A sol-gel derived pH-responsive bovine serum albumin molecularly imprinted poly(ionic liquids) on the surface of multiwall carbon nanotubes.
A pH-responsive surface molecularly imprinted poly(ionic liquids) (MIPILs) was prepared on the surface of multiwall carbon nanotubes (MWCNTs) by a sol-gel technique. The material was synthesized using a 3-aminopropyl triethoxysilane modified multiwall carbon nanotube (MWCNT-APTES) as the substrate, bovine serum albumin (BSA) as the template molecule, an alkoxy-functionalized IL 1-(3-trimethoxysilyl propyl)-3-methyl imidazolium chloride ([TMSPMIM]Cl) as both the functional monomer and the sol-gel catalyst, and tetraethoxysilane (TEOS) as the crosslinking agent. The molecular interaction between BSA and [TMSPMIM]Cl was quantitatively evaluated by UV-vis spectroscopy prior to polymerization so as to identify an optimal template/monomer ratio and the most suitable pH value for the preparation of the MWCNTs@BSA-MIPILs. This strategy was found to be effective to overcome the problems of trial-and-error protocol in molecular imprinting. The optimum synthesis conditions were as follows: template/monomer ratio 7:20, crosslinking agent content 2.0-2.5 mL, temperature 4 °C and pH 8.9 Tris-HCl buffer. The influence of incubation pH on adsorption was also studied. The result showed that the imprinting effect and selectivity improved significantly with increasing incubation pH from 7.7 to 9.9. This is mainly because the non-specific binding from electrostatic and hydrogen bonding interactions decreased greatly with the increase of pH value, which made the specific binding affinity from shape selectivity strengthened instead. The polymers synthesized under the optimal conditions were then characterized by BET surface area measurement, FTIR, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The adsorption capacity, imprinting effect, selective recognition and reusability were also evaluated. The as-prepared MWCNTs@BSA-MIPILs were also found to have a number of advantages including high surface area (134.2 m(2) g(-1)), high adsorption capacity (55.52 mg g(-1)), excellent imprinting effect (imprinting factor of up to 5.84), strong selectivity (selectivity factor of 2.61 and 5.63 for human serum albumin and bovine hemoglobin, respectively), and good reusability.


Preserving the distribution of inorganic arsenic species in groundwater and acid mine drainage samples.
The distribution of inorganic arsenic species must be preserved in the field to eliminate changes caused by metal oxyhydroxide precipitation, photochemical oxidation, and redox reactions. Arsenic species sorb to iron and manganese oxyhydroxide precipitates, and arsenite can be oxidized to arsenate by photolytically produced free radicals in many sample matrices. Several preservatives were evaluated to minimize metal oxyhydroxide precipitation, such as inorganic acids and ethylenediaminetetraacetic acid (EDTA). EDTA was found to work best for all sample matrices tested. Storing samples in opaque polyethylene bottles eliminated the effects of photochemical reactions. The preservation technique was tested on 71 groundwater and six acid mine drainage samples. Concentrations in groundwater samples reached 720 microg-As/L for arsenite and 1080 microg-As/L for arsenate, and acid mine drainage samples reached 13 000 microg-As/L for arsenite and 3700 microg-As/L for arsenate. The arsenic species distribution in the samples ranged from 0 to 90% arsenite. The stability of the preservation technique was established by comparing laboratory arsenic speciation results for samples preserved in the field to results for subsamples speciated onsite. Statistical analyses indicated that the difference between arsenite and arsenate concentrations for samples preserved with EDTA in opaque bottles and field speciation results were analytically insignificant. The percentage change in arsenite:arsenate ratios for a preserved acid mine drainage sample and groundwater sample during a 3-month period was -5 and +3%, respectively.


[Knowing how to deliver healthcare is now as important as having medical knowledge].
Traditionally, the doctor has focused his efforts on mastering medical knowledge. Given the challenges facing him, the medical institutions and the society, it becomes clear that his concern must also be about how this medical knowledge hits the patients and the general population. Knowing how to deliver our care is now as important as having the medical knowledge ! In this article, we present new models of healthcare delivery that we implemented or plan to implement in Geneva, Switzerland.


Stable Low-Dimensional Boron Chalcogenides from Planar Structural Motifs.
There has been growing interest in searching for new low-dimensional (low-D) materials for nanoelectronics and energy applications. Most materials have their structural units extended in three dimensions and connected with chemical bonds. When the dimension is reduced, these bonds will be broken, decreasing the stability and making their experimental realization difficult. Here, we show that stable low-D materials can be made from naturally existing planar structural units. This is demonstrated by first-principles study of boron chalcogenides (B-X), which can have various low-D structures with attractive properties. For example, B2O3 can be the thinnest proton-exchange membrane for fuel cells. B-X are wide-gap semiconductors that can complement the narrow-gap 2D metal dichalcogenides for (opto)electronics. Our work sheds light on the stability of low-D materials and suggests guidelines for rational design of new materials.


A three plus three parameters mechanistic model for viral filtration.
Viral filtration is an expensive regulatory requirement in downstream processing of monoclonal antibodies (mAbs). This process step is typically operated with an overdesigned filter in order to account for any batch to batch variability in the filter, as well as the feed characteristics. Here, we propose a simple, six-parameter mechanistic model for viral filtration where three parameters are membrane-specific while the other three depend on feed characteristics and membrane-feed interactions. Viruses are considered as passive particles which are retained by the membrane on the basis of size exclusion. The model envisages that the viral filter contains two kind of pores: virus-retentive, small-sized pores and non-retentive, large-sized pores. The small-sized pores get blocked during filtration resulting in decrease in active membrane area, while the large-sized pores get constricted during filtration. The length of constricted part increases during filtration and contributes to increase in hydraulic resistance of the filter. Rate of these processes (blocking and constriction) are assumed to be proportional to the instantaneous rate of retention of the viral particles. The general nature of the model is validated with the experimental data on viral filtration for four different commercial membranes used in biotech industries as well as different model viruses. The proposed model has been demonstrated to describe the behavior of filters with very good accuracy. The best-fit model parameter values indicate about the various phenomena that are responsible for differences in the behavior of the membranes as well as change in retention and flux with feed concentration. The proposed model can be used for improving design of virus filters as well as in appropriate sizing of the filters during processing. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1538-1547, 2017.


[Analysis of patients with gastrointestinal neuroendocrine tumor].
We investigated the background factors, histopathological results, and prognosis of patients with gastrointestinal neuroendocrine tumors. The medical records of 42 patients with gastrointestinal neuroendocrine tumors who were diagnosed and treated at our hospital from 2002 to 2012 were collected and retrospectively reviewed. The ratio of male to female patients was 29:13; the mean age was 66.1 years. The tumors were located in the esophagus( 2 patients), stomach( 13 patients), duodenum( 9 patients), colon( 1 patient), and rectum( 18 patients). Regarding the depth of the tumor, invasion of the submucosa( SM) was observed in 26 patients; invasion of the muscularis propria( MP), in 1 patient; invasion of the subserosa( SS), in 3 patients; penetration of the serosa( SE)( AD), in 1 patient, invasion of the adjacent structures( SI)( AI), in 3 patients; and the extent of tumor invasion was unknown in 1 patient. Patients who experienced relapse had a poor prognosis, and all the patients died.


Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: are first conventional doses effective?
The pharmacokinetic/pharmacodynamic index determining β-lactam activity is the percentage of the dosing interval (%T) during which their free serum concentration remains above a critical threshold over the minimum inhibitory concentration (MIC). Regrettably, neither the value of %T nor that of the threshold are clearly defined for critically-ill patients. Areas covered: We review and assess the targets proposed for β-lactams in critical illness by screening the literature since 1997. Depending on the study intention (clinical cure vs. suppression of resistance), targets proposed range from 20%T > 1xMIC to 100%T > 5xMIC. Assessment and comparative analysis of their respective clinical efficacy suggest that a value of 100%T > 4xMIC may be needed. Simulation studies, however, show that this target will not be reached at first dose for the majority of critically-ill patients if using the most commonly recommended doses. Expert commentary: Considering that critically-ill patients are highly vulnerable and likely to experience antibiotic underexposure, and because effective initial treatment is a key determinant of clinical outcome, we support the use of a target of 100%T > 4xMIC, which could not only maximize efficacy but also minimize emergence of resistance. Clinical and microbiological studies are needed to test for the feasibility and effectiveness of reaching such a demanding target.


[Surgical treatment of epilepsy].
In this article the possibilities, indications, methods and results of surgery in epilepsy are summarized in general with the Hungarian experience emphasized. Surgery may provide effective treatment in about 5-10% of the epileptic population. Surgical solution nowadays became an essential treatment in medial temporal epilepsy, if hippocampal sclerosis or other lesion is present, in therapy resistant lesional extratemporal epilepsies and in catastrophic childhood epilepsies if the epileptic disorder is restricted to one hemisphere (Rasmussen syndrome, hemimegalencephaly, Sturge-Weber disease and posttraumatic or postencephalitic hemispherial epilepsies). The algorithms of the presurgical evaluation and the current methods for study the pacemaker area, forbidden zones, and hemispherial functions are treated. The currently used type and techniques of surgery, such as lesionectomy, temporal lobe resections, hemispherotomy, callosotomy, multiple subpial transsections and their indications are described. The newest surgical approaches, as deep brain stimulation, vagal nerve stimulation, and irradiation techniques are also briefly touched. Lastly, we deal with prognostical factors of the surgical outcome, reasons of surgical failures and complications. In a brief chapter the importance of postsurgical rehabilitation is emphasized.


Vertebra identification using template matching modelmp and K-means clustering.
Accurate vertebra detection and segmentation are essential steps for automating the diagnosis of spinal disorders. This study is dedicated to vertebra alignment measurement, the first step in a computer-aided diagnosis tool for cervical spine trauma. Automated vertebral segment alignment determination is a challenging task due to low contrast imaging and noise. A software tool for segmenting vertebrae and detecting subluxations has clinical significance. A robust method was developed and tested for cervical vertebra identification and segmentation that extracts parameters used for vertebra alignment measurement. Our contribution involves a novel combination of a template matching method and an unsupervised clustering algorithm. In this method, we build a geometric vertebra mean model. To achieve vertebra detection, manual selection of the region of interest is performed initially on the input image. Subsequent preprocessing is done to enhance image contrast and detect edges. Candidate vertebra localization is then carried out by using a modified generalized Hough transform (GHT). Next, an adapted cost function is used to compute local voted centers and filter boundary data. Thereafter, a K-means clustering algorithm is applied to obtain clusters distribution corresponding to the targeted vertebrae. These clusters are combined with the vote parameters to detect vertebra centers. Rigid segmentation is then carried out by using GHT parameters. Finally, cervical spine curves are extracted to measure vertebra alignment. The proposed approach was successfully applied to a set of 66 high-resolution X-ray images. Robust detection was achieved in 97.5 % of the 330 tested cervical vertebrae. An automated vertebral identification method was developed and demonstrated to be robust to noise and occlusion. This work presents a first step toward an automated computer-aided diagnosis system for cervical spine trauma detection.


Recognition and treatment of obsessive-compulsive disorder.
Obsessive-compulsive disorder is relatively common; however, its actual incidence has only recently become clear. The neurotransmitter serotonin appears to have a central role in this disorder. Males and females are affected equally, with onset usually occurring in late adolescence. Symptoms include intrusive thoughts that lead the patient to perform repetitive rituals that interfere with daily living. Although patients are typically distressed by these thoughts and rituals, they seldom volunteer their symptoms. Successful diagnosis often requires specific questioning by the physician. Treatment is directed at symptom reduction; however, complete remission of symptoms is unusual. Pharmacologic therapy usually includes clomipramine or antidepressant treatment with selective serotonin reuptake inhibitors, but in dosage ranges higher than those typically used in the treatment of depression. Behavior therapy has also been proved effective, both alone and in conjunction with pharmacologic therapy.


Structure formation in bis(terpyridine) derivative adlayers: molecule-substrate versus molecule-molecule interactions.
The influence of the substrate and the deposition conditions-vapor deposition versus deposition from solution-on the structures formed upon self-assembly of deposited bis(terpyridine) derivative (2,4'-BTP) monolayers on different hexagonal substrates, including highly oriented pyrolytic graphite (HOPG), Au(111), and (111)-oriented Ag thin films, was investigated by high-resolution scanning tunneling microscopy and by model calculations of the intermolecular energies and the lateral corrugation of the substrate-adsorbate interaction. Similar quasi-quadratic network structures with almost the same lattice constants obtained on all substrates are essentially identical to the optimum configuration expected from an optimization of the adlayer structure with C-H...N-type bridging bonds as a structure-determining factor, which underlines a key role of the intermolecular interactions in adlayer order. Slight distortions from the optimum values to form commensurate adlayer structures on the metal substrates and the preferential orientation of the adlayer with respect to the substrate are attributed to the substrate-adsorbate interactions, specifically, the lateral corrugation in the substrate-adsorbate interaction upon lateral displacement and rotation of the adsorbed BTP molecules. The fact that similar adlayer structures are obtained on HOPG under ultrahigh vacuum conditions (solid|gas interface) and on HOPG in trichlorobenzene (solid|liquid interface) indicates that the intermolecular interactions are not severely affected by the solvent.


Intrusion of teeth in the combination implant-to-natural-tooth fixed partial denture: a review of the theories.
This article reviews the literature dealing with the combination implant-to-natural-tooth-supported fixed partial denture. The restoration of masticatory function with a combination implant-to-natural-tooth fixed partial denture is associated with a variety of undesirable clinical sequelae, including the breakage of implant components, damage to the abutment teeth, or intrusion of the abutment teeth. Theories regarding intrusion of abutment teeth combined with implants for fixed partial dentures are only speculative. Several theories are presented to explain the intrusion of natural teeth in association with implant-to-natural-tooth fixed partial dentures. One of the first theories was based on the idea that a lack of normal stimulation of the periodontal ligament produces atrophy of the periodontal ligament and intrusion of the tooth. The remaining theories relate to excessive forces being placed on the natural tooth, resulting in movement of the tooth to a less stressful position. These forces are placed on the tooth by differential energy dissipation, mandibular flexion and torsion, flexion of the fixed partial denture framework, impaired rebound memory, debris impaction or microjamming, or ratchet effect related to the use of precision attachments. Based a review of the literature, a philosophy for treating combination implant-to-natural-tooth restorations is presented.


Disruption of parental-specific expression of imprinted genes in uniparental fetuses.
In mammals, imprinted genes show parental origin-dependent expression based on epigenetic modifications called genomic imprinting (GI), which are established independently during spermatogenesis or oogenesis. Due to GI, uniparental fetuses never develop to term. To determine whether such expression of imprinted genes is maintained in uniparental mouse fetuses, we analyzed the expression of 20 paternally and 11 maternally expressed genes in androgenetic and parthenogenetic fetuses. Four genes of each type were expressed in both groups of fetuses. Furthermore, quantitative analysis showed that expression levels deviated from the presumed levels for some imprinted genes. These results suggest that mechanisms acting in trans between paternal and maternal alleles are involved in the appropriate expression of some imprinted genes.


Cerebrolysin and early neurorehabilitation in patients with acute ischemic stroke: a prospective, randomized, placebo-controlled clinical study.
Background - Stroke represents one of the most important causes of permanent physical or mental disability. A number of recent advances in recovery have reinforced the idea that pharmacological intervention combined with a specific rehabilitation therapy can reduce disability after stroke. Objective - The aim of this trial was to demonstrate the hypothesis that the association of pharmacological treatment with Cerebrolysin to early physical therapy can significantly stimulate the endogenous processes underlying the recovery after an ischemic stroke. Methods and Results - It was a prospective, randomized, double-blind, placebo-controlled clinical study. 60 patients were randomized either to 30 ml/ day Cerebrolysin or to Placebo for 10 consecutive days, starting in the first 24-48 hours after stroke. The pharmacological treatment was paired with early physical rehabilitation. The robust nonparametric evaluation of the National Institute for Health Stroke Scale (NIHSS) demonstrated a large superiority of Cerebrolysin relative to placebo on day 10 with a MW=0.79 (95% CI, 0.65-0.94), respectively on day 30 with MW=0.75 (95% CI, 0.60-0.89). Similar results were found with modified Ranking Scale (mRS) and Barthel Index (BI). Cerebrolysin was safe and well tolerated. Conclusions - Cerebrolysin had a beneficial effect on global neurological status and disability. The beneficial results of this study can be easily applied in the current clinical practice. Abbreviations: BI = Barthel Index; CB = Changes from Baseline; CI = Confidence interval; ICH = International Conference on Harmonization; ITT = intention-to-treat; LB = Lower Bound of Confidence Interval; mRS = modified Rankin Scale; MW = Mann-Whitney; NIHSS = National Institute for Health Stroke Scale; P = P-value; R = Valid Number Reference Group (Placebo); SD = standard deviation; T = Valid Number Test Group (Cerebrolysin); UB = Upper Bound of Confidence Interval.


Effects of the antiallergic drug azelastine hydrochloride on proliferative responses of lymphocytes to food antigens in patients with food-sensitive atopic dermatitis.
We previously reported that the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) or bovine serum albumin (BSA) in children with atopic dermatitis (AD) who are sensitive to hen's egg or cow's milk were significantly higher than those of healthy children and hen's egg- or cow's milk-sensitive children with immediate symptoms. Azelastine hydrochloride is an antiallergic drug used in the treatment of rhinitis and asthma. In this study, we have shown that the proliferative responses of PBMCs to OA are concentration-dependently inhibited by azelastine in patients with AD. Moreover, the inhibition resulted from the effects of azelastine on T-cells.


Evaluation of T cells, B cells and Ig. in tissues of human cutaneous leishmaniasis.
Cutaneous leishmaniasis (CL) is a granulomatous skin disease. The healing of the CL. lesions is attributed to the delayed immunity developed against the amastigotes of the parasite. However, in some cases in spite of the development of strong delayed hypersensitivity CL. lesions failed to heal. In this paper, it was intended to assess the role of immunity in the lesions of human cutaneous leishmaniasis. The results showed that the helper cells predominated the suppressor ones, the mean percentage of B lymphocytes was 25 and the immunoglobulins particularly the IgG were demonstrated by being positively stained. On the other hand, the complement (C3) was within the normal range.


Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma.
FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible FGFR inhibitors-pemigatinib and infigratinib-and an irreversible inhibitor-futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms of resistance have been reported, including secondary FGFR kinase domain mutations. Here, we sought to establish the landscape of acquired resistance to FGFR inhibition and to validate findings in model systems. We examined the spectrum of acquired resistance mechanisms detected in circulating tumor DNA or tumor tissue upon disease progression following FGFR inhibitor therapy in 82 FGFR-altered cholangiocarcinoma patients from 12 published reports. Functional studies of candidate resistance alterations were performed. Overall, 49 of 82 patients (60%) had one or more detectable secondary FGFR2 kinase domain mutations upon acquired resistance. N550 molecular brake and V565 gatekeeper mutations were most common, representing 63% and 47% of all FGFR2 kinase domain mutations, respectively. Functional studies showed different inhibitors displayed unique activity profiles against FGFR2 mutations. Interestingly, disruption of the cysteine residue covalently bound by futibatinib (FGFR2-C492) was rare, observed in 1/42 patients treated with this drug. FGFR2-C492 mutations were insensitive to inhibition by futibatinib but show reduced signaling activity, potentially explaining their low frequency. These data support secondary FGFR2 mutations as the primary mode of acquired resistance to FGFR inhibitors-most commonly N550 and V565 mutations. Thus, development of combination strategies and next-generation FGFR inhibitors targeting the full spectrum of FGFR2 resistance mutations will be critical.


Free radicals in vivo. Covalent binding to lipids.
As one means of determining the extent to which free radical metabolites are involved in the interaction of hepatotoxic drugs with target tissues, we have measured the covalent binding to hepatic lipids of carbon tetrachloride, acetaminophen, 2-furamide, furosemide, dimethylnitrosamine, and bromobenzene. Transesterification of the Folch lipid fraction was required to distinguish radioactive label present but not covalently bound to alkyl residues through radical addition or combination reactions. Although all hepatotoxins were covalently bound to hepatic protein in the range of 1-2 nmoles/mg, thereby confirming tissue alkylation by reactive metabolites under the present experimental conditions, only carbon tetrachloride gave significant covalent binding to the alkyl residues of hepatic lipids (4.34 nmoles/mg). Thus, although these data further support the already well-documented role of a free radical in the reaction of carbon tetrachloride with target tissue molecules, none of the other hepatotoxins gave similar indications. Dimethylnitrosamine did give significant covalent binding to lipids, but the removal of the binding by transesterification indicates that the binding apparently resulted from electrophilic attack on nucleophilic centers present in phospholipids rather than from radical attack on electroneutral alkyl residues of the lipids.


Learning Background-Suppressed Dual-Regression Correlation Filters for Visual Tracking.
The discriminative correlation filter (DCF)-based tracking method has shown good accuracy and efficiency in visual tracking. However, the periodic assumption of sample space causes unwanted boundary effects, restricting the tracker's ability to distinguish between the target and background. Additionally, in the real tracking environment, interference factors such as occlusion, background clutter, and illumination changes cause response aberration and, thus, tracking failure. To address these issues, this work proposed a novel tracking method named the background-suppressed dual-regression correlation filter (BSDCF) for visual tracking. First, we utilize the background-suppressed function to crop out the target features from the global features. In the training step, while introducing the spatial regularity constraint and background response suppression regularization, we construct a dual regression structure to train the target and global filters separately. The aim is to exploit the difference between the output response maps for mutual constraint to highlight the target and suppress the background interference. Furthermore, in the detection step, the global response can be enhanced by a weighted fusion of the target response to further improve the tracking performance in complex scenes. Finally, extensive experiments are conducted on three public benchmarks (including OTB100, TC128, and UAVDT), and the experimental results indicate that the proposed BSDCF tracker achieves tracking performance comparable to many state-of-the-art (SOTA) trackers in a variety of complex situations.


Infections in immunocompromised hosts and organ transplant recipients: essentials.
(1) Why do we need to know anything about these patients? Regardless of their specialties, physicians are increasingly confronted with the side effects of therapies that cause varying degrees of immunosuppression: chemotherapy and stem cell transplantation for cancer, solid organ transplantation, and therapies for autoimmune and rheumatological diseases. The management of these patients is increasingly being returned to community-based physicians. The infectious disease clinician is faced with major challenges. (2) The possible etiologies of infections are diverse; they range from common bacterial and viral pathogens that affect the entire community to opportunistic pathogens that are clinically significant only for immunocompromised hosts. (3) Inflammatory responses are impaired by immunosuppressive therapy, and this results in diminished clinical and radiological findings. Thus, an early diagnosis is much more difficult, but it is the key to successful therapy. Invasive diagnostic procedures are often required. (4) Antimicrobial therapies are often more complex in these patients versus other patients because of the urgency of empiric therapy and the frequency of drug toxicity and drug interactions. (5) Drug interactions and drug toxicity are common. The initiation or cessation of antimicrobial therapies may alter the levels of calcineurin inhibitors, antifungal agents, and other drugs. (6) Graft rejection and graft-versus-host disease may be confused with infections. (7) New pathogens and new manifestations of infections in compromised hosts are also problems: a Pathogens common to individuals with prolonged defects in their cellular immune function (human immunodeficiency virus) and to neutropenic hosts [Rhodococcus, Cryptosporidium, and Penicillium species; Mycobacterium species (eg, Mycobacterium avium complex); and Scedosporium] have been identified in transplant recipients. b Antimicrobial resistance is a major problem [vancomycin-resistant Enterococcus; methicillin-resistant Staphylococcus aureus; Pseudomonas, Stenotrophomonas, and Burkholderia species; fungi (both yeasts and molds); and ganciclovir-resistant cytomegalovirus]. c There are few therapies for newer viral pathogens (eg, human herpesvirus 6, human herpesvirus 8, and BK virus) and common respiratory viruses (eg, respiratory syncytial virus, adenoviruses, and Metapneumovirus). d Patients from endemic regions may have parasites (eg, Chagas disease and Leishmania).


Effect of KOROPASS, an extruded jack bean (Canavalia ensiformis)-derived supplement, on productivity and economic performance of beef cattle.
This study evaluated the effect of feeding a graded amount of extruded jack bean (Canavalia ensiformis) on nutritional status, production performances, and economic performance of beef cattle. The supplement called "KOROPASS" was prepared from the extruded jack bean (according to the extrusion heating process). Sixteen male Friesian-Holstein crossbred cattle were divided into four groups and fed on KOROPASS as per the regimen: R0 (total mixed ration [TMR] without KOROPASS), R1 (TMR supplemented with 3% KOROPASS), R2 (TMR supplemented with 6% KOROPASS), and R3 (TMR supplemented with 9% KOROPASS). The in vivo experiment lasted 44 days. TMR contained 12% crude protein and 60% total digestible nutrient. The consumption and digestibility of dry matter (DM), organic matter (OM), and total protein (TP), feed efficiency, average daily gain, and income over feed cost (IOFC) were evaluated. KOROPASS supplementation significantly increased (p<0.05) beef cattle consumption of DM (from 7.83 [R0] to 8.33 [R1], 8.91 [R2], and 9.69 kg/day [R3]), OM (from 6.72 to 7.17, 7.69, and 8.38 kg/day, respectively), and TP (from 892 to 1020, 1182, and 1406 g/day, respectively). The elevated levels of KOROPASS significantly increased (p<0.05) digestibility in terms of the levels of DM (from 42.9 [R0] to 50.6 [R1], 58.0 [R2], and 63.6% [R3]), OM (from 54.3 to 59.6, 66.3, and 70.6%, respectively), and TP (from 65.0 to 67.1, 75.0, and 80.7%, respectively). Dietary supplementation of KOROPASS significantly increased (p<0.05) metabolizable protein, average daily weight gain, and feed efficiency of beef cattle. Finally, dietary KOROPASS supplementation, especially at 9%, resulted in the highest (p<0.05) IOFC value of beef cattle. Dietary supplementation of KOROPASS improved feed utility, as reflected by the increase in consumption and digestibility of DM, OM, and TP. Further, KOROPASS supplementation improved feed efficiency, growth, and economic performance of beef cattle. The findings indicate the potential value of KOROPASS as a feed supplement for beef cattle.


Momentary mood and coping processes in TMD pain.
Temporomandibular dysfunction (TMD) pain, like many chronic pain problems, appears to be multiply determined. Patients with TMD pain of at least 6 months duration (N = 30) were administered questionnaires measuring dispositional coping styles and appraisals to explore the dynamic interactions of the pain and coping process. Patients were then issued handheld computers that prompted them to record their momentary pain and coping processes 4 times per day for 7 days. Hierarchical linear regression models using both the dispositional and momentary predictors indicated that momentary pain was a function both of dispositional tendency to catastrophize and of momentary measures of catastrophization, self-efficacy, and mood states. Results were seen as supporting a situational model of intervention for chronic TMD pain.


Identification of hepatic copper-binding proteins from tilapia by column chromatography with proteomic approaches.
Although copper is an essential element, it shows cytotoxic effects when present in excessive amounts with the production of hydroxyl radicals, which can damage phospholipids and enzymes. This necessitates a tight cellular control mechanism for copper homeostasis including its uptake and removal. The high copper contents in the liver of tilapia make this fish a suitable model for the study of copper binding proteins (CBPs). The liver was dissected from tilapia injected with Cu(2+) and cytosolic fractions were separated by using Superdex 75 column chromatography followed by atomic absorption spectrometry. Fractions in two major peaks containing CBPs were analyzed by using differential proteomic approaches, and loaded on a Cu chelating ion-immobilized affinity column (Cu-IMAC). Of the 113 differentially expressed proteins in these two peaks, 28 proteins were found to have copper binding ability, including well-characterized CBPs, such as copper transporter ATP7A and metallothionein. The networks of CBPs built up by Ingenuity Pathway Analysis (IPA) would help us to understand the transportation pathway and function of CBPs, which were related to free radical scavenging, cellular development and lipid metabolism. In addition, our results suggest that Cu(2+) would compete with Fe(2+) and Ca(2+) in binding with some target proteins, such as ferritin, transferrin, and calmodulin.


Nursing practice should be informed by the best available evidence, but should all first-level nurses be competent at research appraisal and utilization?
The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) has for many years sought to promote the development of research knowledge and skills in registered nurses and has based its efforts on a particular model of the professional practitioner. This model has each registered nurse as a competent finder, appraiser and utilizer of research evidence. It has a vision of all registered nurses acting as autonomous practitioners, able to adapt their practice according to their own expert assessment of current research findings. Through its powers of strategic direction of nurse training and education, the UKCC has required the national boards to have approved education institutions prepare nurses for this role at both pre- and post-registration level. In this paper we argue that this model has proven ineffective. Our argument suggests that the technical complexity of research, and the skills and time required to find and integrate research evidence, renders such a model unattainable. Evidence from studies of clinical nurses indicates that little progress has in any case been made. Furthermore, the development of the apparatus of clinical governance and the basis of professional accountability further undermine the grounds for this approach. A modified approach is advocated based on the development of research specialists within nursing and the greater use of research-based clinical guidelines.


Synthesis and characterization of a novel organic nitrate NDHP: Role of xanthine oxidoreductase-mediated nitric oxide formation.
In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.


High seroprevalence of Coxiella burnetii infection in Eastern Cantabria (Spain).
Coxiella burnetii is the causative agent of Q fever, a worldwide zoonosis which shows a wide diversity of clinical manifestations. The objective of this seroepidemiological study was to estimate the prevalence of antibodies to C. burnetii in a representative population of the Eastern area of the Cantabrian Community (Northern Spain). A cross-sectional study was conducted in 595 subjects from Eastern Cantabria. Four different zones (one urban and three rural zones) were defined according to the geographical characteristics of the area and the economic activities of the population. The population sample for this study was collected between December 1994 and March 1995, and was stratified by age, sex and municipality of residence. IgG and IgM antibodies against C. burnetii were assayed by an indirect immunofluorescence technique. The prevalence of anti-phase II Coxiella IgG (titre > or = 1:16) was 48.6% (95% confidence interval: 44.6-52.6%), with 81.3% havinga titre of > or = 1:64. The prevalence of IgG increased with age, ranging from 12.0% in people < 15 years to 70.3% in those > 65 years (P < 0.001). The antibody detection rate was higher in males (53.6%) than in females (43.3%) (P < 0.01). The prevalence of anti-phase II Coxiella IgG was less among subjects living in the urban zone (32.8%) than in those living in the other three rural zones: the two situated on the coast (54.0% and 54.9% respectively) and the inner mountainous zone (82.3%) (P < 0.001). The prevalence of C. burnetii infection observed in this study is one of the highest reported in Europe. The eastern area of Cantabria is a hyperendemic area for Q fever.


Specific Strains of Lactic Acid Bacteria Differentially Modulate the Profile of Adipokines In Vitro.
Obesity induces local/systemic inflammation accompanied by increases in macrophage infiltration into adipose tissue and production of inflammatory cytokines, chemokines, and hormones. Previous studies have shown that probiotics could improve the intestinal dysbiosis induced by metabolic diseases such as obesity, diabetes, and metabolic syndrome. Microorganisms could (directly or indirectly) affect adipokine levels due to their capacity to induce translocation of several intestinal microbial antigens into systemic circulation, which could lead to metabolic endotoxemia or produce immunomodulation in different organs. The aim of the present study was to select non-inflammatory lactic acid bacteria (LAB) strains with the capacity to modulate adipokine secretion by the adipose tissue. We wish to elucidate the role of potential probiotic strains in the regulation of the cross talking between immune cells such as macrophages and adipose cells. Mouse macrophage cell line RAW 264.7 was used for evaluating the ability of 14 LAB strains to induce cytokine production. The LAB strains were chosen based on their previously studied beneficial properties in health. Then, in murine adipocyte culture and macrophage-adipocyte coculture, we determined the ability of these strains to induce cytokines and leptin secretion. Tumor necrosis factor alpha, interleukin 6 (IL-6), IL-10, monocyte chemoattractant protein-1, and leptin levels were measured in cell supernatants. We also performed the detection and quantification of leptin receptor (Ob-Rb) expression in macrophage cell lines stimulated by these LAB strains. Differential secretion profile of cytokines in macrophage cells induced by LAB strains was observed. Also, the levels of Ob-Rb expression diverged among different LAB strains. In LAB-stimulated coculture cells (adipocytes and macrophages), we observed differential production of leptin and cytokines. Furthermore, we detected lower production levels in single culture than cocultured cells. The principal component analysis showed an association between the four clusters of strains established according to their inflammatory profiles and leptin adipocyte production and leptin receptor expression in macrophages. We conclude that coculture is the most appropriate system for selecting strains with the ability to modulate adipokine secretion. The use of microorganisms with low and medium inflammatory properties and ability to modulate leptin levels could be a strategy for the treatment of some metabolic diseases associated with dysregulation of immune response.


Endoscopic imaging techniques for detecting early colorectal cancer.
The detection of early colorectal cancer has improved notably since the introduction of bowel cancer screening programmes. This has created new challenges from endoscopic, histological and therapeutic perspectives. Here, we outline the limitations of current clinical practice and ways of implementing optical diagnosis to overcome these limitations. Virtual chromoendoscopy without magnification for predicting or ruling out deep submucosal invasion is useful in real clinical practice for most lesions. However, magnifying virtual chromoendoscopy is needed to make an accurate diagnosis in nonulcerated narrow-band imaging international colorectal endoscopic (NICE) type 3 lesions or NICE type 2 lesions with depressed areas or of nodular mixed type. Finally, dye-based magnifying chromoendoscopy is needed in Japanese NBI Expert Team 2B lesions assessed with magnifying virtual chromoendoscopy. A four-step strategy is proposed, combining white-light assessment, virtual chromoendoscopy without magnification, virtual chromoendoscopy with magnification and dye-based chromoendoscopy with magnification.


A new approach to film dosimetry for high energy photon beams: lateral scatter filtering.
A method of film dosimetry for high energy photon beams is proposed which reduces the required film calibration exposures to a set of films obtained for a small radiation field size and shallow depth (6 cm x 6 cm at 5 cm depth). It involves modification of a compression type polystyrene film phantom to include thin lead foils parallel to the vertical film plane at approximately 1 cm from both sides of the film emulsion. The foils act as high atomic number filters which remove low energy Compton scatter photons that otherwise would cause the film sensitivity to change with field size and depth. The proposed method is best described as "lateral scatter filtering." To validate the proposed method, central axis depth doses and isodose curves for a 4 MV photon beam were determined from films exposed within the modified phantom and the results compared with ionization chamber measurements. When no lateral filtering was used, for field sizes of 6 cm x 6 cm and 25 cm x 25 cm, this comparison demonstrated up to a 65% difference between film and ionization chamber central axis depth dose measurements. When using the lateral scatter filtering technique, less than a 4% difference was observed for these field sizes.


beta-N-methylamino-L-alanine is a low-affinity agonist of metabotropic glutamate receptors.
beta-N-methylamino-L-alanine (L-BMAA) is an excitotoxin whose neurodegenerative effects are associated with its agonist properties at the N-methyl-D-aspartate (NMDA) receptor. We measured the effects of L-BMAA on inositol phosphate (InsP) formation in primary cultured striatal neurons. This culture is almost devoid of glial cells and the pharmacology of glutamate receptors is well-defined. This allowed us to show that L-BMAA induced InsP formation via a direct action at the glutamate metabotropic (Qp) receptors coupled to InsP formation. We demonstrated that L-BMAA is a full-agonist of the Qp receptor, but with a low potency. Therefore, the neurotoxic properties of L-BMAA might implicate the activation of the Qp receptor in association with the NMDA receptor.


Cellular Factors Targeting HIV-1 Transcription and Viral RNA Transcripts.
Restriction factors are structurally and functionally diverse cellular proteins that constitute a first line of defense against viral pathogens. Exceptions exist, but typically these proteins are upregulated by interferons (IFNs), target viral components, and are rapidly evolving due to the continuous virus-host arms race. Restriction factors may target HIV replication at essentially each step of the retroviral replication cycle, and the suppression of viral transcription and the degradation of viral RNA transcripts are emerging as major innate immune defense mechanisms. Recent data show that some antiviral factors, such as the tripartite motif-containing protein 22 (TRIM22) and the g-IFN-inducible protein 16 (IFI16), do not target HIV-1 itself but limit the availability of the cellular transcription factor specificity protein 1 (Sp1), which is critical for effective viral gene expression. In addition, several RNA-interacting cellular factors including RNAse L, the NEDD4-binding protein 1 (N4BP1), and the zinc finger antiviral protein (ZAP) have been identified as important immune effectors against HIV-1 that may be involved in the maintenance of the latent viral reservoirs, representing the major obstacle against viral elimination and cure. Here, we review recent findings on specific cellular antiviral factors targeting HIV-1 transcription or viral RNA transcripts and discuss their potential role in viral latency.


[Comparison of the indirect enzyme-bound immunosorbent method with the hemagglutination inhibition test in detecting Newcastle disease antibodies in vaccinated chickens].
The sensitivity of ELISA and the hemagglutination-inhibition test was comparatively studied in the demonstration of Newcastle disease antibodies in the sera of 57 vaccinated birds. Differences were established in the antibody titers as demonstrated by the two methods. The sensitivity of ELISA was found to be 100 times higher than that of the HI-test. Discussed is the possible use of ELISA in cases where no antibodies or low-titer hemagglutinating ones are demonstrated via the HI-test.


Melt extrusion vs. spray drying: The effect of processing methods on crystalline content of naproxen-povidone formulations.
Our hypothesis is that melt extrusion is a more suitable processing method than spray drying to prepare amorphous solid dispersions of drugs with a high crystallization tendency. Naproxen-povidone K25 was used as the model system in this study. Naproxen-povidone K25 solid dispersions at 30% and 60% drug loadings were characterized by modulated DSC, powder X-ray diffraction, FT-IR, and solid-state 13C NMR to identify phase separation and drug recrystallization during processing and storage. At 30% drug loading, hydrogen bond (H-bond) sites of povidone K25 were not saturated and the glass transition (Tg) temperature of the formulation was higher. As a result, both melt-extruded and spray-dried materials were amorphous initially and remained so after storage at 40°C. At 60% drug loading, H-bond sites were saturated, and Tg was low. We were not able to prepare amorphous materials. The initial crystallinity of the formulations was 0.4%±0.2% and 5.6%±0.6%, and increased to 2.7%±0.3% and 21.6%±1.0% for melt-extruded and spray-dried materials, respectively. Spray-dried material was more susceptible to re-crystallization during processing, due to the high diffusivity of naproxen molecules in the formulation matrix and lack of kinetic stabilization from polymer solution. A larger number of crystalline nucleation sites and high surface area made the spray-dried material more susceptible to recrystallization during storage. This study demonstrated the unique advantages of melt extrusion over spray drying for the preparation of amorphous solid dispersions of naproxen at high drug level.


Differential diagnosis of hypoamylasuria in pancreas allograft recipients with urinary exocrine drainage.
We have studied the histopathologic correlates of a significantly decreased urinary amylase excretion rate (UAER) to determine its reliability in predicting the presence of cellular rejection within pancreas allografts drained via a duodenocystostomy. Significant hypoamylasuria in pancreas allograft recipients was defined as a diminution of greater than 50% in UAER sustained for greater than 36 hr and not associated with a decrease in serum amylase activity. We observed 18 such episodes of hypoamylasuria in 13 of 18 patients receiving pancreas allografts. Pancreaticoduodenal material was obtained during 11 of these episodes, one attempt failed, and for the remaining 6 episodes we obtained 3 renal allograft biopsy specimens. Histopathologic examination of the 14 specimens revealed cellular rejection in 9 (64%), fibrosis in 2 (14%), enzymatic necrosis in 1 (7%), cytomegaloviral pancreatitis in 1 (7%), and no abnormal features in 1 (7%). During these 14 episodes, a genetically identical renal allograft was present for 11 and showed signs of dysfunction in 9; however, the pancreatic histologic features suggested rejection in only 7 of the 9. Thus even the combination of hypoamylasuria and renal dysfunction in recipients of genetically identical organs was not fully reliable in predicting pancreas allograft rejection. In addition, the interval between organ implantation and onset of hypoamylasuria did not predict the histologic diagnosis. As with other solid-organ allografts, biopsy is a useful adjuvant for determining patient management in the presence of organ dysfunction.


Generation of Hydrogen and Methane during Experimental Low-Temperature Reaction of Ultramafic Rocks with Water.
Serpentinization of ultramafic rocks is widely recognized as a source of molecular hydrogen (H2) and methane (CH4) to support microbial activity, but the extent and rates of formation of these compounds in low-temperature, near-surface environments are poorly understood. Laboratory experiments were conducted to examine the production of H2 and CH4 during low-temperature reaction of water with ultramafic rocks and minerals. Experiments were performed by heating olivine or harzburgite with aqueous solutions at 90°C for up to 213 days in glass bottles sealed with butyl rubber stoppers. Although H2 and CH4 increased steadily throughout the experiments, the levels were very similar to those found in mineral-free controls, indicating that the rubber stoppers were the predominant source of these compounds. Levels of H2 above background were observed only during the first few days of reaction of harzburgite when CO2 was added to the headspace, with no detectable production of H2 or CH4 above background during further heating of the harzburgite or in experiments with other mineral reactants. Consequently, our results indicate that production of H2 and CH4 during low-temperature alteration of ultramafic rocks may be much more limited than some recent experimental studies have suggested. We also found no evidence to support a recent report suggesting that spinels in ultramafic rocks may stimulate H2 production. While secondary silicates were observed to precipitate during the experiments, formation of these deposits was dominated by Si released by dissolution of the glass bottles, and reaction of the primary silicate minerals appeared to be very limited. While use of glass bottles and rubber stoppers has become commonplace in experiments intended to study processes that occur during serpentinization of ultramafic rocks at low temperatures, the high levels of H2, CH4, and SiO2 released during heating indicate that these reactor materials are unsuitable for this purpose. Serpentinization-Hydrogen generation-Abiotic methane synthesis. Astrobiology 16, 389-406.


[Information technology in learning sign language].
To develop a technological tool that improves the initial learning of sign language in hearing impaired children. The development of this research was conducted in three phases: the lifting of requirements, design and development of the proposed device, and validation and evaluation device. Through the use of information technology and with the advice of special education professionals, we were able to develop an electronic device that facilitates the learning of sign language in deaf children. This is formed mainly by a graphic touch screen, a voice synthesizer, and a voice recognition system. Validation was performed with the deaf children in the Filadelfia School of the city of Bogotá. A learning methodology was established that improves learning times through a small, portable, lightweight, and educational technological prototype. Tests showed the effectiveness of this prototype, achieving a 32 % reduction in the initial learning time for sign language in deaf children.


Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.
Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus.


Comparative study of image quality for MSCT and CBCT scanners for dentomaxillofacial radiology applications.
The image quality of four cone-beam computed tomography (CBCT) scanners dedicated for dentomaxillofacial imaging and one multi-slice computed tomography (MSCT) scanner was compared. For the MSCT scanner, a clinical and a low-dose protocol for oral indications were evaluated. The image quality was assessed by dedicated software that allows an automated analysis of accuracy measurements and evaluation of metal artefacts on two image quality phantoms. Bone was segmented with sub-millimetre accuracyin all scanners.


Distribution of ascorbate-2-sulfate and distribution, half-life and turnover rates of [1-14C]ascorbic acid in rainbow trout.
Rainbow trout (250 g) were maintained at 15 degrees C for 3 months on a low ascorbic acid diet, given [1-14C]ascorbic acid by gavage, then fed the NAS/NRC requirement 12 times per week. Total urine, fecal water and branchial water were collected daily from five fish placed in metabolism chambers for four successive 5-day periods. Tissue samples were analyzed for 14C, ascorbic acid (C1) and ascorbate-2-sulfate sulfate (C2). Excretion analysis indicated t1/2 = 42 days. After 20 days, the feeding schedule was changed to 3 times per week. Fish fed 14C were sampled after 1, 2, 3 and 4 months. The half-life in each organ except brain was inversely proportional to the dietary level of ascorbate. Concentrations of C1 and C2 in the various tissues reflected dietary intake of vitamin C. Total C (CT = C1 + C2) levels were maintained in the liver even with the low vitamin C diet. Estimates of body pool for C1 are 27-29 mg/kg. At the higher ascorbate intake CT was 92-114 mg/kg, but decreased by 34% at the lower feeding rate to 51-62 mg/kg. Data indicate that there are two or more body pools that include a store of C2, which is readily interconverted in metabolizing tissues to and from C1. Since air and water stable C2 is antiscorbutic for fish, it is the preferred form of ascorbate for fish feeds.


Thermodynamic Calculations to Determine the Optimal Composition of Oxide Catalysts.
Thermodynamic calculations of the optimal compositions of oxide catalysts with different natures are performed based on the theory of catalysis by polyhedra. The obtained compositions of the active catalysts agree with experimental data. The electrostatic potential generated by polyhedra of metal-oxide catalysts in a variety of directions is calculated. The dependence of the sign and magnitude of the potential on the distance from the central metal ion towards the vertex of the polyhedron, the middle of its edge or the centre of the face is estimated. It is assumed that the magnitude of the potential can serve as a reference point for determining active centres, which produce adsorption complexes and intermediate compounds.


Analytical model and experimental verification of an elliptical bridge-type compliant displacement amplification mechanism.
In this paper, an analytical model of elliptical bridge-type compliant mechanism is established. Compared with the traditional bridge mechanism, the elliptical bridge-type compliant mechanism has the advantages of light weight, high natural frequency, and more uniform stress distribution. Based on the strain energy and Castigliano's displacement theorem, a static model for calculating the displacement amplification ratio and input stiffness is established. Then, the Lagrange equation is used to establish the dynamic model to calculate the natural frequency. After that, finite element simulation and experimental test are both used to verify the proposed analytical model. The results show that the maximum error between the analytical model and finite element simulation is within 8.25% and that of the experimental results is within 6.25%. The conclusion of this paper provides an accurate prediction analytical method for the mechanical performance index design of the elliptical compliant mechanism, which has important theoretical significance.


Specific blastogenesis and lymphokine production in DNCB-sensitive human leucocyte cultures stimulated with soluble and particulate DNP-containing antigens.
A soluble hapten (dinitrobenzene sulphonic acid (DNBSO3)) and particulate antigens consisting of DNCB, DNFB or DNBSO3 complexed with erythrocytes, all induce a specific blastogenic response and lymphokine production in leucocyte cultures from human subjects topically sensitized to dinitrochlorobenzene (DNCB). While low concentrations (50-100 mug/ml) of DNBSO3 could be left in human leucocyte cultures the entire 4 or 5 days of culture and result in reasonable levels of blastogenesis, it was found that consistently higher degrees of blast transformation resulted when DNCB-sensitive leucocytes were exposed to high concentrations of DNBSO3 (500 mug/ml) for a short period (2 hr). Cell-free supernatants from DNCB-sensitive leucocyte cultures harvested after 48 hr induced blastogenesis and DNA synthesis in secondary target leucocyte cultures from subjects not sensitized to DNCB. Such a blastogenic factor or lymphokine appeared to stimulate even in the absence of any residual antigen, since DNCB complexed to erythrocytes was removed by simple filtration through a 0-45 mum Millipore filter. In contrast to DNCB complexes, the antigenic activity of DNBSO3 complexed with erythrocytes was not removed by such filtration. Thus, several DNP-containing haptens (DNCB, DNFB, DNBSO3) induce specific lymphocyte transformation and lymphokine production when exposed in several different manners to leucocytes from humans sensitized to DNCB. The ability to use either a particulate or soluble stimulant in vitro offers a versatile system for studying cell-mediated immunity in humans with a broad range of potential applicability in both investigate and clinical medicine.


Pembrolizumab-induced Toxic Epidermal Necrolysis in a Patient with Metastatic Esophageal Adenocarcinoma.
Adverse cutaneous reactions associated with the immune checkpoint inhibitor (ICI) pembrolizumab are well documented, yet life-threatening reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are infrequent.1,2 We present a case of pembrolizumab-induced TEN in a patient with metastatic esophageal adenocarcinoma who was successfully treated with cyclosporine and systemic corticosteroids.


Input-dependent life-cycle inventory model of industrial wastewater-treatment processes in the chemical sector.
Industrial wastewater-treatment systems need to ensure a high level of protection for the environment as a whole. Life-cycle assessment (LCA) comprehensively evaluates the environmental impacts of complex treatment systems, taking into account impacts from auxiliaries and energy consumption as well as emissions. However, the application of LCA is limited by a scarcity of wastewater-specific life-cycle inventory (LCI) data. This study presents a modular gate-to-gate inventory model for industrial wastewater purification in the chemical and related sectors. It enables the calculation of inventory parameters as a function of the wastewater composition and the technologies applied. Forthis purpose, data on energy and auxiliaries' consumption, wastewater composition, and process parameters was collected from chemical industry. On this basis, causal relationships between wastewater input, emissions, and technical inputs were identified. These causal relationships were translated into a generic inventory model. Generic and site-specific data ranges for LCI parameters are provided for the following processes: mechanical-biological treatment, high-pressure wet-air oxidation, nanofiltration, and extraction. The input- and technology-dependent process inventories help to bridge data gaps where primary data are not available. Thus, they substantially help to perform an environmental assessment of industrial wastewater purification in the chemical and associated industries, which may be used, for instance, for technology choices.


[Influence of factors on independence of patients after stroke in early rehabilitation stage].
Brain stroke is the main cause of disability starting from age of 40 years. Due to this disability, a person loses his ability to work because of long-lasting disorders of biosocial functions. According to literature, occupational therapy for such patients, taking regard to their social, cultural and economic background, significantly increases their self-care and independence and helps to educate working skills. OBJECTIVE. To evaluate conditional disorders of patients with stroke under rehabilitation and to establish the influence of extent of brain damage, localization, age and gender on effectiveness of occupational therapy. Study included 47 men and 53 women diagnosed with brain ischemia or hemorrhage (ischemic or hemorrhagic stroke). Out of them, 30 were of working age (18-59 years old) and 70 of non-working age (more than 60 years old). The mean age was 63.4+/-1.2 years. In order to assess the functional status of patients, they were tested using the Functional Independence Measure (FIM). At the start of rehabilitation, the mean FIM score was 47.4+/-16.1 (48.9+/-15.6 for men and 46.3+/-16.6 for women, p>0.05). At the end of early rehabilitation, the mean FIM score reached up to 89.9+/-22.3 (94.7+/-18.9 for men and 85.7+/-24.3 for women, p<0.05). Evaluation of functional status showed that at the start of rehabilitation functional status was worse in women than men, nevertheless, women's functional status improved during rehabilitation, though the difference between men and women still remained. Occupational therapy was less effective for patients who suffered from hemiplegia than for patients with hemiparesis (p<0.01). Older patients (more than 60 years) had more expressed functional disorders, and worse functional recovery comparing with younger, working age patients (18-59 years old). Evaluation of occupational therapy effectiveness at the end of early rehabilitation showed that extent of brain damage influences independence of patients suffering from brain stroke (p<0.01).


Defined tumor cell-host interactions are necessary for malignant growth.
Analyzing the different steps of malignant growth (primary tumor, metastasizing tumor cells, secondary tumor), one recognizes an intense interaction between normal and malignant cells. Tumor cells not only induce activities of normal cells, which normally are rarely activated, but also they exploit properties of normal cells for their own purposes. The major mechanisms and processes of this "parasitism" are described in more detail and the results are discussed. Tumors cannot grow beyond a certain size without a supply of blood and lymph vessels by the host (angiogenesis). Metastasizing tumor cells cannot leave the vessel (extravasate) in which they are transported without the cooperation of the respective endothelial cells of the host. An appropriate environment formed by the host tissues is essential for the settlement of tumor cells at secondary sites. Historically, these are a few examples that show intense cooperation between host and tumor. More are given in the present contribution.


Global pathway view analysis of microRNA clusters in myasthenia gravis.
The significant roles of microRNAs (miRNAs) in the pathogenesis of myasthenia gravis (MG) have been observed in numerous previous studies. The impact of miRNA clusters on immunity has been demonstrated in previous years; however, the regulation of miRNA clusters in MG remains to be elucidated. In the present study, 245 MG risk genes were collected and 99 MG risk pathways enriched by these genes were identified. A catalog of 126 MG risk miRNAs was then created; the MG risk miRNAs were located on each chromosome and a miRNA cluster was defined as a number of miRNAs with a relative distance of <6 kb on the same sub‑band, same band, same region and same chromosome. Furthermore, enrichment analyses were performed using the target genes of the MG risk miRNA clusters, and a number of risk pathways of each miRNA clusters were identified. As a result, 15 significant miRNA clusters associated with MG were identified. Additionally, the most significant pathways of the miRNA clusters were identified to be enriched on chromosomes 9, 19 and 22, characterized by immunity, infection and carcinoma, suggesting that the mechanism of MG may be associated with certain abnormalities of miRNA clusters on chromosomes 9, 19 and 22. The present study provides novel insight into a global pathway view of miRNA clusters in the pathogenesis of MG.


Effect of variations in globulin concentrations on serum radioimmunoassay results, as exemplified by choriogonadotropin.
Variations in serum protein concentrations can affect results of radioimmunoassay of human choriogonadotropin involving either polyethylene glycol or double-antibody methods of separation. Relative to the maximal binding of choriogonadotropin in the presence of normal (30 g/L) globulin concentrations, globulin concentrations of 10 to 60 g/L were associated with maximal binding ranging from 84.9 to 115.6% in the polyethylene glycol system, and from 109.9 to 92.5% in the double-antibody system. This effect was quantitatively much the same throughout the standard curve in the polyethylene glycol system, but diminished with the higher standard concentrations in the double-antibody system. In assays involving polyethylene glycol separation, an increase in globulin was associated with a linear increase in nonspecific binding, but no detectable effect of globulin on nonspecific binding was observed in the double-antibody system. Determination and compensation for nonspecific binding of individual samples (rather than for mean assay nonspecific binding) eliminated the globulin effect in the polyethylene glycol system but not in the double-antibody system.


Evidence-Based Consensus Recommendations for Skin Care in Healthy, Full-Term Neonates in India.
Neonatal skin care practices guided by personal experience and preferences might be substantially different across different hospital settings. The aim of this consensus recommendation is to provide clinical practice guidance to healthcare practitioners on evidence-based neonatal skin care practices from delivery-to-discharge, in hospital settings. A Scientific Advisory Board meeting on "Evidence-based Neonatal Skin Care Practices and Protocols" was held in December 2020 with an expert panel comprising neonatologists, pediatricians, obstetricians and gynecologists and pediatric dermatologist. Comprehensive literature search was performed up to 23 March 2021 using PubMed and Google Scholar to retrieve relevant evidence. Recommendations were developed on critical aspects of skin care in healthy full-term neonates including cleansing at birth, skin-to-skin care, cord care, diaper area care, initial and routine bathing, cleansers and emollients use, and criteria to choose appropriate skin care products. Recommendations include inclusion of skin assessment in routine neonatal care, first bath timing after cardio-respiratory and thermal stabilization, 6-24 hours after birth; bathing with water alone or adding a mild liquid cleanser could be considered appropriate as it does not impact the developing skin barrier; use of emollients is recommended for neonates with higher risk of development of eczema to maintain and enhance skin barrier function and integrity; and inclusion of skin care advice in neonatal discharge checklist. Importance of rigorous quality control, high-quality clinical trials for assessment of baby products, usage of products that are formulated appropriately for newborns, and full label transparency for baby products were highlighted. The panel identified gaps in literature and discussed the scope for future research. These recommendations may help to standardize evidence-based skin care for healthy full-term neonates in Indian hospital settings to improve the quality of care that neonates receive in hospital and facilitate improvement in overall neonatal health outcomes.


Adverse events and discomfort during magnetic resonance imaging in cochlear implant recipients.
Patients with cochlear implants (CIs) should be fully informed before undergoing magnetic resonance imaging (MRI) about the possibility of discomfort or pain. Prior to an MRI scan, patients need to fully understand not only the potential complications but also the potential discomfort that they may experience during the scan. To assess the adverse events during MRI in patients with CIs and to investigate the safety and diagnostic efficiency of MRI in patients with CIs with internal magnets. Retrospective review of the medical records of 18 patients with CIs undergoing MRI between September 2003 and February 2014 at a single tertiary referral center. Sixteen patients underwent MRI in a 1.5-T scanner, and 2 patients underwent MRI in a 3.0-T scanner. Twelve brain MRI scans were performed, and 18 MRI scans were performed in areas outside the brain. Discomfort or pain, adverse events, and auditory performance after MRI were evaluated using medical records or interviews. Thirteen of 18 patients completed their MRI scans (25 of 30 scans). Five patients with head bandages were unable to complete their MRI scans owing to pain; one of these patients experienced magnet displacement, and another underwent surgery for magnet removal and reinsertion. Finally, 1 patient experienced polarity reversal of the magnet. Artifacts induced by the CI internal magnet compromised the diagnosis of ipsilateral brain lesions under 1.5-T MRI. Auditory performance in the CI recipients who had major events was unaffected. Even with protective head bandages, 1.5-T MRI in patients with CIs led to a variety of adverse events, including discomfort or pain and displacement of the internal magnet. Therefore, sedation and careful head positioning may be appropriate for some patients with CIs who undergo MRI, and these patients should be carefully monitored to decrease the likelihood of such adverse effects.


[Clinical course of decompressive surgery for the treatment of lumbar stenosis].
Several authors and publications have focused on comparing the clinical course of nerve root decompressive surgery, with or without fusion, to treat degenerative lumbar stenosis. However, there are not many reports analyzing the clinical course after decompressive surgery of a single nerve root (the most symptomatic one) comparing it with decompression of all the roots in a segment. This study intends to compare the clinical course after decompressing the most symptomatic lumbar nerve root with the release of multiple lumbar nerve roots to relieve neuropathic pain resulting from degenerative lumbar stenosis. A prospective, observational, descriptive longitudinal study was performed. A total of 38 patients were divided into two groups that included each 19 cases. Patients underwent recalibration of either a single nerve root or multiple nerve roots of a segment. Percentages were calculated as well as the Student t test and the Pearson correlation. In group A, a decrease of 46.63 points was seen in the Oswestry scale, representing a 66.73% improvement in pain. In group B, in turn, a mean decrease of 34.54 points was seen in the Oswestry scale, equivalent to a 47.23% improvement in pain, with a Student t in which p = 0.11 and a Pearson correlation coefficient of 0.08. No statistically significant differences were found between both study groups.


Developmental changes in the myosin composition of guinea pig ventricular muscle. Relation to thyroid state and mechanical properties.
In a variety of mammalian species, thyroid hormone regulates the contractile properties of the heart as well as the expression of the alpha and beta heavy chains of myosin. We have previously shown that the plasma levels of thyroid hormone reach a peak immediately after birth in guinea pigs and decline with maturation. We therefore studied age-related changes in the expression of the myosin heavy chains in the guinea pig ventricle in relation to the ventricular mechanical properties and the levels of thyroid hormone. The composition of the myosin heavy chains was characterized by gel electrophoresis and immunoblotting. Anti-beta-chain antibody stained equally myosins from newborns (0-5 days) and adults (75-90 days), while anti-alpha-chain positively decorated only the myosins of euthyroid newborns or of hyperthyroid adults, but not myosins of embryos, hypothyroid newborns or hypothyroid adults. Myosin of euthyroid adults was faintly stained by anti-alpha-chain. The alterations in the composition of myosin corresponded with the "thyroid state" of these groups. The plasma levels of total T3 were 24.3 +/- 2.7, 9.04 +/- 1.2 and 139.0 +/- 9.3 ng/dl (mean +/- SEM) in the euthyroid, hypothyroid and hyperthyroid adults, respectively. In euthyroid and hypothyroid newborns, the plasma levels of T3 were 56.5 +/- 11.9 and 26.5 +/- 9.8 ng/dl, respectively. Within each age group the thyroid state corresponded with maximal twitch tension (Tmax), rates of development of tension and relaxation, time to peak tension and rate of activation.(ABSTRACT TRUNCATED AT 250 WORDS)


Instantaneous Tunneling Flight Time for Wavepacket Transmission through Asymmetric Barriers.
The time it takes a particle to tunnel through the asymmetric Eckart barrier potential is investigated using Gaussian wavepackets, where the barrier serves as a model for the potential along a chemical reaction coordinate. We have previously shown that the, in principle experimentally measurable, tunneling flight time, which determines the time taken by the transmitted particle to traverse the barrier, vanishes for symmetric potentials like the Eckart and square barrier [ Petersen , J. ; Pollak , E. J. Phys. Chem. Lett. 2017 , 9 , 4017 ]. Here we show that the same result is obtained for the asymmetric Eckart barrier potential, and therefore, the zero tunneling flight time seems to be a general result for one-dimensional time-independent potentials. The wavepacket dynamics is simulated using both an exact quantum mechanical method and a classical Wigner prescription. The excellent agreement between the two methods shows that quantum coherences are not important in pure one-dimensional tunneling and reinforces the conclusion that the tunneling flight time vanishes.


Weight-bearing asymmetry in individuals post-hip fracture during the sit to stand task.
Individuals post hip fracture decrease force on the involved limb during sit to stand tasks, creating an asymmetry in vertical ground reaction force. Joint specific differences that underlie asymmetry of the vertical ground reaction force are unknown. The purpose of this study was to compare differences in vertical ground reaction force variables and joint kinetics at the hip and knee in participants post-hip fracture, who were recently discharged from homecare physical therapy to controls. Forty-four community-dwelling older adults, 29 who had a hip fracture and 15 elderly control participant's completed the sit to stand task on an instrumented chair with 3 force plates. T-tests were used to compare clinical tests (Berg Balance Scale, activity balance confidence and gait speed, isokinetic knee strength) and vertical ground reaction force variables. Two-way analyses of variance compared vertical ground reaction force variables and kinetics at the hip and knee between hip fracture and elderly control groups. Pearson correlation coefficients were used to determine correlations between clinical and vertical ground reaction force variables. Vertical ground reaction force variables were significantly lower on the involved side for the hip fracture group compared to the uninvolved side and controls. Lower involved side hip and knee moments and power contributed to lower involved side vertical ground reaction force. Vertical ground reaction force variables and strength had moderate to high correlations with clinical measures. Uninvolved side knee moments and powers were the largest contributors to asymmetrical vertical ground reaction force in participants post-hip fracture. The association of vertical ground reaction force variables and clinical measures of function suggesting reducing vertical ground reaction force asymmetry may contribute to higher levels of function post-hip fracture. Functional and strength training should target the involved knee to reduce vertical ground reaction force asymmetry.


[Staged reconstructive surgery for bronchopleural fistula].
Treatment of bronchopleural fistula after pneumonectomy is still an urgent problem for thoracic surgeons. Transsternal bronchial stump occlusion should be preferable if possible. However, this is not enough for curing in some cases. We present a patient with concomitant cancer and tuberculosis of lungs whose postoperative period was complicated by bronchial stump failure. Preoperative diagnostic data are presented. We describe the indications for surgeries and main surgical stages. Some interventions including reconstructive surgery using a muscle flap led to recovery. Latissimus dorsi muscle flap on thoracodorsal artery is the best option for reconstructive surgical treatment in patients with extensive chest wall defects and thoracostomy.


The role of abnormalities in the corpus callosum in social cognition deficits after Traumatic Brain Injury.
The corpus callosum (CC) is vulnerable to severe traumatic brain injury (TBI). Social cognition requires integration of non-verbal and verbal information in order to understand social behaviour and may be compromised if the CC is damaged. 17 adults with severe, chronic TBI and 17 control participants underwent structural MRI and Diffusion Tensor Imaging. A region of interest analysis examined fractional anisotropy (FA) and mean diffusivity (MD) across regions of the CC. Performance on The Awareness of Social Inference Test (TASIT): part 1 (emotion recognition) and parts 2 and 3 (social inference), was examined in relation to FA and MD. Across participants, higher genu FA values were related to higher TASIT part 3 scores. Increased splenium FA was associated with better performance for TASIT parts 1-3. There was no association between DTI values and TASIT in the controls alone. In the TBI group, FA of the genu and splenium was correlated with TASIT part 3. The pattern of performance was similar when controlling for non-social cognitive ability. In conclusion, social information is complex and multi-modal requiring inter-hemispheric connection. People with TBI, regardless of focal grey matter injury, may lose social cognitive ability due to trauma related changes to the corpus callosum.


Conflicting needs for a Salmonella hypervirulence gene in host and non-host environments.
The Gram-negative pathogen Salmonella enterica harbours a periplasmic D-Ala-D-Ala dipeptidase (termed PcgL), which confers the ability to grow on D-Ala-D-Ala as sole carbon source. We now demonstrate that inactivation of the pcgL gene renders Salmonella hypervirulent. This phenotype results from the accumulation of peptidoglycan-derived D-Ala-D-Ala in the pcgL mutant and not from an intrinsically faster growth rate. Synthetic D-Ala-D-Ala (but not L-Ala-L-Ala or D-Ala) increased the number of wild-type Salmonella in the liver and spleen of mice within 24 h of injection, suggesting that D-Ala-D-Ala interferes with some aspect of innate immunity. However, the pcgL mutant was unable to grow on D-Ala-D-Ala as sole carbon source and was defective for survival in nutrient-poor conditions. We identified clinical isolates lacking D-Ala-D-Ala dipeptidase activity and unable to grow on D-Ala-D-Ala because of inactivation of the pcgL gene. Our data suggest that genes (such as pcgL) that, when mutated make pathogens more virulent, may be retained because their contribution to pathogen fitness in non-host environments outweighs potential advantages of the hypervirulent vari-ant in the infected host.


Nurse practitioners changing health behaviours: one patient at a time.
In 2005, legislation was enacted allowing nurse practitioners (NPs) to practise in British Columbia, Canada. Although substantial human and financial resources had been dedicated to the implementation of the role, no evaluation has been conducted to date. As part of a larger multiphase, mixed-methods study design, which evaluated the integration of NPs into the British Columbia healthcare system, this article describes findings related to changes that result for patients and the implications for the healthcare system when NPs become part of the care process. Using survey and interview data, themes that emerged were patient satisfaction, access to care, and behavioural changes. Findings suggest that patients are satisfied with the care they receive from NPs and that NPs make positive changes to health behaviour.


Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits.
Surfactant protein B (SP-B) is an essential component of pulmonary surfactant, but shorter SP-B sequences may exert equivalent surface activity. We synthesised a peptide based on the amino-terminal domain of SP-B (SP-B1-25), a full length SP-B1-78, and a full length palmitoylated SP-C peptide (SP-C1-35) and compared the in vivo function and sensitivity to plasma inhibition of preparations consisting of mixtures of phospholipids with SP-B1-25 or SP-B1-78 and/or SP-C1-35 to Survanta. Preterm rabbits born at 27 days of gestation were treated at birth with surfactant and ventilated for 60 minutes. At 15 minutes half of them received plasma intratracheally. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured to define lung mechanics. Dynamic compliance and postmortem lung volumes were highest after treatment with a surfactant consisting of an SP-B peptide and SP-C1-35 or Survanta. Plasma instillation decreased dynamic compliance and lung volumes sharply, but the most effective activity was by prior instillation of surfactants containing SP-B1-25. These experiments suggest that the N-terminal domain of SP-B (SP-B1-25) exhibits in vitro and in vivo surface activity and is relatively insensitive to plasma inhibition.


Immunologic patterns in CAPD patients with peritonitis.
Alterations of peritoneal defense mechanisms, i.e. opsonization, phagocytosis, and bacterial killing, may be responsible for the high peritonitis rate in a subgroup of CAPD patients. Peritonitis incidence and in vitro bacterial opsonization has been shown to depend on IgG concentrations in the dialysate and on the ability of macrophages to produce fibronectin. Additionally, a high peritonitis incidence is associated with decreased bactericidal activity of macrophages; thus infective organisms may survive intracellularly despite intact phagocytosis. In some CAPD patients a disturbance in lymphokine and monokine release may be responsible for the reduced ability of their macrophages to kill bacteria.


Development of functional I f channels in mMSCs after transfection with mHCN4: effects on cell morphology and mechanical activity in vitro.
To study the functional properties of I(f) channels and the changes in mechanical activity of mouse mesenchymal stem cells (mMSCs) transfected with mHCN4. mMSCs were purified by using CD11b-immunomagnetic microbeads and transfected with pMSCV-mHCN4-EGFP or pMSCV-EGFP. We examined the kinetic characteristics of the mHCN4 channel. The morphological changes of positively transfected mMSCs were investigated at the same time. The I(f) current recorded from the experimental group was sensitive to extracellular Cs(+) (-44.5 +/- 4.2 vs. -5.5 +/- 1.0 pA/pF, p < 0.001). The half-maximal activation was -99.0 +/- 5.8 mV. The time constant of activation was 451 +/- 61 ms under -140 mV. The control cells did not show the current under the same conditions. The absolute values of half-maximal activation decreased in the presence of cAMP or cGMP in the experimental group (-78.6 +/- 10.4 and -85.7 +/- 8.6 vs. -99.0 +/- 5.8 mV, respectively, p < 0.05). mMSCs transfected with pMSCV-mHCN4-EGFP could form spontaneous beating cells. Extracellular Cs(+) decreased the beating rate significantly (196 +/- 50 vs. 66 +/- 23 bmp, p < 0.01). Functional I(f) channels can be reconstructed in mMSCs infected with mHCN4. mMSCs modified by successful transfection with mHCN4 can differentiate so as to develop spontaneous mechanical activity.


Parasympathetic reactivity and disruptive behavior problems in young children during interactions with their mothers and other adults: A preliminary investigation.
Parasympathetic nervous system influences on cardiac functions-commonly indexed via respiratory sinus arrhythmia (RSA)-are central to self-regulation. RSA suppression during challenging emotional and cognitive tasks is often associated with better emotional and behavioral functioning in preschoolers. However, the links between RSA suppression and child behavior across various challenging interpersonal contexts remains unclear. The present study experimentally evaluated the relationship between child RSA reactivity to adult (mother vs. study staff) direction and disruptive behavior problems in children ages 3-8 with varying levels of disruptive behavior problems (N = 43). Reduced RSA suppression in the context of mothers' play-based direction was associated with more severe child behavior problems. In contrast, RSA suppression in the context of staff play-based direction was not associated with behavior problems. Findings suggest that the association between RSA suppression and child behavior problems may vary by social context (i.e., mother vs. other adult direction-givers). Findings are discussed in regard to RSA as an indicator of autonomic self-regulation that has relevance to child disruptive behavior problems.


Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer.
To analyze if cell-free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing. The average cfDNA concentration was lower in patients of the study group (20±7 ng/μL) in comparison to controls (34±9 ng/μL) and this difference was statistically significant (p<0.001). The SNaPshot analysis detected KRAS c35 mutations in colorectal tumor tissue in 14 cases, but the presence of the mutation was not confirmed in cfDNA extracted from blood samples of these patients. The level of serum cfDNA in CRC is decreased in comparison to patients with hemorrhoids, which questions the usefulness of cfDNA as cancer biomarker. Also, cfDNA does not appear to be suitable as a source for mutation detection in this disease.


[Conformation and Raman spectra of the transfer ribonucleic acid, tRNAAsp].
The structure of yeast tRNAasp in aqueous solution has been studied in sight of Raman spectra recorded between 5 and 82 degrees C. A conformational change is evidenced at 20 degrees C and an endomelting is found around 70 degrees C. This melting temperature, much higher than in tRNA-phe (near 50 degrees C) is interpreted by the presence of a higher number of G-C bases in t RNA asp. At a same temperature, the Raman spectrum of a tRNAasp crystal is quasi-identical than that of an aqueous solution, indicating a high structural similarity except bands corresponding to G, C bases which show a more effective stacking of these bases in the solid.


FKS2 and FKS3 Genes of Opportunistic Human Pathogen Candida albicans Influence Echinocandin Susceptibility.
Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous FKS genes that are evolutionarily conserved. One of these, the essential gene FKS1, encodes the catalytic subunit of glucan synthase, which is the target of echinocandin drugs and also serves as a site of drug resistance. The other two glucan synthase-encoding genes, FKS2 and FKS3, are also expressed, but their roles in resistance are considered unimportant. However, we report here that expression of FKS1 is upregulated in strains lacking either FKS2 or FKS3 Furthermore, in contrast to what is observed in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs, and consistently are tolerant to cell wall-damaging agents. Our data indicate that C. albicansFKS2 and FKS3 can act as negative regulators of FKS1, thereby influencing echinocandin susceptibility.


Prophylactic Treatment of Migraine.
Migraine is a common chronic neurological disease characterized by episodic attacks of headache and associated symptoms. The pharmacological treatment of migraine may be acute or prophylactic, and patients with frequent, severe headaches often require both approaches. Prophylactic treatment is used to reduce the frequency, duration, or severity of attacks, to enhance the benefits of acute treatments, and to improve patient's ability to function normally. Prophylactic treatment may also prevent progression from episodic migraine to chronic migraine and may result in reductions in health-care cost. The currently available pharmacological options for migraine prophylaxis include a wide array of medications. The major medication groups for prophylactic treatment include β-blockers, anticonvulsant, drugs such as topiramate and valproate, antidepressant drugs, such as amitriptyline and selective serotonin and selective serotonin-norepinephrine reuptake inhibitors (SNRIs), calcium channel antagonists and neurotoxins. The agent for prophylactic treatment should be chosen based on the efficacy and side-effect profile of the drug, and the patient's coexistent and comorbid conditions.


PDCD1 PD-1.3 polymorphism and allergic bronchial asthma in Russian and Buryat patients.
The programmed death-1 receptor, PD-1, is a negative regulator of T-cell activation. The PD-1.3 polymorphism of the PD-1 gene (PDCD1) has been previously shown to be associated with several autoimmune and inflammatory disorders including systemic lupus erythematosus and multiple sclerosis. We examined for the first time PD-1.3 association with another inflammatory disease with strong immune component, IgE-mediated bronchial asthma, its severity and its biochemical markers (total serum IgE and IL-4). PD-1.3 G/A was genotyped by PCR-RFLP analysis using two different populations: Caucasian (492 Russian individuals) and Asian (276 Buryat individuals). We found a significant association of the PD-1.3 polymorphism with IgE-mediated bronchial asthma and total serum IgE level in the Russian population. Combined genotype AA+AG was correlated with risk of developing allergic bronchial asthma (OR = 1.78, 95% CI 1.13-2.78, p = 0.011) and lower concentrations of total serum IgE (p = 0.001) compared with the wild-type genotype GG. However, PD-1.3 was not polymorphic in the Buryat population. PD-1.3 polymorphism of the PD-1 gene (PDCD1) may contribute to the development of allergic asthma in the Russians but not in the Buryats. Our results could be helpful for a better understanding of the effect of this polymorphism on the development of diseases with strong immune components.


Beyond depression: examining the role of anxiety and anxiety sensitivity on subjective cognition and functioning in older adults.
Subjective cognitive difficulties in the elderly may serve as potential risk-factors for future, objective decline and conversion to neurodegenerative disorders (e.g., mild cognitive impairment [MCI] and dementia). Though these subjective declines have been associated with depression, and to a lesser extent, anxiety, it is unknown if related constructs (e.g. anxiety sensitivity) and specific kinds of worries (e.g. worry about developing dementia, health anxiety) are related to subjective declines. The current study sought to examine if cognitive concerns related to anxiety sensitivity, dementia worry, and health anxiety added incremental validity beyond general symptoms of anxiety and depression in predicting subjective cognition and functioning in a sample of older adults. Participants were 429 older adults who were at least 60 years old. Participants completed questionnaires on subjective cognition, subjective everyday function, anxiety, depression, anxiety sensitivity, dementia worry, and health anxiety via Qualtrics Panels. Hierarchical multiple regressions were conducted. Our variables of interest (anxiety sensitivity, dementia worry, and health anxiety) added significant variance in predicting subjective cognition and everyday function. Specifically, anxiety sensitivity was related to subjective cognition and functioning, while dementia worry and health anxiety were variably associated. Our results suggest that constructs related to anxiety and worry have a significant relationship with subjective cognition and function in older adults beyond general symptoms of depression and anxiety. Future work should examine if interventions and education may help to decrease anxiety sensitivity and worry about dementia respectively in older adults, which may in tern protect against future subjective declines.


Deep vs. Shallow Learning-based Filters of MSMS Spectra in Support of Protein Search Engines.
Despite the linear relation between the number of observed spectra and the searching time, the current protein search engines, even the parallel versions, could take several hours to search a large amount of MSMS spectra, which can be generated in a short time. After a laborious searching process, some (and at times, majority) of the observed spectra are labeled as non-identifiable. We evaluate the role of machine learning in building an efficient MSMS filter to remove non-identifiable spectra. We compare and evaluate the deep learning algorithm using 9 shallow learning algorithms with different configurations. Using 10 different datasets generated from two different search engines, different instruments, different sizes and from different species, we experimentally show that deep learning models are powerful in filtering MSMS spectra. We also show that our simple features list is significant where other shallow learning algorithms showed encouraging results in filtering the MSMS spectra. Our deep learning model can exclude around 50% of the non-identifiable spectra while losing, on average, only 9% of the identifiable ones. As for shallow learning, algorithms of: Random Forest, Support Vector Machine and Neural Networks showed encouraging results, eliminating, on average, 70% of the non-identifiable spectra while losing around 25% of the identifiable ones. The deep learning algorithm may be especially more useful in instances where the protein(s) of interest are in lower cellular or tissue concentration, while the other algorithms may be more useful for concentrated or more highly expressed proteins.