Histogenesis of the mesocortical area of the mouse telencephalon.
The histogenesis of the mesocortex of the mouse telencephalon was studied by plotting the progress of neuron release on reconstructions of the medial pallial wall. Histological changes were correlated with cell birth date using data obtained from autoradiographs of mice pulse-labelled with tritiated thymidine during the prenatal period of neuron birth. It was found that neuron release for this area began rostrally at about E12-E13 and spread rapidly from this origin in a caudal direction across the medial wall. Neurons accumulating in the intermediate layer were at first more or less equally spaced. About E14, neurons in the outer intermediate layer began to line up to form a 'mesocortical plate'. This plate was formed from older nuclei and therefore overlay a deeper intermediate layer composed of younger cells. The mesocortex continued to develop by progressive withdrawal of younger cells from the deep intermediate layer into more superficial layers of the definitive cortex. In most of the mesocortical area, however, this original pattern was superseded by release of neuron generations which migrated directly to the outer intermediate layer to form a plate of densely packed immature neurons. This population was continuous with a similar population forming the isocortical plate of the lateral telencephalic wall. It was postulated that the wave of neuron birth and release which gave rise to the isocortical plate was propagated beyond the isocortical boundary into mesocortical territory as far as the boundaries of the subiculum, indusium griseum and anterior hippocampal rudiment.


Resistance Management for San Jose Scale (Hemiptera: Diaspididae).
The San Jose scale Diaspidiotus perniciosus Comstock is one of the most important pests of deciduous fruit trees. The major cause of recent outbreaks in apple orchards is thought to be the development of insecticide resistance, specifically organophosphates. The first report was given in North America, and now, in Chile. In the present study, San Jose scale populations collected from two central regions of Chile were checked for their susceptibility to different mode of action insecticides in order to establish alternatives to manage this pest. No evidence of cross resistance between organophosphates insecticides and acetamiprid, buprofezin, pyriproxyfen, spirotetramat, sulfoxaflor, or thiacloprid was found. Baselines of LC50-LC95 for different life stages of San Jose scale are given, as reference to future studies of resistance monitoring. The systemic activity of acetamiprid, spirotetramat, and thiacloprid was higher than the contact residue effect of these compounds. For sulfoxaflor, both values were similar. Program treatments including one or more of these compounds are compared in efficacy and impact on resistance ratio values. In order to preserve new insecticides as an important tool to control San Jose scale, resistance management programs should be implemented, considering insecticide mode of action classes alternated or mixed.


Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis.
Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. We hypothesized that changes in Von Willebrand factor (VWF) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin in melioidosis, and investigated whether this impacted on outcome. We recruited 52 controls and 34 culture-confirmed melioidosis patients at Sappasithiprasong Hospital in Ubon Ratchathani, Thailand. All subjects were diabetic. Platelet counts in melioidosis patients were lower compared to controls (p = 0.0001) and correlated with mortality (p = 0.02). VWF antigen levels were higher in patients (geometric mean, 478 U/dl) compared to controls (166 U/dL, p<0.0001). The high levels of VWF in melioidosis appeared to be due to increased endothelial stimulation (VWF propeptide levels were elevated, p<0.0001) and reduced clearance (ADAMTS13 reduction, p<0.0001). However, VWF antigen levels did not correlate with platelet counts implying that thrombocytopenia in acute melioidosis has an alternative cause. Thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis. Further studies on the role of thrombocytopenia in B. pseudomallei infection are needed.


PCR-based analysis of the intergenic spacers of the Nor loci on the A genomes of Triticum diploids and polyploids.
We present DNA sequence data showing population variation in the intergenic spacer (IGS) regions of the ribosomal DNAs (rDNAs) on the A genomes of 27 diploid and polyploid wheats. PCRs (polymerase chain reactions) specific for the A(m) genome gave products with five populations of Triticum monococcum but did not give products with AABB or AABBDD wheats. PCRs specific to the A(u) genome of T. urartu gave products with all the AABB and AABBDD polyploids that were tested, but not with T. monococcum. AAGG tetraploids gave products only with the A(u)-specific primers, but the AAAAGG hexaploid T. zhukovskyi gave products with both the A(u) and A(m) primers. Phylogenetic analysis showed a substantial degree of IGS divergence for both the A(m) and A(u) genomes in diploids and polyploids compared with other genomes of Triticum and Aegilops. The rate of evolution of the IGS is much greater than previously reported for the internal transcribed region of the rDNAs but the view that the IGS only gives random noise is rejected, the IGS sequences presented here reflecting the general evolutionary trends affecting the wheat genome as a whole.


[Construction of RNA-containing virus-like nanoparticles expression vector with cysteine residues on surface and fluorescent decoration].
Site-directed mutagenesis was performed at the codon 15 of the MS2 bacteriophage coat protein gene,which had been cloned to the virus-like particles expression vector containing non-self RNA fragment. The produced expression vector,termed pARSC, was transformed to E. coli DH5alpha. The positive clones were selected and proliferated. The harvested cells were treated with sonication and the supernatant was then subjected to linear sucrose density gradients centrifugation (15% to 60%) at 32000 r/min for 4 h at 4 degrees C. The virus-like particles, VLP-Cy, were collected at 35% sucrose density. The particles were examined by transmission electron microscopy and the spherical viral particles of approximately 27 nm in diameter were found. The thiolated VLP-Cy was then chemically modified with fluorescein -5'-maleimide. The covalent fluorescent labeling was confirmed by absorption analysis, SDS-PAGE and MALDI-TOF mass spectroscopy. This is the first report of preparation of RNA-containing natural fluorescent nanoparticles. The study highlight the versatility of MS2 bacteriophage capsids as building blocks for functional nanomaterials construction for a variety of application purposes.


Echocardiographic evaluation with hemodynamic correlation of the left ventricle in mitral stenosis.
The value of echocardiographic measurement of left ventricle volume and ejection fraction and of mitral valve area in patients with mitral stenosis has been assessed. All patients referred because of mitral stenosis have been studied by M-mode and two-dimensional echocardiography, by right and left heart catheterization, ventriculography and selective coronary angiography. Patients with other congenital or acquired heart disease or with coronary artery disease were excluded from this study. The selection lead to a series of 39 pts, all with a typical history of Rheumatic Fever: all these pts were divided in three groups according to the degree of mitral stenosis, classified as "mild", if valvular area was greater than 1.8 cm2 (8 pts), "moderate" between 1-1.8 cm2 (15 pts) and "severe" if valvular areas was less than 1 cm2 (16 pts). In all groups echocardiography underestimated left ventricular volumes as well as stroke volumes. Statistical correlation has not been excellent: the best result was again obtained in the calculation of ejection fraction (r = 0.91, P less than 0.001), confirming our previous results in a group of patients with mitral regurgitation. Cross-sectional two-dimensional echocardiography has confirmed, furthermore, as a sensitive and suitable procedure in assessing the mitral valve area (r = 0,87 P less than 0.001); at our experience echocardiography under-estimate mitral area in the cases of severe mitral stenosis.


[Recurrent parotid enlargement following coronary angiography].
We report a case of a 56-year old patient with coronary heart disease and subacute myocardial infarction who presented with acute sialadenitis after twice undergoing coronary angiography. Acute sialadenitis ('iodide mumps') after exposure to contrast medium is characterized by a fast, painless and bilateral swelling of the salivary glands. It is usually self-limiting but can occur after re-exposure to the contrast agent.


Eastern Baltic region vs. Western Europe: modelling age related changes in the pubic symphysis and the auricular surface.
Objectives. The present study addresses the following two main questions: a) Is the pattern of skeletal ageing observed in well-known western European reference collections applicable to modern eastern Baltic populations, or are population-specific standards needed? b) What are the consequences for estimating the age-at-death distribution in the target population when differences in the estimates from reference data are not taken into account? Materials and methods. The dataset consists of a modern Lithuanian osteological reference collection, which is the only collection of this type in the eastern Baltic countries (n = 381); and two major western European reference collections, Coimbra (n = 264) and Spitalfields (n = 239). The age-related changes were evaluated using the scoring systems of Suchey-Brooks (Brooks & Suchey 1990) and Lovejoy et al. (1985), and were modelled via regression models for multinomial responses. A controlled experiment based on simulations and the Rostock Manifesto estimation protocol (Wood et al. 2002) was then carried out to assess the effect of using estimates from different reference samples and different regression models on estimates of the age-at-death distribution in the hypothetical target population. Results. The following key results were obtained in this study. a) The morphological alterations in the pubic symphysis were much faster among women than among men at comparable ages in all three reference samples. In contrast, we found no strong evidence in any of the reference samples that sex is an important factor to explain rate of changes in the auricular surface. b) The rate of ageing in the pubic symphysis seems to be similar across the three reference samples, but there is little evidence of a similar pattern in the auricular surface. That is, the estimated rate of age-related changes in the auricular surface was much faster in the LORC and the Coimbra samples than in the Spitalfields sample. c) The results of simulations showed that the differences in the estimates from the reference data result in noticeably different age-at-death distributions in the target population. Thus, a degree bias may be expected if estimates from the western European reference data are used to collect information on ages at death in the eastern Baltic region based on the changes in the auricular surface. d) Moreover, the bias is expected to be more pronounced if the fitted regression model improperly describes the reference data. Conclusions. Differences in the timing of age-related changes in skeletal traits are to be expected among European reference samples, and cannot be ignored when seeking to reliably estimate an age-at-death distribution in the target population. This form of bias should be taken into consideration in further studies of skeletal samples from the eastern Baltic region.


Induction of T4 DNA ligase in a recombinant strain of Escherichia coli.
The kinetics of cell growth and foreign protein production, as well as factors affecting protein stability, were studied and optimized in batch and fed-batch fermentations of a recombinant strain of Escherichia coli. The pL promoter from bacteriophage lambda under the control of a temperature-sensitive cl represser, with the entire construct integrated into the E. coli chromosome through the use of a defective bacteriophage lambda lysogen, was used to direct the synthesis of T4 DNA ligase. The biphasic fermentations consisted of a primary growth phase at 30 degrees C followed by an induction phase which was initiated by shifting the temperature to 42 degrees C. In the fed-batch fermentations, additional nutrients were added at the time of initiating induction. Maintenance of sufficiently high concentrations of the organic substrates (glucose and casamino acids) during the induction phase was required for continued cell growth at 42 degrees C. Such growth was essential for T4 DNA ligase formation and in vivo stability. Hence, fed-batch fermentations produced the highest yield of the foreign protein Commensurate with providing lower total amounts of substrates. In such cases, high cell densities (6 g dry wt/L) with substantial intracellular levels of T4 DNA ligase (4.6% total cellular protein, or 2.7% of the dry biomass) were achieved.


Impact of a Digital Tool on Pharmacy Students' Ability to Perform Medication Reviews: A Randomized Controlled Trial.
Digital Medication Review Tools (DMRTs) are increasingly important in pharmacy practice. To ensure that young pharmacists are sufficiently competent to perform medication reviews after graduation, the introduction of DMRTs teaching in academic education is necessary. The aim of our study was to demonstrate the effect of DMRTs use on pharmacy students' performance when conducting a medication review (MR) in a randomized controlled pre-post design. Forty-one pharmacy students were asked to complete a MR within 60 min, followed by a 10-min consultation with (intervention group) and without a DMRT (control group). The MR performance was subdivided into four categories: communication skills, subjective and objective patient data, assessment, and plan. Performance was assessed using objective structured clinical examinations (OSCEs) and analytical checklists. With the use of DMRTs, the overall performance was improved by 17.0% compared to the control group (p < 0.01). Improvement through DMRTs was seen in the subcategories "Assessment" and "Plan". Furthermore, pharmacy students liked using DMRTs and felt more confident overall. Our study results demonstrate that DMRTs improve the performance of MRs, hence DMRTs should become an integral part of pharmacy curriculum. Consequently, digitally enabled pharmacists using DMRTs will be better prepared for their professional careers in pharmacy practice.


Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling.
Severe noise-induced damage to the inner ear leads to auditory nerve fiber degeneration thereby reducing the neural input to the cochlear nucleus (CN). Paradoxically, this leads to a significant increase in spontaneous activity in the CN which has been linked to tinnitus, hyperacusis and ear pain. The biological mechanisms that lead to an increased spontaneous activity are largely unknown, but could arise from changes in glutamatergic or GABAergic neurotransmission or neuroinflammation. To test this hypothesis, we unilaterally exposed rats for 2h to a 126dB SPL narrow band noise centered at 12kHz. Hearing loss measured by auditory brainstem responses exceeded 55dB from 6 to 32kHz. The mRNA from the exposed CN was harvested at 14 or 28days post-exposure and qRT-PCR analysis was performed on 168 genes involved in neural inflammation, neuropathic pain and glutamatergic or GABAergic neurotransmission. Expression levels of mRNA of Slc17a6 and Gabrg3, involved in excitation and inhibition respectively, were significantly increased at 28days post-exposure, suggesting a possible role in the CN spontaneous hyperactivity associated with tinnitus and hyperacusis. In the pain and inflammatory array, noise exposure upregulated mRNA expression levels of four pain/inflammatory genes, Tlr2, Oprd1, Kcnq3 and Ntrk1 and decreased mRNA expression levels of two more genes, Ccl12 and Il1β. Pain/inflammatory gene expression changes via Ntrk1 signaling may induce sterile inflammation, neuropathic pain, microglial activation and migration of nerve fibers from the trigeminal, cuneate and vestibular nuclei into the CN. These changes could contribute to somatic tinnitus, hyperacusis and otalgia.


Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain.
18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of 18F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested the effects of MAO-B inhibition on 18F-THK5351 brain uptake using PET and autoradiography. Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline 18F-AZD4694 and 18F-THK5351 scans in order to quantify brain amyloid and PHF load, respectively. A second 18F-THK5351 scan was conducted 1 week later, 1 h after a 10-mg oral dose of selegiline. Three out of eight patients also had a third 18F-THK5351 scan 9-28 days after the selegiline administration. The primary outcome measure was standardized uptake value (SUV), calculated using tissue radioactivity concentration from 50 to 70 min after 18F-THK5351 injection, normalizing for body weight and injected radioactivity. The SUV ratio (SUVR) was determined using the cerebellar cortex as the reference region. 18F-THK5351 competition autoradiography studies in postmortem tissue were conducted using 150 and 500 nM selegiline. At baseline, 18F-THK5351 SUVs were highest in the basal ganglia (0.64 ± 0.11) and thalamus (0.62 ± 0.14). In the post-selegiline scans, the regional SUVs were reduced on average by 36.7% to 51.8%, with the greatest reduction noted in the thalamus (51.8%) and basal ganglia (51.4%). MAO-B inhibition also reduced 18F-THK5351 SUVs in the cerebellar cortex (41.6%). The SUVs remained reduced in the three patients imaged at 9-28 days. Tissue autoradiography confirmed the effects of MAO-B inhibition on 18F-THK5351 uptake. These results indicate that the interpretation of 18F-THK5351 PET images, with respect to tau, is confounded by the high MAO-B availability across the entire brain. In addition, the heterogeneous MAO-B availability across the cortex may limit the interpretation of 18F-THK5351 scans using reference region methods.


Economic impact of using fesoterodine for the treatment of overactive bladder with urge urinary incontinence in a vulnerable elderly population in the United States.
To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective. A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2-15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI). When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization. From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.


Effects of stimulation area and temperature rates on offset analgesia.
Offset analgesia describes the effect of a slightly reduced nociceptive stimulus, resulting in a disproportionate large reduction in the pain perception. This effect may be associated with descending pain inhibition, but parameters influencing this phenomenon are poorly understood. In this study, 2 separate experiments were conducted to investigate both, the spatial aspects of offset analgesia and the influence of different rates of temperature rise. In both experiments, 29 healthy participants received individualized and heat-based offset analgesia paradigms applied to the forearm, with continuous assessment of pain intensity. In experiment 1, offset analgesia paradigms with 3 different rates of temperature rise were applied, whereas in experiment 2, offset analgesia paradigms with 2 different heat application areas were used. The results of experiment 1 showed that different temperature rates had no effect on the offset analgesia response (P > 0.05). Experiment 2, however, showed the influence of the size of a stimulated area on offset analgesia (P = 0.009), which can be explained mainly by the influence of spatial summation of pain and habituation processes. The study showed a lack of influence of different temperature rates on offset analgesia; however, spatial aspects of offset analgesia could be identified. These are most likely based on spatial summation of pain and altered adaptation to pain.


Glucose transport by mixed ruminal bacteria from a cow.
The glucose transport of mixed ruminal bacteria harvested from a holstein cow fed 5.0 kg of Italian ryegrass and 1.5 kg of flaked corn a day was investigated. The Eadie-Hofstee plot characterized two transport systems: a high-affinity, low-velocity system and a low-affinity, high-velocity system. The former system (K(m) = 16 microM; Vmax = 2.2 nmol/min/mg of protein) is considered dominant under this feeding condition based on the glucose concentration in the rumen (< 1 mM). In light of the facts that the protonophore SF6847 and the lipophilic triphenylmethyl phosphonium ion had no effect on the high-affinity system and an artificially generated proton gradient and electrical potential across the cell membrane did not increase glucose transport, a proton motive force is not be involved in the system. On the other hand, from the facts that chlorhexidine inhibited about 90% of the high-affinity system while iodoacetate showed no significant effect, and a high phosphoenolpyruvate-dependent phosphorylation of glucose was actually shown, the phosphoenolpyruvate-dependent phosphotransferase system is considered the main system in the high-affinity system. Moreover, as shown by the facts that harmaline inhibited about 30% of the high-affinity system and the artificially generated sodium gradient across the cell membrane significantly stimulated glucose transport, this system also includes sodium symport to some degree. The high-affinity system was sensitive to a decrease in pH (< 6.5) and was inhibited by the presence of sucrose, mannose, and fructose.


Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Gossypium.
Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous study found the HMGR genes underwent gene expansion in Gossypium raimondii, but the characteristics and evolution of the HMGR gene family in Gossypium genus are unclear. In this study, genome-wide identification and comparative study of HMGR gene family were carried out in three Gossypium species with genome sequences, i.e., G. raimondii, Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR genes were identified in G. raimondii, G. arboreum, and G. hirsutum, respectively. The results indicated that the HMGR genes underwent gene expansion and a unique gene cluster containing four HMGR genes was found in all the three Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR genes had occurred in their common ancestor. There was a pseudogene that had a 10-bp deletion resulting in a frameshift mutation and could not be translated into functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The expression profiles of the two pseudogenes showed that they had tissue-specific expression. Additionally, the expression pattern of the pseudogene in the A-subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of G. hirsutum. Our results provide useful information for understanding cytosolic terpene biosynthesis in Gossypium species.


A Comprehensive Review on Preparation, Evaluation and Applications of Deformable Liposomes.
Elastic or deformable liposomes are phospholipid-based vesicular drug delivery systems that help improve the delivery of therapeutic agents through the intact skin membrane due to their deformable characteristics that overcome the problems of conventional liposomes. In the present review, different types of deformable liposomes such as transfersomes, ethosomes, menthosomes, invasomes and transethosome are studied, and their mechanism of action, characterization, preparation methods, and applications in pharmaceutical technology through topical, transdermal, nasal and oral routes for effective drug delivery are compared for their potential transdermal delivery of poorly permeable drugs. Due to the deformable characteristics of these vehicles, it resulted in modulation of increased drug encapsulation efficiency, permeation and penetration of the drug into or through the skin membrane and are found to be more effective than conventional drug delivery systems. So deformable liposomes can, therefore, be considered as a promising way of delivering the drugs transdermally.


Differential brain transcriptome of beta4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain?
Studies using mice with beta4 nicotinic acetylcholine receptor (nAChR) subunit deficiency (beta4-/- mice) helped reveal the roles of this subunit in bradycardiac response to vagal stimulation, nicotine-induced seizure activity and anxiety. To identify genes that might be related to beta4-containing nAChRs activity, we compared the mRNA expression profiles of brains from beta4-/- and wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes significantly differentiated between these two experimental groups. Of them, the two most downregulated were spastic paraplegia 21 (human) homolog (Spg21) and 6-pyruvoyl-tetrahydropterin synthase (Pts) genes. Since the targeted mutagenesis of the beta4 nAChR subunit was done by using two mouse strains, 129SvEv and C57BL/6J, it is possible that the genes closely linked to the mutated beta4 gene represent the 129SvEv allele and not the control C57BL/6J-driven allele. We examined this possibility by using public database and quantitative RT-PCR. The expression levels of Spg21 and Pts genes that, like the beta4 gene, are localized on mouse chromosome 9, as well as the expression levels of other genes located on this chromosome, were dependent on the mouse background strain. The 67 differentially expressed genes that are not located on chromosome 9 were further analyzed for overrepresented functional annotations and transcription regulatory elements compared with the entire microarray. Genes encoding for proteins involved in tyrosine phosphatase activity, calcium ion binding, cell growth and/or maintenance, and chromosome organization were overrepresented. Our data enhance the understanding of the molecular interactions involved in the beta4 nAChR subunit function. They also emphasize the need for careful interpretation of expression microarray studies done on genetically manipulated animals.


Body mass index percentiles versus body composition assessments: Challenges for disease risk classifications in children.
Identifying at-risk children with optimal specificity and sensitivity to allow for the appropriate intervention strategies to be implemented is crucial to improving the health and well-being of children. We determined relationships of body mass indexes for age and sex percentile (BMI%) classifications to actual body composition using validated and convenient methodologies and compared fat and non-fat mass estimates to normative cut-off reference values to determine guideline reliability. We hypothesized that we would achieve an improved ability to identify at-risk children using simple, non-invasive body composition and index measures. Cross-sectional study of a volunteer convenience sample of 1,064 (537 boys) young children comparing Body Fat Percentage (BF%), Fat Mass Index (FMI), Fat-Free Mass Index (FFMI), determined via rapid bioimpedance methods vs. BMI% in children. Comparisons determined among weight classifications and boys vs. girls. Amongst all subjects BMI% was generally correlated to body composition measures and indexes but nearly one quarter of children in the low-risk classifications (healthy weight or overweight BMI%) had higher BF% and/or lower FFMI than recommended standards. Substantial evidence of higher than expected fatness and or sarcopenia was found relative to risk status. Inaccuracies were more common in girls than boys and girls were found to have consistently higher BF% at any BMI%. The population studied raises concerns regarding actual risks for children of healthy or overweight categorized BMI% since many had higher than expected BF% and potential sarcopenia. When body composition and FMI and FFMI are used in conjunction with BMI% improved sensitivity, and accuracy of identifying children who may benefit from appropriate interventions results. These additional measures could help guide clinical decision making in settings of disease-risks stratifications and interventions.


Extended endonasal endoscopic approach for anterior midline skull base lesions.
In recent years, extended endoscopic endonasal approach (EEEA) has been used as an alternative to transcranial approaches in the treatment of anterior midline skull base lesions. We retrospectively reviewed our cases operated using this technique and compared the results with current literature. The data of 24 patients who were operated using EEEA in our department between 2010-2018 were retrospectively analyzed. The lesions were located in the midline between the posterior wall of the frontal sinus and tuberculum sella. Tumor locations, histopathological diagnoses, surgical techniques, outcomes and complications were documented. Eleven patients were female and 13 were male. Their ages ranged between 18-75 years (mean 40.5 years). Considering their locations; 12 were in the anterior fossa (50 %), 7 were in the tuberculum sella (29.1 %), and 5 were in both anatomic sites (20.8 %). Histopathologically, our series consisted of 15 meningiomas, 6 osteomas, 2 dermoid tumors and 1 metastatic carcinoma. We achieved gross total resection in 75 % of our patients. Ten patients presented with visual complaints and 7 of them improved postoperatively. Postoperative cerebrospinal fluid leakage (CSF) was observed in 3 patients and one of them developed meningitis and subsequently died of sepsis. Although the number of cases is low, EEEA seems like a safe, effective and well-tolerated treatment modality for anterior midline skull base lesions. But strict preventive measures should be taken for a possible CSF leak.


Incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with neuromuscular scoliosis: A STROBE-compliant retrospective observational analysis.
Factors influencing massive blood loss for neuromuscular scoliosis (NMS) patients.Despite advances in surgical and anesthetic techniques, scoliosis surgery is still associated with intraoperative massive blood loss, which can result in postoperative mortality and morbidity. The aim of this study was to assess the incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with NMS.A retrospective review of adolescents who underwent posterior spinal instrumentation and fusion for NMS was performed. Perioperative variables and data were recorded. Massive blood loss was defined as an estimated blood loss that exceeds 30% of total blood volume.We obtained data for 114 patients, of whom 63 (55%) had intraoperative massive blood loss. Compared with those without, patients with massive blood loss were more likely to be older, have lower body mass indexes (BMIs), larger Cobb angles, more fused levels, more osteotomy procedures, and prolonged duration of operation. Logistic regression analysis identified the number of fused levels to be more than 12 (P = 0.003, odds ratio = 6.614, 95% confidence interval [CI]: 1.891-23.131), BMI lower than 16.8 kg/m (P = 0.025, odds ratio = 3.293, 95% CI: 1.159-9.357), age greater than 15 years (P = 0.014, odds ratio = 3.505, 95% CI: 1.259-9.761), and duration of operation longer than 4.4 hours (P = 0.016, odds ratio = 3.746, 95% CI: 1.428-9.822) as influencing factors. Patients with massive blood loss are associated with more intraoperative colloids infusion and blood transfusions (red blood cell and fresh frozen plasma), as well as postoperative drainage volume.In adolescents with NMS who underwent posterior spinal instrumentation and fusion operations, intraoperative massive blood loss is common. The number of fused levels, BMI, age, and duration of operation are factors influencing intraoperative massive blood loss.


Modulation of the Electrochemical Reactivity of Solubilized Redox Active Polymers via Polyelectrolyte Dynamics.
Redox active polymers (RAPs) are electrochemically versatile materials that find key applications in energy storage, sensing, and surface modification. In spite of the ubiquity of RAP-modified electrodes, a critical knowledge gap exists in the understanding of the electrochemistry of soluble RAPs and their relation to polyelectrolyte dynamics. Here, we explore for the first time the intersection between polyelectrolyte behavior and the electrochemical response that highly soluble and highly substituted RAPs with viologen, ferrocene, and nitrostyrene moieties elicit at electrodes. This comprehensive study of RAP electrolytes over several orders of magnitude in concentration and ionic strength reveals distinct signatures consistent with surface confined, colloidal, and bulk-like electrochemical behavior. These differences emerge across polyelectrolyte packing regimes and are strongly modulated by changes in RAP coil size and electrostatic interactions with the electrode. We found that, unlike monomer motifs, simple changes in the ionic strength caused variations over 1 order of magnitude in the current measured at the electrode. In addition, the thermodynamics of adsorbed RAP films were also affected, giving rise to standard reduction potential shifts leading to redox kinetic effects as a result of the mediating nature of the RAP film in equilibrium with the solution. Full electrochemical characterization via transient and steady-state techniques, including the use of ultramicroelectrodes and the rotating disk electrode, were correlated to dynamic light scattering, ellipsometry, and viscometric analysis. These methods helped elucidate the relationship between electrochemical behavior and RAP coil size, film thickness, and polyelectrolyte packing regime. This study underscores the role of electrostatics in modulating the reactivity of redox polyelectrolytes.


Antifouling Zwitterionic Nanofibrous Wound Dressing for Long-Lasting Antibacterial Photodynamic Therapy.
Nanofibrous mats as a wound dressing have received great attention in recent year. The development of biocompatible dressings with antibiofouling capability and long-lasting antibacterial properties is important but challenging. Antibacterial photodynamic therapy (aPDT) effectively eliminates pathogens via a photodynamic process that can circumvent the emergence of antibiotic-resistant pathogens. In this study, we integrated the zwitterionic materials (2-methacryloyloxyethyl phosphorylcholine (MPC) moiety) and aPDT photosensitizer, methylene blue (MB), to fabricate a long-lasting antibacterial nanofibrous mat using electrospinning technology. The prepared nanofibers possessed an appropriate water absorption and retention ability, superior cytocompatibility, and antibiofouling ability against both proteins and L929 cell adhesion. MB-loaded nanofibrous mats have exhibited superior aPDT against Gram-positive Staphylococcus aureus compared to Gram-negative Escherichia coli under moderate irradiation (100 W m-2) due to the presence of an extra outer membrane of Gram-negative bacteria serving as a protective barrier. In vitro release study demonstrated that the nanofibrous mat had a long-lasting drug release profile, which can efficiently suppress bacterial growth via aPDT. The antibacterial ability of the MB-loaded nanofibrous mat was commensurate or slightly inferior to antibiotics such as tetracycline and kanamycin, suggesting that it has the potential to be used as an antibiotic alternative. Overall, this zwitterionic nanofibrous mat with long-lasting aPDT function and nonadherent properties has potential as a promising antibacterial wound dressing.


Exploring the Learning Psychology Mobilization of Music Majors Through Innovative Teaching Methods Under the Background of New Curriculum Reform.
The research expects to explore the psychological mobilization of innovative teaching methods of Music Majors under the new curriculum reform. The relevant theories of college students' innovative teaching methods are analyzed under deep learning together with the innovation and construction of music courses. Thereupon, college students' psychological mobilization is studied. Firstly, the relationship between innovation and entrepreneurship teaching and deep learning is obtained through a literature review. Secondly, the music classroom model is designed based on the deep learning theory, and the four dimensions of the music curriculum are defined to innovate and optimize the music teaching model. Finally, the Questionnaire Survey (QS) is used to analyze the design classroom model. Only 15% of the 180 respondents understand the concept of deep learning, 32% like interactive music learning, and 36% like competitive comparative music classroom learning. And the students who study instrumental music have higher significant differences in learning motivation than those who study vocal music. In addition to classroom learning, 16% of people improve their music skills through music equipment. College students like interactive music classes and competitive comparison classes that can give more play to their subjective initiative. After the new curriculum reform, the music curriculum based on deep learning can stimulate students' interest in learning and participate in the mobilization of students' learning psychology. Therefore, in the future of music education and teaching, there is a need to pay more attention to students' psychological status. The research results can provide references and practical significance for the innovative teaching activities of music classrooms after the new curriculum reform.


Cultural competence in end-of-life care: terms, definitions, and conceptual models from the British literature.
Cultural competency is increasingly recommended in policy and practice to improve end-of-life (EoL) care for minority ethnic groups in multicultural societies. It is imperative to critically analyze this approach to understand its underlying concepts. Our aim was to appraise cultural competency approaches described in the British literature on EoL care and minority ethnic groups. This is a critical review. Articles on cultural competency were identified from a systematic review of the literature on minority ethnic groups and EoL care in the United Kingdom. Terms, definitions, and conceptual models of cultural competency approaches were identified and situated according to purpose, components, and origin. Content analysis of definitions and models was carried out to identify key components. One-hundred thirteen articles on minority ethnic groups and EoL care in the United Kingdom were identified. Over half (n=60) contained a term, definition, or model for cultural competency. In all, 17 terms, 17 definitions, and 8 models were identified. The most frequently used term was "culturally sensitive," though "cultural competence" was defined more often. Definitions contained one or more of the components: "cognitive," "implementation," or "outcome." Models were categorized for teaching or use in patient assessment. Approaches were predominantly of American origin. The variety of terms, definitions, and models underpinning cultural competency approaches demonstrates a lack of conceptual clarity, and potentially complicates implementation. Further research is needed to compare the use of cultural competency approaches in diverse cultures and settings, and to assess the impact of such approaches on patient outcomes.


Collection of autologous blood before elective hip replacement. A comparison of the results with the collection of two and four units.
The need for allogeneic blood can be reduced effectively with the use of preoperatively donated autologous blood. However, this collection also results in the waste of autologous blood in a considerable number of patients. In order to reduce overcollection, we requested that the amount of autologous blood donated before a total hip replacement be decreased from four units to two units. We then compared the amount of allogeneic blood required for fifty patients who had donated two units of autologous blood with that of fifty historical controls who had donated four units. The patients were matched for sex, initial hemoglobin concentration, and blood loss. There was no significant difference in the percentage of autologous donors who received additional allogeneic blood; 20 per cent (ten) of the patients who had donated two units and 16 per cent (eight) of the patients who had donated four units required allogeneic blood (p = 0.12). Eighteen autologous units from the patients who had donated two units and fifty-one units from the patients who had donated four units were discarded. The erythropoietic response, measured by the increase in the reticulocyte count, was comparable for the two groups. Iron stores, measured as the serum ferritin concentration, were lower after the drawing of four units (33 +/- 39 micrograms per liter) compared with after the drawing of two units (49 +/- 29 micrograms per liter) (p = 0.03). The donation of two units of blood does not increase the exposure to allogeneic blood compared with the exposure after the donation of four units by patients who are going to have a total hip replacement.(ABSTRACT TRUNCATED AT 250 WORDS)


Upregulation of human telomerase reverse transcriptase mRNA expression by in vitro transfection of hepatitis B virus X gene into human hepatocarcinoma and cholangiocarcinoma cells.
To study the changes of human telomerase reverse transcriptase (hTERT) mRNA expression in human hepatocarcinoma cell lines (HepG2) and cholangiocarcinoma cell lines (QBC939) after HBx gene transfection and to illustrate the significance of transcriptional regulation of hTERT gene by HBx gene in the carcinogenesis. HepG2 and QBC939 cell lines were cultured and co-transfected with eukaryotic expression vector containing the HBx coding region and cloning vector containing enhanced green fluorescent protein (EGFP) coding sequence using lipid-mediated gene transduction technique. Thirty-six hours after transfection, EGFP expression in cells was used as the indicator of successful transfection. Flow cytometry was performed to determine the transfection efficiency. Cells were harvested and total RNA was extracted using TRIzol reagent. The expression of hTERT mRNA in HepG2 and QBC939 cell lines was assayed by reverse transcription-polymerase chain reaction. The expression of HBx protein in both cell lines was detected by immunocytochemical staining and Western blotting. Flow cytometry showed that the transfection efficiency was 46.4% in HepG2 cells and 29.6% in QBC939 cells for both HBx gene expression vector and blank vector. The expression of hTERT mRNA was meaningfully increased in HepG2 and QBC939 cell lines when transfected with HBx gene expression vector compared to those transfected with OPTI-MEM medium and blank vector. Immunocytochemical staining and Western blotting revealed HBx protein expression in HepG2 and QBC939 cells only when transfected with HBx gene. HBx gene transfection can upregulate the transcriptional expression of hTERT mRNA. The transactivation of hTERT gene by HBx gene is a newfound mechanism for pathogenesis of hepatocarcinomas and cholangiocarcinomas after HBV infection.


Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: Safety, efficacy, and pharmacokinetic results.
Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b).


Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis.
Breast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME. n = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher's and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan-Meier method. The proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2- subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome. The TME dynamics of HR+/HER2- PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.


Brugada-like electrocardiographic changes induced by fever.
As "time is myocardium" in the settings of acute myocardial infarction, it is important to make the diagnosis as quickly as possible, and a high clinical suspicion is needed to avoid missing the diagnosis, resulting in unwarranted interventions. The electrocardiogram is a crucial tool in the identification of acute chest pain, enabling a detailed analysis of patterns of ST-segment elevation. We describe the case of a 22-year-old man who presented with fever, with dynamic electrocardiographic changes similar to the Brugada syndrome. These electrocardiographic anomalies disappeared when the temperature returned to normal.


Cigarette smoke exposure of school children: effect of passive smoking and vitamin E supplementation on blood antioxidant status.
Despite similar vitamin E concentrations, erythrocytes of 25 children of smoking parents had an increased tendency (p < 0.01) to peroxidize in vitro as compared with those of 28 children of nonsmoking parents. This difference was abolished by vitamin E supplementation (100 mg alpha-tocopherol acetate/day for 14 days). The increased susceptibility to erythrocyte peroxidation in the smokers may reflect lower erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase and superoxide dismutase activities (p < 0.001, p < 0.005, and p < 0.02, respectively) in children of smoking parents. Children of smoking parents seem to be under sustained oxidant stress with increased plasma-conjugated dienes (p < 0.01) and dehydroascorbate (p < 0.002) concentrations. Total plasma cholesterol was similar in children of smoking and nonsmoking parents, and was unaffected by vitamin E supplementation. Indices of sustained oxidant stress in children of smoking parents were partially ameliorated by vitamin E supplementation.


Dosing strategies to optimize currently available anti-MRSA treatment options (Part 1: IV options).
Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a predominant pathogen resulting in significant morbidity and mortality. Optimal dosing of anti-MRSA agents is needed to help prevent the development of antimicrobial resistance and to increase the likelihood of a favorable clinical outcome. Areas covered: This review summarizes the available data for antimicrobials routinely used for MRSA infections that are not administered orally or topically. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 - Present) search was performed to identify relevant literature for this review. Expert commentary: Improvements in MIC determination and therapeutic drug monitoring are needed to fully implement individualized dosing that optimizes antimicrobial pharmacodynamics.Additional data will become available for these agents in regards to effectiveness for severe MRSA infections and pharmacokinetic data for special patient populations.


Differential effects of sodium lauryl sulphate and non-anoic acid on the expression of CD1a and ICAM-1 in human epidermis.
Normal human skin was exposed to two different detergents, sodium lauryl sulphate in distilled water and non-anoic acid in isopropanol at different concentrations. The detergents were applied under occlusion in epicutaneous tests for 24 h and biopsies were taken at 24 or 48 h. Frozen sections were labelled with monoclonal antibodies against CD1a, CD3 and ICAM-1. The evaluation of the labelled sections showed that there were differential effects on the expression of ICAM-1 and CD1a+ cells in epidermis. After non-anoic acid application ICAM-reactivity could not be detected and there was a decrease of staining for CD1a after exposure to 80% non-anoic acid. Sodium lauryl sulphate treatment, however, induced ICAM-1 expression on keratinocytes and had minor effects on the number of CD1a+ cells. ICAM-1 expression was also detected in normal epidermis in 3 of 9 unexposed control biopsies and after occlusion with the vehicles distilled water and isopropanol. An increased amount of CD3+ cells was found in the skin exposed to both detergents. The results show that there are dose and time dependent variations in the epidermal response to irritants which might influence the immunological events taken place in the epidermis.


Comorbidities in hereditary angioedema-A population-based cohort study.
In hereditary angioedema (HAE), low levels (type 1) or defect in function (type 2) of the serine-protease inhibitor C1 Inhibitor protein results in activation of the classical pathway of the complement system as well as the contact system. Here, we investigated the risk of comorbidities in HAE. Individuals with HAE (n = 239; identified through a physician made diagnosis) and a control cohort from the general population (n = 2383; matched for age, gender, and county of residence) were compared with the Swedish inpatient, cause of death, cancer, and prescription registers. Conditional logistic regression was used to analyze the data. Increased risk of cardiovascular disease (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.32-2.54), including arterial (OR 6.74; 95% CI 1.89-24.06) and venous thromboembolic disease (OR 4.20; 95% CI 2.42-7.23) as well as hypertension (OR 1.64; 95% CI 1.12-2.39) was seen in HAE. There was also an increased number of individuals diagnosed with hyperlipidemia (OR 2.01; 95% CI 1.16-3.50) among HAE patients. Furthermore, the risk of autoimmune disease was increased (OR 1.65; 95% CI 1.15-2.35) being particularly pronounced for systemic lupus erythematosus (OR 71.87; 95% CI 8.80-586.7). The risk of having two or more autoimmune diseases was also higher among HAE patients (p = 0.017). In contrast, the risk of cancer was not increased. Data from the prescription register revealed higher prescription rates of drugs against hypertension, hypothyroidism, and hyperlipidemia among HAE patients. The results warrant for awareness and prevention of comorbid conditions, in particular, thromboembolic and autoimmune diseases in HAE. Future prophylactic interventions may modify these risks.


The role of mutations in epigenetic regulators in myeloid malignancies.
Over the past decade, genomic studies have identified a number of novel and recurrent somatic mutations that affect epigenetic patterning in patients with myeloid malignancies, including myeloproliferative neoplasms, myelodysplastic syndrome, and acute myeloid leukemia. Many of these mutations occur in genes with established roles in the regulation and maintenance of DNA methylation and/or chromatin modifications in hematopoietic stem/progenitor cells. Subsequent genetic and functional studies have revealed that these mutations affect epigenetic patterning in myeloid diseases. In this review, we discuss historical and recent studies implicating epigenetic modifiers in the development and evolution of the various myeloid malignancies and discuss how this knowledge has and will lead to future clinical and biologic insights.


Unprecedented opportunities and promise for cancer prevention research.
Cancer prevention encompasses a wide range of highly developed science and clinical impact. Enunciating these two aspects in the same breath highlights the crucial link between them. The breadth and excitement of current opportunities in the science of cancer prevention have never been greater. Major avenues of such research include the extent and effect of premalignancy, the molecular underpinnings of carcinogenesis and related prevention targets, in vitro model systems of the progression of normal human epithelial cells to tumorigenesis, molecular risk stratification and pharmacogenomic approaches, and many more. We describe the clinical impacts of cancer prevention (with examples in the areas of molecular targeting, vaccines, epidemiology, and behavioral science) and the stage-setting science that facilitated them. In addition, discussed are new prevention opportunities such as interactions between stromal and microenvironmental factors, the control of premalignant stem cell phenotypes through epigenetic reprogramming, and neoplastic cells and various stress responses including those involving telomere biology. The promise of this science, particularly integrative, interdisciplinary research, is to hasten the ability of clinical prevention to reduce the burden of cancer.


Ultrasonography in crossed renal ectopia.
Five cases of crossed renal ectopia, three fused and two unfused, which were identified sonographically are presented. Bowel occupying the contralateral renal fossa can mimic mass or kidney and lead to confusion. A crossed-fused kidney can mimic a single kidney with a duplicated system or a kidney with a renal mass. A characteristic anterior and/or posterior notch provides a major clue to the correct diagnosis. In addition, correlation with plain radiographs and/or barium studies demonstrating bowel in the contralateral renal fossa, as well as real-time examination demonstrating peristalsis, should aid in the correct diagnosis.


[Prion dementias: nosology and diagnostic difficulties in the spectrum of Creutzfeld-Jakob encephalopathy].
Creutzfeldt-Jakob disease (CJD) is one form of subacute prion diseases with spongiform encephalopathy. Hereditary, infectious and sporadic types of the disorder can be distinguished. The abnormal transformation of the prion protein, relevant in the normal synaptic transmission is considered as an important factor in the development of this disease. Gerstmann-Sträussler-Scheinker syndrome (GSS) and familial fatal insomnia (FFI) are the other diseases belonging to the same disease spectrum. The common feature of these disorders is that the different mutation of the same prion protein could result in different phenotypes and symptoms. CJD is considered as a neurologic disorder but the clinical symptoms and differential diagnosis of the disease are also relevant problems in psychiatry. Because of the early onset of dementia and the psychotic and delusive symptoms, the patients with CJD are frequently admitted to psychiatric wards. Recently worldwide public interest has been focused on prion dementias because of the possible human transmission of bovine spongiform encephalopathy in the UK. The diagnostic problems of our seven CJD patients diagnosed since 1991 in the catchment area of Szeged city are discussed in the view of recent findings of molecular biology, nosology, diagnostic and therapeutic problems of this devastating disease.


Effects of dimethoate in male mice reproductive parameters.
The aim of the current study was to investigate the ability of dimethoate (DMT) to induce reprotoxicity in male mice. The dose (20 mg/kg/day) was given orally for 30 days. A significant decrease in sperm count, motility and viability and a significant increase of morphologically abnormal spermatozoa percent in DMT treated mice was observed. Testicular Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) activities were inhibited. Also, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in testis of DMT mice. In addition, gene expression of glutathione peroxidase 4 (GPx4) was quantified in RNA samples extracted from the testis by real-time reverse transcription-polymerase chain reaction (RT-PCR). Compared with control, mRNA expression of GPx4 was slightly decreased after DMT-exposure.


Positive and negative regulation of seed germination by the Arabidopsis GA hormone receptors, GID1a, b, and c.
Epistasis analysis of gid1 single and double mutants revealed that GID1c is a key positive regulator of seed germination, whereas the GID1b receptor can negatively regulate germination in dormant seeds and in the dark. The GID1 GA receptors were expected to positively regulate germination because the plant hormone gibberellin (GA) is required for seed germination in Arabidopsis thaliana. The three GA hormone receptors, GID1a, GID1b, and GID1c, positively regulate GA responses via GA/GID1-stimulated destruction of DELLA (Asp-Glu-Leu-Leu-Ala) repressors of GA responses. The fact that the gid1abc triple mutant but not gid1 double mutants fail to germinate indicates that all three GA receptors can positively regulate non-dormant seed germination in the light. It was known that the gid1abc triple mutant fails to lose dormancy through the dormancy breaking treatments of cold stratification (moist chilling of seeds) and dry after-ripening (a period of dry storage). Previous work suggested that there may be some specialization of GID1 gene function during germination because GID1b mRNA expression was more highly induced by after-ripening, whereas GID1a and GID1c mRNA levels were more highly induced by cold stratification. In light-germinated dormant seeds, the gid1b mutation can partly rescue the germination efficiency of gid1a but not of gid1c seeds. Thus, GID1b can function as an upstream negative regulator GID1c, a positive regulator of dormant seed germination. Further experiments showed that GID1b can negatively regulate dark germination. Wild-type Arabidopsis seeds do not germinate well in the dark. The gid1b and gid1ab double mutants germinated much more efficiently than wild type, gid1c, or gid1ac mutants in the dark. The observation that the gid1ab double mutant also shows increased dark germination suggests that GID1b, and to some extent GID1a, can act as upstream negative regulators of GID1c. Since the gid1abc triple mutant failed to germinate in the dark, it appears that GID1c is a key downstream positive regulator of dark germination. This genetic analysis indicates that the three GID1 receptors have partially specialized functions in GA signaling.


White matter: organization and functional relevance.
Norman Geschwind's landmark paper in 1965, "Disconnexion Syndromes in Animals and Man," inspired a generation of investigators to consider the effects of focal brain lesions disrupting higher brain functions. Although Geschwind viewed disconnection as resulting from either white or gray matter lesions, his signature article drew upon the insights of 19th century neurologists and firmly established white matter within the vocabulary of behavioral neurology, neuropsychology, and cognitive neuroscience. This influence, and the advent of sensitive neuroimaging techniques later in the 20th century, led to white matter gradually gaining more attention as an essential component of distributed neural networks subserving cognition and emotion. Today, whereas focal white matter lesions remain central to the pathogenesis of classic neurobehavioral syndromes, diffuse white matter involvement is regarded as increasingly relevant to a wide variety of dementia syndromes and a host of neuropsychiatric disorders as well. In parallel, better understanding of the neurobiology of brain white matter at all ages has been achieved. While much remains to be explored, a general conceptual formulation is that white matter supports information transfer to complement the information processing carried out by gray matter. As knowledge of the organization and functional relevance of white matter continues to advance, improved understanding of the role of myelinated tracts in higher function can be anticipated, and with it many clinical benefits.


Sirtuin 6 protects human retinal pigment epithelium cells from LPS-induced inflammation and apoptosis partly by regulating autophagy.
Lipopolysaccharides (LPS)-induced retinal inflammation is an important factor in retinal diseases. This study was aimed to investigate the effect of Sirt6 on LPS-induced retinal injury. ARPE-19 cells were incubated with LPS to induce inflammation. The cell viability was determined using CCK-8 assay. The mRNA level and protein expression of corresponding genes was detected using qRT-PCR and western blot, respectively. The production of inflammatory cytokines was measured using ELISA kit. The levels of oxidative stress-related factors were measured using their detection kits. Cell apoptosis was observed using TUNEL assay. The results showed that Sirt6 was downregulated after LPS treatment. Sirt6 strengthened LPS-induced autophagy by promoting the expression of LC3II/I, beclin1 and ATG5. Sirt6 treatment significantly inhibited LPS-induced inflammation, oxidative stress and cell apoptosis, which was then partly abolished by 3 MA. These results suggest Sirt6 to be an important regulator for LPS-induced inflammation, oxidative stress, and apoptosis partly by regulating cell autophagy.


Circularly Polarized Luminescence of Cyclometalated Platinum(II) Complex Excimers: Large Difference between Isomers.
A series of platinum(II) complexes bearing a chiral β-diketonato ligand and a cyclometalated ligand have been prepared. The platinum(II) complexes, (SP-4-3)-[Pt(ppy)(D-tac)] (ppy = 2-phenylpyridine, D-tac = 3-trifluoroacetyl-(D)-camphor), (SP-4-4)-[Pt(ppy)(D-tac)], (SP-4-3)-[Pt(ppy)(D-pbc)] (D-pbc = 3-perfluorobutyryl-(D)-camphor), and (SP-4-4)-[Pt(ppy)(D-pbc)], and their enantiomers were isolated and characterized by elemental analysis, NMR, and X-ray structural analysis. Photoisomerization between SP-4-3 (trans) and SP-4-4 (cis) isomers was observed. Green emission due to the monomer was observed in diluted solutions for all complexes. Higher quantum yields and longer lifetimes of green emission were observed in nonpolar solvents compared to polar solvents. The two geometrical isomers had surprisingly different excimer formation efficiencies. For the trans isomers, orange emission due to the excimers was observed in nonpolar solvents at high concentrations, whereas negligible intensities of the excimer emission were observed for the cis isomers. The formation of the excimers was evaluated by emission decay and time-resolved emission spectra. For the trans isomers, the green emission due to the monomer showed negligible CPL signals, but the orange emission gave pronounced CPL signals. The dissymmetry factors, g-values, of the excimer CPL (glum = 0.002) were enhanced over those of the circular dichroism (gabs = 0.0002, glum/gabs = 10). The intensities of the emission and the CPL of the excimer under oxygen were very small, although those under an argon atmosphere were very strong. Therefore, the emission color of the trans-isomers was changed from green to orange by deoxygenation.


Should we worry about meconium? A controlled study of neonatal outcome.
Over a 7 month period 131 cases with intrapartum draining of meconium-stained liquor (MSL) were reviewed and the neonatal outcome compared to that of all deliveries during the same time. Mean Apgars were significantly lower and the proportion of neonates with poor Apgar scores was higher if thick meconium was present, but not for thin meconium. Prolonged labour was more common and associated with a particularly worse outcome in the MSL group. Caesarean sections were performed twice as frequently, failure to progress being the indication in more than half the cases. Close monitoring of labour in the presence of MSL (particularly thick MSL) is important to detect failure to progress and fetal distress early.


Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to biologic and lifestyle characteristics.
In 10 years of follow-up of 7705 Japanese men living in Hawaii, aged 45-68 years and judged free of coronary heart disease (CHD) at the initial examination during 1965-1968, a total of 511 new CHD cases were identified: fatal CHD, 139; nonfatal myocardial infarction (MI), 216; acute coronary insufficiency, 55; and uncomplicated angina pectoris (AP), 101. The incidence rate of fatal CHD and nonfatal MI for this cohort is less than half the rate for US whites and approximately twice the rate for Japanese men in Japan. The relationships of 14 biologic and lifestyle characteristics measured at baseline examination to the incidence of total CHD and specific manifestations of CHD were examined in bivariate and multivariate analyses. In bivariate analyses, all variables except heart rate were significantly related to the risk of total CHD after adjustment for age. However, when an independent contribution of each variable to CHD risk was evaluated in multiple logistic analyses in which all other variables were taken into account, the numbers of risk factors retaining significant associations varied by clinical subgroup of CHD. Among the characteristics studied, systolic blood pressure was the most powerful and consistent risk factor for all manifestations except AP. Cigarette smoking showed a similar pattern. Serum cholesterol was significantly associated with fatal CHD and nonfatal MI, but its contribution to CHD risk was less potent than systolic blood pressure or cigarette smoking. Glucose intolerance was strongly associated with fatal CHD, but with no other manifestations of CHD. Alcohol consumption demonstrated a strong protective effect upon fatal CHD and nonfatal MI. Uncomplicated AP was distinguished from other CHD manifestations by the lack of association with most of the known major risk factors for CHD, including blood pressure, serum cholesterol, and cigarette smoking.


Preparation and characterization of chitosan/β-cyclodextrin nanoparticles containing plasmid DNA encoding interleukin-12.
Interleukin-12 (IL-12) as a cytokine has been proved to possess antitumor effects via stimulating the immune system. Non-viral gene delivery systems offer several advantages, including easiness in production, low cost, safety; low immunogenicity and can carry higher amounts of genetic material without limitation on their sizes.pUMVC3-hIL12 loaded Low Molecular Weight chitosan/β-cyclodextrin (LMW CS/CD) nanoparticles were prepared using ionotropic gelation method and characterized in terms of size, zeta potential, polydispersity index, morphology, loading efficiency and cytotoxicity against the CT-26 colon carcinoma cell line.All prepared particles were spherical in shape and nano-sized (171.3±2.165 nm, PdI: 0.231±0.014) and exhibited a positive zeta potential (34.3±1.55). The nanoparticles demonstrated good DNA encapsulation efficiencies (83.315%±2.067). Prepared pUMVC3-hIL12 loaded LMW CS/CD nanoparticles showed no cell toxicity in murine CT-26 colon carcinoma cells. At the concentration of 0.1 µg/ml of nanoparticles, the transfection ability was obviously higher than that of the naked DNA.LMW CS/CD-plasmid DNA nanoparticles encoding IL-12 prepared using ionotropic gelation method with no toxic effect on the tested cells can be considered as a basis for further gene delivery studies both in vitro and in vivo to enhance the expression of IL-12.


Complex approaches to study complex trait genetics in multiple sclerosis.
Multiple sclerosis (MS) is a complex trait disorder defined by several genes and their interactions with environmental factors. A comprehensive exploration of the susceptibility variants had not been feasible until recently when new developments in biotechnology and bioinformatics made possible sequencing of the whole human genome, cataloguing of nucleotide variants and alignments of these variants in haplotypes. Earlier observations from epidemiological, candidate gene and linkage studies provided ample evidence to support a complex genetic determination of MS. New biotechnology and bioinformatics resources have been recently applied to further successful explorations of the disease. These efforts were paralleled by more careful and reliable ascertainments of disease phenotypes, collaborations among specialized centers to generate sufficient sample size and involvement of clinician-scientists capable of working both on the clinical and scientific study sides. Data obtained from the whole genome association studies (GWAS) elevated our understanding of MS genetics to a new level by identifying an extensive list of genetic determinants. Pathway analyses of MS-associated variants provided evidence to support the immune etiology of the disease. Future research will likely explore how environmental factors interact with the genome, and contribute to the abnormal immune activation and inflammation. This review summarizes the outcomes of MS genetic explorations including those of recent GWAS, and highlights practical consequences of genetic and genomic studies by pointing out as to how the derived data facilitate further elucidation of MS pathogenesis. A better understanding of disease processes is necessary for future advancements in therapeutics and the development of disease prevention strategies.


The Social and Productive Impacts of Zambia's Child Grant.
Accumulated evidence from dozens of cash transfer programs across the world suggest that there are few interventions that can match the range of impacts and cost-effectiveness of a small, predictable monetary transfer to poor families in developing countries. However, individual published impact assessments typically focus on only one program and one outcome. This article presents two-year impacts of the Zambian Government's Child Grant, an unconditional cash transfer to families with children under age five, across a wide range of domains including consumption, productive activity and women and children's outcomes, making this one of the first studies to assess both protective and productive impacts of a national unconditional cash transfer program. We show strong impacts on consumption, food security, savings and productive activity. However, impacts in areas such as child nutritional status and schooling depend on initial conditions of the household, suggesting that cash alone is not enough to solve all constraints faced by these poor, rural households. Nevertheless, the apparent transformative effects of this program suggest that unconditional transfers in very poor settings can contribute to both protection and development outcomes.


Surfactant therapy of newborn rabbits impairs lung macrophage bactericidal activity.
Because in vitro studies indicate that pulmonary alveolar macrophages (PAM's) filled with phospholipid vesicles have depressed microbicidal capacity, we tested the intrapulmonary bactericidal activity of newborn PAM's after surfactant treatment. Term newborn rabbits received intratracheally either homologous surfactant or one of two artificial phospholipid vesicle preparations followed by pulmonary aerosol infection with group B streptococci (GBS). Four hours after lung infection, phagocytic killing of GBS was reduced by 70-90% in animals treated with the homologous and one of the artificial surfactants compared with untreated animals or animals that received intrapulmonary injections of the surfactant vehicle (P less than 0.02). The other artificial phospholipid preparation decreased intrapulmonary inactivation of GBS by 30-40% compared with the controls. The phospholipid vesicles in the three preparations were avidly ingested and processed by newborn PAM's. The diminished in vivo killing of GBS was not attributed to decreased viability or phagocytic behavior of the PAM's toward GBS. The bactericidal defect that was evident in the newborn PAM's appeared related to the uptake of large phospholipid vesicles in the preparations rather than to the phospholipid content of the surfactants themselves. When in vitro conditions that stimulated the alveolar environment were used, the natural surfactant preparation promoted GBS proliferation, whereas the artificial preparations did not. Our findings indicate that surfactant administration reduces the bactericidal activity of neonatal PAM's. We conclude that additional investigations are needed to ascertain the effect of surfactant replacement therapy on lost defenses of the lung.


Microbiome characterization of alpine water springs for human consumption reveals site- and usage-specific microbial signatures.
The microbiome of water springs is gaining increasing interest, especially in water intended for human consumption. However, the knowledge about large-scale patterns in water springs microbiome is still incomplete. The presence of bacteria in water sources used for human consumption is a major concern for health authorities; nonetheless, the standard microbiological quality checks are focused only on pathogenic species and total microbial load. Using 16S rRNA high throughput sequencing, we characterized the microbiome from 38 water springs in Trentino (Northern Italy) for 2 consecutive years in order to gain precious insights on the microbiome composition of these unexplored yet hardly exploited environments. The microbiological studies were integrated with standard measurements of physico-chemical parameters performed by the Provincial Office for Environmental Monitoring in order to highlight some of the dynamics influencing the microbial communities of these waters. We found that alpha diversity showed consistent patterns of variation overtime, and showed a strong positive correlation with the water nitrate concentration and negatively with fixed residue, electrical conductivity, and calcium concentration. Surprisingly, alpha diversity did not show any significant correlation with neither pH nor temperature. We found that despite their remarkable stability, different water springs display different coefficients of variation in alpha diversity, and that springs used for similar purposes showed similar microbiomes. Furthermore, the springs could be grouped according to the number of shared species into three major groups: low, mid, and high number of shared taxa, and those three groups of springs were consistent with the spring usage. Species belonging to the phyla Planctomycetes and Verrucomicrobia were prevalent and at relatively high abundance in springs classified as low number of shared species, whereas the phylum Lentisphaerae and the Candidate Phyla radiation were prevalent at higher abundance in the mineral and potable springs. The present study constitutes an example for standard water spring monitoring integrated with microbial community composition on a regional scale, and provides information which could be useful in the design and application of future water management policies in Trentino.


Health information on the internet: evaluating greek health portals and depicting users' attitudes in West Macedonia, Greece.
The increasing use of communication networks help individuals, organizations and governments to access this information as an every day practice to support their decision-making procedures. Information seekers use the web to get hold of information that exists on the Internet. A lot of times this information has to do health. The existence of health portals has made life easier for the people that need this information. However, the quality of portal interfaces as well as the portal content has many times been in doubt. Many surveys have obtained results that are negative as far as health portal quality is concerned. The purpose of this paper is to evaluate a representative selection of Greek health portals from the actual users' point of view. The evaluation takes place at a small town of North-West Greece called Ptolemais. Questionnaires and interviews as well as interface evaluation techniques are used. The outcome seems positive for the Greek health portals. The study is extended to get some estimate of simple and professional users' attitudes upon seeking health related information on the internet in Greek. The conclusions of this study regarding information preferences of health information seekers are compared to international surveys.


Dying by Suicide in Nursing Homes: A Preventable End of Life Outcome for Older Residents.
Suicide research and suicide prevention have given comparatively little attention to the older adult residents of nursing homes. This population is characterized by advanced age, significant infirmity, limited autonomy and social connections, and other factors associated with high suicide risk such as self-neglect. However, little is known of the actual incidence and prevalence of suicide in older adults in such residential care settings, partly because of how such deaths are reported. Suicide risk screenings are nominal, facility staff lack training to identify signs of suicidality, and suicide prevention programs are not common in the nursing home industry. These deficits can be remedied by increasing awareness among family members, facility caregivers, contracted providers, community aging services, accrediting and regulatory agencies, and residents.


A novel GoldNano Carb test for rapid phenotypic detection of carbapenemases, particularly OXA type, in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.
To develop a simple gold nanoparticle (AuNP)-based colorimetric test, GoldNano Carb (GoldC), for detecting carbapenemase production in Gram-negative bacteria, compared with updated Carba NP (CNP) and CarbAcineto NP (CAcNP) tests by using PCR methods as gold standard. Ninety-nine carbapenemase-producing Enterobacteriaceae (CPE), Pseudomonas spp. and Acinetobacter spp. isolates and 89 non-CPE isolates were tested by the GoldC and CNP. Additionally, the CAcNP was performed in the Acinetobacter spp. isolates. The final imipenem (imipenem/cilastatin form) concentration was 5 mg/mL for all three tests. For the GoldC, the imipenem powder was added directly to bacterial cell suspension in distilled water prior to detection of acid product by the citrate-capped AuNP solution. An AuNP change from red to purple, blue or green indicates carbapenemase activity. The GoldC detected all carbapenemase producers except one OXA-23-like producer (99.0% sensitivity), whereas 11 carbapenemase producers (10 Acinetobacter and 1 P. aeruginosa) were CNP negative (88.9% sensitivity). However, the GoldC and CNP provided 100% and 98.6% sensitivity, respectively, for the CPE and Pseudomonas spp. Both tests gave one false positive from CTX-M-1-like-producing Enterobacter spp. (98.9% specificity). The GoldC and CAcNP detected 96.7% and 93.3% of the Acinetobacter spp. isolates, respectively. Interestingly, times to positivity by the GoldC were markedly shorter than those by the CNP (76.8% versus 36.2% positive at 5 min) and CAcNP (43.3% at 5 min versus 20% within 30 min). The GoldC is fast, easy, highly sensitive and inexpensive (∼$0.25 per test), suggesting that it may be suitable for routine carbapenemase detection in low-resource settings for infection control or epidemiological purposes.


Effect of the Implementation of Interdisciplinary Discharge Planning on Treatment Adherence and Readmission in Patients Undergoing Coronary Artery Angioplasty.
To determine the effect of interdisciplinary discharge planning on treatment adherence and readmission in the patients undergoing coronary artery angioplasty in the south of Iran in 2020. This experimental study had an intervention group and a control group with pre-test and post-test. 70 patients participated in the study who were randomly divided into the groups (intervention group (n=35) and control group (n=35)). In the intervention group, discharge planning was performed based on an interdisciplinary approach. Treatment adherence before, immediately, and one month after the intervention was evaluated with a 10-question survey scored from 1 to 5 (maximum score = 50), as well as readmission three months after the discharge was examined in both groups. Before the intervention, there was no statistically significant difference between the intervention and the control groups in the treatment adherence score (18.22 versus 17.37; p=0.84) but immediately and one month after the intervention statistically significant differences between the groups were showed (21.51 versus 46.14 and 23.28 versus 43.12, respectively; p<0.001). Within three months after discharge, the readmission rate was 11.4% in the control group, while no readmission was reported in the intervention group. Within three months after discharge, the readmission rate was 11.4% in the control group, while no readmission was reported in the intervention group. The implementation of interdisciplinary discharge planning had positive effects on treatment adherence and readmission rate in patients undergoing coronary artery angioplasty; therefore, it is suggested that health care system managers make the necessary plans to institutionalize this new educational approach for other patients discharge planning.


Refining Prescription Warning Labels Using Patient Feedback: A Qualitative Study.
The complexity of written medication information hinders patients' understanding and leads to patient misuse of prescribed medications. Incorporating patient feedback in designing prescription warning labels (PWLs) is crucial in enhancing patient comprehension of medication warning instructions. This qualitative study explored patient feedback on five newly designed PWLs. In-depth semi-structured face-to-face interviews were conducted with 21 patients, who were 18 years and older, spoke English, and took a prescription medication. These patients were shown different variations of the five most commonly used PWLs-Take with Food, Do not Drink Alcohol, Take with a Full glass of Water, Do not Chew or Break, and Protect from Sunlight. The 60-minute interviews explored feedback on patient comprehension of the PWL instructions and their suggestions for improving the clarity of the PWLs. At the end of the interview, patient self-reported socio-demographic information was collected with a 3-minute survey and a brief health literacy assessment was completed using the Newest Vital Sign. Twenty-one patients completed the interviews. Most patients were female (n = 15, 71.4%) with ages ranging from 23 to 66 years old (mean: 47.6 ± 13.3). The mean health literacy score was 2.4 on a scale of 0-6. Qualitative content analysis based on the text, pictures, and placement of the PWLs on the pill bottle showed preferences for including 'WARNING' on the PWL to create alertness, inclusion of a picture together with the text, yellow color highlighting behind the text, and placement of the PWL on the front of the pill bottle. Although patients had positive opinions of the redesigned PWLs, patients wanted further improvements to the content and design of the PWLs for enhanced clarity and understandability.


The self-disproportionation of enantiomers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities?
This commentary discusses an important, though not widely appreciated, chiral phenomenon of molecular chirality that effectively always occurs whenever nonracemic samples are subjected to practically any physicochemical process (e.g., force field, recrystallization, sublimation, even distillation, etc.) under totally achiral conditions external to the sample itself. The phenomenon is termed as the self-disproportionation of enantiomers (SDE) and though ubiquitous, its presence may not always be readily apparent, or workers may be otherwise oblivious to its effects. In the particular case of chromatography, when the SDE is apparent, the enantiomeric excess (ee) of the chiral compound is observed to vary across an eluted peak, with anterior eluted portions either enantioenriched or enantiodepleted relative to the ee of the starting material, and conversely for the posterior eluted portions. Herein, we highlight various aspects of the SDE phenomenon as it pertains to chromatography and, in particular, the effect of scaling down chromatographic systems, the potential risk of problems that the SDE can cause, as well as opportunities for practical applications of the phenomenon, possible new occurrences of the SDE phenomenon to be searched for, and unrealized opportunities.


Functionalization of quinoxalines by using TMP bases: preparation of tetracyclic heterocycles with high photoluminescene quantum yields.
Tetracyclic heterocycles that exhibit high photoluminescence quantum yields were synthesized by anellation reactions of mono-, di-, and trifunctionalized 2,3-dichloroquinoxalines. Thus, treatment of 2,3-dichloroquinoxaline with TMPLi (TMP = 2,2,6,6-tetramethylpiperidyl) allows a regioselective lithiation in position 5. Quenching with various electrophiles (iodine, (BrCl2 C)2 , allylic bromide, acid chloride, aryl iodide) leads to 5-functionalized 2,3-dichloroquinoxalines. Further functionalization in positions 6 and 8 can be achieved by using TMPLi or TMPMgCl⋅LiCl furnishing a range of new di- and tri-functionalized 2,3-dichloroquinoxalines. The chlorine atoms are readily substituted by anellation with 1,2-diphenols or 1,2-dithiophenols leading to a series of new tetracyclic compounds. These materials exhibit strong, tunable optical absorption and emission in the blue and green spectral region. The substituted O-heterocyclic compounds exhibit particularly high photoluminescence quantum yields of up to 90%, which renders them interesting candidates for fluorescence imaging applications.


Shaping urban environments to improve respiratory health: recommendations for research, planning, and policy.
Urban areas carry a large burden of acute (infectious) and chronic respiratory diseases due to environmental conditions such as high levels of air pollution and high population densities. Car-dominated cities often lack walkable areas, which reduces opportunities for physical activity that are fundamentally important for healthy lungs. The already restricted amount of green space available-with often poorly selected plants-could produce pollen and subsequently provoke or worsen allergic diseases. Less affluent neighbourhoods often carry a larger respiratory disease burden. A multisectoral approach with more diverse policy measures and urban innovations is needed to reduce air pollution (eg, low emission zones), to increase public space for walking and cycling (eg, low traffic neighbourhoods, superblocks, 15-minute cities, and car-free cities), and to develop green cities (eg, planting of low-allergy trees). Stricter EU air quality guidelines can push these transformations to improve the respiratory health of citizens. Advocacy by medical respiratory societies can also make an important contribution to such changes.


A fluorescent assay for ceramide synthase activity.
The sphingolipids are a diverse family of lipids with important roles in membrane compartmentalization, intracellular signaling, and cell-cell recognition. The central sphingolipid metabolite is ceramide, formed by the transfer of a variable length fatty acid from coenzyme A to a sphingoid base, generally sphingosine or dihydrosphingosine (sphinganine) in mammals. This reaction is catalyzed by a family of six ceramide synthases (CerS1-6). CerS activity is usually assayed using either radioactive substrates or LC-MS/MS. We describe a CerS assay with fluorescent, NBD-labeled sphinganine as substrate. The assay is readily able to detect endogenous CerS activity when using amounts of cell or tissue homogenate protein that are lower than those reported for the radioactive assay, and the Michaelis-Menten constant was essentially the same for NBD-sphinganine and unlabeled sphinganine, indicating that NBD-sphinganine is a good substrate for these enzymes. Using our assay, we confirm that the new clinical immunosuppressant FTY720 is a competitive inhibitor of CerS activity, and show that inhibition requires the compound's lipid tail and amine headgroup. In summary, we describe a fluorescent assay for CerS activity that circumvents the need to use radioactive substrates, while being more accessible and cheaper than LC-MS based assays.


Production of interleukin-1-alpha and -beta by human peripheral polymorphonuclear neutrophils.
The mechanism of the production of interleukin-1 (IL-1) by human peripheral polymorphonuclear neutrophils (PMN) was investigated. Supernatants of PMN stimulated with 30 micrograms/ml lipopolysaccharide (LPS) were used as extracellular IL-1 and supernatants of their lysate as intracellular IL-1 source. IL-1 activity was measured by the C3H/HeJ thymocyte co-mitogenic assay. The supernatants from PMN stimulated with LPS for 72 h showed IL-1 activity which had an apparent molecular weight of 15-20 kilodaltons and pI of 5.0 and more than 8.5. It was neutralized with anti-IL-1 antibodies and it lacked IL-2 activity. Our time course study of the IL-1 assay with neutralization by anti-IL-1-alpha and -beta antibodies indicated that the extracellular IL-1-beta activity appeared predominantly in the early incubation periods, whereas alpha activity appeared predominantly in the late periods. Intracellular IL-1-alpha but not beta activity was detected mainly at the intermediate incubation periods. These data indicate that PMN stimulated with LPS produce both IL-1-alpha and -beta, and release IL-1-beta first and IL-1-alpha later.


[A case of primary lung cancer in a young female with tongue cancer].
We describe a case of lung tumor in a 33-year-old woman with tongue cancer. She had noticed a painful sensation in her tongue in April 2000. The results of a physical examination showed a 22 x 11 mm ulcerated lesion on the right side of her tongue. A biopsy specimen showed a moderately differentiated squamous cell carcinoma. A preoperative chest radiograph showed no evidence of pulmonary metastasis. No neck lymphadenopathy was found. The tongue cancer was resected in September 2000, and the pathological stage was T2 N0 M0. A solitary pulmonary lesion appeared 8 months after the surgery. A Histological examination of a transbronchial lung biopsy specimen showed a moderately differentiated squamous cell carcinoma. It was difficult to distinguish histopathologically or immunohistochemically between a second primary tumor and a metastasis, but the pulmonary lesion was considered to be a second primary tumor on the basis of a single endobronchial lesion that appeared after the T2 tongue cancer with no regional recurrence or cervical lymphadenopathy. Treatment with chemotherapy and irradiation was not effective and the patient died 3 months after the diagnosis of lung cancer.