[RNA, unlike DNA, binds to aurintricarboxylic acid via covalent bonds: molecular-biological and spectroscopic evidence].
A selective interaction of ATA with RNA, unlike DNA, when isolating nucleic acids from plant materials was established. The data concerning the binding strength of highly purified RNAATA and DNAATA preparations to nitrocellulose and nylon filters under conditions of high ionic strength are presented. The interrelation of ATA RNA-tropism and absence of adsorption capability of chemical modified RNAATA the backbone was observed. Using IR spectroscopy under the procedure of multi-broken complete light reflection, a formation of ATA and RNA complex was fixed via phosphoric-ether bond (P-O-C), which was absent in the case of DNAATA. The obtained data raise the problem of RNAATA application in molecular biology experiments.


Effects of cigarette smoke and dietary vitamin E levels on selected lung and hepatic biotransformation enzymes in mice.
Young male C57BL mice were exposed nose-only to cigarette smoke 20 min/day for 8 weeks while maintained on diets containing 0, 5, and 100 ppm of vitamin E. Smoking had no effect on hepatic aryl hydrocarbon hydroxylase (AHH), UDP-glucuronyltransferase, glutathione S-transferase, parathion desulfurase, or parathion esterase activity. Lung AHH activity was increased in all smoke-exposed mice, although the increase was significantly less in animals maintained on the vitamin E-free diet. All mice on the vitamin E-free diet showed reduced lung AHH activity and increased hepatic lipid peroxidation. No other biotransformations tested were significantly altered by varying vitamin E concentrations alone or in combination with cigarette smoke. For all vitamin E diets, both the smoke-exposed and sham-treated mice gained significantly less weight than the control animals. This effect was attributed to stress induced by restraint of the animals within the smoking apparatus. The results of these experiments show that both cigarette smoke and vitamin E-deficient diets may affect xenobiotic metabolism but that the combination does not appear to alter markedly their individual effects or to induce ones not previously observed.


Noninvasive Hemodynamic Measurements During Neurosurgical Procedures in Sitting Position.
Neurosurgical procedures in sitting position need advanced cardiovascular monitoring. Transesophageal echocardiography (TEE) to measure cardiac output (CO)/cardiac index (CI) and stroke volume (SV), and invasive arterial blood pressure measurements for systolic (ABPsys), diastolic (ABPdiast) and mean arterial pressure (MAP) are established monitoring technologies for these kind of procedures. A noninvasive device for continuous monitoring of blood pressure and CO based on a modified Penaz technique (volume-clamp method) was introduced recently. In the present study the noninvasive blood pressure measurements were compared with invasive arterial blood pressure monitoring, and the noninvasive CO monitoring to TEE measurements. Measurements of blood pressure and CO were performed in 35 patients before/after giving a fluid bolus and a change from supine to sitting position, start of surgery, and repositioning from sitting to supine at the end of surgery. Data pairs from the noninvasive device (Nexfin HD) versus arterial line measurements (ABPsys, ABPdiast, MAP) and versus TEE (CO, CI, SV) were compared using Bland-Altman analysis and percentage error. All parameters compared (CO, CI, SV, ABPsys, ABPdiast, MAP) showed a large bias and wide limits of agreement. Percentage error was above 30% for all parameters except ABPsys. The noninvasive device based on a modified Penaz technique cannot replace arterial blood pressure monitoring or TEE in anesthetized patients undergoing neurosurgery in sitting position.


Electrode and cuvette for rapid continuous CO2 tension and pH measurement in blood.
An electrode and cuvette system has been developed for the continuous and rapid measurement of either blood CO2 tension or pH. The CO2 electrode consists of a 1.5-mm-diameter flat-tip glass pH electrode covered by a film of carbonic anhydrase solution, over which a 25-micron-thick dimethyl silicone membrane is attached. Porous ceramic filled with 20% polyacrylamide, equilibrated with a salt solution, serves as a salt bridge between a Ag-AgCl reference electrode and the pH electrode surface. The electrode is housed in a four-port cuvette assembly. Blood from a vessel of interest is delivered to the cuvette by means of an occlusive roller pump. The cuvette maintains the electrode and blood at a constant temperature and directs a continuous jet of blood against the electrode surface. The cuvette also allows for easy and frequent calibration of the electrode with either gas or liquid standards. The 90% response time of the CO2 electrode is 3.0 s for liquids and 1.3 s for gases. Removal of the dimethyl silicone membrane and carbonic anhydrase film yields a pH electrode that can continuously measure blood pH with a 90% response time of 1.6 s.


Clinical boundaries in adult cases of large B cell lymphoma with IRF4 rearrangement.
Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) is a recently described entity included in the revised 4th edition of the WHO Classification of Haematolymphoid Tumours (2017). Here we highlight the difficulties in classification of those cases which arise in adult patients with unusual clinical features. We present three cases with morphological and immunohistochemical features consistent with large B-cell lymphoma arising in adult patients, which were found to have isolated IRF4 rearrangements on FISH analysis. Each patient presented with advanced-stage disease and had a history of immunosuppression; clinical features that are not typical of LBCL-IRF4 and which make the distinction from DLBCL, not otherwise specified (NOS) challenging. We propose that the clinical boundaries of LBCL-IRF4 arising in adult patients need further delineation to allow distinction from true cases of DLBCL, NOS.


Physiotherapy clinical education in Australia: an exploration of clinical educator characteristics, confidence and training requirements.
Objectives The aim of this study was to describe physiotherapists' involvement, confidence and training needs in the provision of student clinical education (CE) in Australia. Methods A valid and reliable cross-sectional online survey instrument was used to collect data from physiotherapists employed in public and private healthcare facilities in Australia. Survey questions included participant personal and professional characteristics, participation in CE-related continuing professional development (CPD) and confidence in components of CE. Results In all, 170 (34%) physiotherapists (mean age 37 years; mean years clinical experience 13 years) completed the survey. Most participants (68%) were currently involved in CE, over half (56%) had completed CE-related CPD and many (56%) reported a need for more CPD. Participants with no previous CE experience were less confident (P≤0.05) in all components of CE. Participants with less clinical experience were less confident in managing challenging students (P=0.003), multiple students (P=<0.001) and competing workplace and education duties (P=<0.001). Conclusions Physiotherapists with varying professional characteristics were involved in CE. Although many participants had attended CE-related CPD, many reported that more training was required. Future training for clinical educators should be tailored to participants' level of experience and focus on the components of CE in which they feel least confident. What is known about the topic? The ability of physiotherapists to confidently assume a clinical educator role may affect their willingness to be clinical educators in the future and the students' perceptions of clinical placement quality. CPD relating to CE may help prepare physiotherapists for the clinical educator role. What does this paper add? There is a lack of information regarding physiotherapists' involvement in CE, completion of CE-related CPD or perceived levels of confidence in various aspects of the clinical educator role, such as placement organisation, teaching, assessment and the provision of feedback. This study describes the involvement of physiotherapists in CE in Australia, including their demographic and professional characteristics, participation in CE-related CPD and confidence in various components of CE. What are the implications for practitioners? Several recommendations regarding future CE-related CPD have resulted from this study, including tailoring CPD to the needs of physiotherapists based on their level of clinical or CE experience, focusing CPD on the aspects of CE in which physiotherapists feel least confident and raising the awareness of and improving accessibility to CPD opportunities in this area.


Family transfers and long-term care: An analysis of the WHO Study on global AGEing and adult health (SAGE).
Populations globally are ageing, resulting in increased need for long-term care. Where social welfare systems are insufficient, these costs may fall to other family members. We set out to estimate the association between long-term care needs and family transfers in selected low- and middle- income countries. We used data from the World Health Organization's Study on global AGEing and adult health (SAGE). Using regression, we analysed the relationship between long-term care needs in older households and i) odds of receiving net positive transfers from family outside the household and ii) the amount of transfer received, controlling for relevant socio-demographic characteristics. The proportion of household members requiring long-term care was significantly associated with receiving net positive transfers in China (OR: 1.76; p = 0.023), Ghana (OR: 2.79; p = 0.073), Russia (OR: 3.50; p < 0.001). There was a statistically significant association with amount of transfer received only in Mexico (B: 541.62; p = 0.010). In selected LMICs, receiving family transfers is common among older households, and associated with requiring long-term care. Further research is needed to better understand drivers of observed associations and identify ways in which financial protection of older adults' long-term care needs can be improved.


Molecular cloning and expression in COS-1 cells of pig kidney aminopeptidase P.
Aminopeptidase P (AP-P; X-Pro aminopeptidase; EC 22.214.171.124), a key enzyme in the metabolism of the vasodilator bradykinin, has been cloned from a pig kidney cortex cDNA library following the use of the PCR to identify sub-libraries enriched in AP-P clones. The complete primary sequence of the enzyme has been deduced from a full-length cDNA clone. This predicts a protein of 673 amino acids with a cleavable N-terminal signal sequence and six potential N-linked glycosylation sites. A stretch of mainly hydrophobic amino acids at the C-terminus is predicted to co-ordinate the attachment of a glycosyl-phosphatidylinositol (GPI) membrane anchor. Although AP-P is a zinc metallopeptidase, the predicted primary sequence does not contain any recognizable zinc-binding motif. Transient expression of AP-P cDNA in COS-1 cells resulted in enzymic activity characteristic of AP-P, namely apstatin- and EDTA-sensitive hydrolysis of bradykinin and Gly-Pro-Hyp. The expressed protein was recognized as a polypeptide of M(r)91,000 under reducing conditions, following immunoblotting of COS-1 membranes with a polyclonal antibody raised against purified pig kidney AP-P. The presence of a GPI anchor on expressed AP-P was established by demonstrating release of the enzyme from a membrane fraction following treatment with bacterial phosphatidylinositol-specific phospholipase C and its corresponding conversion from an amphipathic to a hydrophilic form, as assessed by phase separation in Triton X-114. Sequence comparisons confirm that AP-P is a member of the proline peptidase family of hydrolytic enzymes and is unrelated in sequence to other brush-border membrane peptidases.


Diversification of myco-heterotrophic angiosperms: evidence from Burmanniaceae.
Myco-heterotrophy evolved independently several times during angiosperm evolution. Although many species of myco-heterotrophic plants are highly endemic and long-distance dispersal seems unlikely, some genera are widely dispersed and have pantropical distributions, often with large disjunctions. Traditionally this has been interpreted as evidence for an old age of these taxa. However, due to their scarcity and highly reduced plastid genomes our understanding about the evolutionary histories of the angiosperm myco-heterotrophic groups is poor. We provide a hypothesis for the diversification of the myco-heterotrophic family Burmanniaceae. Phylogenetic inference, combined with biogeographical analyses, molecular divergence time estimates, and diversification analyses suggest that Burmanniaceae originated in West Gondwana and started to diversify during the Late Cretaceous. Diversification and migration of the species-rich pantropical genera Burmannia and Gymnosiphon display congruent patterns. Diversification began during the Eocene, when global temperatures peaked and tropical forests occurred at low latitudes. Simultaneous migration from the New to the Old World in Burmannia and Gymnosiphon occurred via boreotropical migration routes. Subsequent Oligocene cooling and breakup of boreotropical flora ended New-Old World migration and caused a gradual decrease in diversification rate in Burmanniaceae. Our results indicate that extant diversity and pantropical distribution of myco-heterotrophic Burmanniaceae is the result of diversification and boreotropical migration during the Eocene when tropical rain forest expanded dramatically.


Release of high molecular weight DNA from Neurospora crassa using enzymic digestions.
Methods are described that allow extraction of high molecular weight DNA from germinated conidia of Neurospora crassa. By labelling DNA with ribonucleosides, early conidia were shown to be active in DNA synthesis. These cells when treated with the enzyme Zymolyase became fragile and could be readily lysed with ionic detergents to release high molecular weight DNA. The DNA extracted from Zymolyase treated cells on to alkaline sucrose gradients sedimented as a heterogeneous species of up to 150 x 10(6) molecular weight. A minor DNA species (presumably mitochondrial) of 20 x 10(6) molecular weight comprised 2-7% of the total. The identity of the DNA was confirmed by sensitivity to DNAase, the diphenylamine assay and TLC. Sedimentation patterns were unaffected by protease digestions and no anomalous high speed rotor effects were evident. Isopycnic gradients suggested that the DNA released was uncomplexed with either protein or carbohydrates. Sepharose chromatography of extracted, RNAase-treated Zymolyase lysate resulted in clearly separate high molecular weight DNA and RNA-protein elution profiles. UV light preferentially inhibited nuclear DNA synthesis and drastically reduced the size and amount of nascent DNA being synthesized in the excision defective uvs-2 mutant. Sites in parental DNA sensitive to Micrococcus luteus UV endonuclease were measured in cells made permeable with Triton X-100.


A new Early Permian reptile and its significance in early diapsid evolution.
The initial stages of evolution of Diapsida (the large clade that includes not only snakes, lizards, crocodiles and birds, but also dinosaurs and numerous other extinct taxa) is clouded by an exceedingly poor Palaeozoic fossil record. Previous studies had indicated a 38 Myr gap between the first appearance of the oldest diapsid clade (Araeoscelidia), ca 304 million years ago (Ma), and that of its sister group in the Middle Permian (ca 266 Ma). Two new reptile skulls from the Richards Spur locality, Lower Permian of Oklahoma, represent a new diapsid reptile: Orovenator mayorum n. gen. et sp. A phylogenetic analysis identifies O. mayorum as the oldest and most basal member of the araeoscelidian sister group. As Richards Spur has recently been dated to 289 Ma, the new diapsid neatly spans the above gap by appearing 15 Myr after the origin of Diapsida. The presence of O. mayorum at Richards Spur, which records a diverse upland fauna, suggests that initial stages in the evolution of non-araeoscelidian diapsids may have been tied to upland environments. This hypothesis is consonant with the overall scant record for non-araeoscelidian diapsids during the Permian Period, when the well-known terrestrial vertebrate communities are preserved almost exclusively in lowland deltaic, flood plain and lacustrine sedimentary rocks.


Contact electrification induced interfacial reactions and direct electrochemical nanoimprint lithography in n-type gallium arsenate wafer.
Although metal assisted chemical etching (MacEtch) has emerged as a versatile micro-nanofabrication method for semiconductors, the chemical mechanism remains ambiguous in terms of both thermodynamics and kinetics. Here we demonstrate an innovative phenomenon, i.e., the contact electrification between platinum (Pt) and an n-type gallium arsenide (100) wafer (n-GaAs) can induce interfacial redox reactions. Because of their different work functions, when the Pt electrode comes into contact with n-GaAs, electrons will move from n-GaAs to Pt and form a contact electric field at the Pt/n-GaAs junction until their electron Fermi levels (EF) become equal. In the presence of an electrolyte, the potential of the Pt/electrolyte interface will shift due to the contact electricity and induce the spontaneous reduction of MnO4- anions on the Pt surface. Because the equilibrium of contact electrification is disturbed, electrons will transfer from n-GaAs to Pt through the tunneling effect. Thus, the accumulated positive holes at the n-GaAs/electrolyte interface make n-GaAs dissolve anodically along the Pt/n-GaAs/electrolyte 3-phase interface. Based on this principle, we developed a direct electrochemical nanoimprint lithography method applicable to crystalline semiconductors.


Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo.
MAP (mitogen-activated protein) kinase is shown to phosphorylate baculovirally expressed Raf-1 in vitro, generating one major tryptic phosphopeptide which co-migrated with a peptide from Raf-1 32P-labelled in situ. This peptide also undergoes an insulin-dependent increase in labelling. Thus the serine/threonine kinase Raf-1 may be a substrate for MAP kinase in vivo.


[Electroophthalmological, Fluorescence angiographical and computer perimetrical examinations in cases of contusio bulbi (author's transl)].
In seven patients with diminished visual acuity, caused by oedema of the retina after contusio bulbi, the EOG, the photopic and the scotopic ERG as well as the VECP, elicited by luminance (H-EP) on the one hand and by pattern reversal-stimulation (M-EP) on the other hand, were registered. These registrations were made both during and after the acute phase. The results were then compared with the results of the normal fellow eyes. Additional fluorescence-angiographic and computer-perimetric examinations were performed. All EOG and ERG components studied showed a significant reduction in the acute phase and a significant increase -- with the exception of the photopic b-wave -- in the regression of the oedema of the retina. However, the values of the affected eyes never reached the values of the normal fellow eyes. The different behaviour of the H-EPs and the M-EPs is striking. While the medium values of the H-EPs showed little reduction in all examinations, the M-EPs showed a highly significant decrease or increase, with the visual acuity and the M-EP showing corresponding behaviour.


Fatty acid-induced endoplasmic reticulum stress promoted lipid accumulation in calf hepatocytes, and endoplasmic reticulum stress existed in the liver of severe fatty liver cows.
Disruption of endoplasmic reticulum (ER) homeostasis, often termed ER stress, is intrinsically linked with perturbation of lipid metabolism in humans and mice. Whether ER homeostasis is affected in cows experiencing fatty liver is unknown. The aim of this study was to investigate the potential role of ER stress in hepatic lipid accumulation in calf hepatocytes and ER stress status in dairy cows with severe fatty liver. In vitro experiments were conducted in which hepatocytes were isolated from calves and treated with different concentrations of fatty acids, tauroursodeoxycholic acid (TUDCA; a canonical inhibitor of ER stress), or both. The increase in phosphorylation level of protein kinase RNA-like ER kinase (PERK) and inositol requiring protein-1α (IRE1α) proteins, and the cleavage of activating transcription factor-6 (ATF6) protein in response to increasing doses of fatty acids (which were reversed by TUDCA treatment) in primary hepatocytes underscored a mechanistic link between fatty acids and ER stress. In addition, fatty acid treatment increased the abundance of sterol regulatory element-binding protein 1c, acetyl-CoA carboxylase-α, fatty acid synthase, and diacylglycerol acyltransferase 1, and lipid accumulation in calf primary hepatocytes, whereas inhibition of ER stress by incubating with TUDCA significantly weakened these effects. Overall, results in vitro indicate that inhibition of ER stress in calf hepatocytes alleviates fatty acid-induced lipid accumulation by downregulating the expression of lipogenic genes. In vivo experiments, liver and blood samples were collected from cows diagnosed as healthy (n = 15) or with severe fatty liver (n = 15). The phosphorylation level of PERK and IRE1α, the cleavage of ATF6 protein, and the abundance of several unfolded protein response genes (78 kDa glucose-regulated protein, AMP-dependent transcription factor 4, and spliced X-box binding protein 1) were greater in liver of cows with severe fatty liver. The present in vivo study confirms the occurrence of ER stress in dairy cows with severe fatty liver. Considering the causative role of fatty acid-induced ER stress in hepatic lipid accumulation in calf hepatocytes, the existence of ER stress in the liver of severe fatty liver cows may presage its participation in fatty liver progression in dairy cows. However, the mechanistic relationship between ER stress and fatty liver in dairy cows remain to be determined.


Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary Tuberculosis.
Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10× albumin (g/dL) + 0.005× lymphocyte count (/μL)," was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p<0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smear-positive HIV-negative pulmonary tuberculosis inpatients.


Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study.
Tetrahydrocurcumin (THC) also referred to as 'white curcumin', is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6 nm and zeta potential of -22 mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51% ± 2.15% and 69.56% ± 1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi's equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p ≤ 0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.


Modeling of atmospheric disturbances in meteorological pictures.
This paper describes a model-based approach to perform tracking of extratropical atmospheric disturbances from a sequence of satellite cloud-cover images. More precisely, it deals with the estimation of motion of these spiral-shaped cloud systems (both translational and rotational motion), and the measurement of the evolution of their shape. Tracking is achieved by recording from one image to the next the changes of the model parameter values. A maximum likelihood criterion is used in the process of fitting model to sensed data. The defined model takes into account geometric and intensity aspects. Such an approach readily yields global information on the disturbance cloud system of interest. As a requirement in such an application is robustness to noise, to this end two versions of the modeling have been considered.


Peace through a healing transformation of human dignity: possibilities and dilemmas in global health and peace.
Collective violence leads to grievous harm for affected populations, impacting both combatants and noncombatants. In recent years there has been an increased focus on the relationship between peace and health, with the World Health Organization calling for health professionals to engage in efforts to promote peace. While the notion of "health as a bridge for peace" is promising, there are many ambiguities in this emerging field, creating moral and practical dilemmas. In this manuscript I will discuss some of the challenges within the paradigm of health and peace using an exemplar of my research within the Israeli-Palestinian conflict.


Pharmacologic considerations in the treatment of injured athletes with nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve discomfort and enhance the rate of recovery from athletic injuries. A clear understanding of general pharmacologic principles may help the health care professional to optimize therapeutic outcomes and minimize undesirable effects. Such principles include onset and duration of drug action, potency, half-life, steady state, and the impact of exercise and disease on drug absorption, metabolism, and excretion. I searched the MEDLINE and CINAHL data- bases from 1983 to 1997 for the terms "anti-inflammatory drugs," "NSAIDs," "sports medicine," "injury," and "rehabilitation." The NSAIDs exert their mechanism of action primarily through the inhibition of arachidonic acid metabolism. A basic understanding of this mechanism on the part of the health care professional facilitates an understanding of potential side effects and drug interactions, especially those related to increased blood clotting time, diminished kidney function, and occurrence of gastrointestinal discomfort. The effectiveness of NSAIDs in increasing the rate of healing and relieving pain and inflammation can be affected by variables such as the extent of injury, drug dosing, duration of therapy, and the specific drug used. SOME GENERAL THERAPEUTIC CONCEPTS THAT SHOULD BE CONSIDERED BEFORE USING NSAIDS INCLUDE THE FOLLOWING: (1) Only 1 of these agents should be used at a time in a patient. (2) They should preferably be given with food. (3) Specific outcomes should be delineated. (4) Each patient's physical condition and medical history should be considered before NSAIDs are instituted.


Association of Age, Systolic Blood Pressure, and Heart Rate with Adult Morbidity and Mortality after Urgent Care Visits.
Little data exists to help urgent care (UC) clinicians predict morbidity and mortality risk. Age, systolic blood pressure (SBP), and heart rate (HR) are easily obtainable and have been used in other settings to predict short-term risk of deterioration. We hypothesized that there is a relationship between advancing age, SBP, HR, and short-term health outcomes in the UC setting. We collected retrospective data from 28 UC clinics and 22 hospitals in the Intermountain Healthcare system between years 2008-2013. Adult patients (≥18 years) were included if they had a unique UC visit and HR or SBP data. Three endpoints following UC visit were assessed: emergency department (ED) visit within three days, hospitalization within three days, and death within seven days. We analyzed associations between age, SBP, HR and endpoints using local regression with a binomial likelihood. Five age groups were chosen from previously published national surveys. Vital sign (VS) distributions were determined for each age group, and the central tendency was compared against previously published norms (90-120mmHg for SBP and 60-100bpm for HR.). A total of 1,720,207 encounters (714,339 unique patients) met the inclusion criteria; 51,446 encounters (2.99%) had ED visit within three days; 12,397 (0.72%) experienced hospitalization within three days; 302 (0.02%) died within seven days of UC visit. Heart rate and SBP combined with advanced age predicted the probability of ED visit (p<0.0001) and hospitalization (p<0.0001) following UC visit. Significant associations between advancing age and death (p<0.0001), and VS and death (p<0.0001) were observed. Odds ratios of risk were highest for elderly patients with lower SBP or higher HR. Observed distributions of SBP were higher than published normal ranges for all age groups. Among adults seeking care in the UC, associations between HR and SBP and likelihood of ED visits and hospitalization were more pronounced with advancing age. Death following UC visit had a more limited association with advancing age or the VS evaluated. Rapidly increasing risk below SBP of 100-110 mmHg in older patients suggests that accepted normal ranges for SBP may need to be redefined for patients treated in the UC clinic.


[The estimation of ionizing irradiation impact on Vicia cracca cenopopulations growing on the territory contaminated with the wastes of radium production].
The radiation exposure on cenopopulations Vicea cracca L. growing on the territory contaminated with the wastes of radium production was estimated. The relationship between the chromosome aberration in seedlings root tip cells and irradiation dose was found to be linear. The significant cytogenetic effects in chronically irradiated Vicia cracca cenopopulation are observed at doses (equal to 0.006-0.7 Gy) 10 times upward the natural radiation background level. The reduced reproductive success (significantly increased embryonic lethal mutation level) is observed at weighted absorbed doses (equal to 0.2-0.7 Gy) up to 200-700 times higher than the natural radiation background level. It is showh, that the radiation hygienic standards of permissible exposure are noticeably stricter that the radioecological limits.


Identification of rare alleles and their carriers using compressed se(que)nsing.
Identification of rare variants by resequencing is important both for detecting novel variations and for screening individuals for known disease alleles. New technologies enable low-cost resequencing of target regions, although it is still prohibitive to test more than a few individuals. We propose a novel pooling design that enables the recovery of novel or known rare alleles and their carriers in groups of individuals. The method is based on a Compressed Sensing (CS) approach, which is general, simple and efficient. CS allows the use of generic algorithmic tools for simultaneous identification of multiple variants and their carriers. We model the experimental procedure and show via computer simulations that it enables the recovery of rare alleles and their carriers in larger groups than were possible before. Our approach can also be combined with barcoding techniques to provide a feasible solution based on current resequencing costs. For example, when targeting a small enough genomic region (∼100 bp) and using only ∼10 sequencing lanes and ∼10 distinct barcodes per lane, one recovers the identity of 4 rare allele carriers out of a population of over 4000 individuals. We demonstrate the performance of our approach over several publicly available experimental data sets.


Corticosteroids for the management of cancer-related pain in adults.
One of the most feared symptoms associated with cancer is pain. Opioids remain the mainstay of pain treatment but corticosteroids are often used concurrently as co- or adjuvant analgesics. Due to their anti-inflammatory mechanism of action, corticosteroids are said to provide effective analgesia for pain associated with inflammation and in the management of cancer-related complications such as brain metastasis and spinal cord compression. However, corticosteroids have a wide range of adverse effects that are dose and time dependent. To evaluate the efficacy of corticosteroids in treating cancer-related pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 4), MEDLINE (OVID) (1966 to 29 September 2014), EMBASE (OVID) (1970 to 29 September 2014), CINAHL (1982 to 29 September 2014), Science Citation Index (Web of Science) (1899 to 29 September 2014) and Conference Proceedings Citation Index - Science (Web of Science) (1990 to 29 September 2014). Any randomised or prospective controlled trial that included patients over 18 years with cancer-related pain were eligible for the review. Corticosteroids were compared to placebo or usual treatment and/or supportive care. All review authors independently assessed trial quality and extracted data. We used arithmetic means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). Fifteen studies met the inclusion criteria, enrolling 1926 participants. The trial size varied from 20 to 598 patients. Most studies compared corticosteroids, particularly dexamethasone, to standard therapy. We included six studies with data at one week in the meta-analysis for pain intensity; no data were available at that time point for the remaining studies. Corticosteroid therapy resulted in less pain (measured on a scale of 0 to 10 with a lower score indicating less pain) compared to control at one week (MD 0.84 lower pain, 95% CI 1.38 to 0.30 lower; low quality evidence). Adverse events were poorly documented. Factors limiting statistical analysis included the lack of standardised measurements of pain and the use of different agents, dosages, comparisons and routes of drug delivery. Subgroup analysis according to type of cancer was not possible. The quality of this evidence was limited by the risk of bias of the studies and small sample size. The results were also compromised by attrition, with data missing for the enrolled patients. The evidence for the efficacy of corticosteroids for pain control in cancer patients is weak. Significant pain relief was noted in some studies, albeit only for a short period of time. This could be important for patients with poor clinical status. Further trials, with increased numbers of participants, are needed to evaluate the safety and effectiveness of corticosteroids for the management cancer pain in adults, and to establish an ideal dose, duration of therapy and route of administration.


Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine.
Citrus aurantium L. (bitter orange) extracts that contain p-synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p-synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p-synephrine. Numerous studies have been conducted with respect to p-synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p-synephrine exerts its effects through multiple actions, which are discussed. Because p-synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.


[Sugary drinks and glycemia].
Obesity prevalence is increasing all over the world. Most affected are people changing from a traditional lifestyle to an environment with both availability of high energy diet and less physical activity. Glycemic index (GI) is a measure of dietary glycemic carbohydrates, representing their ability to raise blood glucose concentrations. It refers to the postprandial blood glucose response expressed as a percentage of the response to a reference food (glucose or white bread) containing the same carbohydrate content. Given the present high consumption of sugary drinks, the putative contribution of these products to obesity deserves investigation. The aim of this study was to determine the GI of some drinks from the Portuguese market. Postprandial glycemia after ingestion of apple Frutis, peach Frutis, Green tea Frutea, green tea, black tea, lupin infusion, rooibos infusion, raftilose solution or bran solution has been determined for two hours in a caucasian population of young adults of any sex, 17 to 24 years of age. Apple Frutis GI was found to be 54.3, i.e., a low GI; Frutea Green tea had a GI of 64.7, considered as a moderate GI; peach Frutis showed a high GI, 86.6. Green and Black teas as well as rooibos and lupin infusions, all with added glucose (25 g), did not change glycemic response in comparison with the reference solution (water with 25 g glucose). No differences were seen after raftilose and bran solutions by comparison with the reference solution. GI information may help the choice of carbohydrates to include in a healthy diet. Formerly considered as a parameter of interest to diabetic patients, it may actually interest anybody concerned with a healthy diet. This study has been performed by medical and nutritional science students, who observed glycemic excursions in themselves, after drink ingestion. This experiment allowed them to see the impressive rise of glycemia after ingestion of a sugary drink, by comparison with basal levels which would not rise if plain water or other nonsugary drink had been ingested.


Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope®.
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScope® registry. For 208 Scedosporium spp. infections solid organ transplantation (n = 58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n = 28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n = 26, 46.4% versus n = 12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificans.


Reliability of 3H-thymidine labeling index: cell proliferation of colorectal carcinoma in three different centers.
Although the 3H-thymidine labeling index (TLI) has been used extensively as a biologic marker of increased susceptibility to neoplasms or as a prognostic indicator of the clinical outcome in cancer patients, there is still some concern regarding its accuracy and reliability as a marker of cell replication. A study on the prognostic value of TLI in colorectal cancer gave us the ability to evaluate how such a measurement may vary in different laboratories. A total of 150 malignant tumors of the large bowel were studied in the period from 1988 to 1989. Microautoradiography was carried out in tumor fragments taken at surgery. There were only slight differences among the three centers involved in the investigation, mainly as regards the culture medium, exposure time, and the addition of O2 + CO2 during the incubation. No significant difference was observed among TLI values recorded in the three centers (18.3 +/- 0.9; 17.4 +/- 0.9; 15.7 +/- 1.0 mean +/- SE), and the ranges of values were almost identical. Similarly, the numbers of total and of labeled cells counted for each patient were comparable among the three centers. The frequency distribution of TLI showed a peak value between 10 and 19.9% in all three centers. Moreover, more than 80% of the observed values were within the range of 10 to 29.9%. In addition, the neoplastic areas with the highest proliferative activity ("high" TLI) showed a frequency distribution once again rather similar among the three centers.(ABSTRACT TRUNCATED AT 250 WORDS)


Choroidal Cavitary Disorders.
The structure and functions of the choroid have been long acknowledged but the pathophysiology behind various anomalies has been difficult to understand until the advent of optical coherence tomography (OCT). With OCT imaging, choroidal cavitations appear as optically empty spaces between the outer retinal and choroidal layers with attenuation or loss of outer retinal layers. Choroidal cavitations are found in the posterior pole and seen in conditions such as pathologic myopia, north carolina macular dystrophy (NCMD), focal choroidal excavation (FCE), and torpedo maculopathy (TM). To date, these disorders have not been linked. A commonality they all share is malformation of the RPE-photoreceptor-choroid complex. The following report describes the differences and similarities of choroidal cavitation amongst the different retinal disorders and emphasizes the importance of multimodal imaging in the detection and management of potential complications.


Lung-surfactant-meconium interaction: in vitro study in bulk and at the air-solution interface.
Lung surfactants (LSs) form a monolayer at the lung's alveoli air-solution interface and play a crucial role in making normal breathing possible by reducing the surface tension. LS are affected by various agents that hamper their normal functioning. Tobacco smoke [Bringezu, F.; Pinkerton, K. E.; Zasadzinski, J. A. Langmuir 2003, 19, 2900-2907] and meconium, the first excrement of the newborn, are examples for such LS poison. In neonates, intrauterine aspiration of meconium is a known cause for morbidity and mortality. We studied in vitro the interactions between modified porcine LSs (Curosurf), used as LS replacement, and meconium, as well as between their artificial analogues, phospholipids mixture, and taurocholic acid (TA), respectively. The interactions were examined both in the bulk solution and at the air-water interface, representing the pre- and postnatal situations. It was found that the artificial analogues represent the natural system reliably and exhibit similar effects. TA, a principle component of bile, is an amphiphilic sterol compound in which the hydrophilic and hydrophobic moieties are presented at different faces of the sterol plane. Here we found that TA affects the structure of both monolayers at the interface and surfactant aggregates in solution. A likely poisoning mechanism is by stereoselective penetration of TA into the lamellar or monolayer structures, thus disrupting the contiguous structure of the intact monolayer or the bilayer vesicle structure.


Membrane-mediated action of the endocannabinoid anandamide on membrane proteins: implications for understanding the receptor-independent mechanism.
Endocannabinoids are amphiphilic molecules that play crucial neurophysiological functions acting as lipid messengers. Antagonists and knockdown of the classical CB1 and CB2 cannabinoid receptors do not completely abolish many endocannabinoid activities, supporting the idea of a mechanism independent of receptors whose mode of action remains unclear. Here we combine gramicidin A (gA) single channel recordings and membrane capacitance measurements to investigate the lipid bilayer-modifying activity of endocannabinoids. Single channel recordings show that the incorporation of endocannabinoids into lipid bilayers reduces the free energy necessary for gramicidin channels to transit from the monomeric to the dimeric conformation. Membrane capacitance demonstrates that the endocannabinoid anandamide has limited effects on the overall structure of the lipid bilayers. Our results associated with the theory of membrane elastic deformation reveal that the action of endocannabinoids on membrane proteins can involve local adjustments of the lipid/protein hydrophobic interface. The current findings shed new light on the receptor-independent mode of action of endocannabinoids on membrane proteins, with important implications towards their neurobiological function.


Effects of glutamines and glutamates at sites of covalent modification of a methyl-accepting transducer.
Chemotactic transducer proteins of Escherichia coli contain four or five methyl-accepting glutamates that are crucial for sensory adaptation and gradient sensing. Two residues arise from posttranslational deamidation of glutamines to yield methyl-accepting glutamates. We addressed the significance of this arrangement by creating two mutated trg genes: trg(5E), coding for a transducer in which all five modification sites were synthesized as glutamates, and trg(5Q), in which all five were glutamines. We found that the normal (3E,2Q) configuration was not an absolute requirement for synthesis, assembly, or stable maintenance of transducers. Both mutant proteins were methylated, although Trg(5Q) had a reduced number of methyl-accepting sites because two glutamines at adjacent residues were blocked for deamidation and thus could not become methyl-accepting glutamates. The glutamine-glutamate balance had striking effects on signaling state. Trg(5E) was in a strong counterclockwise signaling configuration, and Trg(5Q) was in a strong clockwise signaling induced by ligand binding, and alanines substituted at modification sites had an intermediate effect. Chemotactic migration by growing cells containing trg(5E) or trg(5Q) exhibited reduced effectiveness, probably reflecting perturbations of the counterclockwise/clockwise ratio caused by newly synthesized transducers not modified rapidly enough to produce a balanced signaling state during growth. These defects were evident for cells in which other transducers were not available to contribute to balanced signaling or were present at lower levels than the mutant proteins.


Experimental characterisation and modelling of breast Cooper's ligaments.
The aim of this study was to characterise the mechanical behaviour of Cooper's ligaments. Such ligaments are collagenous breast tissue that create a three-dimensional structure over the entire breast volume. Ten ligaments were extracted from a human cadaver, from which 28 samples were cut and used to perform uniaxial tensile tests. Histological analysis showed that the main direction of the fibres visible to the naked eye corresponds to the orientation of the fibres on a microscopic scale. The specimens were cut according to this orientation, which allowed the sample to be stretched in the main fibre direction. From these experimental stretch/stress curves, an original anisotropic hyperelastic constitutive law is proposed to model the behaviour of Cooper's ligaments and the material parameter validity is discussed.


Volume-staged versus dose-staged stereotactic radiosurgery outcomes for large brain arteriovenous malformations: a systematic review.
OBJECTIVE Several recent studies have improved our understanding of the outcomes of volume-staged (VS) and dose-staged (DS) stereotactic radiosurgery (SRS) for the treatment of large (volume > 10 cm3) brain arteriovenous malformations (AVMs). In light of these recent additions to the literature, the aim of this systematic review is to provide an updated comparison of VS-SRS and DS-SRS for large AVMs. METHODS A systematic review of the literature was performed using PubMed to identify cohorts of 5 or more patients with large AVMs who had been treated with VS-SRS or DS-SRS. Baseline data and post-SRS outcomes were extracted for analysis. RESULTS A total of 11 VS-SRS and 10 DS-SRS studies comprising 299 and 219 eligible patients, respectively, were included for analysis. The mean obliteration rates for VS-SRS and DS-SRS were 41.2% (95% CI 31.4%-50.9%) and 32.3% (95% CI 15.9%-48.8%), respectively. Based on pooled individual patient data, the outcomes for patients treated with VS-SRS were obliteration in 40.3% (110/273), symptomatic radiation-induced changes (RICs) in 13.7% (44/322), post-SRS hemorrhage in 19.5% (50/256), and death in 7.4% (24/323); whereas the outcomes for patients treated with DS-SRS were obliteration in 32.7% (72/220), symptomatic RICs in 12.2% (31/254), post-SRS hemorrhage in 10.6% (30/282), and death in 4.6% (13/281). CONCLUSIONS Volume-staged SRS appears to afford higher obliteration rates than those achieved with DS-SRS, although with a less favorable complication profile. Therefore, VS-SRS or DS-SRS may be a reasonable treatment approach for large AVMs, either as stand-alone therapy or as a component of a multimodality management strategy.


CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer.
While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results. In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control. This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.


Sex-specific predictors of the prehypertension-to-hypertension progression: community-based cohort of a West-Asian population.
We aimed to predict prehypertension-to-hypertension progression rate among a West-Asian adult population. We analyzed data on 3449 adults (mean age 41.0 years), prehypertensive at baseline, attending at least one follow-up visit, contributing 25,079 person-years follow-up. A proportional hazard regression analysis was implemented to model the interval-censored progression-free survival time data using readily-assessable, commonly-available information. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI) indices were calculated to examine whether simple clinical information could help improve prediction of prehypertension-to-hypertension progression rate based on the blood pressure measures. During a median seven-year follow-up 1412 prehypertensive patients progressed to hypertension with annual progression rate (95% confidence intervals (CIs)) being 56.9 (52.9-61.2) per 1000 women and 55.7 (51.7-60.0) per 1000 men (p = 0.007). High-density lipoprotein cholesterol levels were inversely associated with prehypertension-to-hypertension progression rate only among women (hazard ratio (1-SD): 0.93, 95% CIs: 0.86-0.100). Marital status retained its predictability among women even after multivariate adjustments. In both men and women, age, blood pressure measures, waist-to-height ratio, fasting plasma glucose and a history of cardiovascular disease independently predicted prehypertension-to-hypertension rate. The absolute (0.114, 95% CIs: 0.107-0.120) and relative (2.638, 95% CIs: 2.374-2.903) IDI and cutpoint-based (0.213, 95% CIs: 0.156-0.269) and cutpoint-free NRI (0.523, 95% CIs: 0.455-0.591) indicated that the prediction of the prehypertension-to-hypertension progression was improved by multivariable-models compared with blood pressure measures alone. Easily-assessable, commonly-available information helped improve predictability of blood pressure measures for prehypertension-to-hypertension progression. Women's psycho-social characteristics (marital status) should be considered in prevention of prehypertension-to-hypertension progression.


Assessment of efficiency and safety of the comprehensive Chemotherapy Assistance Program for ordering oncology medications.
To assess whether the newly developed Comprehensive Chemotherapy Assistance Program (CAP) decreases errors and increases performance efficiency in ordering oncology medications as compared to the existing Computerized Physician Order Entry (CPOE) system, the Order Communication System (OCS). All chemotherapy prescriptions ordered using OCS and CAP systems during the first year of CAP implementation were prospectively analyzed to identify near-miss cases. The efficiency outcomes were determined in a trial setting with eight predefined hypothetical chemotherapy regimens, each with four measures of the average time, movement distance on the screen, maximum input interval time, and number of mouse or keystrokes per order. A total of 14 physicians participated in the study, and each regimen was ordered twice, once using CAP and once using OCS. For all near-miss types, CAP orders showed significant improvements as compared with OCS orders (p<0.0001). For CAP orders, incorrect dose and agent errors were reduced by 43.9% and 31.6%, respectively. Compared with OCS orders, regimen defects, drug omissions, and incorrect data input errors were reduced by more than 70% for CAP orders. For all four efficiency measures, a statistically significant competence was identified when physicians ordered a chemotherapy prescription with CAP as compared with OCS (p<0.0001). These results demonstrate the superiority of CAP over the existing CPOE system for ordering oncology medications with regard to safety and efficiency.


Partitioning of polychlorinated biphenyls between Arctic seawater and size-fractionated zooplankton.
Concentrations of hydrophobic organic contaminants in zooplankton have been hypothesized to be governed by either near-equilibrium partitioning with surrounding water, growth dilution, or biomagnification. Concentrations of 17 polychlorinated biphenyls (PCBs) were measured in size-fractionated zooplankton, in phytoplankton (> 0.7 microm), and in the dissolved water phase (< 0.7 microm) in the surface water of the northern Barents Sea marginal ice zone east and north of Spitsbergen (Norway) and in the central Arctic Ocean at 89 degrees N. The linear partition model was used to indirectly assess if PCBs were equilibrated between water and the extractable organic matter (EOM) of zooplankton. As an independent test, the relation between the EOM-normalized partition coefficient (log K(EOM)) and trophic level (TL) of the zooplankton (based on delta 15N) was investigated. All log K-log K(OW) regressions were significant (n=18, p < 0.05, r2 = 0.65-0.95), being consistent with near-equilibrium partitioning and indirectly suggesting the absence of biomagnification. No correlation was found between log K(EOM) and TL, further supporting the apparent absence of biomagnification in zooplankton. One implication of these results is a reduced uncertainty in modeling of food web uptake, in which kinetic parameterizations of biodilution or biomagnification in zooplankton may be replaced by a simpler parameterization based on equilibrium partitioning.


A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity.
Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job's method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758+/-0.130 U at a concentration of 0.99 microM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.


Impact of chronic toxoplasmosis in pregnancy: association between maternal seropositivity for Toxoplasma gondii IgG antibodies and fetal growth restriction.
Insults caused by acute infections during the gestational period on fetal development are known; however, new evidence suggests that chronic infectious diseases can also impact the maternal immune status and lead to negative consequences for the neonate. This study investigated the association between the prevalence of specific antibodies in pregnant women and alterations in fetal development at birth. A follow-up study evaluated women during the gestational period and their respective newborns at delivery time. The pregnant women were tested for the presence of antibodies to infectious agents: Toxoplasma gondii (T. gondii), cytomegalovirus (CMV), syphilis, human immunodeficiency virus (HIV), hepatitis B and C. Semi-structured questionnaires were administered to the pregnant women at the time of recruitment after obtaining informed consent. Detailed information about the newborns was extracted from medical records. The seroprevalence of chronic T. gondii infection, as determined by the presence of IgG antibodies against the protozoan, was found to be 56.2%, while the overall prevalence of CMV IgG antibodies was 96.3%. Non-primiparous pregnant women from socio-economic classes, less affluent groups, and skilled working-class individuals had higher chances of testing positive for specific T. gondii IgG antibodies. Newborns classified as small for gestational age represented 12.9% of the total. Those born to mothers seropositive for anti-T. gondii IgG antibodies were 9.4 times more likely to be born small for gestational age (p = 0.035). The results suggest that chronic T. gondii infection may contribute to higher rates of newborns with growth restriction. These findings add to a growing body of evidence regarding the impact of chronic infectious diseases on intrauterine fetal development.


Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review.
Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.


Neurosurgical management of frontal lobe epilepsy in children.
Pediatric frontal lobe epilepsy (FLE) remains a challenging condition for neurosurgeons and epileptologists to manage. Postoperative seizure outcomes remain far inferior to those observed in temporal lobe epilepsies, possibly due to inherent difficulties in delineating and subsequently completely resecting responsible epileptogenic regions. In this study, the authors review their institutional experience with the surgical management of FLE and attempt to find predictors that may help to improve seizure outcome in this population. All surgically treated cases of intractable FLE from 1990 to 2008 were reviewed. Demographic information, preoperative and intraoperative imaging and electrophysiological investigations, and follow-up seizure outcome were assessed. Inferential statistics were performed to look for potential predictors of seizure outcome. Forty patients (20 male, 20 female) underwent surgical management of FLE during the study period. Patients were an average of 5.6 years old at the time of FLE onset and 11.7 years at the time of surgery; patients were followed for a mean of 40.25 months. Most patients displayed typical FLE semiology. Twenty-eight patients had discrete lesions identified on MRI. Eight patients underwent 2 operations. Cortical dysplasia was the most common pathological diagnosis. Engel Class I outcome was obtained in 25 patients (62.5%), while Engel Class II outcome was observed in 5 patients (12.5%). No statistically significant predictors of outcome were found. Control of FLE remains a challenging problem. Favorable seizure outcome, obtained in 62% of patients in this series, is still not as easily obtained in FLE as it is in temporal lobe epilepsy. While no statistically significant predictors of seizure outcome were revealed in this study, patients with FLE continue to require extensive workup and investigation to arrive at a logical and comprehensive neurosurgical treatment plan. Future studies with improved neuroimaging and advanced invasive monitoring strategies may well help define factors for success in this form of epilepsy that is difficult to control.


Repression of nitrogen catabolic genes by ammonia and glutamine in nitrogen-limited continuous cultures of Saccharomyces cerevisiae.
Growth of Saccharomyces cerevisiae on ammonia and glutamine decreases the expression of many nitrogen catabolic genes to low levels. To discriminate between ammonia- and glutamine-driven repression of GAP1, PUT4, GDH1 and GLN1, a gln1-37 mutant was used. This mutant is not able to convert ammonia into glutamine. Glutamine-limited continuous cultures were used to completely derepress the expression of GAP1, PUT4, GDH1 and GLN1. Following an ammonia pulse, the expression of GAP1, PUT4 and GDH1 decreased while the intracellular glutamine concentration remained constant, both in the cytoplasm and in the vacuole. Therefore, it was concluded that ammonia causes gene repression independent of the intracellular glutamine concentration. The expression of GLN1 was not decreased by an ammonia pulse but solely by a glutamine pulse. Analysis of the mRNA levels of ILV5 and HIS4 showed that the response of the two biosynthetic genes, GDH1 and GLN1, to ammonia and glutamine in the wild-type and gln1-37 was not due to changes in general transcription of biosynthetic genes. Ure2p has been shown to be an essential element for nitrogen-regulated gene expression. Deletion of URE2 in the gln1-37 background prevented repression of gene expression by ammonia, showing that the ammonia-induced repression is not caused by a general stress response but represents a specific signal for nitrogen catabolite regulation.


[Effect of semipermissive conditions on recombination involving the early genes of bacteriophage T4 in amber-mutants. I. Effect of amber-mutation in gene 43].
Recombination frequencies between rII markers of bacteriophage T4 under conditions of partial inhibition of several early functions of the phage by amber mutations have been studied. Mutations in genes 33, 42 and 45 did not affect significantly recombination frequencies. Mutations in genes 32, 44 and 46 inhibited it. It has been found that effects of double mutations in pairs of genes: 43 and 30; 43 and 52; 43 and 33; 43 and 46; 43 and 32 were consistent with theoretically expected additive effects of corresponding single mutations. The presence of double mutations in pairs of genes: 43 and 41; 43 and 42, 43 and 44, 43 and 45 caused evident deviations from additivity. These deviations could reflect specific interactions of respective pairs of genes products under phage T4 recombination. Possible mechanisms of some of the effects observed are discussed.


Is preeclampsia associated with restless legs syndrome?
Restless legs syndrome (RLS) is a common neurologic disorder. Secondary RLS includes pregnancy and iron deficiency. Prevalence of RLS in pregnancy ranges from 11% to 27%. We aimed to assess the frequency and characteristics of RLS in pregnancy in a Peruvian population and to evaluate the possible pregnancy or delivery complications due to RLS. We assessed 218 consecutive expectant mothers at the inpatient clinic of the Hospital San Bartolome in Lima, Peru. Assessment was performed by using the standard diagnostic criteria for RLS and by using a clinical and diagnostic interview. Questionnaires for RLS severity, idiopathic RLS (IRLS), and excessive daytime sleepiness (EDS) according to the Epworth sleepiness scale (ESS) were used. Blood examination was performed for hemoglobin and hematocrit. For comparison, RLS patients were matched for age and body mass index (BMI) with pregnant women without RLS. Out of 218 patients, 40 (18.4%) fulfilled diagnostic criteria for RLS. In RLS patients, prophylactic iron supplementation therapy during pregnancy was less frequently taken (P=.02). Pregnant women with RLS had a higher ESS score than pregnant controls (10.6 +/- 3.1 vs 7.6. +/- 3.6; P<.001). Preeclampsia was more frequent in RLS (7/40 vs 1/39; P=.03). In our study, RLS was frequent in pregnant Peruvian women, especially in those without prophylactic iron supplementation. RLS patients described more EDS. Preeclampsia was more common in RLS. Our study is the first study to indicate a possible association between RLS and preeclampsia.


Impact of methicillin resistance on the outcome of patients with bacteremia caused by Staphylococcus aureus.
Uncertainties remain about the contribution of methicillin resistance to morbidity and mortality associated with bacteremia caused by Staphylococcus aureus. To assess the impact of methicillin resistance on patient outcome after staphylococcal bacteremia. We investigated a cohort of 145 patients with methicillin-sensitive S aureus bloodstream infection (MSSA BSI) and 39 patients with methicillin-resistant S aureus bloodstream infection (MRSA BSI) and further performed a pairwise-matched (1:1) case-control study. All patients in the University Hospital of Geneva, Geneva, Switzerland, with clinically significant staphylococcal bacteremia between January 1, 1994, and December 31, 1995, were included in the study. For the case-control study, cases were defined as patients with MRSA BSI; control patients with MSSA BSI were selected in a stepwise manner according to the following matching variables: age, sex, number of comorbidities, severity of underlying illness, and prior length of stay in the hospital. Matching was successful for 97% of the cohort. The in-hospital mortality after staphylococcal bacteremia. In the population-based study, the relative hazard of death among patients with MRSA BSI (n = 39, 14 deaths, 36% fatality rate) compared with patients with MSSA BSI (n = 145, 40 deaths, 28% fatality rate) was 1.1 (95% confidence interval, 0.5-2.1), after adjusting for age and length of stay from admission to the onset of bloodstream infection. Following pairwise matching (n = 38), the in-hospital mortality was 34% in both groups (odds ratio, 1.0; 95% confidence interval, 0.4-2.5). Infection was the probable or definite cause of death in 54% of patients with MRSA BSI and 69% of patients with MSSA BSI who died. Methicillin resistance in patients with S aureus bacteremia had no significant impact on patient outcome as measured by in-hospital mortality after adjustment was made for major confounders.


Higher potency of N-(4-hydroxyphenyl)retinamide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines.
Most human non-small cell lung cancer (NSCLC) cell lines are refractory to all-trans-retinoic acid (ATRA). Recently, N-(4-hydroxyphenyl)retinamide (4HPR) was found to induce apoptosis in various tumor cells. In this study, we compared and contrasted the effects of 4HPR and ATRA on the growth and apoptosis of 10 NSCLC cell lines and normal human bronchial epithelial (NHBE) cells. All of the cancer cell lines and the NHBE cells were sensitive to 10 microM 4HPR, and their numbers decreased to <20% of the controls after a 5-day treatment, whereas ATRA decreased cell numbers to about 50% of the controls in three cell lines and was less effective in the rest of the tumor cell lines. ATRA inhibited the growth of the NHBE cells by 70-80%. 4HPR induced apoptosis in most of the cells, including the ATRA-resistant ones, as evidenced by a DNA fragmentation assay. No correlation was found between growth inhibition by 4HPR and the expression of retinoic acid receptor beta (determined by Northern blotting and PCR), p53, or Bcl-2 proteins (analyzed by Western blotting). These results demonstrate that 4HPR is more potent than ATRA in inducing apoptosis in NSCLC cells and suggest that further clinical trials for prevention and therapy of NSCLC using 4HPR are warranted.


Conditioned hearing sensitivity reduction in a bottlenose dolphin (Tursiops truncatus).
The conditioned change in hearing sensitivity during a warning sound preceding a loud sound was investigated in the bottlenose dolphin. Hearing sensitivity was measured using pip-train test stimuli and auditory evoked potential recording. When the test/warning stimulus with a frequency of 22.5 or 32 kHz preceded the loud sound with a frequency of 22.5 kHz and a sound pressure level of 165 dB re. 1 μPa rms, hearing thresholds before the loud sound increased relative to the baseline. The threshold increased up to 15 dB. In order to further investigate whether the observed threshold increase was due to conditioning, the dependence of the effect on warning duration and inter-trial interval was investigated. The duration of the warning substantially influenced the effect. Shorter warnings resulted in deeper suppression of responses and higher threshold increases than longer warnings. In contrast, the effect was nearly independent of the duration of the inter-trial interval, i.e. it was independent of the delay from the loud sound to the test/warning sound in the subsequent trial. These data are considered as evidence that the observed hearing threshold increases were not a result of the unconditioned effect of the loud sound and were instead a manifestation of a conditioned dampening of hearing when the bottlenose dolphin anticipated the quick appearance of a loud sound in the same way as previously demonstrated in the false killer whale.


Three Layers of Intestinal γδ T Cells Talk Different Languages With the Microbiota.
The mucosal surfaces of our body are the main contact site where the immune system encounters non-self molecules from food-derived antigens, pathogens, and symbiotic bacteria. γδ T cells are one of the most abundant populations in the gut. Firstly, they include intestinal intraepithelial lymphocytes, which screen and maintain the intestinal barrier integrity in close contact with the epithelium. A second layer of intestinal γδ T cells is found among lamina propria lymphocytes (LPL)s. These γδ LPLs are able to produce IL-17 and likely have functional overlap with local Th17 cells and innate lymphoid cells. In addition, a third population of γδ T cells resides within the Peyer´s patches, where it is probably involved in antigen presentation and supports the mucosal humoral immunity. Current obstacles in understanding γδ T cells in the gut include the lack of information on cognate ligands of the γδ TCR and an incomplete understanding of their physiological role. In this review, we summarize and discuss what is known about different subpopulations of γδ T cells in the murine and human gut and we discuss their interactions with the gut microbiota in the context of homeostasis and pathogenic infections.


dbAPIS: a database of anti-prokaryotic immune system genes.
Anti-prokaryotic immune system (APIS) proteins, typically encoded by phages, prophages, and plasmids, inhibit prokaryotic immune systems (e.g. restriction modification, toxin-antitoxin, CRISPR-Cas). A growing number of APIS genes have been characterized and dispersed in the literature. Here we developed dbAPIS (https://bcb.unl.edu/dbAPIS), as the first literature curated data repository for experimentally verified APIS genes and their associated protein families. The key features of dbAPIS include: (i) experimentally verified APIS genes with their protein sequences, functional annotation, PDB or AlphaFold predicted structures, genomic context, sequence and structural homologs from different microbiome/virome databases; (ii) classification of APIS proteins into sequence-based families and construction of hidden Markov models (HMMs); (iii) user-friendly web interface for data browsing by the inhibited immune system types or by the hosts, and functions for searching and batch downloading of pre-computed data; (iv) Inclusion of all types of APIS proteins (except for anti-CRISPRs) that inhibit a variety of prokaryotic defense systems (e.g. RM, TA, CBASS, Thoeris, Gabija). The current release of dbAPIS contains 41 verified APIS proteins and ∼4400 sequence homologs of 92 families and 38 clans. dbAPIS will facilitate the discovery of novel anti-defense genes and genomic islands in phages, by providing a user-friendly data repository and a web resource for an easy homology search against known APIS proteins.


Crystal and molecular structure of a pentagonal dodecahedrane.
The successful synthesis of a pentagonal dodecahedrane molecule has been achieved. Obtained by a sequence of 20 stereochemically controlled steps beginning with the readily available cyclopentadienide anion, the 1,16-dimethyl derivative has D(3d) symmetry and unusual physical properties. The x-ray crystal structure shows that the alkyl groups cause only small distortions from pure dodecahedral symmetry.


Covalent methionylation of Escherichia coli methionyl-tRNA synthethase: identification of the labeled amino acid residues by matrix-assisted laser desorption-ionization mass spectrometry.
Methionyl-adenylate, the mixed carboxylic-phosphoric acid anhydride synthesized by methionyl-tRNA synthetase (MetRS) is capable of reacting with this synthetase or other proteins, by forming an isopeptide bond with the epsilon-NH2 group of lysyl residues. It is proposed that the mechanism for the in vitro methionylation of MetRS might be accounted for by the in situ covalent reaction of methionyl-adenylate with lysine side chains surrounding the active center of the enzyme, as well as by exchange of the label between donor and acceptor proteins. Following the incorporation of 7.0 +/- 0.5 mol of methionine per mol of a monomeric truncated methionyl-tRNA synthetase species, the enzymic activities of [32P]PPi-ATP isotopic exchange and tRNA(Met) aminoacylation were lowered by 75% and more than 90%, respectively. The addition of tRNA(Met) protected the enzyme against inactivation and methionine incorporation. Matrix-assisted laser desorption-ionization mass spectrometry designated lysines-114, -132, -142 (or -147), -270, -282, -335, -362, -402, -439, -465, and -547 of truncated methionyl-tRNA synthetase as the target residues for covalent binding of methionine. These lysyl residues are distributed at the surface of the enzyme between three regions [114-150], [270-362], and [402-465], all of which were previously shown to be involved in catalysis or to be located in the binding sites of the three substrates, methionine, ATP, and tRNA.


[A young man with mononucleosis and swelling of the right eye].
Treatment of acute infections in the upper airways comprises a significant part of direct healthcare expenditure and is a challenge for healthcare professionals. In Norway, 11,495 hospitalized days were recorded for acute infections (influenza and pneumonia excluded) in the upper airways in 2008. Acute bacterial rhinosinusitis (ABRS) is defined as inflammation of the nose and the paranasal sinuses characterized by both 1): symptoms of nasal blockage/obstruction/congestion or nasal discharge, and/or facial pain/pressure and 2): endoscopic signs of mucopurulent discharge from middle meatus and/or CT changes within the osteomeatal complex/sinuses. After 12 weeks of symptoms the definition changes to chronic rhinosinusitis. With antibiotic treatment of complicated ABRS we see fewer severe complications, but they still occur. Due to anatomical proximity of the orbit and intracranial structures a localized spread of the infection is especially unfortunate and potentially dangerous. We present a case report (with pan sinusitis and grave local complications) from the ear, nose and throat department in St. Olav's University Hospital in Trondheim, Norway.


[Hypothesis of the changes in the frequency of asthma].
Review of the literature reveals sporadic but true increases in the prevalence and death rates for asthma over the past 25 years. Although changes in hereditary, allergic and environmental factors must be considered as possible causes of this increase, its suddenness points to risk factors that change rapidly. Such is the case with atmospheric pollutants, notably nitrogen dioxide and particles, both of which have been shown to have adverse effects on the tracheobronchial tree. These pollutants tend to concentrate inside homes, especially since the early 1980s, when the energy crisis brought about changes in the home environment.


Rheumatic diseases and malignancies.
There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify.Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis.On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments.


Health literacy and the use of healthcare services in Belgium.
Most of the existing studies demonstrating the relationships between health literacy and health service use have been conducted outside Europe and cannot be generalised to European healthcare systems. Moreover, the majority of studies measure healthcare use via self-reports. This study investigated whether health literacy is related to the use of health services measured objectively via patient records in a European country. 9617 members of a Belgian health insurance fund (59% females, ages 18-88 years, mean age 55.8 years) completed an online questionnaire including the 16-item European Health Literacy Survey Questionnaire (HLS-EU-Q) and agreed to have their responses linked to the insurance fund's health service use records. A two-part model approach was used to assess the association between health literacy and the use of healthcare services and the costs related, adjusting for personal and behavioural characteristics. Low health literacy is associated with more admissions to 1-day clinics, general practitioner (GP) home consultations, psychiatrist consultations and ambulance transports, and with longer stays in general hospitals. Associations with psychiatric hospitalisations and specialist consultations are also found but are not significant when correction for multiple comparisons is applied. In contrast, health literacy is not significantly related to the number of GP consultations, admissions to 1-day surgical clinics or emergency consultations. The relationship between health literacy and medication use is inconsistent. The results partly confirm that low health literacy is associated with greater use of healthcare services, and especially of more specialised services. Improving the health literacy of the population can be an effective strategy to promote a more (cost)-effective use of the healthcare services and thus contribute to population health.


Desmoplastic Small Round Cell Tumor of the Head and Neck: A Clinicopathological, Immunohistochemical and Molecular Analysis of Three Cases with Literature Review.
Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignancy typically originating from the abdominal or pelvic cavity. DSRCT presenting as a primary head and neck tumor has rarely been described in the literature. We present three cases of DSRCT arising in the head and neck to further characterize its clinicopathological features. All three patients were male and aged 36, 30 and 17 years. The involved sites included the orbit (1 case) and submandibular gland (2 cases). The tumors ranged in size from 2.4 to 3.5 cm (mean, 2.1 cm). Histologically, all tumors showed irregular-shaped, variable-sized nests of small round cells deposited in an abundant desmoplastic stroma. Tumor cells contained scant amounts of eosinophilic cytoplasm and small hyperchromatic nuclei with inconspicuous nucleoli. Immunohistochemically, the tumors were positive for keratin (AE1/AE3) (3/3), desmin (3/3), vimentin (2/2), NSE (1/1) and EMA (1/1). Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of EWSR1 and WT1 rearrangements in all three cases. All patients received surgery and adjuvant chemotherapy and/or radiotherapy. There was no evidence of recurrence and metastasis in two patients, and the third suffered lung metastasis. DSRCT arising in the head and neck represents an extremely rare condition. It is easily mistaken as poorly differentiated carcinoma due to similar morphology and expression of epithelial markers. Immunohistochemistry assay in conjunction with molecular detection of EWSR1::WT1 fusion will be helpful for arriving at an accurate diagnosis to avoid misdiagnosis and inappropriate treatment.


Dispersion of Endoplasmic Reticulum-associated Compartments by 4-phenyl Butyric Acid in Yeast Cells.
In yeast Saccharomyces cerevisiae cells, some aberrant multimembrane-spanning proteins are not transported to the cell surface but form and are accumulated in endoplasmic reticulum (ER)-derived subcompartments, known as the ER-associated compartments (ERACs), which are observed as puncta under fluorescence microscopy. Here we show that a mutant of the cell surface protein Pma1, Pma1-2308, was accumulated in the ERACs, as well as the heterologously expressed mammalian cystic fibrosis transmembrane conductance regulator (CFTR), in yeast cells. Pma1-2308 and CFTR were located on the same ERACs. We also note that treatment of cells with 4-phenyl butyric acid (4-PBA) compromised the ERAC formation by Pma1-2308 and CFTR, suggesting that 4-PBA exerts a chaperone-like function in yeast cells. Intriguingly, unlike ER stress induced by the canonical ER stressor tunicamycin, ER stress that was induced by Pma1-2308 was aggravated by 4-PBA. We assume that this observation demonstrates a beneficial aspect of ERACs, and thus propose that the ERACs are formed through aggregation of aberrant transmembrane proteins and work as the accumulation sites of multiple ERAC-forming proteins for their sequestration.Key words: protein aggregation, organelle, unfolded protein response, ER stress, 4-PBA.


Endoscopic techniques for retrieval of proximally migrated biliary stents: the Amsterdam experience.
Endoscopic retrieval of proximally migrated biliary plastic stents may be technically challenging and sometimes unsuccessful. Despite the widespread use of such stents, there are few reports on the technique for retrieval of migrated stents. We reviewed the records of patients who were found to have proximally migrated biliary stents during the last 3 years at a tertiary referral center. Our study analyzed the various techniques used for endoscopic retrieval and evaluated the factors influencing the choice of a particular technique. Endoscopic retrieval of a proximally migrated stent was attempted in 41 patients and was successful in 37 (90%). The retrieval techniques included Dormia basket, balloon, balloon and basket, basket and ball tip catheter, forceps, and Soehendra stent retriever. The Dormia basket technique was successful in the majority of cases. Proximally migrated biliary stents can be successfully removed endoscopically in most cases. The choice of a retrieval technique is dependent on several factors including biliary ductal dilatation, depth of stent migration, distal stent impaction and biliary stricture distal to the migrated stent. The placement of an additional stent alongside an irretrievable stent is a satisfactory alternative to retrieval.


Characterization of bioadsorbent produced using incorporated treatment of chemical and carbonization procedures.
The production of bioadsorbent from palm kernel shell (PKS) and coconut shell (CS) pretreated with 30% phosphoric acid (H3PO4) was optimized using the response surface methodology (RSM). Iodine adsorption for both bioadsorbents was optimized by central composite design. Two parameters including the H3PO4 pretreatment temperature and carbonization temperature were determined as significant factors to improve the iodine adsorption of the bioadsorbent. Statistical analysis results divulge that both factors had significant effect on the iodine adsorption for the bioadsorbent. From the RSM analysis, it was suggested that using 80 and 79°C as H3PO4 pretreatment temperature and 714 and 715°C as carbonization temperature would enhance the iodine adsorption of the CS and PKS bioadsobent, respectively. These results indicated that H3PO4 is a good pretreatment for preparing PKS and CS prior to carbonization process to produce bioadsorbent with well-developed microporous and mesoporous volume. The effort to produce alternative high grade and inexpensive adsorbent derived from lignocellulosic biomass, particularly in the nut shell form was implied in this research.


A self-organizing neural tree for large-set pattern classification.
Neural networks have been successfully applied to various pattern classification problems in terms of their learning ability, high discrimination power, and excellent generalization ability. However, for the case of classifying large-set and complex patterns, the greater part of conventional neural networks suffer from several difficulties such as the determination of the structure and size of the network, the computational complexity, and so on. In this paper, to cope with these difficulties, we propose a structurally adaptive intelligent neural tree (SAINT). The basic idea is to partition hierarchically input pattern space using a tree-structured network which is composed of subnetworks with topology-preserving mapping ability. The main advantage of SAINT is that it attempts to find automatically a network structure and size suitable for the classification of large-set and complex patterns through structure adaptation. Experimental results reveal that SAINT is very effective for the classification of large-set real world handwritten characters with high variations, as well as multilingual, multifont, and multisize large-set characters.


Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions.
The strong correlation between a bone's architectural properties and the mechanical forces that it experiences has long been attributed to the existence of a cell that not only detects mechanical load but also structurally adapts the bone matrix to counter it. One of the most likely cellular candidates for such a "mechanostat" is the osteocyte, which resides within the mineralized bone matrix and is perfectly situated to detect mechanically induced signals. However, as osteocytes can neither form nor resorb bone, it has been hypothesized that they orchestrate mechanically induced bone remodeling by coordinating the actions of cells residing on the bone surface, such as osteoblasts. To investigate this hypothesis, we developed a novel osteocyte-osteoblast coculture model that mimics in vivo systems by permitting us to expose osteocytes to physiological levels of fluid shear while shielding osteoblasts from it. Our results show that osteocytes exposed to a fluid shear rate of 4.4 dyn/cm(2) rapidly increase the alkaline phosphatase activity of the shielded osteoblasts and that osteocytic-osteoblastic physical contact is a prerequisite. Furthermore, both functional gap junctional intercellular communication and the mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 signaling pathway are essential components in the osteoblastic response to osteocyte communicated mechanical signals. By utilizing other nonosteocytic coculture models, we also show that the ability to mediate osteoblastic alkaline phosphatase levels in response to the application of fluid shear is a phenomena unique to osteocytes and is not reproduced by other mesenchymal cell types.


Are animals stuck in time or are they chronesthetic creatures?
Although psychologists study both the objective (behavior) and the subjective (phenomenology) components of cognition, we argue that an overemphasis on the subjective drives a wedge between psychology and other closely related scientific disciplines, such as comparative studies of cognition and artificial intelligence. This wedge is particularly apparent in contemporary studies of episodic recollection and future planning, two related abilities that many have assumed to be unique to humans. We shall challenge this doctrine. To do so, we shall adopt an ethological approach to comparative cognition and this necessitates two requirements. The first is that memory and planning need to be characterized in terms of objectively defined properties as opposed to purely phenomenological ones; the ability to remember what happened, where, and how long ago is a critical behavioral criterion for episodic memory. The second requirement is the identification of an ethological context in which these memories would confer a selective advantage. As a consequence, we turn this debate into an empirical evaluation in nonlinguistic animals and one embodied in synthetic creatures. Indeed, our behavioral conception of flexibly deployable information about "what, where, and when" has so far supported a comparative cognition in animals as diverse as corvids and primates. We argue that this approach may clarify and challenge ideas that have been based solely on research with human subjects, without the need to be constrained by phenomenological assumptions based on human-centric ways of thinking.


Nonaffine rearrangements of atoms in deformed and quiescent binary glasses.
The influence of periodic shear deformation on nonaffine atomic displacements in an amorphous solid is examined via molecular dynamics simulations. We study the three-dimensional Kob-Andersen binary mixture model at a finite temperature. It is found that when the material is periodically strained, most of the atoms undergo repetitive nonaffine displacements with amplitudes that are broadly distributed. We show that particles with large amplitudes of nonaffine displacements are organized into compact clusters. With increasing strain amplitude, spatial correlations of nonaffine displacements become increasingly long-ranged, although they remain present even in a quiescent system due to thermal fluctuations.


Discovery of potent and effective inhibitors containing sulfoxide structures targeting EML4-ALK rearrangement and EGFR mutant non-small cell lung cancer.
For non-small cell lung cancer patients with dual mutations in EGFR and ALK, there are currently no effective therapies. Consequently, novel EGFR/ALK dual-target inhibitors are urgently needed for the treatment of NSCLC. Here, we designed a series of highly effective small molecule dual inhibitors of ALK and EGFR. The biological evaluation highlighted that most of these new compounds could effectively inhibit both ALK and EGFR in enzymatic and cellular assays. Compound (+)-8l was investigated for its antitumor properties, and it was found that (+)-8l blocked the phosphorylation of EGFR and ALK induced by ligands and inhibited phosphorylation-ERK and phosphorylation-AKT induced by ligands. Furthermore, (+)-8l also induces apoptosis and G0/G1 cell cycle arrest in cancer cells and inhibits proliferation, migration, and invasion. Notably, (+)-8l significantly suppressed tumor growth in the H1975 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.11%), PC9 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.61%) and EML4 ALK-Baf3 cell-inoculated xenograft model (30 mg/kg/d, TGI: 80.86%). These results highlight the differentiated potential of (+)-8l to inhibit ALK rearrangement and EGFR mutation in NSCLC.


Preparation of Ampicillin Surface Molecularly Imprinted Polymers for Its Selective Recognition of Ampicillin in Eggs Samples.
Surface-imprinted polymers (MIPs) microspheres with the ability to specifically recognize water-soluble molecules were prepared using self-made monodisperse porous poly(chloromethylstyrene-co-divinylbenzene) beads as the solid-phase matrix and ampicillin (AMP) as the template molecule. MIPs were synthesized using different template molecule: monomer: crosslinker ratios and the optimum preparation ratio were obtained by measuring adsorption. The maximum equilibrium amount of adsorption by the MIPs reached 115.62 mg/g. Scatchard analysis indicated that the MIPs contained two types of recognition sites: specific and nonspecific. Based on the adsorption kinetics, adsorption equilibrium was reached after 30 minutes. Penicillin G, amoxicillin, and sulbactam acid were used as competitive molecules to research the selective adsorption capacity of the MIPs. The imprinted material was found to have good selectivity with selectivity coefficients for penicillin G, amoxicillin, and sulbactam acid of 5.74, 6.83, and 7.25, respectively. The MIPs were used as solid-phase extraction filler, resulting in successful enrichment and separation of ampicillin residue from egg samples. Standard addition recovery experiments revealed that recovery was good with recoveries from the spiked samples ranging from 91.5 to 94.9% and relative standard deviations from 3.6 to 4.2%. The solid-phase extraction MIPs microcolumn was reused 10 times, where it maintained a recovery rate of over 80%. This work presents a sensitive, fast, and convenient method for the determination of trace ampicillin in food samples.