Defects in insulin binding and autophosphorylation of erythrocyte insulin receptors in patients with syndromes of severe insulin resistance and their parents.
Genetic forms of severe insulin resistance are often characterized by alterations in binding and/or kinase properties of the insulin receptor. To evaluate whether alterations in insulin receptor kinase of erythrocytes can be used as genetic markers, we studied patients with two apparently inherited conditions of severe insulin resistance (leprechaunism and the type A syndrome of insulin resistance) and their families. In the two propositi, [125I]insulin binding to intact erythrocytes was decreased by 64% and 45%, respectively. This was primarily due to a decrease in receptor number and was found in intact cells and solubilization of the receptors. Similar insulin binding defects were found on monocytes. Insulin-stimulated tyrosine kinase activity of the solubilized receptor from erythrocytes was also decreased and to a similar extent as binding. Parents of neither patient had clinical manifestations of leprechaunism or the type A syndrome. Furthermore, no alterations in insulin receptor binding or kinase activity were found in erythrocytes from the mothers. Insulin binding in the father of the type A patient was also normal, whereas the father of the leprechaun had decreased receptor affinity. Receptors extracted from the both fathers' cells had a 40-60% decrease in maximal insulin-stimulated phosphorylation and significant rightward shifts of the insulin dose-response curves (ED50, 141 and 42 ng/mL, respectively; control ED50, 16 ng/mL). The finding of biochemical defects in insulin receptor kinase activity in clinically unaffected parents of patients suggests that these alterations may be useful genetic markers and more sensitive than insulin binding studies for studying pattern of inheritance of these diseases.


Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells.
The mechanism of action of oral cladribine, recently licensed for relapsing multiple sclerosis, is unknown. To determine whether cladribine depletes memory B cells consistent with our recent hypothesis that effective, disease-modifying treatments act by physical/functional depletion of memory B cells. A cross-sectional study examined 40 people with multiple sclerosis at the end of the first cycle of alemtuzumab or injectable cladribine. The relative proportions and absolute numbers of peripheral blood B lymphocyte subsets were measured using flow cytometry. Cell-subtype expression of genes involved in cladribine metabolism was examined from data in public repositories. Cladribine markedly depleted class-switched and unswitched memory B cells to levels comparable with alemtuzumab, but without the associated initial lymphopenia. CD3+ T cell depletion was modest. The mRNA expression of metabolism genes varied between lymphocyte subsets. A high ratio of deoxycytidine kinase to group I cytosolic 5' nucleotidase expression was present in B cells and was particularly high in mature, memory and notably germinal centre B cells, but not plasma cells. Selective B cell cytotoxicity coupled with slow repopulation kinetics results in long-term, memory B cell depletion by cladribine. These may offer a new target, possibly with potential biomarker activity, for future drug development.


Metastatic liver disease and fulminant hepatic failure: presentation of a case and review of the literature.
Although liver metastases are commonly found in cancer patients, fulminant hepatic failure (FHF) secondary to diffuse liver infiltration is rare. Furthermore, clinical presentation and laboratory findings are obscure and far from being pathognomonic for the disease. We report a case of a patient who died in the intensive care unit of our hospital from multiple organ failure syndrome secondary to FHF, as a result of liver infiltration from poorly differentiated small cell lung carcinoma. We also present the current knowledge about the clinical picture, laboratory findings and physical history of neoplastic liver-metastasis-induced FHF.


6-MONTH INFANT BRAIN MRI SEGMENTATION GUIDED BY 24-MONTH DATA USING CYCLE-CONSISTENT ADVERSARIAL NETWORKS.
Due to the extremely low intensity contrast between the white matter (WM) and the gray matter (GM) at around 6 months of age (the isointense phase), it is difficult for manual annotation, hence the number of training labels is highly limited. Consequently, it is still challenging to automatically segment isointense infant brain MRI. Meanwhile, the contrast of intensity images in the early adult phase, such as 24 months of age, is a relatively better, which can be easily segmented by the well-developed tools, e.g., FreeSurfer. Therefore, the question is how could we employ these high-contrast images (such as 24-month-old images) to guide the segmentation of 6-month-old images. Motivated by the above purpose, we propose a method to explore the 24-month-old images for a reliable tissue segmentation of 6-month-old images. Specifically, we design a 3D-cycleGAN-Seg architecture to generate synthetic images of the isointense phase by transferring appearances between the two time-points. To guarantee the tissue segmentation consistency between 6-month-old and 24-month-old images, we employ features from generated segmentations to guide the training of the generator network. To further improve the quality of synthetic images, we propose a feature matching loss that computes the cosine distance between unpaired segmentation features of the real and fake images. Then, the transferred of 24-month-old images is used to jointly train the segmentation model on the 6-month-old images. Experimental results demonstrate a superior performance of the proposed method compared with the existing deep learning-based methods.


Congenital chloride diarrhoea: case report and review of the literature.
Congenital chloride diarrhoea (CCD) usually presents with abdominal distension, visible peristalsis and watery stools from birth that show chloride loss of more than 90 mmol/l. It may mimic low intestinal obstruction on antenatal ultrasound scanning after 30 weeks' gestation. This condition has been reported mainly from Finland. We report a case of CCD in a Saudi boy which was suspected antenatally, confirmed post-natally and managed successfully.


Performance evaluation and quality assurance of computed tomography scanners, with illustrations from the EMI, ACTA, and Delta scanners.
Performance evaluation of equipment for computed tomography (CT) involves the integration of: (a) establishing performance criteria; (b) designing and implementing test procedures; and (c) reconciling test results in terms of desired performance. Precision (noise), contrast scale, linearity, accuracy, spatial independence, spatial resolution, artifacts, reproducible performance, and patient exposure are several parameters discussed, as are problems of measurement with regard to non-water bath scanners. Performance and quality control tests for the ACTA, Delta, and EMI scanners are outlined. Guidance for the prospective purchaser of CT equipment is presented as a summary of the ideas discussed.


Adult circadian behavior in Drosophila requires developmental expression of cycle, but not period.
Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LN(v)s) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LN(v)s resulted in abnormal peptidergic small-LN(v) dorsal projections, and (2) PER expression rhythms in the adult LN(v)s appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex.


Solvent-switched benzylic methylene functionalization: addition, ring-opening, cyclization, and unexpected cleavage of C-O and C-C bonds.
Intermolecular benzylic methylene functionalization of exo-cyclic enol ethers has been achieved using imines as reagents and potassium tert-butoxide as the catalyst. Depending on the solvent used, the reaction proceeds by two pathways. In THF, an addition/elimination reaction of exo-cyclic enol ethers with imines provides dihydroisobenzofuran derivatives in good yield. In DMSO, an addition/ring-opening/cyclization cascade reaction occurs with unexpected cleavage of C-O and C-C bonds, affording isoquinolin-1(2H)-one products in high yield under ambient reaction conditions.


Spatial averaging method based on adaptive weight for imaging photoplethysmography.
Imaging photoplethysmography (iPPG) is a non-contact measuring technology for several physiological parameters reflecting personal health status without a special sensor. However, the pulse signal obtained using the iPPG usually is contaminated by various noises, and the intensity of the interesting pulse signal is relatively weak compared to the noises, emphasizing the necessity of obtaining high-quality pulse signals to measure physiological parameters correctly. Various regions of the face harbor distinct pulse information. We propose a spatial averaging method based on adaptive weights, which can obtain high-quality pulse signals by applying different weights to facial sub-regions of interest (sub-ROIs; sROIs). First, the facial ROI is divided into seven sROIs and the coarse heart rate (HR) is calculated from them. Next, the signal-to-noise ratio (SNR) of the raw signal obtained from each sROI is calculated using the coarse HR, and then a high-quality pulse signal is obtained by assigning positive or negative weights to each sROI based on the SNRs. We compare our method with others through the quality analysis of the obtained pulse signals using the self-collected database and the public database PURE. The comparison results show that the proposed method can provide a better pulse signal compared to other methods under various resolutions and states. This proposed method can obtain the pulse signal with better quality, which is helpful to accurately measure physiological parameters, such as HR and HR variability.


Minocycline attenuates microglial activation but fails to mitigate degeneration in inferior olive and pontine nuclei after focal cerebellar lesion.
Degenerative changes in areas remote from the primary lesion site have been linked to the clinical outcome of focal brain damage, and inflammatory mechanisms have been considered to play a key role in the pathogenesis of these remote cell death phenomena. Minocycline is a tetracycline derivative, therapeutically effective in various experimental models of central nervous system (CNS) injuries that include inflammatory and apoptotic mechanisms, although recent findings have yielded mixed results. In this study, we investigated the effectiveness of minocycline treatment in reducing remote cell death. Glial activation and neuronal loss in precerebellar stations following cerebellar lesion were investigated using immunohistochemistry and Western blot techniques. Our results show that minocycline was effective in reducing microglial activations in axotomized precerebellar nuclei, but failed to mitigate either astrocytic response or neuronal loss. This finding supports the role of minocycline in modulating inflammatory response after CNS lesion and suggests its ineffectiveness in influencing degenerative phenomena in areas remote from the primary lesion site.


Ceramide and Regulation of Vascular Tone.
In addition to playing a role as a structural component of cellular membranes, ceramide is now clearly recognized as a bioactive lipid implicated in a variety of physiological functions. This review aims to provide updated information on the role of ceramide in the regulation of vascular tone. Ceramide may induce vasodilator or vasoconstrictor effects by interacting with several signaling pathways in endothelial and smooth muscle cells. There is a clear, albeit complex, interaction between ceramide and redox signaling. In fact, reactive oxygen species (ROS) activate different ceramide generating pathways and, conversely, ceramide is known to increase ROS production. In recent years, ceramide has emerged as a novel key player in oxygen sensing in vascular cells and mediating vascular responses of crucial physiological relevance such as hypoxic pulmonary vasoconstriction (HPV) or normoxic ductus arteriosus constriction. Likewise, a growing body of evidence over the last years suggests that exaggerated production of vascular ceramide may have detrimental effects in a number of pathological processes including cardiovascular and lung diseases.


Design and Development of Low- and Medium-Viscosity Alginate Beads Loaded with Pluronic® F-127 Nanomicelles.
The anionic polymer sodium alginate, a linear copolymer of guluronic and mannuronic acids, is primarily present in brown algae. Copolymers are used in the sodium alginate preparation process to confer on the material strength and flexibility. Micelles and other polymeric nanoparticles are frequently made using the triblock copolymer Pluronic® F-127. The purpose of the present study is to determine the effect of sodium alginate's viscosity (low and medium) and the presence of Pluronic® F-127 micelles on the swelling behavior of the prepared pure beads and those loaded with Pluronic® F-127 micelles. The Pluronic® F-127 nanomicelles have a size of 120 nm. The swelling studies were carried out at pH = 1.2 (simulated gastric fluid-SGF) for two hours and at pH = 6.8 (simulated intestinal fluid-SIF) for four more hours. The swelling of both low- and medium-viscosity alginate beads was minor at pH = 1.2, irrespective of the use of Pluronic® F-127 nanomicelles. At pH = 6.8, without Pluronic® F-127, the beads showed an enhanced swelling ratio for the first four hours, which was even higher in the medium-viscosity alginate beads. With the addition of Pluronic® F-127, the beads were dissolved in the first and second hour, in the case of the low- and medium-alginate's viscosity, respectively. In other words, the behavior of the mixed hydrogels was the same during the swelling experiments. Therefore, the presence of Pluronic® F-127 nanomicelles and medium-viscosity sodium alginate leads to a higher swelling ratio. A model drug, acetyl salicylic acid (ASA), was also encapsulated in the mixed beads and ASA's release studies were performed. In conclusion, the prepared systems, which are well characterized, show potential as delivery platforms for the oral delivery of active pharmaceutical ingredients and biopharmaceuticals.


Ethics and academic integrity.
Academics from across the globe must navigate ever-increasing demands for research, practice, and educational productivity. With the increased demands, nurse faculty must choose value priorities and actions that reflect academic integrity. What does it mean to choose actions that reflect personal integrity in the academic arena? This article begins an important nursing philosophical and theoretical discussion that members and future members of the discipline of nursing must reflect upon and grapple with as they consider what it potentially means to act with straight thinking and integrity in academics.


Morphology and meiotic segregation in spermatozoa from men of proven fertility.
Estimates of semen parameters are important for defining normal ranges, which are currently established by 1999 World Health Organization guidelines. However, it is well known that semen evaluation is questionable because it is necessary for only 1 sperm to be able to reach and fertilize the oocyte. Spermiogram parameters and sperm morphology, evaluated by transmission electron microscopy (TEM), were performed on semen samples from 25 men of proven fertility. Despite a generally normal sperm concentration, progressive motility was reduced in 9 cases. Sperm characteristics were evaluated with an established technique, and the mean of the percentages of sperm pathologies were confirmed by comparing to previous reports. A comparison of apoptosis and necrosis in the samples, as detected by TEM and an annexin V/propidium iodide assay, was also performed. Fluorescence in situ hybridization was carried out on the same samples using probes for chromosomes 18, X, and Y. The mean value of the frequency of total aneuploidy in the analyzed group was 0.627% (25th percentile = 0.563%; median = 0.625%; 75th percentile = 0.690%). This study of the incidence of disomy and diploidy in spermatozoa from fertile, apparently normal individuals is important for making comparisons with infertile cohorts to determine the real increase of aneuploidy in those cohorts.


[Femur first in hip arthroplasty--the concept of combined anteversion].
The concept of combined anteversion for total hip arthroplasty (THA) proposes a relationship between the cup and stem components that theoretically maximises the postoperative range of motion and minimises the risk for impingement of the joint. Using computer-assisted navigation tools, an anteversion angle of the cup component can be made to be dependent on the antetorsion angle of the stem component (or vice versa). We studied how this functional concept would be different from the traditional cup placement according to the Lewinnek safe zone. We prospectively reviewed 42 patients (42 hips) who underwent imageless, computer-assisted THA with cementless implants due to osteoarthritis between May and October 2008. Using computer navigation, we determined the cup anteversion with optimised containment and measured femoral stem antetorsion. Our goal was to implant the original implants with a combined anteversion of 37 degrees. Mean cup anteversion was 22.5 degrees, mean combined anteversion was 35.2 degrees. Femoral antetorsion ranged from -13 to 38 degrees (mean: 18 degrees). Mean anteversion of the trial cup with optimised containment was 15.9 degrees and therefore close to the recommendation according to the Lewinnek safe zone. The total postoperative range of motion (flexion, extension, abduction, internal/external rotation) as measured with the navigation system intraoperatively was 209 degrees compared to 94 degrees measured clinically preoperatively. No THA dislocation occurred during the test. The combined anteversion concept results in a cup position with more anteversion when compared to the traditional cup placement according to the Lewinnek safe zone. In this context, modern navigation techniques open a new frontier for an optimised component position. Placing the cup and stem in relation to the anteversion for both components allows consideration of the patient-specific biomechanics.


Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces.
Weight loss diets for humans that are based on a high intake of protein but low intake of fermentable carbohydrate may alter microbial activity and bacterial populations in the large intestine and thus impact on gut health. In this study, 19 healthy, obese (body mass index range, 30 to 42) volunteers were given in succession three different diets: maintenance (M) for 3 days (399 g carbohydrate/day) and then high protein/medium (164 g/day) carbohydrate (HPMC) and high protein/low (24 g/day) carbohydrate (HPLC) each for 4 weeks. Stool samples were collected at the end of each dietary regimen. Total fecal short-chain fatty acids were 114 mM, 74 mM, and 56 mM (P < 0.001) for M, HPMC, and HPLC diets, respectively, and there was a disproportionate reduction in fecal butyrate (18 mM, 9 mM, and 4 mM, respectively; P < 0.001) with decreasing carbohydrate. Major groups of fecal bacteria were monitored using nine 16S rRNA-targeted fluorescence in situ hybridization probes, relative to counts obtained with the broad probe Eub338. No significant change was seen in the relative counts of the bacteroides (Bac303) (mean, 29.6%) or the clostridial cluster XIVa (Erec482, 23.3%), cluster IX (Prop853, 9.3%), or cluster IV (Fprau645, 11.6%; Rbro730 plus Rfla729, 9.3%) groups. In contrast, the Roseburia spp. and Eubacterium rectale subgroup of cluster XIVa (11%, 8%, and 3% for M, HPMC, and HPLC, respectively; P < 0.001) and bifidobacteria (4%, 2.1%, and 1.9%, respectively; P = 0.026) decreased as carbohydrate intake decreased. The abundance of butyrate-producing bacteria related to Roseburia spp. and E. rectale correlated well with the decline in fecal butyrate.


Brilliant Sm, Eu, Tb, and Dy chiral lanthanide complexes with strong circularly polarized luminescence.
The synthesis, characterization, and luminescent behavior of trivalent Sm, Eu, Dy, and Tb complexes of two enantiomeric, octadentate, chiral, 2-hydroxyisophthalamide ligands are reported. These complexes are highly luminescent in solution. Functionalization of the achiral parent ligand with a chiral 1-phenylethylamine substituent on the open face of the complex in close proximity to the metal center yields complexes with strong circularly polarized luminescence (CPL) activity. This appears to be the first example of a system utilizing the same ligand architecture to sensitize four different lanthanide cations and display CPL activity. The luminescence dissymmetry factor, g(lum), recorded for the Eu(III) complex is one of the highest values reported, and this is the first time the CPL effect has been demonstrated for a Sm(III) complex with a chiral ligand. The combination of high luminescence intensity with CPL activity should enable new bioanalytical applications of macromolecules in chiral environments.


[Spatiotemporal variability of soil fertility parameters in Xinhui District of Guangdong Province].
By the methods of geostatistics and GIS, this paper studied the spatial distribution patterns of pH, organic matter, total nitrogen (N) and total phosphorus (P) in cultivated soils of Xinhui District, Guangdong Province from 1982 to 2003. The paired samples t test and Kriging results showed that soil pH and organic matter content were significantly lower in 2003 than in 1982, while the contents of soil total N and total P were in adverse. The spatial distribution of test parameters changed to different degrees over the past 20 years. Soil pH tended to decrease in most areas of the study district, soil organic matter decreased except at the banks of Yinzhou Lake and parts of south and northwest, soil total N increased in most areas except the parts of east and northwest, and soil total P increased in most areas.


Identification of major loci and genomic regions controlling acid and volatile content in tomato fruit: implications for flavor improvement.
Plant metabolites are important to world food security due to their roles in crop yield and nutritional quality. Here we report the metabolic profile of 300 tomato accessions (Solanum lycopersicum and related wild species) by quantifying 60 primary and secondary metabolites, including volatile organic compounds, over a period of 2 yr. Metabolite content and genetic inheritance of metabolites varied broadly, both within and between different genetic groups. Using genotype information gained from 10 000 single nucleotide polymorphism markers, we performed a metabolite genome-wide association mapping (GWAS) study. We identified 79 associations influencing 13 primary and 19 secondary metabolites with large effects at high resolution. Four genome regions were detected, highlighting clusters of associations controlling the variation of several metabolites. Local linkage disequilibrium analysis and allele mining identified possible candidate genes which may modulate the content of metabolites that are of significant importance for human diet and fruit consumption. We precisely characterized two associations involved in fruit acidity and phenylpropanoid volatile production. Taken together, this study reveals complex and distinct metabolite regulation in tomato subspecies and demonstrates that GWAS is a powerful tool for gene-metabolite annotation and identification, pathways elucidation, and further crop improvement.


Structure of the rat argininosuccinate lyase gene: close similarity to chicken delta-crystallin genes.
Argininosuccinate lyase (EC 126.96.36.199) is an enzyme of arginine biosynthesis and is also involved in the urea cycle in the liver of ureotelic animals. A comparison of cDNA-derived amino acid sequences revealed that argininosuccinate lyase is highly homologous with chicken delta-crystallin, a major structural protein of the eye lens. The gene for the rat argininosuccinate lyase was cloned and its structure was determined. This gene is a single-copy gene about 14 kilobases long and is split into 16 exons. A comparison with chicken delta-crystallin genes revealed that all introns interrupt the protein-coding regions at homologous positions. This close similarity in structural organization provides strong evidence for the view of Piatigorsky et al. [Piatigorsky, J., O'Brien, W. E., Norman, B. L., Kalmuck, K., Wistow, G., Borras, T., Nickerson, J. M. & Wawrousek, E. F. (1988) Proc. Natl. Acad. Sci. USA 85, 3479-3483] that chicken delta 1- and delta 2-crystallin genes evolved by recruitment and duplication of the preexisting argininosuccinate lyase gene and that delta 2-crystallin is probably the direct homologue argininosuccinate lyase.


Patient Perceptions Regarding Outpatient Hip and Knee Arthroplasties.
There has been increasing interest in outpatient total joint arthroplasty (TJA) in the orthopedic community, but how patients feel about outpatient TJA is unknown. The purpose of this study was to understand patient perspectives on hip and knee replacements performed in an outpatient setting. We surveyed 110 consecutive patients scheduled for primary TJA in an academic suburban arthroplasty practice regarding their knowledge and perceptions of outpatient TJA. Questionnaires were administered during preoperative clinic visits before discussion of surgery location, length of stay, and before preoperative joint replacement education. Fifty-seven percent of respondents were female, and 42.7% were aged 65 years or older. Very few patients expected same-day discharge (n = 3) or a one night stay in the hospital (n = 17). Fifty-four percent of patients were expected to stay in the hospital two or more nights. Only 54.5% of patients were aware that outpatient TJA is an option, with 55.3% of men and 31.7% of women reporting that they were comfortable with outpatient TJA (P = .030). In contrast, 61% and 72.8% believed that faster recovery and decreased likelihood of infection are likely advantages of outpatient TJA. Interestingly, 51.9% felt ambulatory surgery centers are as safe as hospitals, and 62.6% believed that home is the best place to recovery from TJA. These observations suggest that there is need for patient education regarding outpatient TJA. As outpatient procedures become more common, it is essential that patients understand the ambulatory surgery process, the benefits and risks of same day discharge, and their role in a successful outpatient experience.


The bacterial surface: general considerations towards design and function.
The shape of bacteria is determined by the wall which surrounds the protoplast. This enveloping structure resides in diverse chemical and organizational forms and is of fundamental importance for several aspects of cellular life and growth. This article discusses these general aspects and serves as an introduction to the journal issue and to the more specific papers which follow in the section.


Type-specific oncogenic human papillomavirus infection in high grade cervical disease in New Zealand.
The national Human Papillomavirus (HPV) Immunisation Programme in New Zealand was introduced in 2008, and involves routine vaccination of girls 12-13 years with a catch-up for females aged up to 19 years. The aims of this study were to measure the pre-vaccination prevalence of oncogenic HPV infection in women aged 20-69 years who were participating in the New Zealand National Cervical Screening Programme (NZ-NCSP) and who were: (1) referred with high grade cytology with a subsequent histologically-confirmed high grade cervical intraepithelial neoplasia (CIN2/3) or adenocarcinoma in situ (AIS); or (2) were in the wider group of women who had a cytological prediction of high grade squamous disease or glandular abnormality (ASC-H/ HSIL+/AGC/AIS). Women aged 20-69 years appearing on the NZ-NCSP register between August 2009-February 2011 with a cytology record of ASC-H/HSIL+/AGC/AIS were invited to participate in the study. Liquid-based cytology specimens were tested for 37 HPV types using Linear Array genotyping. The prevalence of type-specific HPV infection was reported within women with histologically-confirmed CIN 2/3 and within the wider group with ASC-H/HSIL+/AGC/AIS cytology. Age-specific trends for the relative proportion of HPV 16/18 vs. other oncogenic types in CIN2/3 were assessed. A total of 594 women with ASC-H/HSIL+/AGC/AIS cytology and a valid HPV test were recruited; of these 356 (60%) had confirmed CIN2/3 and 6 (1%) had confirmed AIS or glandular dysplasia. Positivity rates for any oncogenic HPV infection and for HPV16 and/or 18 within confirmed CIN2/3-AIS were 95% (95%CI: 92-97%) and 60% (54-65%) respectively; in all women with ASC-H/HSIL+/AGC/AIS cytology it was 87% (84-89%) and 53% (49-57%), respectively. The most common reported HPV types in women with CIN 2/3 were 16 (51%), 52 (19%), 31 (17%), 33 (13%) and 18 (12%). A trend for higher rates of HPV 16/18 infection compared to other oncogenic types was observed in younger women (p=0.0006). The prevalence of HPV 16/18 in confirmed high grade disease in New Zealand is comparable to that observed in Australia and European countries. Test positivity rates for type 52 appear higher than in comparable studies in other developed countries. A greater proportion of high grade lesions in younger women appear to be associated with HPV 16/18 infection.


Exacerbation of pneumomediastinum after air travel in a patient with dermatomyositis.
Although the presence of pneumothorax is generally considered an absolute contraindication to air travel, reports on pneumomediastinum after air travel are extremely rare. Moreover, to the best of our knowledge, exacerbation of existing pneumomediastinum after commercial air travel has never been reported. We report on a case of a patient (the first case that we are aware of) who suffered exacerbation of pneumomediastinum after commercial air travel. This patient, with confirmed pneumomediastinum before air travel, flew to our city for medical care without being warned about exacerbation by the local hospital or airlines. Obvious exacerbation of pneumomediastinum and subcutaneous emphysema was noticed after the travel. Subsequently, a diagnosis of amyopathic dermatomyositis with interstitial lung disease and pneumomediastinum was made. The patient died despite treatment with corticosteroid, cyclophosphamide and intravenous immunoglobulin. This report discusses this rare condition and offers suggestions regarding air travel for patients with presence of pneumomediastinum at the time of flight.


Intranasal Atomization of Ketamine, Medetomidine and Butorphanol in Pet Rabbits Using a Mucosal Atomization Device.
A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to intramuscular administration, of a mix of anesthetic drugs in pet rabbits. In total, 104 mixed-breed pet rabbits, undergoing various types of surgery, received a combination of ketamine, medetomidine, and butorphanol (20, 0.4, and 0.2 mg/kg) by intranasal atomization using a Mucosal Atomization Device (Group MAD) or intramuscular administration (Group IM). When required, isoflurane was dispensed through a face mask. At the end of the procedures, atipamezole was administered using the same routes in the respective Groups. There were no differences in time to loss of righting reflex between the groups, while differences were found for the need for isoflurane (higher in Group MAD) and recovery time, occurring earlier in Group MAD. The results suggest that intranasal atomization of a combination of ketamine, medetomidine, and butorphanol produces a lighter depth of anesthesia in pet rabbits, compared to intramuscular administration. Intranasal atomization can be performed to administer sedative and anesthetic drugs, avoiding the algic stimulus related to the intramuscular inoculation of drugs.


Metformin potentiates the antigluconeogenic action of insulin.
The interaction of metformin and insulin in the control of hepatic gluconeogenesis was examined in isolated hepatocytes from 48h starved rats using lactate (10(-2) mol/l) with pyruvate (10(-3) mol/l) as substrate. During 1 h incubations in the absence of added insulin, 10(-2) and 10(-3) mol/l metformin reduced gluconeogenesis by 65% and 59% respectively, but lower concentrations of metformin were not effective. Insulin alone (10(-6)-10(-8) mol/l) reduced (37%-16%) gluconeogenesis. The effect of insulin was enhanced (further reductions of 11%-24%) by 5 x 10(-4) mol/l metformin, although this concentration of metformin was not effective in the absence of insulin. At lower insulin concentrations (10(-9) and 10(-10) mol/l) which did not significantly affect gluconeogenesis alone, 5 x 10(-4) mol/l metformin decreased gluconeogenesis (32% and 28% respectively). At 10(-10) mol/l insulin, metformin concentrations of 10(-3)-10(-7) mol/l decreased gluconeogenesis by 60-20%. The results suggest that therapeutic concentrations of metformin may act synergistically with physiological concentrations of insulin to suppress hepatic gluconeogenesis.


Dynamic Behaviors of Solvent Molecules Restricted in Poly (Acryl Amide) Gels Analyzed by Dielectric and Diffusion NMR Spectroscopy.
Dynamics of solvent molecules restricted in poly (acryl amide) gels immersed in solvent mixtures of acetone⁻, 1,4-dioxane⁻, and dimethyl sulfoxide⁻water were analyzed by the time domain reflectometry method of dielectric spectroscopy and the pulse field gradient method of nuclear magnetic resonance. Restrictions of dynamic behaviors of solvent molecules were evaluated from relaxation parameters such as the relaxation time, its distribution parameter, and the relaxation strength obtained by dielectric measurements, and similar behaviors with polymer concentration dependences for the solutions were obtained except for the high polymer concentration in collapsed gels. Scaling analyses for the relaxation time and diffusion coefficient respectively normalized by those for bulk solvent suggested that the scaling exponent determined from the scaling variable defined as a ratio of the size of solvent molecule to mesh size of polymer networks were three and unity, respectively, except for collapsed gels. The difference in these components reflects characteristic molecular interactions in the rotational and translational diffusions, and offered a physical picture of the restriction of solvent dynamics. A universal treatment of slow dynamics due to the restriction from polymer chains suggests a new methodology of characterization of water structures.


Speech Perception With Novel Stimulation Strategies for CombinedCochleo-Vestibular Systems.
Cochlear implants are very well established in the rehabilitation of hearing loss and are regarded as the most successful neuroprostheses to date. While a lot of progress has also been made in the neighboring field of specific vestibular implants, some diseases affect the entire inner ear, leading to both hearing and vestibular hypo- or dysfunction. The proximity of the cochlear and vestibular organs suggests a single combined implant as a means to alleviate the associated impairments. While both organs can be stimulated in a similar way with electric pulses applied through implanted electrodes, the typical phase durations needed in the vestibular system seem to be substantially larger than those typically needed in the cochlear system. Therefore, when using sequential stimulation in a combined implant, the pulse stream to the cochlea is interrupted by comparatively large gaps in which vestibular stimulation can occur. We investigate the impact of these gaps in the auditory stream on speech perception. Specifically, we compare a number of stimulation strategies with different gap lengths and distributions and evaluate whether it is feasible to use them without having a noticeable decline in perception and quality of speech. This is a prerequisite for any practicable stimulation strategy of a combined system and can be investigated even in recipients of a normal cochlear implant. Our results show that there is no significant deterioration in speech perception for the different strategies examined in this paper, leaving the strategies as viable candidates for prospective combined cochleo-vestibular implants.


Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the common feature of tissue-nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. To evaluate the role of TNAP in MVC, we developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells in an X-linked manner. Hemizygous overexpressor male mice (Tagln-Cre(+/-) ; Hprt(ALPL) (/Y) or TNAP-OE) show extensive vascular calcification, high blood pressure, and cardiac hypertrophy, and have a median age of death of 44 days, whereas the cardiovascular phenotype is much less pronounced and life expectancy is longer in heterozygous (Tagln-Cre(+/-) ; Hprt(ALPL) (/-) ) female TNAP-OE mice. Gene expression analysis showed upregulation of osteoblast and chondrocyte markers and decreased expression of vascular smooth muscle markers in the aortas of TNAP-OE mice. Through medicinal chemistry efforts, we developed inhibitors of TNAP with drug-like pharmacokinetic characteristics. TNAP-OE mice were treated with the prototypical TNAP inhibitor SBI-425 or vehicle to evaluate the feasibility of TNAP inhibition in vivo. Treatment with this inhibitor significantly reduced aortic calcification and cardiac hypertrophy, and extended lifespan over vehicle-treated controls, in the absence of secondary effects on the skeleton. This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target.


Porcine Small Intestinal Submucosa Mesh to Treat Inguinal Hernia in Young Adults Using Laparoscopic Inguinal Hernia Repair: A Retrospective Controlled Study.
The authors evaluated the effects and clinical value of small intestinal submucosa (SIS) mesh to treat inguinal hernia in young adults by the laparoscopic method. The clinical data of 357 cases with inguinal hernia using SIS mesh in our hospital were analyzed retrospectively from June 2014 to June 2018. All cases were divided into 2 groups according to the surgical method. Operation time, hospital stay, cost, postoperative complications, and complications during follow-up were analyzed. Of the 357 patients, 202 (56.6%) underwent Lichtenstein repair and 155 (43.4%) underwent transabdominal preperitoneal (TAPP) repair. Operation time and hospital costs of the Lichtenstein group were significantly lower compared with the TAPP group (P<0.05). The incidence of seroma in the Lichtenstein group was lower than that in the TAPP group at 1 week, 1 month, and 3 months postoperatively with significant differences (P<0.05). Perioperative pain scores in the Lichtenstein group were higher than the TAPP group (P<0.05). No statistical difference was observed for hospital stay between 2 groups (P>0.05). In the Lichtenstein group, 1 case recurred during the follow-up period (0.5%). No intestinal obstruction or intestinal fistula occurred in any patient during the follow-up period. The effect of SIS mesh was positive whether the patient underwent a Lichtenstein or TAPP method. Seroma was more common in the TAPP method that may cause lower postoperative pain. Therefore, we recommend individualized treatment.


The P gene of rodent brain-adapted measles virus plays a critical role in neurovirulence.
In rare cases, measles virus (MV) in children leads to fatal neurological complications such as primary measles encephalitis, post-acute measles encephalitis, subacute sclerosing panencephalitis and measles inclusion-body encephalitis. To investigate the pathogenesis of MV-induced encephalitis, rodent brain-adapted MV strains CAM/RB and CAMR40 were generated. These strains acquired mutations to adapt to the rodent brain during 40 passages in rat brain. However, it is still unknown which genes confer the neurovirulence of MV. We previously established a rescue system for recombinant MVs possessing the backbone of wild-type strain HL, an avirulent strain in mice. In the present study, to identify the genes in CAMR40 that elicit neurovirulence, we generated chimeric recombinant MVs based on strain HL. As a result, recombinant wild-type MV in which the haemagglutinin (H) gene was substituted with that of CAMR40 caused a non-lethal mild disease in mice, while additional substitution of the HL phosphoprotein (P) gene with that of strain CAMR40 caused lethal severe neurological signs comparable to those of CAMR40. These results clearly indicated that, in addition to the H gene, the P gene is required for the neurovirulence of MV CAMR40.


Oxidant-dependent chemoselectivity in the gold-catalyzed oxidative cyclizations of 3,4,6,6-tetrasubstituted 3,5-dien-1-ynes.
A distinct chemoselectivity in the gold-catalyzed oxidative cyclization of 3,5-dien-1-ynes was observed when 3,5-dichloropyridine N-oxide replaced 8-methylquinoline N-oxide as the oxidant; the resulting cyclopentadienyl aldehydes were obtained in good yields. The altered chemoselectivity is attributed to a prior enyne cyclization in the presence of 3,5-dichloropyridine N-oxides. The use of N-iminopyridium ylide enables a similar iminocyclization reaction to give cyclopentadienyl imines efficiently. Our experimental data support a prior gold-catalyzed cyclization of 3,5-dien-1-ynes to form gold carbene, followed by the oxidation with N-oxide.


Propofol-induced pancreatitis: recurrence of pancreatitis after rechallenge.
We report a case of pancreatitis, which occurred while the patient was on a propofol drip and then recurred after resolution following an inadvertent rechallenge with propofol. The initial episode was associated with hypertriglyceridemia, whereas the latter was not. The association between propofol and pancreatitis is definite and may occur independently of significant hypertriglyceridemia.


False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?
Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.


Disrupted structural connectome is associated with both psychometric and real-world neuropsychological impairment in diffuse traumatic brain injury.
Traumatic brain injury (TBI) is likely to disrupt structural network properties due to diffuse white matter pathology. The present study aimed to detect alterations in structural network topology in TBI and relate them to cognitive and real-world behavioral impairment. Twenty-two people with moderate to severe TBI with mostly diffuse pathology and 18 demographically matched healthy controls were included in the final analysis. Graph theoretical network analysis was applied to diffusion tensor imaging (DTI) data to characterize structural connectivity in both groups. Neuropsychological functions were assessed by a battery of psychometric tests and the Frontal Systems Behavior Scale (FrSBe). Local connection-wise analysis demonstrated reduced structural connectivity in TBI arising from subcortical areas including thalamus, caudate, and hippocampus. Global network metrics revealed that shortest path length in participants with TBI was longer compared to controls, and that this reduced network efficiency was associated with worse performance in executive function and verbal learning. The shortest path length measure was also correlated with family-reported FrSBe scores. These findings support the notion that the diffuse form of neuropathology caused by TBI results in alterations in structural connectivity that contribute to cognitive and real-world behavioral impairment.


Allosteric communication in the dynein motor domain.
Dyneins power microtubule motility using ring-shaped, AAA-containing motor domains. Here, we report X-ray and electron microscopy (EM) structures of yeast dynein bound to different ATP analogs, which collectively provide insight into the roles of dynein's two major ATPase sites, AAA1 and AAA3, in the conformational change mechanism. ATP binding to AAA1 triggers a cascade of conformational changes that propagate to all six AAA domains and cause a large movement of the "linker," dynein's mechanical element. In contrast to the role of AAA1 in driving motility, nucleotide transitions in AAA3 gate the transmission of conformational changes between AAA1 and the linker, suggesting that AAA3 acts as a regulatory switch. Further structural and mutational studies also uncover a role for the linker in regulating the catalytic cycle of AAA1. Together, these results reveal how dynein's two major ATP-binding sites initiate and modulate conformational changes in the motor domain during motility.


Urban homelessness and poverty during economic prosperity and welfare reform: changes in self-reported comorbidities, insurance, and sources for usual care, 1995-1997.
Little is known of how homeless and other urban poor populations have fared during the robust economy and within structural changes in health care delivery and entitlement programs of the 1990s. This is important in determining the need for population-specific services during a vigorous economy with low unemployment and increasing Medicaid managed-care penetration. This study compared health insurance status and availability of a source for usual medical care, psychiatric and substance abuse comorbidities, and perceived causes of homelessness in homeless adults surveyed in 1995 and 1997. Cross-sectional, community-based surveys were conducted in 1995 and 1997 at sites frequented by urban homeless adults residing in Pittsburgh, Pennsylvania. Self-reported medical, mental health, and substance abuse comorbidities, health insurance, and source for usual care were measured. Compared to the 388 individuals surveyed in 1995, the 267 homeless adults surveyed in 1997 had more medical comorbidity (56.6% vs. 30.2%, P <.001) and mental health comorbidity (44.9% vs. 36.9%, P =.04) and required more chronic medication (52.1% vs. 30.3%, P <.001). More respondents in 1997 than 1995 reported having no health insurance (41.4% vs. 29.4%, P <.001). While there was no difference in the overall proportion reporting a source for usual care (78.3% in 1997 vs. 80.2% in 1995, P =.55), fewer persons reported use of the emergency department and more persons reported using a shelterbased clinic for usual care in 1997 compared with 1995. These findings suggest more need for medical care among homeless and urban poor persons in 1997 compared with 1995 and support the continued need for outreach and support services despite a vigorous economy.


Loss of DGKε induces endothelial cell activation and death independently of complement activation.
Atypical hemolytic uremic syndrome (aHUS) is classically described to result from a dysregulation of the complement alternative pathway, leading to glomerular endothelial cell (EC) damage and thrombosis. However, recent findings in families with aHUS of mutations in the DGKE gene, which is not an integral component of the complement cascade, led us to consider other pathophysiologic mechanisms for this disease. Here, we demonstrate that loss of DGKε expression/activity in EC induces an increase in ICAM-1 and tissue factor expression through the upregulation of p38-MAPK-mediated signals, thus highlighting a proinflammatory and prothrombotic phenotype of DGKε-deficient ECs. More interestingly, DGKE silencing also increases EC apoptosis and impairs EC migration and angiogenesis in vitro, suggesting that DGKE loss-of-function mutations impair EC repair and angiogenesis in vivo. Conversely, DGKE knockdown moderately decreases the expression of the complement inhibitory protein MCP on quiescent EC, but does not induce complement deposition on their surface in vitro. Collectively, our data strongly suggest that in DGKE-associated aHUS patients, thrombotic microangiopathy results from impaired EC proliferation and angiogenesis rather than complement-mediated EC lesions. Our study expands the current knowledge of aHUS mechanisms and has implications for the treatment of patients with isolated DGKE mutations.


Challenges for malaria vector control in sub-Saharan Africa: Resistance and behavioral adaptations in Anopheles populations.
Over the past decade, global malaria-related mortality has declined dramatically because of combined international actions that have defined and prioritized national and regional efforts to reduce the incidence of malaria, with the ultimate goal of eradication. Vector control strategies using insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in African countries have contributed significantly to the declining incidence of malaria. However, the effectiveness of malaria control is threatened by increasing insecticide resistance and behavioral changes in Anopheles vectors. Thus, there is an urgent need to ensure that future programmes are designed to address these threats and protect the progress made so far in controlling malaria. This review summarizes the current malaria vector control tools and discusses about the critical threats to vector control programme and vector management.


Cerium-Based Electrocatalysts for Oxygen Evolution/Reduction Reactions: Progress and Perspectives.
Ce-based materials have been widely used in photocatalysis and other fields because of their rich redox pairs and oxygen vacancies, despite research on the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) remaining scare. However, most pristine cerium-based materials, such as CeO2, are non-conductive materials. Therefore, how to obtain highly conductive and stable OER/ORR electrocatalysts is currently a hot research topic. To overcome these limitations, researchers have proposed a variety of strategies to promote the development of Ce-based electrocatalysts in recent years. This progress report focuses on reviewing new strategies concerning three categories of Ce-based electrocatalysts: metal-organic framework (MOF) derivatives, structure tuning, and polymetallic doping. It also puts forward the main existing problems and future prospects. The content of cerium in the crust is about 0.0046%, which is the highest among the rare earth elements. As a low-cost rare earth material, Ce-based materials have a bright future in the field of electrocatalysis due to replacing precious metal and some transition metals.


Excessive Pap smears due to opportunistic cervical cancer screening.
The study aimed to analyze the Pap smears carried out for cervical cancer screening according to Ministry of Health guidelines. All smear tests carried out within the public health system in Campinas in 2003 were analyzed. All tests that did not conform to the guidelines were considered excessive. The guidelines recommend screening once every three years for all women aged 25 to 59 after they have received two negative smears. This study showed that the majority of women initiated screening prior to 25 years of age and the periodicity was predominantly annual, followed by biannual tests. In conclusion, 63.4% of tests were excessive. The screening coverage was 14.76%, but if all the tests had been performed as recommended, the final coverage over three years could have reached 65.4%. Thus it is possible to increase the coverage with the available resources since the screening works like an organized program.


Molecular strategy for identification in Aspergillus section Flavi.
Aspergillus flavus is one of the most common contaminants that produces aflatoxins in foodstuffs. It is also a human allergen and a pathogen of animals and plants. Aspergillus flavus is included in the Aspergillus section Flavi that comprises 11 closely related species producing different profiles of secondary metabolites. A six-step strategy has been developed that allows identification of nine of the 11 species. First, three real-time PCR reactions allowed us to discriminate four groups within the section: (1) A. flavus/Aspergillus oryzae/Aspergillus minisclerotigenes/Aspergillus parvisclerotigenus; (2) Aspergillus parasiticus/Aspergillus sojae/Aspergillus arachidicola; (3) Aspergillus tamarii/Aspergillus bombycis/Aspergillus pseudotamarii; and (4) Aspergillus nomius. Secondly, random amplification of polymorphic DNA (RAPD) amplifications or SmaI digestion allowed us to differentiate (1) A. flavus, A. oryzae and A. minisclerotigenes; (2) A. parasiticus, A. sojae and A. arachidicola; (3) A. tamarii, A. bombycis and A. pseudotamarii. Among the 11 species, only A. parvisclerotigenus cannot be differentiated from A. flavus. Using the results of real-time PCR, RAPD and SmaI digestion, a decision-making tree was drawn up to identify nine of the 11 species of section Flavi. In contrast to conventional morphological methods, which are often time-consuming, the molecular strategy proposed here is based mainly on real-time PCR, which is rapid and requires minimal handling.


Messenger RNA Decay.
This chapter discusses several topics relating to the mechanisms of mRNA decay. These topics include the following: important physical properties of mRNA molecules that can alter their stability; methods for determining mRNA half-lives; the genetics and biochemistry of proteins and enzymes involved in mRNA decay; posttranscriptional modification of mRNAs; the cellular location of the mRNA decay apparatus; regulation of mRNA decay; the relationships among mRNA decay, tRNA maturation, and ribosomal RNA processing; and biochemical models for mRNA decay. Escherichia coli has multiple pathways for ensuring the effective decay of mRNAs and mRNA decay is closely linked to the cell's overall RNA metabolism. Finally, the chapter highlights important unanswered questions regarding both the mechanism and importance of mRNA decay.


Influence of aspirin on pilocarpine-induced epilepsy in mice.
Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.


A Monte-Carlo simulation of ionic conductivity and viscosity of highly concentrated electrolytes based on a pseudo-lattice model.
Simulating three transport phenomena-ionic conductivity, viscosity, and self-diffusion coefficient-in a common Monte-Carlo framework, we discuss their relationship to the intermolecular interactions of electrolyte solutions at high concentrations (C/mol l-1 ∼ 1). The simulation is predicated on a pseudolattice model of the solution. The ions and solvents (collectively termed "molecules") are considered dimensionless points occupying the lattice sites. The molecular transport is realized by a repetition of swapping two adjacent molecules by the stochastic Gibbs sampling process based on simple intermolecular interactions. The framework has been validated by the fact that the simulated ionic conductivity and dynamic viscosity of 1:1- and 2:1-salts qualitatively well represent the experimental data. The magnitude of the Coulombic interaction itself is not reflected in the ionic conductivity, but the extent to which the Coulombic interaction is shielded by the dielectric constant has a significant influence. On the other hand, the dielectric constant barely influences the viscosity, while the magnitude of the Coulombic interaction is directly reflected in the viscosity.


Cytopathology of pleural mesotheliomas.
Pleural mesothelioma is a rare and highly malignant tumor that has shown increasing incidence. In approximately 90% of patients the tumor manifests initially as recurrent, unilateral, bloody pleural effusions; in the remaining 10% of patients the tumor is detected by chest radiography. As a result, pleural mesotheliomas can be diagnosed by cytologic examination of pleural effusions or transthoracic fine-needle aspirates; the cytologic manifestations of such an examination are described in detail. Additionally, the handling of cytologic specimens, diagnostic problems, and the value and limitations of immunocytochemical and electron microscopic studies and other ancillary techniques in the cytologic identification of pleural mesotheliomas are discussed.


Temperature change in children undergoing magnetic resonance imaging-An observational cohort study.
An increasing number of children undergo magnetic resonance imaging requiring anesthesia or sedation to ensure their immobility; however, magnetic resonance imaging may increase body temperature whereas sedation or anesthesia may decrease it. We investigated changes in body temperature in children who underwent sedation or anesthesia for magnetic resonance imaging. Children aged 12 weeks-12 years undergoing anesthesia and magnetic resonance imaging were included in this prospective observational study. Tympanic body temperature was measured before and after magnetic resonance imaging, and the difference between measurements was calculated. Associations between the temperature difference and patient- or procedure-related factors were evaluated with linear and logistic regression analysis. A total of 74 children were included, of whom 5 (7%) had a temperature increase ≥0.5°C. Mean temperature difference was -0.24°C (SD 0.48) for the entire group and -0.28°C for the youngest children (0-2 years). The temperature difference correlated positively with the duration of imaging (unadjusted coefficient 0.26, 95% confidence interval (CI), (0.01; 0.52)). In this study of sedated or anesthetized children undergoing magnetic resonance imaging, clinically relevant increases in body temperature above 0.5°C were only found in a few patients. However, longer imaging duration tended to be associated with increased body temperature.


Endovascular versus open repair for popliteal aneurysm: a review on limb salvage and reintervention rates.
Open repair remains the gold standard technique for popliteal aneurysm repair. However, the endovascular approach has gained increased popularity. Comparison between these techniques remain crucial to aid the physician choice, yet, data on mid-term outcomes lack in the literature. The present review aims to compare the limb salvage and reintervention rates in these different approaches. A comprehensive literature review was conducted to identify publications on endovascular treatment or open repair of popliteal artery aneurysms (PAAs). Primary endpoints were reintervention and limb salvage. Twenty-seven studies were selected for analysis describing a total of 5425 patients: 1651 PAAs underwent endovascular repair and 4166 PAAs were treated with open surgery. The technical success rates varied between 83.3% to 100% in the endovascular group and 79% to 100% in the open repair. For endovascular repair, the limb salvage at 1 year ranged between 84.2% and 100%, at 3 years between 88.9% and 100%; and at 5 years between 64.7% and 100%. The reintervention rate at 1 year ranged between 3.7% and 21%, at 3 years between 18.9% and 28%, and at 5 years between 34.5% and 38%. For open repair, the limb salvage varied between 94.3% and 100% at 1 year, 94.5% and 99% at 3 years, and 86.4% to 97% at 5 years. Regarding the reintervention rate, at 1 year was 12.8% and 13%, at 3 years 3.6% and 12%, and at 5 years varied between 15.7% and 30%. Both endovascular and open repair of popliteal aneurysms represent safe options for popliteal aneurysm repair. Yet, on mid-term, open repair is associated with greater limb salvage and fewer reintervention rates. Still, further studies are needed to access the long-term durability of this technique and its suitability in emergency settings.


Innovative Program Delivery and Determinants of Frequent Visitation to a Mobile Medical Clinic in an Urban Setting.
The Community Health Care Van (CHCV) is a mobile medical clinic (MMC) that has served vulnerable populations in New Haven, Connecticut since 1993. This study explores utilization patterns to understand if certain populations frequently rely upon non-traditional health care within a representative MMC. Patient characteristics, services used, and visitation frequency were described and compared for 8,415 unique clients making 29,728 visits. Negative binomial regression was used to model the impact of specific indicators on visitation. Clients receiving buprenorphine had the highest visitation rates, with 2.09 visits per person-year. Increased CHCV visitation was positively associated with being foreign-born (additional 3.42 visits on average, p < .001), injection drug use (additional 1.69 visits on average, p < .001) and having hypertension (additional 1.09 visits on average, p < .001). As the Affordable Care Act has increased health insurance coverage, MMCs will continue their role in assisting entry into continuous health care and offering low-threshold acute care for urban vulnerable populations.


Spectroscopic properties of tyrosyl radicals in dipeptides.
Redox-active tyrosine residues play important roles in long-distance electron reactions in enzymes, including prostaglandin H synthase, galactose oxidase, ribonucleotide reductase, and photosystem II. Magnetic resonance and vibrational spectroscopy provide methods with which to study the structures of redox-active amino acids in proteins. In this report, ultraviolet photolysis was used to generate tyrosyl radicals from polycrystalline tyrosinate or dipeptides, and the structure of the radical was investigated with EPR and reaction-induced FT-IR spectroscopy at 77 K. Photolysis at 77 K is expected to generate a neutral tyrosyl radical through oxidation of the aromatic ring. EPR and FT-IR results obtained from (13)C-labeled tyrosine were consistent with that expectation. Surprisingly, labeling of the tyrosyl amino group with (15)N also resulted in isotope-shifted bands in the photolysis spectrum. The force constant of a NH deformation mode increased when the tyrosyl radical was generated. These data suggest an interaction between the pi system of the tyrosyl radical and the amino group. In spectra acquired from the dipeptides, evidence for a sequence-dependent interaction between the tyrosyl radical and the amide bond of the dipeptide was also obtained. We postulate that perturbation of the amino or the amide/imide groups may occur through a spin polarization mechanism, which is indirectly detected as a change in NH force constant. This conclusion is supported by density functional calculations, which suggest a conformationally sensitive delocalization of spin density onto the amino and carboxylate groups of the tyrosyl radical. These experiments provide a step toward a detailed spectral interpretation for protein-based tyrosyl radicals.


Beta2 integrins are not required for tyrosine phosphorylation of paxillin in human neutrophils.
Although many of the receptors mediating neutrophil (polymorphonuclear leukocyte (PMN)) adhesion to extracellular matrix (ECM) proteins have been identified, the signal transduction pathways leading to cell spreading are not clearly defined. Studies showing that protein tyrosine phosphorylation increases with PMN adhesion suggest that phosphorylation is critical for adhesion-dependent processes. In other cells, increased tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin are thought to play pivotal roles in ECM-mediated signaling. In the present study we compared the tyrosine phosphorylation of FAK and paxillin in PMNs plated onto thrombospondin (TSP) or laminin (LN). Increased tyrosine phosphorylation of paxillin correlated with adhesion and spreading of PMNs plated onto LN or TSP. In PMNs adherent to LN, the kinetics of FAK phosphorylation preceded the kinetics of paxillin phosphorylation, suggesting that paxillin may be a downstream target of FAK. In contrast, FAK was not phosphorylated in PMNs spread on TSP. These findings suggested activation of different signaling pathways in TSP- vs LN-adherent PMNs. Others have proposed that paxillin phosphorylation requires beta2 integrins. Therefore, we used PMNs from a patient with leukocyte adhesion deficiency (LAD), lacking beta2 integrins, to determine whether these receptors were necessary for paxillin phosphorylation. LAD PMNs did not adhere to LN, and consequently, there was no tyrosine phosphorylation of FAK or paxillin. In contrast, paxillin, but not FAK, was phosphorylated in LAD PMNs adherent and spread on TSP. These results indicate that ECM-beta2 integrin-mediated signaling initiates the FAK/paxillin signaling pathway(s), while TSP-mediated signaling results in paxillin phosphorylation independent of FAK phosphorylation.


Evaluation of a monoclonal antibody-based test for detection of Helicobacter pylori-specific antigen in stool samples from mice.
A test using monoclonal antibodies for detection of antigen in stool samples was compared with culture and histology for noninfected (n = 25), Helicobacter pylori-infected (n = 25), and Helicobacter felis-infected (n = 6) mice. Sensitivity and specificity were 96%. The monoclonal antibody-based test is therefore a noninvasive technique that is able to diagnose H. pylori infection in mice.


Principles of Design of Clinical Trials for Prevention and Treatment of Alzheimer's Disease and Aging-Associated Cognitive Decline in the ACH2.0 Perspective: Potential Outcomes, Challenges, and Solutions.
With the Amyloid Cascade Hypothesis (ACH) largely discredited, the ACH2.0 theory of Alzheimer's disease (AD) has been recently introduced. Within the framework of the ACH2.0, AD is triggered by amyloid-β protein precursor (AβPP)-derived intraneuronal Aβ (iAβ) and is driven by iAβ produced in the AβPP-independent pathway and retained intraneuronally. In this paradigm, the depletion of extracellular Aβ or suppression of Aβ production by AβPP proteolysis, the two sources of AβPP-derived iAβ, would be futile in symptomatic AD, due to its reliance on iAβ generated independently of AβPP, but effective in preventing AD and treating Aging-Associated Cognitive Decline (AACD) driven, in the ACH2.0 framework, by AβPP-derived iAβ. The observed effect of lecanemab and donanemab, interpreted in the ACH2.0 perspective, supports this notion and mandates AD-preventive clinical trials. Such trials are currently in progress. They are likely, however, to fail or to yield deceptive results if conducted conventionally. The present study considers concepts of design of clinical trials of lecanemab, donanemab, or any other drug, targeting the influx of AβPP-derived iAβ, in prevention of AD and treatment of AACD. It analyzes possible outcomes and explains why selection of high-risk asymptomatic participants seems reasonable but is not. It argues that outcomes of such AD preventive trials could be grossly misleading, discusses inevitable potential problems, and proposes feasible solutions. It advocates the initial evaluation of this type of drugs in clinical trials for treatment of AACD. Whereas AD protective trials of these drugs are potentially of an impractical length, AACD clinical trials are expected to yield unequivocal results within a relatively short duration. Moreover, success of the latter, in addition to its intrinsic value, would constitute a proof of concept for the former. Furthermore, this study introduces concepts of the active versus passive iAβ depletion, contends that targeted degradation of iAβ is the best therapeutic strategy for both prevention and treatment of AD and AACD, proposes potential iAβ-degrading drugs, and describes their feasible and unambiguous evaluation in clinical trials.


[Helicobacter pylori gastritis manifested by acute anemia].
Helicobacter pylori gastritis usually manifests as recurrent abdominal pain but is sometimes discovered upon evaluation for digestive tract bleeding with severe anemia. An 11-year-old who was not under medication and had no history of pain was admitted for isolated regenerative anemia (5.6 g/dl) due to digestive tract bleeding. Laboratory tests showed only low serum iron and ferritin levels. Endoscopy disclosed hemorrhagic inflammation of the duodenal cap and antritis with a hillocky appearance. The diagnosis of H. pylori infection was established on the basis of the finding of curved Gram-negative rods on the smears and of a positive urea test. There was moderate interstitial antritis. The patient was given an H2 antagonist (ranitidine) and amoxicillin with tinidazole for six weeks. Serum IgG antibodies against H. pylori were found in the child's parents and siblings, with the exception of a 7 month old infant. A ten year old sister had been hospitalized two years earlier for hemorrhagic duodenitis ascribed at the time to use of acetylsalicylic acid. H. pylori has been reported in 40% to 95% of pediatric patients with primary gastritis. Physicians should be familiar with this frequent, often familial disease. Management rests on concomitant administration of two antimicrobials and an acid secretion inhibitor to the index patient and family members. Endoscopy is too invasive to be appropriate for monitoring the outcome. In practice, recovery is affirmed on the basis of resolution of clinical manifestations and decreased levels of anti-H. pylori antibodies.


The effects of sodium, hydrogen and magnesium ions on mitochondrial calcium sequestration in adult rat ventricular myocytes.
The effect of Na+, H+ and Mg2+ ions on net calcium exchange induced in digitonin-treated myocytes has been investigated. Raising the [Na] from 1.4 to 31.4 mM revealed a sodium-sensitive fraction of net calcium exchange with a K1/2 for Na+ ions of 12 mM, alongside the respiration-dependent accumulation of calcium. An acidosis, but not an alkalosis, was found to depress both of these processes. Mg2+ ions exerted an effect solely on the respiration-dependent calcium sequestration. A simple semi-empirical model based on the experimental data was formulated to assess the effects that altering sarcoplasmic [Na+] and [H+] would have on the calcium-handling properties of cardiac mitochondria. It is concluded that part of the inotropic effects of these ions could be mediated via this organelle.


Radioimmunoassay of human pancreatic amylase in serum and urine.
The purification of human pancreatic amylase (EC 22.214.171.124) and the development of a radioimmunoassay for this enzyme is described. The enzyme was purified from a normal pancreas obtained at autopsy and antibodies were produced in rabbits. The purified pancreatic amylase was radioiodinated and the radioimmunassay was developed. Analytic recoveries in serum and urine specimens were 99 and 96%, respectively, and day-to-day precision was less than 10%. The assay gave a 20% cross-reactivity with salivary amylase.


Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infections in Filipino children.
The role of Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infection (ALRI) was studied by serologic analysis of 216 Filipino children less than five years old living in periurban slums and middle-class neighborhoods. Diagnostic antibody responses to M. pneumoniae and C. trachomatis were observed in 18 (8.3%) and five (4.3%), respectively, of the cases with ALRI. These bacteria are not susceptible to the antimicrobial treatments currently recommended for the treatment of ALRI in developing countries.


The interplay of half-site sequence and spacing on the activity of direct repeat thyroid hormone response elements.
Direct repeats of the hexamer AGGTCA can serve as response elements for vitamin D, thyroid hormone, or retinoic acid. The specificity of the response appears to reside in the spacing between the hexamers, with response elements for vitamin D restricted to direct repeats separated by a 3-base pair (bp) spacer, thyroid hormone a 4-bp spacer, and retinoic acid a 5-bp spacer (3-4-5 rule). Recently we have shown that the optimum thyroid hormone receptor binding site consists of an 8-bp sequence (TAAGGTCA), not a hexamer. Therefore we tested whether the 3-4-5 rule is valid for octamer sequence direct repeats. In transfection experiments octamer direct repeats with 3-, 4-, or 5-bp spacers conferred equivalently strong thyroid hormone responses, although a repeat with a 9-bp spacer was substantially weaker. For the 4- and 5-bp spacer constructs, the 5' half-site octamer had as strong an influence on thyroid hormone induction as did the 3' half-site octamer, although for the 3-bp spacer construct the 5' octamer was marginally less potent than the 3' octamer. Transfection and gel shift experiments did not suggest a simple correlation between the binding of thyroid hormone receptor-retinoid X receptor heterodimers and thyroid hormone induction from these response elements. We conclude that half-site sequence can override the effect of spacing in determining the hormone responsiveness of a direct repeat response element. In addition, the thyroid hormone response may not be due simply to the binding of thyroid hormone receptor-retinoid X receptor heterodimers to the DNA.


Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a.
Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine. DZNeP and Aristeromycin showed high inhibitory activity against AHCY. Treatment of the prostate cancer cells with DZNeP led to SAH accumulation and decreased levels of homocysteine and histone H3K27 methylation. SAH accumulation and cell growth inhibition were confirmed after siRNA-mediated AHCY knockdown. To further understand why AHCY inhibitors decreased prostate cancer cell growth, we performed microRNA expression profiling with LNCaP-hr cells. Mir-26a, which is involved in regulation of EZH2 expression, was upregulated in Aristeromycin-treated LNCaP-hr cells. A reporter assay established with the EZH2 3'-UTR confirmed that transfection of microRNA precursor molecules for miR-26a decreased the EZH2 3'-UTR luciferase activity. Meanwhile, an antisense microRNA inhibitor for miR-26a recovered the luciferase activity. The present findings suggest, at least in part, that miR-26a induced by an AHCY inhibitor can regulate oncogenic EZH2 expression, and could thus be an important mechanism of action for AHCY inhibitors in the treatment of prostate cancer.


[Multiple proximal coronaro-pulmonary fistulae. Review of the literature apropos of a new case].
The authors report a new case of multiple proximal coronaro-pulmonary fistula between right coronary arteries, anterior interventricular artery and the trunk of the pulmonary artery, in a 64 year-old female patient with chest pain and a continuous murmur located in the third left intercostal space. The coronary steal is demonstrated by a myocardial scintigraphy during stress with return to normal after surgical ligation. A review of the literature enabled to find 33 cases of this major congenital anomaly of the coronary arteries, defined as an abnormal communication between at least two main coronary vessels and the trunk of the pulmonary artery. This results in a left-right shunt, usually minor without any repercussions on the right cavities and pulmonary pressures. The entire clinical, electrocardiographic, radiological, sonographic, scintigraphic, haemodynamic and angiographic picture is reported for these 33 cases. A physiopathological discussion is proposed. The course of this disease is usually favorable (only one case of myocardial infarction was published, without cardiac failure. Osler's endocarditis or sudden death); this seems to authorize simple monitoring as a logical therapeutic approach except when a myocardial ischemia secondary to coronary steal is demonstrated, imposing a surgical correction.


Post bone marrow transplant sera and persisting mast cell colonies.
Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.


[Single stage excision for an intractable brain abscess and free rectus abdominis flap for reconstruction of the anterior skull base].
A case is presented of the frontal brain abscess following resection of squamous cell carcinoma of the maxillary sinus who had undergone reconstruction of the anterior skull base using a free rectus abdominis muscle flap. Local flap, ex. galeal flap, can be used for separating the cranial space from the paranasal sinuses and the nasopharynx, but it cannot provide reliable separation and protection of the brain from bacterial flora of the upper airway and it is too weak to support the brain in cases where orbital exenteration has been performed. The distant flaps such as the pectoralis major musculocutaneous flap, on the other hand, can provide a good alternative for reconstruction of the anterior skull base in such difficult cases, but frequently requires a secondary division of the pedicle. The free flap can circumvent such problems. We used the free rectus abdominis muscle flap and the postoperative course was uneventful. A bone graft was not necessary to reconstruct the anterior skull base.


A comparison of growth and development of three major agricultural insect pests infected with Heliothis virescens ascovirus 3h (HvAV-3h).
Ascoviruses are double-stranded DNA viruses that are pathogenic to lepidopteran hosts, particularly noctuid larvae. Infection of a larva is characterized by retarded growth, reduced feeding and yellowish body color. In this paper, we reported the growth and development of three major agricultural noctuid insect pests, Helicoverpa armigera (Hübner), Spodoptera exigua (Hübner) and Spodoptera litura (Fabricius), infected with Heliothis virescens ascovirus 3h (HvAV-3h). Using 10-fold serial dilutions (0 to 7) of HvAV-3h-containing hemolymph to infect S. litura larvae, we found no significant difference in larval mortalities from 0 to 10(3)-fold dilutions; however, significant differences were observed at 10(4)-fold dilution and above. Using a 10-fold dilution of HvAV-3h-containing hemolymph to infect H. armigera, S. exigua and S. litura larvae, we found that the growth and development were significantly affected. All infected larvae could not pupate; the survival times of treated H. armigera, S. litura and S. exigua larvae were significantly longer than untreated control larvae. Body weight showed significant difference between treated and untreated control group from day 1 after inoculation in H. armigera and S. exigua, but day 2 in S. litura. Additionally, food intake also showed significant difference between treated and untreated control group from day 2 after inoculation in H. armigera and S. litura, but day 3 in S. exigua.


Synthesis of shape controlled ferrite nanoparticles by sonochemical technique.
Synthesis of magnetic iron oxides/ferrites in the nano scale by sonochemical synthesis has become prominent recently. This technique facilitates the synthesis of magnetic particles in the nano scale attributed to the hotspot mechanism arising due to acoustic cavitation induced chemical reaction. Generally volatile organometallic precursor compounds favoring the formation of fully amorphous particles have been used to synthesize various nano magnetic materials. We report here the synthesis of ultrafine, < 10 nm magnetic iron oxide nanoparticles by sonochemical technique starting with a non-volatile precursor iron salt such as iron citrate which seems to favor the formation of semi crystalline/crystalline particles as the reaction takes place either in the interfacial region or in the bulk solution. Mono dispersed, ultra fine, approximately 4 nm spherical shaped magnetic maghemite particles having a saturation magnetization of 58.2 emu/g and coercivity of 118 Oe were obtained at low values of pH, 10 while higher pH, 11-13 favored the formation of elongated, cylindrical, acicular particles with a reduced magnetization. The coercivity was also found to decrease with increasing pH, with it being 118 Oe at pH 10 and 3 Oe at pH 13. When the ultrasound amplitude/intensity was low, 38% heat treatment of the samples at 300 degrees C (at pH 10) was required to make them crystalline, while application of high intensity ultrasound, 50% amplitude served as a single step mechanism for obtaining crystalline maghemite particles. The maghemite particles obtained at a pH of 10 could find applications in information storage media.


The Grocery Store Food Environment in Northern Greenland and Its Implications for the Health of Reproductive Age Women.
The population of Greenland is diminishing and environmental and social shifts implicate food availability and the health of reproductive age women. There is little knowledge of the grocery store food environment in Greenland. To address this gap and provide baseline information the present study measured food availability in five grocery stores in northern Greenland. As well, 15 interviews were conducted with reproductive age women, three grocery store managers were interviewed and one interview was conducted with a food distribution manager. Results show few fresh fruits and vegetables are available in grocery stores and in some stores no fresh foods are available. In Kullorsuaq, the primary location for this study, the Nutrition Environment Measures Survey in Stores score in spring 2016 was (3/30) and the Freedman Grocery Store Survey Score was (11/49). Interview results highlight a need to increase communication within the food system and to tailor food distribution policies to the Arctic context with longer term planning protocols for food distribution. These findings can be used to inform future food store environment research in Greenland and for informing policies that improve healthful food availability in grocery stores in northern Greenland.


Phytotoxicity of new furan-derived aminophosphonic acids, N-aryl furaldimines and 5-nitrofuraldimine.
The aim of this work was to synthesize selected furaldimines and their aminophosphonic derivatives and evaluation the phytotoxicity of new obtained products according to OECD 208 Guideline. Four Schiff bases, N-furfurylidene-p-anisidine (1a), N-furfurylidene-p-toluidine (1b), N-furfurylidene-benzhydrylamine (1c), and N-(2-nitrofurfurylidene)-p-toluidine (1d) were synthesized and three new furan-derived N-substituted aminomethylphosphonic acids, namely: 2-furyl N-(p-methoxyphenyl)-aminomethylphosphonic acid (2a), 2-furyl N-(p-methylphenyl)-aminomethylphosphonic acid (2b) and 2-furyl N-(diphenylmethyl)-aminomethylphosphonic acid (2c) were synthesized by the addition of in situ generated bis-(trimethylsilyl) phosphite to azomethine bond of corresponding Schiff bases 1a-c. Three Schiff bases 1a-b and 1d as well as all three aminophosphonic acids 2a-c were analyzed in regard with their phytotoxicity toward two plants, radish (Raphanus sativus) and oat (Avena sativa). It has been found that tested N-furfurylidene-p-anisidine (1a), N-(2-nitrofurfurylidene)-p-toluidine (1d) and aminophosphonic acids 2a-c are toxic for selected plants. N-furfurylidene-p-toluidine (1b) did not show any ecotoxicological impact in used plant growth test.


Laterality as an indicator of emotional stress in ewes and lambs during a separation test.
We assessed motor laterality in sheep to explore species-specific brain hemi-field dominance and how this could be affected by genetic or developmental factors. Further, we investigated whether directionality and strength of laterality could be linked to emotional stress in ewes and their lambs during partial separation. Forty-three ewes and their singleton lambs were scored on the (left/right) direction of turn in a y-maze to rejoin a conspecific (laterality test). Further, their behavioural response (i.e. time spent near the fence, vocalisations, and activity level) during forced separation by an open-mesh fence was assessed (separation test). Individual laterality was recorded for 44.2% ewes (significant right bias) and 81.4% lambs (equally biased to the left and the right). There was no significant association in side bias between dams and offspring. The Chi-squared test revealed a significant population bias for both groups (p < 0.05). Evolutionary adaptive strategies or stimuli-related visual laterality may provide explanation for this decision-making process. Absolute strength of laterality (irrespective of side) was high (Kolmogorov-Smirnov test, dams: D = 0.2; p < 0.001; lambs: D = 0.36, p < 0.0001). The Wilcoxon test showed that lateralised lambs and dams spent significantly more time near each other during separation than non-lateralised animals (p < 0.05), and that lateralised dams were also more active than non-lateralised ones. Arguably, the lateralised animals showed a greater attraction to their pair because they were more disturbed and thus required greater reassurance. The data show that measures of laterality offer a potential novel non-invasive indicator of separation stress.


[Structured therapeutic interruption in patients infected with HIV-1 experiencing a block in their antiretroviral treatment: preliminary results].
Structured therapeutic interruption (STI) has been offered to HIV-1 infected patients with virological failure (viral load > 1500 copies/mL) of potent antiretroviral therapy (ART) (three or four drugs for at least one year). CD4 lymphocyte count, HIV-1 viral load, clinical status, were assessed every month during STI and after ART reintroduction. Genotype analysis by plasma virus sequencing was done before and after treatment interruption. The results of 14 patients who resumed ART for at least two months are presented. Median duration of STI was 7.5 months (range: 2-13 months). Median CD4 count was low (45/mm3) when treatment was stopped, and decreased during STI (-37/mm3 after six months). Several patients exhibited important CD4 diminutions. Viral load slightly increased (+0.83 log at M6). Few clinical events occurred: one: severe HIV-related prurigo and one CMV viremia. Reversion of resistance mutations was only seen in 2/13 (15: 4%) patients (who had previously a major CD4 deficiency, and a long treatment history), a partial reversion occurred in 5/13 (38.5%) subjects, and the mutations didn't change in the other cases (genotyping non interpretable in the last patient). ART reintroduction induced a good immune response: CD4/mm3 after six months, with significant increases in 10/14 subjects. There was an initial viral response (median viral load: -2.34 log at M1), but a quick rebound most often occurred. However, viral load remained < 50 copies/mL in four patients. In conclusion, a rapid and important decline in CD4 cell count can occur when treatment is discontinued, in patients with virological failure of ART, but the clinical risk appears to be limited. Treatment re-initiation induces a good response, but virologically transient in most cases. Patients with a shift to wild-type virus seem to have a better response.


[LAPAROSCOPIC CERVICOISTHMIC CERCLAGE - OUR EXPERIENCE.]
The authors share their experience with 7 women to whom a laparoscopic cervical cerclage before pregnancy has been placed. No intraoperative or postoperative complications were experienced. The indications, technique, positive and negative features of vaginal, abdominal and laparoscopic cerclage are discussed.


Topological disorder in peripheral vision.
One of the most striking properties of the mammalian visual system is that it is only the central part of the visual field, the fovea, where vision is most acute. The superiority of the fovea is particularly evident in tasks requiring accurate spatial localization. It is currently thought that peripheral spatial uncertainty is a simple consequence of the decreased sampling grain of the peripheral field. We show that the topological fidelity of the afferent projection declines with eccentricity away from the fovea and that it is this rather than the sampling grain that underlies the poorer performance of the periphery in tasks involving spatial localization. The combination of normal sampling and a disordered topology results in the periphery having good sensitivity for detection but poor sensitivity for object recognition.


[Biomarker].
The most serious complication of Kawasaki disease(KD) is coronary artery lesions (CAL), which mainly occur in patients with the incomplete form of KD and intravenous gamma-globulin therapy non-responsiveness (IVIG non-responsiveness). Recently, numerous biomarkers for diagnosis of the incomplete form of KD, endothelial dysfunction, and myocardial disturbance, as well as for the prediction of CAL formation and IVIG non- responsiveness, have been reported. However, a useful single biomarker has yet to be described. Pentraxin 3 (PTX3), endothelin-1(ET-1), brain natriuretic peptide(BNP) and N-terminal pro-brain natriuretic peptide are produced and secreted from vascular and/or myocardial tissue, and are very useful for diagnosis of the incomplete form of KD, and for the prediction of IVIG non-responsiveness and CAL formation in the acute phase. Further- more, some biomarkers are helpful for evaluating chronic coronary arteritis and atheroscle- rosis in the convalescent phase of KD.


Receptor-mediated endocytosis of macromolecules and strategy to enhance their transport in alveolar epithelial cells.
Pulmonary delivery is an attractive administration route for therapeutic proteins and peptides. In this context, endocytosis/transcytosis at the distal lung epithelial barrier is an important process in the pulmonary absorption of therapeutic macromolecules. The alveolar epithelium is comprised of type I and type II cells. Understanding the transport mechanisms in these cells is essential for the development of efficient pulmonary delivery systems of therapeutic macromolecules. Endocytic pathways for albumin and insulin in alveolar epithelial cells and possible receptors for the endocytosis are discussed. Strategies to enhance the endocytosis and pulmonary absorption of macromolecules are also discussed, by focusing on the effects of cationic poly(amino acid)s. Although the surface area occupied by type II cells in alveoli is much smaller than that covered by type I cells, type II cells may significantly contribute to the endocytosis/transcytosis of macromolecules such as albumin. Identification of the receptors involved in the cellular uptake of each macromolecule is prerequisite for the understanding and regulation of its transport into and across alveolar epithelial cells. Establishment of novel in-vitro culture cell models of type I and type II cells would be a great help for the future advance of this research field.


A Quality Improvement Initiative to Reduce Unnecessary Screening Chest Radiographs in a Pediatric ICU.
The Critical Care Societies Collaborative included not ordering diagnostic tests at regular intervals as one of their Choosing Wisely initiatives. A reduction in unnecessary chest radiographs (CXRs) can help reduce exposure to radiation and eliminate health care waste. We aimed to reduce daily screening CXRs in a pediatric ICU (PICU) by 20% from baseline within 4 months of implementation of CXR criteria. All intubated patients in the PICU were included in this quality improvement project. Patients with tracheostomies were excluded. We developed criteria delineating which patients were most likely to benefit from a daily screening CXR, and these criteria were discussed for each patient on rounds. Patients on extracorporeal membrane oxygenation, on high-frequency oscillatory ventilation, or on high support on conventional mechanical ventilation were included as needing a daily screening CXR. We tracked the percentage of intubated subjects receiving a screening CXR as an outcome measure. Unplanned extubations and the number of non-screening CXRs per intubated subject were followed as balancing measures. The percentage of intubated subjects receiving a daily screening CXR was reduced from 79% to 31%. There was no increase in frequency of unplanned extubations or number of non-screening CXRs. With an estimated subject charge of roughly $270 and hospital cost of $54 per CXR, this project led to an estimated $300,000 in patient charge savings and $60,000 in hospital cost savings. Adopting criteria to delineate which patients are most likely to benefit from screening CXRs can lead to a reduction in the percentage of intubated patients receiving screening CXRs without appearing to increase harm.