance and sensitivity may necessitate an individual correction. The place of hemodialysis in the management of severe intoxications will also be discussed. Besides, it is advised to use digoxin instead of digitoxin in patients on CIH.


Reoviruses and the host cell.
Reovirus infection of target cells can perturb cell cycle regulation and induce apoptosis. Differences in the capacity of reovirus strains to induce cell cycle arrest at G1 and G2/M have been mapped to the viral S1 genome segment, which also determines differences in the ability of reovirus strains to induce apoptosis and to activate specific mitogen-activated protein kinase (MAPK) cascades selectively. Reovirus-induced apoptosis involves members of the tumor necrosis factor (TNF) superfamily of death receptors and is associated with activation of both death receptor- and mitochondrial-associated caspases. Reovirus infection is also associated with the activation of a variety of transcription factors, including nuclear factor (NF)-kappaB. Junctional adhesion molecule (JAM) has recently been identified as a novel reovirus receptor. Reovirus binding to JAM appears to be required for induction of apoptosis and activation of NF-kappaB, although the precise cellular pathways involved have not yet been identified.


Magnesium Oxide (MgO) pH-sensitive Sensing Membrane in Electrolyte-Insulator-Semiconductor Structures with CF4 Plasma Treatment.
Magnesium oxide (MgO) sensing membranes in pH-sensitive electrolyte-insulator-semiconductor structures were fabricated on silicon substrate. To optimize the sensing capability of the membrane, CF4 plasma was incorporated to improve the material quality of MgO films. Multiple material analyses including FESEM, XRD, AFM, and SIMS indicate that plasma treatment might enhance the crystallization and increase the grain size. Therefore, the sensing behaviors in terms of sensitivity, linearity, hysteresis effects, and drift rates might be improved. MgO-based EIS membranes with CF4 plasma treatment show promise for future industrial biosensing applications.


Needs and Satisfaction Analysis of Patients and Referring Physicians in an Outpatient Cataract Service.
To ensure efficient use of resources within outpatient services, constant patient flow is vital. This can be achieved by addressing the wishes and needs of all relevant stakeholders. The present study aims to show how the needs and present satisfaction of patients and referring physicians can be determined in the context of an outpatient cataract service. It presents the conclusions that can be drawn for the design of the service. To assess needs and satisfaction, we developed a patient questionnaire and a referring physician questionnaire. Promoters and detractors for referral were identified following the concept of the net promoter score, a market research instrument. 339 (38%) patients and 26 (45%) referring physicians of the main referring group answered the questionnaires. The most important characteristics for referring physicians were quality of treatment, patient satisfaction, and communication in case of queries as well as speed of sending the doctor's letter. When making their decision on a cataract centre, the patients prioritised professional reputation, previous experience with the clinic, and recommendation of their ophthalmologist as well as customary appointment scheduling. The two groups influence each other's recommendation or choice. Simultaneous analysis of patients and referring physicians is therefore essential. Overall, patients and referring physicians are highly satisfied with the cataract service of the university medical centre. Beyond that, however, various potentials for improvement could be identified. In summary, this report describes a comprehensive approach to assess needs and satisfaction of patients and referring physicians in an outpatient clinic trying to sustainably improve patient care.


Mechanism and Consequences of The Impaired Hif-1α Response to Hypoxia in Human Proximal Tubular HK-2 Cells Exposed to High Glucose.
Renal hypoxia and loss of proximal tubular cells (PTC) are relevant in diabetic nephropathy. Hypoxia inhibits hypoxia-inducible factor-1α (HIF-1α) degradation, which leads to cellular adaptive responses through HIF-1-dependent activation of gene hypoxia-responsive elements (HRE). However, the diabetic microenvironment represses the HIF-1/HRE response in PTC. Here we studied the mechanism and consequences of impaired HIF-1α regulation in human proximal tubular HK-2 cells incubated in hyperglycemia. Inhibition at different levels of the canonical pathway of HIF-1α degradation did not activate the HIF-1/HRE response under hyperglycemia, except when proteasome was inhibited. Further studies suggested that hyperglycemia disrupts the interaction of HIF-1α with Hsp90, a known cause of proteasomal degradation of HIF-1α. Impaired HIF-1α regulation in cells exposed to hyperglycemic, hypoxic diabetic-like milieu led to diminished production of vascular endothelial growth factor-A and inhibition of cell migration (responses respectively involved in tubular protection and repair). These effects, as well as impaired HIF-1α regulation, were reproduced in normoglycemia in HK-2 cells incubated with microparticles released by HK-2 cells exposed to diabetic-like milieu. In summary, these results highlight the role of proteasome-dependent mechanisms of HIF-1α degradation on diabetes-induced HK-2 cells dysfunction and suggest that cell-derived microparticles may mediate negative effects of the diabetic milieu on PTC.


Characteristic Immunohematological Parameters of Migratory (Vespertilio murinus Linnaeus, 1758) and Resident (Myotis dasycneme Boie, 1825) Bat Species of the Ural Fauna.
The results of the first comparative analysis of hematological parameters of bats from natural populations of the Ural region are presented: the pond bat (Myotis dasycneme Boie, 1825), which is a resident species, and the two-colored bat (Vespertilio murinus Linnaeus, 1758), which is a migratory species. Significant differences in the content of white blood cells (p = 0.05), red blood cells and platelets (p = 0.001) were shown. Interspecific differences were found in the leukograms of the studied bats both in the content of granulocytes (p = 0.04) and agranulocytes (p = 0.05). Migrating V. murinus are characterized by a significant contribution of the nonspecific protective system of the blood (54.9%) to the adaptive reactions of the body. In the pond bat, a pronounced lymphocytic profile (58.5%) indicates the activation of acquired adaptive immunity. Two-colored bats in comparison with pond bats are characterized by a higher level of innate immunity.


Robotic-assisted systems for the safe and reliable treatment of femoral neck fractures: retrospective cohort study.
Robots are being used in a wide range of surgical procedures. However, in clinical practice, the efficacy of orthopedic robotic-assisted treatment of femoral neck fractures is still poorly reported, particularly in terms of screw placement accuracy, femoral neck fracture healing rates and postoperative functional recovery. Moreover, there is a lack of comparative analysis between robot-assisted surgery and traditional surgical approaches. The purpose of this study was to compare the clinical outcomes of patients with femoral neck fractures treated with TiRobot-assisted hollow screw fixation with those of patients with femoral neck fractures treated with traditional surgical approaches. This study included 112 patients with femoral neck fracture who were treated from March 2017 to October 2021 with percutaneous hollow screw internal fixation. These included 56 cases in the TiRobot-assisted surgery group and 56 cases in the standard surgery group. After at least 1 year of follow-up, the treatment outcomes of the two groups were compared, including the amount of intraoperative bleeding, the duration of intraoperative fluoroscopy, the number of guide pin positioning adjustments, the length of hospital stay, the accuracy rate of screw placement, the final Harris Hip Score, the fracture healing rate, and the rate of femoral head necrosis. Statistical analysis software was used to process and analyze the result. The TiRobot-assisted group had a statistically significant improvement over the control group in terms of intraoperative bleeding, the duration of intraoperative fluoroscopy, the number of guide pin positioning adjustments, length of hospital stay, accuracy of screw placement and incidence of femoral head necrosis (P < 0.05). There was no statistically significant difference in time to surgery, final Harris hip score and fracture healing rate (P > 0.05). This study shows that TiRobot-assisted surgery has the advantages of short hospital stay, high safety, minimally invasive, high success rate of nail placement, and can reduce the amount of intraoperative radiation and the incidence of femoral head necrosis, thus achieving satisfactory clinical outcomes, and is worthy of clinical promotion.


Usefulness of the laser-cut, fully covered, self-expandable metallic stent for endoscopic ultrasound-guided hepaticogastrostomy.
Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has many associated adverse events. We evaluated the clinical efficacy and safety of the laser-cut, fully covered, self-expandable metallic stent (FCSEMS) for this procedure. This single-center, retrospective study included cases where EUS-HGS with a laser-cut FCSEMS was performed for malignant biliary obstruction. Technical and clinical success, time to recurrent biliary obstruction (TRBO), procedure time, adverse events, and re-interventions were evaluated. There were 95 eligible cases. Technical and clinical success rates were 100.0% and 95.8%, respectively. Median TRBO was 398 days. RBO causes were hyperplasia (7.4%), debris (3.2%), and migration (4.2%). Adverse events occurred in nine cases (9.5%). Non-occlusion and focal cholangitis occurred in four cases (4.2%) each. Nineteen patients (20%) underwent combined EUS-HGS (CH) procedures: antegrade stenting, bridging methods, plastic stent anchoring in SEMS, and EUS-hepaticoduodenostomy. The solely EUS-HGS (SH) group had significantly longer median TRBO than the CH group (398 vs 246 days, P = .04). There were no significant differences in adverse events between the two groups. Re-intervention was performed in 29 cases (technical success rate: 100.0%). Laser-cut FCSEMS can be safely placed in the bile duct and easily applied during re-intervention, making it useful in EUS-HGS.


Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys.
Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(+)/tumor necrosis factor alpha(+) (TNF-alpha(+)) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2(+) (IL-2(+)) and polyfunctional IFN-gamma(+)/TNF-alpha(+)/IL-2(+) T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8(+) and CD4(+) T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.


High temperature aqueous ammonia pretreatment and post-washing enhance the high solids enzymatic hydrolysis of corn stover.
Aqueous ammonia pretreatment was optimized and the limiting factors in high solids enzymatic hydrolysis were assessed. The recommended pretreatment condition to achieve high enzymatic yield was: 180 °C, 20% (w/w) ammonia, 30 min, and 20% solids content. FT-IR and GC-MS results indicated that most of the lignin was degraded to soluble fragments after pretreatment. The pretreated solids after post-washing showed higher enzymatic digestibility at high solids loading than that without washing. The washed solids required lower cellulase and xylanase dosage than unwashed solids to achieve high sugar yield. Enzymatic conversions were declined with the increased solids loading of pretreated solids, pretreated-washed solids, and filter papers. The results indicated that solids loading in enzymatic hydrolysis was an important factor affecting sugar yield. The increasing concentration of glucose and ligno-phenolics mainly inhibited the enzymatic hydrolysis of aqueous ammonia pretreated corn stover.


[Colorectal cancer and preoperative geriatric assessment].
With the ageing of the population and the increase in the incidence of cancer in the population over 75 years of age, a partnership between geriatricians and oncologists is becoming necessary to optimise the management of these patients. There is great variability in the profiles of elderly patients and age cannot be the only criterion of the decision making. Thus, it is necessary to identify patients who will benefit from an in-depth geriatric assessment (IGA) and the G8 screening tool used in oncology consultations allows to do so. The EGA offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status of the person, and has been shown to have prognostic value for survival and relevance in guiding treatment choices.


Weathering alters the profile of trace metals and organic compounds in leachates and bioavailability extracts from microplastics of trail running shoes.
Microplastics (MPs) from rubber outsoles of trail running shoes may contribute significantly to contamination in protected areas. In the natural environment, weathering processes can damage MP molecular structure and alter the mobility of inorganic and organic compounds used as additives in rubber. In this study, we characterised changes in the surface morphology, functional groups, and thermal stability of MPs weathered on and below the soil surface over 12 weeks, and analysed inorganic and organic additives in leachates (0.01M CaCl2) and bioaccessibility extracts (ethyl acetate). Weathering conditions included UVC irradiation at 25 °C and 80% soil moisture. Microplastics on the soil surface exhibited cracking, fragmentation, and increased extractability of zinc, sulphur, titanium and fatty acids. Microplastics below the soil surface were not significantly physically or chemically altered, however zinc leachability increased following extended weathering by up to 155%. Bioaccessibility of thiol, aromatic and cyclic organic additives decreased from both surface and sub-surface MPs over the 12 week weathering period, but there was evidence of an increase in transformation by-products. Microplastic toxicity may be significantly altered by environmental conditions and MP weathering. It is critical ecotoxicological studies use weathered MPs to assess impacts on rare and endemic species found in protected spaces.


Okra (Abelmoschus esculentus) in a refugee context in East Africa: Kitchen gardening helps with mineral provision.
Kitchen gardening is considered a way to reconnect with agriculture and complement the cereal-based relief food offered to refugees in East Africa. This work aimed at profiling mineral content of okra in four refugee camps and settlements located in Ethiopia and Uganda and its contribution to adequate intake (AIs) or recommended dietary allowances (RDAs) for young children and pregnant and lactating women (PLW). The study also evaluated the applicability of portable X-ray fluorescence (PXRF) as compared with inductively coupled plasma mass spectrometry (ICP-MS) for mineral profiling of okra powder samples. The contents of minerals (mg kg-1) from the ICP-MS readings were in the following ranges: K (14,385-33,294), Ca (2610-14,090), P (3178-13,248), Mg (3896-7986), Cu (3.81-19.3), Fe (75.7-1243), Zn (33-141) and Mn (23.1-261). Regardless of geographic origin, at low-end consumption probability (17 g day-1 for young children and 68 g day-1 for PLW), okra could contribute ˂ 15% (2.7-12.9%) AI for macro-minerals (K and Ca). In addition, the contributions to RDA values for Fe and Zn, elements of known public health interest, ranged from 4.5 to 34.7% for young children. Interestingly, regression lines revealed strong agreement between ICP-MS and PXRF readings for Mn and Zn, with R2 values > 0.91. This information is useful in support of nutrition-sensitive kitchen gardening programs through scaling culturally important crops in refugee settings. The online version contains supplementary material available at 10.1007/s42452-021-04898-6.


Epidemiology of traumatic brain injury in children receiving intensive care in the UK.
To describe the epidemiology of children with traumatic brain injury (TBI) admitted to paediatric intensive care units (PICUs) in the UK. Prospective collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Eire between February 2001 and August 2003. The UK prevalence rate for children (0-14 years) admitted to intensive care with TBI between February 2001 and August 2003 was 5.6 per 100,000 population per year (95% Poisson exact confidence intervals 5.17 to 6.05). Children admitted to PICUs with TBI were more deprived than the population as a whole (mean Townsend score for TBI admissions 1.19 v 0). The commonest mechanism of injury was a pedestrian accident (36%), most often occurring in children over 10. There was a significant summer peak in admissions in children under 10 years. Time of injury peaked in the late afternoon and early evening, a pattern that remained constant across the days of the week. Injuries involving motor vehicles have the highest mortality rates (23% of vehicle occupants, 12% of pedestrians) compared with cyclists (8%) and falls (3%). In two thirds of admissions (65%) TBI was an isolated injury. TBI in children requiring intensive care is more common in those from poorer backgrounds who have been involved in accidents as pedestrians. The summer peak in injury occurrence for 0-10 year olds and late afternoon timing give clear targets for community based injury prevention.


Aptamer-capture based assays for human neutrophil elastase.
Human neutrophil elastase (HNE) is a multifunctional serine protease, involved in infection defense, inflammatory process regulation, and physiopathological processes of several diseases. We developed aptamer-capture based assays for human neutrophil elastase with different substrates and solid supports to meet different demands, such as simplicity, sensitivity, and high throughput. Aptamers against HNE were immobilized on magnetic beads or microplates as affinity ligands to capture HNE, and then the enriched HNE catalyzed the conversion of chromogenic substrates or fluorogenic substrates to products. The measurement of the generated enzymatic products enabled the final detection of HNE. In the assay using chromogenic substrates and aptamer modified magnetic beads, 0.4 pM HNE could be successfully detected. The sensitivity of the assay was further improved by using fluorogenic substrates, and a detection limit of HNE at 20 fM was achieved. The use of aptamer-coated microplates instead of aptamer modified magnetic beads in the assays also allowed the sensitive detection of HNE, offering advantages in fast sample handling and measurement. The established assays for HNE displayed good specificity, and proteins including serum albumin, transferrin, immunoglobulin G, thrombin, porcine pancreatic elastase, trypsin, proteinase K, chymotrypsin, lysozyme, cathepsin G, and proteinase 3 did not cause interference in the detection of HNE.


Tight binding of bulky fluorescent derivatives of adenosine to the low affinity E2ATP site leads to inhibition of Na+/K+-ATPase. Analysis of structural requirements of fluorescent ATP derivatives with a Koshland-Némethy-Filmer model of two interacting ATP sites.
A Koshland-Némethy-Filmer model of two cooperating ATP sites has previously been shown to explain the kinetics of inhibition of Na+/K+-ATPase (EC 188.8.131.52) by dansylated ATP (Thoenges, D., and Schoner, W. (1997) J. Biol. Chem. 272, 16315-16321). The present work demonstrates that this model adequately describes all types of interactions and kinetics of a number of ATP analogs that differ in their cooperativity of the high and low affinity ATP binding sites of the enzyme. 2',3'-O(2,4,6-trinitrophenyl)ATP binds in a negative cooperative way to the E1ATP site (Kd = 0.7 microM) and to the E2ATP site (Kd = 210 microM), but 3'(2')-O-methylanthraniloyl-ATP in a positive cooperative way with a lower affinity to the E1ATP binding site (Kd = 200 microM) than to the E2ATP binding site (Kd = 80 microM). 3'(2')-O(5-Fluor-2,4-dinitrophenyl)-ATP, however, binds in a noncooperative way, with equal affinities to both ATP binding sites (Kd = 10 microM). In a research for the structural parameters determining ATP site specificity and cooperativity, we became aware that structural flexibility of ribose is necessary for catalysis. Moreover, puckering of the ring atoms in the ribose is essential for the interaction between ATP sites in Na+/K+-ATPase. A number of derivatives of 2'(3')-O-adenosine with bulky fluorescent substitutes bind with high affinity to the E2ATP site and inhibit Na+/K+-ATPase activity. Evidently, an increased number of interactions of such a bulky adenosine with the enzyme protein tightens binding to the E2ATP site.


Differential effect of the GPIIb/IIIa antagonist orbofiban on human platelet aggregate formation in vitro.
Platelet microaggregates have been demonstrated in the systemic circulation of patients with atherosclerotic cardiovascular diseases. Glycoprotein IIb/IIIa antagonists have been reported to play roles in platelet activation, which may be associated with pro-thrombotic events. We report the effect of the orally active GPIIb/IIIa antagonist, orbofiban, on human platelet microaggregate formation in vitro. Laser light scatter (LSS) technology was used to monitor small, medium and large platelet aggregates formed in platelet-rich plasma in response to ADP or thrombin receptor activating peptide (TRAP)-6. ADP at 0.5 microM induced only small platelet aggregates that were prevented by orbofiban in a concentration-dependent manner. Likewise, orbofiban dissolved small aggregates after their formation. In marked contrast, in the presence of strong agonist stimulation (20 microM ADP or 3 microM TRAP-6) which generated primarily large platelet aggregates, orbofiban blocked the large aggregates while significantly augmenting small aggregates by three- to sixfold. The data suggest that GPIIb/IIIa antagonists do not induce platelet microaggregation directly but may augment small platelet microaggregate formation indirectly at conditions of strong stimuli. The percentage of the microaggregate population expressing P-selectin remained the same in the presence of orbofiban, indicating that these small microaggregates remain activated, although the mean intensity of expression was diminished, possibly reflecting the reduced size of the particles or density of P-selectin molecules. In summary, an increase in small platelet microaggregates might have contributed to pro-thrombotic events in orbofiban-treated patients.


Systematic experiments to establish the spatial distribution of physiologically effective stimuli of unidentified nature.
Many persons react to a kind of external agent by unconscious muscular reactions if they move across a place where this agent is supposed to be particularly active. Such places normally coincide with geological discontinuities, such as water veins, mineral ores. Practitioners of this art of detecting claim that the reaction patterns on different levels above ground are identical as vertical projections of the source pattern, this without perceptible attenuation. In some cases the supposed source was believed to have been found up to several hundred meters below ground surface. The statement of perpendicular propagation, which is the subject of this paper, is of prime importance for an approach towards understanding and all kinds of prospecting.


Correlations between chemical bonding and magnetic exchange interactions: synthesis, crystal structures, and magnetic properties of the new family RE2AlGe2 (RE = Tb-Tm, Lu).
Six new rare-earth metal germanides with general formula RE2Al(1-x)Ge(2+x) (RE = Tb-Tm, Lu; 0.13(2) ≤ x ≤ 0.37(2)) have been synthesized by direct fusion of the corresponding elements. Their structures have been established by single-crystal diffraction to crystallize with the orthorhombic space group Immm (no. 74), adopting the W2CoB2 structure type. The Al and Ge atoms are arranged in alternating planar layers, made of rhombic- and hexagonal-fragments. The rare-earth metal substructure consists of puckered four-connected nets. Electronic structure calculations support the coloring of the Ge and Al sites and account for the existence of a small homogeneity range. DC magnetization measurements for all specimens are also presented; based on the RKKY and mean-field theories for antiferromagnets, relationships between the chemical bonding and exchange interactions are discussed.


A Kelch Domain-Containing F-Box Coding Gene Negatively Regulates Flavonoid Accumulation in Muskmelon.
The flavonoids are phenylpropanoid-derived metabolites that are ubiquitous in plants, playing many roles in growth and development. Recently, we observed that fruit rinds of yellow casaba muskmelons (Cucumis melo 'Inodorous Group') accumulate naringenin chalcone, a yellow flavonoid pigment. With RNA-sequencing analysis of bulked segregants representing the tails of a population segregating for naringenin chalcone accumulation followed by fine mapping and genetic transformation, we identified a Kelch domain-containing F-box protein coding (CmKFB) gene that, when expressed, negatively regulates naringenin chalcone accumulation. Additional metabolite analysis indicated that downstream flavonoids are accumulated together with naringenin chalcone, whereas CmKFB expression diverts the biochemical flux toward coumarins and general phenylpropanoids. These results show that CmKFB functions as a posttranscriptional regulator that diverts flavonoid metabolic flux.


Guanosine promotes B16F10 melanoma cell differentiation through PKC-ERK 1/2 pathway.
Malignant melanoma is one of the most lethal cancers. Nowadays, several anti-melanoma therapies have been employed. However, the poor prognosis and/or the increased toxicity of those treatments clearly demonstrate the requirement of searching for new drugs or novel combined chemotherapeutic protocols, contemplating both effectiveness and low toxicity. Guanosine (Guo) has been used in combination with acriflavina to potentiate the latter's antitumor activity, through still unknown mechanisms. Here, we show that Guo induces B16F10 melanoma cell differentiation, attested by growth arrest, dendrite-like outgrowth and increased melanogenesis, and also reduced motility. A sustained ERK 1/2 phosphorylation was observed after Guo treatment and ERK inhibition led to blockage of dendritogenesis. Intracellular cyclic AMP was not involved in ERK activation, since its levels remained unchanged. Protein kinase C (PKC), in contrast to phospholipase C (PLC), inhibition completely prevented ERK activation. While the classical melanoma differentiation agent forskolin activates cAMP-PKA-Raf-MEK-ERK pathway in B16F10 cells, here we suggest that a cAMP-independent, PKC-ERK axis is involved in Guo-induced B16F10 differentiation. Altogether, our results show that Guo acts as a differentiating agent, with cytostatic rather than cytotoxic properties, leading to a decreased melanoma malignancy. Thus, we propose that Guo may be envisaged in combination with lower doses of conventional anti-melanoma drugs, in an attempt to prevent or diminish their adverse effects.


Exploring quality improvement for diabetes care in First Nations communities in Canada: a multiple case study.
Indigenous peoples in Canada experience higher rates of diabetes and worse outcomes than non-Indigenous populations in Canada. Strategies are needed to address underlying health inequities and improve access to quality diabetes care. As part of the national FORGE AHEAD Research Program, this study explores two primary healthcare teams' quality improvement (QI) process of developing and implementing strategies to improve the quality of diabetes care in First Nations communities in Canada. This study utilized a community-based participatory and qualitative case study methodology. Multiple qualitative data sources were analyzed to understand: (1) how knowledge and information was used to inform the teams' QI process; (2) how the process was influenced by the context of primary care services within communities; and (3) the factors that supported or hindered their QI process. The findings of this study demonstrate how teams drew upon multiple sources of knowledge and information to inform their QI work, the importance of strengthening relationships and building relationships with the community, the influence of organizational support and capacity, and the key factors that facilitated QI efforts. This study contributes to the ongoing calls for research in understanding the process and factors affecting the implementation of QI strategies, particularly within Indigenous communities. The knowledge generated may help inform community action and the future development, implementation and scale-up of QI programs in Indigenous communities in Canada and globally.


Prediction of biological development effects on drag forces of ceramic hull coating using Reynolds-averaged Navier-Stokes-based solver.
Ships in service feature surfaces that exhibit biofouling, which alters the hydrodynamics of the vessels, thus affecting their normal displacement and significantly increasing their fuel consumption. The application of three types of ceramic coatings as ecological, effective and durable alternatives to commercial silicone-based marine coatings is investigated in this study. Three different ceramic glazes and two control commercial paints are analysed in an actual environment during 20 months of exposure to simulate the navigation conditions such that growth and roughness data can be obtained and then applied to computational fluid dynamics (CFD) software using an open-source Reynolds-averaged Navier-Stokes solver. The CFD results are validated under smooth hull conditions with a full-scale Kriso Container Ship (KCS) model and with different levels of hull roughness. The developed approach shows that the drag in hulls coated with conventional paint is 19% greater than that in hulls with ceramic coating.


Modification of whey protein isolate by ultrasound-assisted pH shift for complexation with carboxymethylcellulose: Structure and interfacial properties.
The application of whey protein isolate (WPI) is limited because of its compact spherical structure. In this study, ultrasound-assisted pH shift was employed to modify WPI for complexation with carboxymethylcellulose (CMC). The foaming and emulsifying properties of WPI/CMC complexes were investigated. The results demonstrate that the pretreatment of ultrasound-assisted pH 12 shift increased the content of free sulfhydryl groups from 16.5 μmol/g to 34.7 μmol/g and enhanced protein hydrophobicity from 311.4 to 370.6 (p < 0.05). Compared to the complexes formed by untreated WPI and CMC, the complexes pretreated with ultrasound-assisted pH 12 shift had a smaller size of 293.4 nm and a more uniform distribution. Furthermore, WPI/CMC complexes pretreated by ultrasound-assisted pH 12 shift exhibited higher emulsifying activity and emulsion stability index, which were increased by 8.9 % and 42.6 % respectively, in comparison with the control group (p < 0.05). A positive correlation was found between the surface hydrophobicity of WPI and emulsifying activity of WPI/CMC complexes. Ultrasound-assisted pH 2 shift improved the foaming capacity of complexes by 28.3 % over the control (p < 0.05). All the results indicate that the interfacial properties of WPI/CMC complexes can be improved significantly by the combination of pH shift and ultrasound.


Upregulation of the parietal cortex improves freezing of gait in Parkinson's disease.
BACKGROUND The posterior parietal cortex (PPC) is a key brain area for visuospatial processing and locomotion. It has been repetitively shown to be involved in the neural correlates of freezing of gait (FOG), a common symptom of Parkinson's disease (PD). However, current neuroimaging modalities do not allow to precisely determine the role of the PPC during real FOG episodes. OBJECTIVES The purpose of this study was to modulate the PPC cortical excitability using repetitive transcranial magnetic stimulation (rTMS) to determine whether the PPC contributes to FOG or compensates for dysfunctional neural networks to reduce FOG. METHODS Fourteen participants with PD who experience freezing took part in a proof of principle study consisting of three experimental sessions targeting the PPC with inhibitory, excitatory, and sham rTMS. Objective FOG outcomes and cortical excitability measurements were acquired before and after each stimulation protocol. RESULTS Increasing PPC excitability resulted in significantly fewer freezing episodes and percent time frozen during a FOG-provoking task. This reduction in FOG most likely emerged from the trend in PPC inhibiting the lower leg motor cortex excitability. CONCLUSION Our results suggest that the recruitment of the PPC is linked to less FOG, providing support for the beneficial role of the PPC upregulation in preventing FOG. This could potentially be linked to a reduction of the cortical input burden on the basal ganglia prior to FOG. Excitatory rTMS interventions targeting the PPC may have the potential to reduce FOG.


Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone.
Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG. The aim of our study was to comprehensively document the stem-like capacities of seven in-use pediatric glioma cell cultures (Res259, UW479, SF188, KNS42, SF8628, HJSD-DIPG-007 and HJSD-DIPG-012) using parallel in vitro assays assessing stem cell-related protein expression, multipotency, self-renewal and proliferation/quiescence, and in vivo investigation of their tumorigenicity and invasiveness. Data obtained from in vitro experiments revealed glioma subtype-dependent expression of stem cell-related markers and varying abilities for differentiation, self-renewal, and proliferation/quiescence. Among tested cultures, DMG H3-K27 altered cultures displayed a particular pattern of stem-like markers expression and a higher fraction of cells with self-renewal potential. Four cultures displaying distinctive stem-like profiles were further tested for their ability to initiate tumors and invade the brain tissue in mouse orthotopic xenografts. The selected cell cultures all showed a great tumor formation capacity, but only DMG H3-K27 altered cells demonstrated a highly infiltrative phenotype. Interestingly, we detected DMG H3-K27 altered cells relocated in the subventricular zone (SVZ), which has been previously described as a neurogenic area, but also a potential niche for brain tumor cells. Finally, we observed an SVZ-induced phenotypic modulation of the glioma cells, as evidenced by their increased proliferation rate. In conclusion, this study recapitulated a systematic stem-like profiling of various pediatric glioma cell cultures and call to a deeper characterization of DMG H3-K27 altered cells nested in the SVZ.


Further evidence that substance P partly mediates the action of cholecystokinin octapeptide (CCK-8) on the guinea pig ileum but not gall bladder: studies with a substance P antagonist.
The substance P antagonist, [D-Pro4-D- Trp7 ,9,10]substance P4-11, caused a pig parallel shift to the right of the cholecystokinin (CCK-8) dose-response curve in guinea pig ileum longitudinal muscle without changing the maximal contraction. The shift of the CCK-8 dose response was markedly reduced after desensitization of the tissues to substance P (SP). The SP antagonist had no effect upon CCK-8 responses of the guinea pig gall bladder, [125I]CCK pancreatic binding or contractions of the guinea pig ileum produced by acetylcholine or electrical stimulation. The data provide additional evidence for the involvement of SP in the action of CCK-8 on the guinea pig ileum but not the gall bladder.


Association of obstructive sleep apnea with severity of patients hospitalized for acute asthma.
Studies suggest that obstructive sleep apnea (OSA) is associated with suboptimal disease control and worse chronic severity of asthma. However, little is known about the relations of OSA with acute asthma severity in hospitalized patients. To investigate the association of OSA with acute asthma severity. This is a retrospective cohort study (2010-2013) using State Inpatient Databases from 8 geographically diverse states in the United States. The outcomes were markers of acute severity, including mechanical ventilation use, hospital length of stay, and in-hospital mortality. To determine the association of interest, we fit multivariable logistic regression models, adjusting for age, sex, race/ethnicity, primary insurance, household income, patient residence, comorbidities, hospital state, and hospitalization year. We repeated the analysis for children aged 6 to 17 years. Among 73,408 adult patients hospitalized for acute asthma, 10.3% had OSA. Coexistent OSA was associated with a significantly higher risk of noninvasive positive pressure ventilation use (14.9% vs 3.1%; unadjusted odds ratio, 6.48; 95% CI, 5.88-7.13; adjusted odds ratio, 5.20; 95% CI, 4.65-5.80), whereas coexistent OSA was not significantly associated with the risk of invasive mechanical ventilation use. Patients with OSA had 37% longer hospital length of stay (unadjusted incidence rate ratio, 1.37; 95% CI, 1.33-1.40); this significant association persisted in the multivariable model (incidence rate ratio, 1.13; 95% CI, 1.10-1.17). The in-hospital mortality did not significantly differ between groups. These findings were consistent in both obesity and nonobesity groups and in 27,935 children. Among patients hospitalized for acute asthma, OSA was associated with a higher risk of noninvasive positive pressure ventilation use and longer length of stay compared with those without OSA.


Cellular and molecular biology of optineurin.
Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other neurodegenerative diseases, and Paget's disease of bone. This review describes the characteristics of optineurin and summarizes the cellular and molecular biology investigations conducted so far on optineurin. Data from a number of laboratories indicate that optineurin is a cytosolic protein containing 577 amino acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin, transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NF-κB pathway, antiviral, and antibacteria signaling. Mutation or alteration of homeostasis of optineurin (such as overexpression or knockdown) results in adverse consequences in the cells, leading to the development of neurodegenerative diseases including glaucoma.


Unlocking the potential of plant phenotyping data through integration and data-driven approaches.
Plant phenotyping has emerged as a comprehensive field of research as the result of significant advancements in the application of imaging sensors for high-throughput data collection. The flip side is the risk of drowning in the massive amounts of data generated by automated phenotyping systems. Currently, the major challenge lies in data management, on the level of data annotation and proper metadata collection, and in progressing towards synergism across data collection and analyses. Progress in data analyses includes efforts towards the integration of phenotypic and -omics data resources for bridging the phenotype-genotype gap and obtaining in-depth insights into fundamental plant processes.


[Effect of tadalafil 5mg daily treatment on penile haemodynamics in patients with erectile dysfunction].
Phosphodiesterase-5 inhibitors (PDE-5) are the first-line treatment. ED diagnostic and evaluation methods are clinical: erection self-perception and evaluation questionnaires. It is necessary to identify predictive markers to choose the best drug and the best dose for each individual patient. This study seeks to evaluate the effect of tadalafil 5mg daily treatment on penile haemodynamics (penis in flaccidity, using doppler ultrasound, without using alprostadil) and to study if these changes are clinically associated. 40 patients who started treatment with tadalafil 5mg daily were consecutively selected in a prospective study. Each patient underwent a penile doppler ultrasound and completed questionnaires (IIEF-6, EHS, SEP-2, SEP-3) at three different times: before starting the treatment, at 3 months and at 6 months (within the last 30 days without treatment). Tadalafil 5mg daily treatment for 3 months did not result in significant modifications to VPS and AS. There was clinical improvement according to the questionnaires after three months of treatment, which was not maintained at 6 months. Neither a clinical-radiological correlation nor a haemodynamic value predicting response to treatment could be established.


Mechanism of intramedullary high intensity area on T2-weighted magnetic resonance imaging in osteoid osteoma: a possible role of COX-2 expression.
To study the mechanism and pathophysiology of the development of intramedullary high intensity areas on T2-weighted magnetic resonance images (MRI) in cases of osteoid osteoma, we examined the expression of cyclooxygenase-2 (COX-2) in the nidus and surrounding bone tissues. In all six cases showing a marked intramedullary high intensity area adjacent to the nidus before surgery, neoplastic osteoblasts inside the nidus showed strong and diffuse COX-2 immunoreactivity. On the other hand, the osteoblasts rimming the surrounding reactive bone were COX-2 negative. In two cases examined by reverse transcription-polymerase chain reaction (RT-PCR), COX-2 mRNA was detected in abundance in the nidus. Histologically, vascular dilatation together with intramedullary edema was observed in all cases, which was probably reflected as a high intensity area on T2-weighted MRI. From our study, a high level of COX-2 expression in neoplastic osteoblasts in the nidus of osteoid osteomas may cause the secondary changes depicted by MRI.


Parental assessment of developmental delay in children: some limitations and hazards.
According to a study published in the present issue of Acta Paediatrica, mothers' reports of developmental delays in children of preschool age were associated with socio-economic factors. For the present, developmental screening procedures using parental assessments cannot be considered evidence based. National health service systems ensuring preventive health care for all children, regardless of socio-economic background, will form a more solid basis for early detection and treatment.


Bioengineering thermodynamics of biological cells.
Cells are open complex thermodynamic systems. They can be also regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transports phenomena can occur across the cells membranes. Moreover, cells can also actively modify their behaviours in relation to changes in their environment. Different thermo-electro-biochemical behaviours occur between health and disease states. But, all the living systems waste heat, which is no more than the result of their internal irreversibility. This heat is dissipated into the environment. But, this wasted heat represent also a sort of information, which outflows from the cell toward its environment, completely accessible to any observer. The analysis of irreversibility related to this wasted heat can represent a new approach to study the behaviour of the cells themselves and to control their behaviours. So, this approach allows us to consider the living systems as black boxes and analyze only the inflows and outflows and their changes in relation to the modification of the environment. Therefore, information on the systems can be obtained by analyzing the changes in the cell heat wasted in relation to external perturbations. The bioengineering thermodynamics bases are summarized and used to analyse possible controls of the calls behaviours based on the control of the ions fluxes across the cells membranes.


Practical recommendations for the clinical evaluation of patients with hereditary ataxia and hereditary spastic paraplegia.
Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP.