Impact of adenotonsillectomy on quality of life in children with obstructive sleep disorders.
To determine the impact of adenotonsillectomy on quality of life (QOL) in children with obstructive sleep disorders (OSDs) before and after surgery. Prospective, observational, before-and-after trial. Seven tertiary pediatric otolaryngology practices. Convenience sample of 101 children (mean age, 6.2 years) with adenotonsillar hypertrophy and OSD scheduled for adenotonsillectomy. Adenotonsillectomy was performed in children for OSDs. Quality of life was assessed using the Obstructive Sleep Disorders-6 survey, a validated instrument for detecting QOL change in children with OSDs. Surveys were completed at the initial office visit (visit 1), the day of surgery (visit 2), and at the postoperative office visit (visit 3). Physical characteristics were assessed using tonsillar and orocraniofacial scales (visit 1). Satisfaction with health care decisions was assessed using the Satisfaction With Decision and Satisfaction With Office Visit scales (visit 1). Short-term changes in QOL before (visits 1 and 2) and after (visits 2 and 3) surgery. Changes in QOL before surgery were trivial or small, and smaller than changes after surgery (mean change score, 0.18 vs 2.3; P<.001). Large, moderate, and small improvements in QOL were seen in 74.5%, 6.1%, and 7.1% of children, respectively. Sleep disturbance, caregiver concern, and physical suffering were the most improved domains, although significant changes also occurred for speech and swallowing problems, emotional disturbance, and activity limitations. Five percent of children had poorer QOL after surgery, but no predictive factors were identified. Adenotonsillectomy produces large improvements in at least short-term QOL in most children with OSDs.


Extended-spectrum beta-lactamase-producing Enterobacteriaceae in community and private health care centers.
In 1999, 39 of 2,599 isolates of the family Enterobacteriaceae (1.5%) collected by eight private laboratories in the Aquitaine region in France produced an extended-spectrum beta-lactamase (ESBL). Among these were 19 Enterobacter aerogenes isolates; 8 Klebsiella pneumoniae isolates; 6 Escherichia coli isolates; 3 Proteus mirabilis isolates; and 1 isolate each of Serratia marcescens, Morganella morganii, and Providencia stuartii. ESBL producers were isolated from 38 patients, including 33 residents of 11 clinics or nursing homes and 5 ambulatory patients. Seven different ESBLs were characterized. These mainly consisted of TEM-24 (25 isolates) and TEM-21 (9 isolates), but TEM-15 (2 isolates) and TEM-3, TEM-19, SHV-4, and CTX-M-1 (1 isolate each) were also characterized. Seven strains showed the coexistence of different TEM- and/or SHV-encoding genes, including a new SHV-1 variant, SHV-44, defined by the substitution R205L previously reported for SHV-3 in association with S238G. The epidemiology of the ESBL producers was investigated by random amplification of polymorphic DNA, typing by enterobacterial repetitive intergenic consensus PCR, analysis of resistance cotransferred with the ESBL, and analysis of the restriction profiles of the ESBL-encoding plasmids. Of the TEM-24-expressing strains, 18 were E. aerogenes isolates, including 9 from the same clinic, that were representatives of the epidemic clone disseminating in France. Of the TEM-21-producing strains that belonged to different species of the family Enterobacteriaceae (E. coli, K. pneumoniae, and P. mirabilis), 8 were isolated in the same nursing home. Outbreaks due to strain and/or plasmid dissemination in these clinic and nursing home were demonstrated. The presence of ESBL producers in five ambulatory patients probably resulted from nosocomial acquisition. Our data highlight the serious need to monitor patients for ESBL-producing Enterobacteriaceae in general practice.


Comparative thyroidology: thyroid gland location and iodothyronine dynamics in Mozambique tilapia (Oreochromis mossambicus Peters) and common carp (Cyprinus carpio L.).
In teleosts, the thyroid gland is mostly found in the subpharyngeal region. However, in several species thyroid follicles are found in, for example, heart, head kidney and kidney. Such heterotopic thyroid follicles are active, and considered to work in concert with the subpharyngeal thyroid. In Mozambique tilapia (Oreochromis mossambicus) thyroid activity is, indeed, restricted to the subpharyngeal region; in common carp (Cyprinus carpio) the functional endocrine thyroid is associated with renal tissues. The subpharyngeal follicles of carp comprise only 10% of the total thyroid tissue, and these follicles neither accumulate iodide nor synthesize or secrete thyroid hormones to a significant degree. Although the shape and size of carp subpharyngeal and renal follicles vary, the epithelial cell height of the thyrocytes and thyroxine immunoreactivity do not differ, which suggests that the activity of the carp subpharyngeal thyroid follicles is dormant. Differences in thyroid physiology between the two fish species were further assessed at the level of peripheral thyroid hormone metabolism. Carp clears plasma of thyroid hormones faster than tilapia does. Furthermore, a significant amount of conjugated thyroid hormones was observed in the plasma of tilapia, which was preceded by the occurrence of thyroid hormone conjugates in the subpharyngeal region and coincides with the appearance of conjugates in the surrounding water. Apparently, plasma thyroid hormone conjugates in tilapia originate from the thyroid gland and function in the excretion of thyroid hormones. Our data illustrate the variability in teleostean thyroidology, an important notion for those studying thyroid physiology.


A model for the irradiance responses of photosynthesis.
The analysis of the irradiance responses of photosynthetic processes, such as the quantum efficiencies of electron transport by photosystems I and II (PSI and PSII) or the rate of carbon dioxide fixation, is limited by the lack of mechanistically based analytical model for these processes. Starting with a model of P700 redox state, we develop a series of analytical functions which can be used to fit the irradiance responses of the quantum yields for electron transport by PSI and PSII, the irradiance responses of electron transport by PSI and PSII, and even the irradiance response of the fixation rate of carbon dioxide. These functions depend on two or three parameters so they can be fit to typical irradiance response data. We illustrate by example the use of these functions in various applications and discuss further use and development of the basic model described in detail here.


Arsenate removal by nanostructured ZrO2 spheres.
A new zirconium oxide-based media for arsenate removal from water was fabricated and evaluated in batch and continuous flow experiments. Highly porous (epsilonp approximately 0.9) nanostructured zirconium oxide spheres were fabricated by the impregnation of macroporous ion-exchange media (CalRes 2103, Calgon) with zirconium salt; the media was then ashed at T > 750 +/- 50 degrees C to remove the organic polymer resin and obtain ZrO2 spheres. The spheres generally ranged from 200 to 800 microm in diameter, and consisted of ZrO2 nanoastructures generally ranging between 20 and 100 nm. They also exhibited monoclinic and tetragonal crystalline structures, and had an isoelectric point of 5.6. Equilibrium batch experiments were conducted in 10 mM NaHCO3 buffered nanopure water at three pH values (6.4,7.3, and 8.3) with 120 microg/L As(V). Data were fit with the Freundlich isotherm equation (q(e) = Kx CE(1/n)), resulting in an intensity parameter (1/n) of approximately 0.33 and capacity parameters (K) ranging from 115 to 400 (microg As(V) g(-1) dry media)(L microg(-1))1/n. The pore diffusion coefficient and toruosity were estimated to be 6.4 x 10(-6) cm2 s(-1) and 1.3, respectively. For a packed bed adsorbent operating at a loading rate of 11.5 m3 m(-2) hr(-1) in a realistic continuous flow experiment, the external mass transport coefficient was estimated to be kf approximately 6.3 x 10(-3) cm s(-1). The pore diffusion coefficient and the external mass transport coefficient were used with the pore surface diffusion model (PSDM) to predict the arsenate breakthrough curve. A short bed adsorbent (SBA) test was conducted under the same conditions to validate the model. In this study, surface diffusion was ignored because the particles have a very high porosity. The validated model was used to predict arsenate breakthrough in a simulated full-scale system. The overall combined use of modeling, material characterization, equilibria, and kinetics tests determined the suitability of the media for arsenate treatment cheaper, easier, faster, and with less media than a long duration pilot test would have. Although the fabricated zirconium oxide spheres exhibited adsorption capacity comparable to some commercially available media such as iron based (hydr)oxides, the high cost of fabrication may render the media not feasible for wide use in commercial applications. However, the very high porosity of this media provides for improved pore diffusion and faster overall mass transport, which may be critical for applications where mass transport is the limiting factor.


Arachnoid Welding-A Simple and Economical Method of Arachnoid Closure to Prevent Cerebrospinal Fluid Leak.
Collection of cerebrospinal fluid (CSF) in the subdural compartment is a major cause of postoperative morbidity, especially for posterior fossa surgeries. Arachnoid closure techniques, including suturing of the arachnoid and use of synthetic sealants, have been described in the literature. However, they are not always feasible or effective and have not been universally adopted. We describe the technique of arachnoid welding for a case of brainstem cavernoma. This is a simple, cost-effective, and easily reproducible technique using readily available bipolar cautery kept at a low-current setting. At the end of surgery, the arachnoid leaflets are closely approximated, and bipolar cautery is used to seal the edges together. An illustrative video shows the technical nuances of this procedure. This technique can also be applied for arachnoid closure at other cranial and spinal sites. Arachnoid closure can act as an effective natural barrier to keep CSF in its physiological subarachnoid compartment. It provides an additional barrier to prevent CSF leak. It also prevents morbidity associated with adhesions and arachnoiditis. Proper closure of arachnoid makes durotomy during repeat surgery much easier and avoids injury to the underlying pia. A brief review of related literature shows the benefits of closing the arachnoid before dural closure and the different techniques that have been described so far. The arachnoid welding technique has a wide application, is easy to learn, and can be used especially for posterior fossa surgeries in which rates of CSF leak are the highest.


Relations between the aromaticity and magnetic dipole transitions in the electronic spectra of hetero[8]circulenes.
Magnetically induced current densities have been calculated at the second-order Møller-Plesset perturbation theory (MP2) level for seven hetero[8]circulenes and their dicationic and dianionic forms. Calculations of the magnetic dipole transition moments have also been carried out at the algebraic diagrammatic construction (ADC(2)) and the second-order approximate coupled-cluster (CC2) levels. The calculations show that the degree of aromaticity and the size of the magnetic dipole transition moment of the lowest magnetic-dipole allowed excited state are related. We show that neutral hetero[8]circulenes are weakly antiaromatic when the first excited state with a large magnetic dipole transition moment of 10-16 a.u. lies at high energies (∼2.8-3.5 eV). For the dications, this transition often lies at much lower energies. Hetero[8]circulene dications with large magnetic dipole transition moments are strongly antiaromatic. The lowest excited states of the hetero[8]circulene dianions have very small magnetic dipole transition moments implying that they are aromatic.


Expression and manipulation of phosphoenolpyruvate carboxykinase 1 identifies a role for malate metabolism in stomatal closure.
Malate, along with potassium and chloride ions, is an important solute for maintaining turgor pressure during stomatal opening. Although malate is exported from guard cells during stomatal closure, there is controversy as to whether malate is also metabolised. We provide evidence that phosphoenolpyruvate carboxykinase (PEPCK), an enzyme involved in malate metabolism and gluconeogenesis, is necessary for full stomatal closure in the dark. Analysis of the Arabidopsis PCK1 gene promoter indicated that this PEPCK isoform is specifically expressed in guard cells and trichomes of the leaf. Spatially distinct promoter elements were found to be required for post-germinative, vascular expression and guard cell/trichome expression of PCK1. We show that pck1 mutant plants have reduced drought tolerance, and show increased stomatal conductance and wider stomatal apertures compared with the wild type. During light-dark transients the PEPCK mutant plants show both increased overall stomatal conductance and less responsiveness of the stomata to darkness than the wild type, indicating that stomata get 'jammed' in the open position. These results show that malate metabolism is important during dark-induced stomatal closure and that PEPCK is involved in this process.


The complete mitogenome of Cylindrus obtusus (Helicidae, Ariantinae) using Illumina next generation sequencing.
This study describes how the complete mitogenome of a terrestrial snail, Cylindrus obtusus (Draparnaud, 1805) was sequenced without PCRs from a collection specimen that had been in 70% ethanol for 8 years. The mitogenome was obtained with Illumina GAIIx shot gun sequencing. Although the used specimen was collected relatively recently and kept in a DNA-friendly preservative (not formalin as frequently used with old museum specimens), we believe that the exclusion of PCRs as facilitated by NGS (Next Generation Sequencing) removes a great obstacle in DNA sequencing of collection specimens. A brief comparison is made between our Illumina GAIIx approach and a similar study that made use of the Roche 454-FLX platform. The mtDNA sequence of C. obtusus is 14,610 bases in length (about 0.5 kb larger than other stylommatophoran mitogenomes reported hitherto) and contains the 37 genes (13 protein coding genes, two rRNAs and 22 tRNAs) typical for metazoans. Except for a swap between the position of tRNA-Pro and tRNA-Ala, the gene arrangement of C. obtusus is identical to that reported for Cepaea nemoralis. The 'aberrant' rearrangement of tRNA-Thr and COIII compared to that of other Sigmurethra (and the majority of gastropods), is not unique for C. nemoralis (subfamily Helicinae), but is also shown to occur in C. obtusus (subfamily Ariantinae) and might be a synapomorphy for the family Helicidae. Natural history collections potentially harbor a wealth of information for the field of evolutionary genetics, but it can be difficult to amplify DNA from such specimens (due to DNA degradation for instance). Because NGS techniques do not rely on primer-directed amplification (PCR) and allow DNA to be fragmented (DNA gets sheared during library preparation), NGS could be a valuable tool for retrieving DNA sequence data from such specimens. A comparison between Illumina GAIIx and the Roche 454 platform suggests that the former might be more suited for de novo sequencing of mitogenomes.


Quantification and Visualization of Reliable Hemodynamics Evaluation Based on Non-Contact Arteriovenous Fistula Measurement.
The condition of arteriovenous fistula (AVF) blood flow is typically checked by using auscultation; however, auscultation should require a qualitative judgment dependent on the skills of doctors, and further attention to contact infection is required. For these reasons, this study developed a non-contact and non-invasive medical device to measure the pulse wave of AVFs by applying optical imaging technology. As a first step toward realization of the quantification judgment based on non-contact AVF measurement, we experimentally validated the developed system, whereby the hemodynamics of 168 subjects were visually and quantitatively evaluated based on clinical tests. Based on the evaluation results, the fundamental statistical characteristics of the non-contact measurement, including the average and median values, and distribution of measured signal-to-noise power ratio, were demonstrated. The clinical test results contributed to the future construction of quantified criteria for the AVF condition with the non-contact measurement.


The endothelium of clear corneal transplants.
The endothelium of 36 clear penetrating keratoplasties, performed 1 to 19 years previously, was examined and photographed with the clinical specular microscope. There were fewer central endothelial cells in the transplants than in normal corneas. There was no significant correlation between graft endothelial cell density and corneal thickness, rejection episodes, the disease necessitating kertoplasty, or the method of donor tissue preservation. Corneas transplanted from younger donors to younger recipients had significantly more central endothelial cells. Transplanted corneas appeared to lose endothelial cells over a period of time, just as normal corneas do.


Prevalent PCR ribotypes of clinical and environmental strains of Clostridium difficile isolated from intensive-therapy unit patients in Kuwait.
Ninety-five isolates of Clostridium difficile from symptomatic and asymptomatic patients and 18 from their environment in the intensive-therapy units (ITUs) of four teaching hospitals in Kuwait were typed by PCR amplification of rRNA intergenic spacer regions (PCR ribotyping). A total of 32 different ribotypes was detected among the clinical isolates. The predominant ribotypes from the clinical isolates were types 097 and 078, which accounted for approximately 40 % of all isolates in the ITUs in Kuwait. Ribotypes 097 (toxigenic), 078 (toxigenic) and 039 (non-toxigenic) were three distinct clones that were circulating in all four hospitals. Ribotypes 097, 078 and 076 (i.e. 50 % of isolates from symptomatic patients) were the predominant isolates associated with C. difficile-associated disease (CDAD). The environmental isolates belonged to a diverse range of ribotypes, with no particular types common to all the hospitals. Ribotype 078 was found only in the patient environment in Mubarak hospital, while ribotype 097 was restricted to Amiri hospital. The hospital environment occupied by symptomatic as well as symptom-free patients was contaminated with C. difficile. Eight new strains that did not match any in the PCR ribotype library established at the PHLS Anaerobe Reference Unit, Cardiff, UK, were assigned ribotypes 105, 125, 128, 129, 131, 134, 140 and 141. These findings show that the isolates associated with CDAD in Kuwait are different from those found in the UK and some other European countries.


Particlelike distributions of the Higgs field nonminimally coupled to gravity.
When the Higgs field is nonminimally coupled to gravity, there exists a family of spherically symmetric particlelike solutions to the field equations. These monopoles are the only globally regular and asymptotically flat distributions with finite energy of the Higgs field around compact objects. Moreover, spontaneous scalarization is strongly amplified for specific values of their mass and compactness.


Conservation genomics: disequilibrium mapping of domestic cattle chromosomal segments in North American bison populations.
Introgressive hybridization is one of the major threats to species conservation, and is often induced by human influence on the natural habitat of wildlife species. The ability to accurately identify introgression is critical to understanding its importance in evolution and effective conservation management of species. Hybridization between North American bison (Bison bison) and domestic cattle (Bos taurus) as a result of human activities has been recorded for over 100 years, and domestic cattle mitochondrial DNA was previously detected in bison populations. In this study, linked microsatellite markers were used to identify domestic cattle chromosomal segments in 14 genomic regions from 14 bison populations. Cattle nuclear introgression was identified in five populations, with an average frequency per population ranging from 0.56% to 1.80%. This study represents the first use of linked molecular markers to examine introgression between mammalian species and the first demonstration of domestic cattle nuclear introgression in bison. To date, six public bison populations have been identified with no evidence of mitochondrial or nuclear domestic cattle introgression, providing information critical to the future management of bison genetic resources. The ability to identify even low levels of introgression resulting from historic hybridization events suggests that the use of linked molecular markers to identify introgression is a significant development in the study of introgressive hybridization across a broad range of taxa.


IKKα regulates human keratinocyte migration through surveillance of the redox environment.
Although the functions of H2O2 in epidermal wound repair are conserved throughout evolution, the underlying signaling mechanisms are largely unknown. In this study we used human keratinocytes (HEK001) to investigate H2O2-dependent wound repair mechanisms. Scratch wounding led to H2O2 production in two or three cell layers at the wound margin within ∼30 min and subsequent cysteine modification of proteins via sulfenylation. Intriguingly, exogenous H2O2 treatment resulted in preferential sulfenylation of keratinocytes that adopted a migratory phenotype and detached from neighboring cells, suggesting that one of the primary functions of H2O2 is to stimulate signaling factors involved in cell migration. Based on previous findings that revealed epidermal growth factor receptor (EGFR) involvement in H2O2-dependent cell migration, we analyzed oxidation of a candidate upstream target, the inhibitor of κB kinase α (IKKα; encoded by CHUK), as a mechanism of action. We show that IKKα is sulfenylated at a conserved cysteine residue in the kinase domain, which correlates with de-repression of EGF promoter activity and increased EGF expression. Thus, this indicates that IKKα promotes migration through dynamic interactions with the EGF promoter depending on the redox state within cells.


Retinoschisin is a peripheral membrane protein with affinity for anionic phospholipids and affected by divalent cations.
Retinoschisin (RS) is a retina-specific, secreted protein implicated in X-linked juvenile retinoschisis and essential for the structural and functional integrity of the retina. This biochemical characterization and ultrastructural localization of RS in intact murine retina was performed to further understanding of the molecular basis of its function. Subcellular fractions and fractions enriched in photoreceptor inner and outer segments were prepared from mouse retina by differential or density gradient ultracentrifugation. Immunoblot analysis was used to assess the expression of RS in various subcellular compartments and its fractionation into soluble phase on treatment of retinal cell membranes with several solubilizing reagents. RS-lipid interactions were evaluated by a protein-lipid overlay assay that used wild-type and mutant forms of RS discoidin domain glutathione S-transferase (GST) fusion proteins. The subcellular localization of RS in mouse retina was visualized by pre-embedding immunogold electron microscopy. Ultrastructure was evaluated by transmission electron microscopy. RS was intimately associated with cell membranes of the retina. It was found to cluster on the outer leaflet of the plasma membrane of the photoreceptor inner segments, which synthesize and secrete it. It was released from the membrane at high pH, which is characteristic of a peripheral membrane protein. It was extracted from the membrane by the nonionic detergent NP-40, together with glycerophospholipids. Protein-lipid overlay assays indicated a preferential interaction between RS and anioic phospholipids. Extraction of RS from the membrane was inhibited by divalent cations. Photoreceptor inner segment morphology was markedly affected in RS(-)(/y) mice, which failed to express RS protein. RS in intact retina is a peripheral membrane protein. Although distributed over the two membrane faces, RS is associated primarily with the outer leaflet of the inner segment plasma membrane through anionic phospholipids and divalent cations. RS's localization in photoreceptors and its biochemical properties suggest a functional role locally, at the site of secretion and membrane adhesion, in maintaining the photoreceptor inner segment stability and architecture.


Using Optical Coherence Tomography to Reveal the Hidden History of The Landsdowne Virgin of the Yarnwinder by Leonardo da Vinci and Studio.
Optical coherence tomography (OCT) was used for non-invasive examination of a well-known, yet complex, painting from the studio of Leonardo da Vinci in combination with routine imaging in various bands of electromagnetic radiation. In contrast with these techniques, OCT provides depth-resolved information. Three post-processing modalities were explored: cross-sectional views, maps of scattering from given depths, and their 3D models. Some hidden alterations of the painting owing to past restorations were traced: retouching and overpainting with their positioning within varnish layers as well as indications of a former transfer to canvas.


High cAMP in spores of Dictyostelium discoideum: association with spore dormancy and inhibition of germination.
Signalling mechanisms involving cAMP have a well-documented role in the coordination of multicellular development and differentiation leading to spore formation in the social amoeba, Dictyostelium discoideum. The involvement of cAMP in the poorly understood developmental stages of spore dormancy and germination have been investigated in this study. Dormant spores contained up to 11-fold more cAMP than nascent amoebae. The spore cAMP levels were not constant, but typically underwent a surge at 14-18 d when spores acquired the ability to germinate spontaneously. The high cAMP levels decreased only during successful spore germination, i.e. emergence of nascent amoebae. The temporal pattern of cAMP decrease was complex and unique to the method of spore activation, supporting our hypothesis that exogenously (e.g. heat) activated and autoactivated spores germinate by different mechanisms. During heat-induced activation, transcription of acg (a gene encoding adenylyl cyclase associated with germination) correlated well with spore cAMP content. Young wild-type spores, incapable of spontaneous germination, maintained a uniformly high cAMP level, and spore cAMP levels also remained high if germination was inhibited. When activated spores were deactivated by applying increased osmotic pressure, cAMP concentrations rose and ultimately levelled off at the high levels typical of dormant spores. The correlation between high cAMP and failure to germinate was also evident when autoactivation was inhibited by the cAMP analogue, 8-bromo-cAMP. Also, spores from a strain (HTY217) with unrestrained protein kinase A activity were incapable of spontaneous germination. Overall, our experiments provide evidence for continued cAMP signalling in spores up to 18 d after sporulation and for linkages between elevated cAMP, spore deactivation and inhibition of spontaneous germination.


In the first 3 months after stroke is progressive resistance training safe and does it improve activity? A systematic review.
BACKGROUND Progressive resistance training (PRT) can improve strength and function in people with chronic stroke, but less is known about whether this intervention is safe and beneficial during the first 3 months following stroke. OBJECTIVE To systematically review the evidence about the safety and effectiveness of PRT to improve activity in people within the first 3 months after stroke. METHODS After database searching and selection of studies a risk of bias assessment was conducted. Data for the primary outcome of safety was synthesised descriptively and meta-analyses for other outcomes were conducted using a random effects model. RESULTS The quality of the 5 included studies ranged from good to excellent (mean 24.2, range 20-28). For the trials investigating adverse events, none reported any significant increase in events after PRT. There was high level evidence that PRT had little or no effect on strength (SMD (standardized mean difference) 0.17, 95% CI -0.16 to 0.50, I(2) = 0%). There were no significant benefit for upper limb function (SMD 0.11, 95% CI -0.41 to 0.63, I(2) = 0%) and mobility (SMD 0.11, 95% CI -0.21 to 0.43, I(2) = 27%) after PRT compared with controls. CONCLUSIONS There was no evidence reported that PRT is unsafe in people within the first 3 months after stroke, although there was a lack of reporting about adverse events. The lack of demonstration of effect in improving muscle strength and activity suggests there is insufficient evidence to recommend the prescription of PRT for people within the first 3 months after stroke.


Significance of Tsukushi in lung cancer.
Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan (SLRP) family, plays multifunctional roles by interacting with signaling molecules during development. However, the role of TSK in cancer remains unknown. The aim of the present study was to investigate the biological significance of TSK in lung cancer. Immunohistochemistry of lung cancer tissues and reverse transcription polymerase chain reaction (PCR) of lung cancer cell lines were carried out to detect TSK. Then, RNA sequence analysis, Gene Ontology analysis, quantitative real-time PCR, western blotting, cell counting assay, invasion assays, and xenograft studies were done in a human lung adenocarcinoma cell line, H1975 with modification of TSK expression levels, in order to investigate its biological roles, in particular epithelial-mesenchymal transition (EMT) and proliferation. TSK was found to be highly expressed in lung cancer tissues and cell lines. Modification of TSK expression levels in H1975 resulted in changes in molecules related to EMT, including cadherin-1, snail family transcriptional repressor 1, snail family transcriptional repressor 2, and vimentin. The results of cell counting and xenograft assays showed that TSK promotes cell proliferation. In lung cancer cells, TSK is expressed more highly than the other SLRPs family members, and regulates the EMT and proliferation. Thus, TSK may be a key coordinator of multiple pathways and an important structural element in the lung cancer microenvironment.


Impact of the peginterferon-α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV-co-infected patients with the unfavourable non-CC IL28B genotypes.
Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.


Process evaluation of a web-based stress management program to promote psychological well-being in a sample of white-collar workers in Japan.
The purpose of this study was to conduct process evaluation of a web-based stress management program, which was designed to improve psychological well-being as a positive psychological function of humans. A total of 168 employees participated in the intervention. The pre-test was conducted at the time of registration and the post-test upon the completion of the program. Participants are requested to evaluate program sessions by answering four questions (informative, enjoyment, intention to act, self-efficacy belief). Participant evaluations of the sessions were also used as the mediating variable that influences program outcomes. For analysis, we built a model based on the program impact theory and conducted path analysis. Result revealed the majority of participants evaluated the program affirmatively in all sessions and the participant evaluations about the sessions directly predicted changes in psychological well-being (beta=0.29, p<0.01), and changes in the psychological well-being predicted changes in the scores of CES-D (Center for Epidemiologic Studies Depression Rating Scale), which represent the level of depression (beta=0.50, p<0.001). In conclusion, the program can be effective if the participants feel enjoyment, and increase their intention and self-efficacy belief to cope with stress.


[Reflections on and contributions to the Ministry of Health's Integrated Plan on Health Surveillance Actions for People Exposed to Pesticides].
This paper highlights the issue of human and environmental contamination caused by abusive and undue use of pesticides and of its consequences for human health and the environment. It seeks to present reflections on and contributions to the Ministry of Health's Integrated Plan on Health Surveillance Actions for People Exposed to Pesticides arising from the Federal District Assessment and Control Project for Human and Environmental Exposure. The methodology used in this study consisted of reading and analysis of reports from the aforementioned projects, as well as participating in preliminary meetings for drafting the General Coordination Plan for Environmental Health Surveillance and the workshop entitled "The integration of Occupational Health Surveillance and Sanitary Vigilance: the information issue." This was coordinated by the Occupational Health Working Group of the Brazilian Public Health Association and in meetings and workshops of the Federal District Project. The outcome of the discussions suggests that the investigation strategy used is a positive contribution and that the Federal District Project may serve as a pilot project for the Ministry of Health's Integrated Plan.


Comparison of bicycle and treadmill radionuclide angiocardiography.
The purpose of this study was to test motion-correction algorithms for initial-transit radionuclide angiocardiograms acquired at rest and during bicycle and treadmill exercise. Treadmill data was spatially reoriented by computer software designed to eliminate motion of a 125I point source simultaneously recorded at a lower energy window. A second algorithm based on left ventricular centroid counts further corrected for motion on all studies. Exercise left ventricular ejection fraction was higher on the treadmill (0.68 +/- 0.07) compared to the bicycle (0.64 +/- 0.08) (p less than 0.0001, r = 0.88). Treadmill exercise also resulted in larger end-diastolic volumes (180 +/- 30 versus 157 +/- 36, p less than 0.0001), stroke volumes (124 +/- 28 versus 101 +/- 29, p less than 0.0001) and cardiac outputs (19.9 +/- 4.6 versus 15.9 +/- 5.0, p less than 0.0001). Similar variances for these hemodynamic measurements suggest that the mean differences observed were physiologic and that error from body motion was effectively corrected by this approach. We conclude that the measurement of left ventricular function during treadmill exercise, when combined with these techniques for correcting motion, is a reasonable alternative to conventional bicycle exercise.


Cellular interactions in the generation of cytolytic T lymphocyte responses: role of Ia-positive splenic adherent cells in presentation in H-2 antigen.
Splenic adherent cells are required for generation of both primary and, at limiting antigen dose, secondary allogeneic responses of cytolytic T lymphocytes to intact stimulator cells. Secondary responses to purified allogeneic plasma membranes or purified H-2Kk antigens in liposomes are also dependent upon splenic adherent cells. Generation of these responses requires the presence of an Ia-positive. Thy 1,2-negative, radiation-resistant cell in the splenic adherent cell population that is adherent to glass, plastic, and nylon wool. Stimulation of cytolytic T lymphocyte precursors with purified H-2Kk alloantigen bound to Ia+ splenic adherent cells is 10-20 times more efficient than stimulation with antigen added directly to culture. Furthermore, a marked decrease in the response of cytolytic T lymphocytes to liposomes was observed when antiserum against Iad specific for the Ia of the responder cells was added to culture. These results demonstrate that, for purified proteins of the major histocompatibility complex, antigen presentation by Ia+ splenic adherent cells plays a role in the generation of a cytolytic T lymphocyte response.


[Membrane reception of thyroid hormones].
Comparative and competitive analyses of thyroxine (T4) and triiodothyronine (T3) binding to highly purified rat liver, brain and lung cell plasma membranes were carried out. The dependence of hormone binding on the time, temperature and concentration was studied. The effects of trypsin and partial delipidation on the binding parameters of thyroid hormones were investigated. Two thyroid hormone-binding sites were detected in cell plasma membranes of all tissues under study. The maximal binding of T4 to rat liver membranes and the maximal binding of T3 to rat brain membranes was observed in all experiments, the affinity for T3 being higher than that for T4. An important role of both protein and lipid components of plasma membranes in the membrane reception of thyroid hormones is proposed.


Applying Lessons From Rheumatology to Better Understand Long COVID.
Long COVID can sometimes be attributed to organ damage and well-characterized pathophysiology, but more often there is no evidence of organ damage or abnormal biomarkers. This is most evident in patients with mild to moderate initial SARS-CoV-2 infection who were not hospitalized. Their persistent symptoms are strikingly similar to those of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome, including fatigue, post-exertional malaise, myalgias/arthralgias, and sleep and cognitive disturbances in 50% to 100% of cases. Analogous pathophysiologic pathways in fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID include host-microbial interactions in the absence of direct tissue invasion and absence of systemic autoimmunity, with evidence for immune dysregulation as well as autonomic, peripheral, and central nervous system dysfunction. Current treatment of long COVID has been based on multidisciplinary management recommended for FM and ME/CFS and has been formalized and made widely available by funding for nationwide long COVID clinics. Long COVID and its treatment should be distinguished by the presence or absence of organ damage. The acknowledged role of patient engagement in research and open dialogue regarding work and disability noted in long COVID may have meaningful impact on patients with FM and ME/CFS. Hopefully, advances in basic long COVID research will aid in understanding FM and ME/CFS, and rheumatologists should thus be involved in such research and patient care.


Clinical aspects of basic calcium phosphate crystal deposition.
Our present understanding of the mechanisms of pathologic calcification is quite limited. Therefore, no reliable method exists to prevent calcium crystal deposition. Low doses of warfarin have been employed in some cases of soft tissue calcification because it depresses the synthesis of the vitamin K-dependent GLA protein (gamma carboxyglutamic acid), which has been implicated in the process of calcification. Reports of success must be tempered by the lack of a controlled study. Probenecid has also been utilized in the treatment of calcinosis.


Probing the determinants of protein stability: comparison of class A beta-lactamases.
Five class A beta-lactamases produced by various mesophilic bacterial species have been compared. Although closely related in primary and overall structures, these enzymes exhibit very different stabilities. In order to investigate the factors responsible for these differences, several features deduced from the amino acid composition and three-dimensional structures were studied for the five proteins. This analysis revealed that higher stability appeared to correlate with increased numbers of intramolecular hydrogen bonds and of salt bridges. By contrast, the global hydrophobicity of the protein seemed to play a relatively minor role. A strongly unfavourable balance between charged residues and the presence of a cis-peptide bond preceding a non-proline residue might also contribute to the particularly low stability of two of the enzymes.


Reviewing lessons learnt of SARS in Singapore during planning for influenza pandemic.
There were many lessons learnt in Singapore's fight against SARS, and they have proven to be all the more important in our preparations for an influenza pandemic. The following lessons are discussed in this paper including: the widespread ramifications among the various sectors in Singapore (individuals, organizations, community and economy), the first principles of outbreak response, need for enhanced infectious disease control measures, high demands on the healthcare system, the role of management policies implementation and dissemination, multidisciplinary involvement, importance of communication, and business continuity planning.


Isolation of the Buchnera aphidicola flagellum basal body complexes from the Buchnera membrane.
Buchnera aphidicola is an intracellular bacterial symbiont of aphids and maintains a small genome of only 600 kbps. Buchnera is thought to maintain only genes relevant to the symbiosis with its aphid host. Curiously, the Buchnera genome contains gene clusters coding for flagellum basal body structural proteins and for flagellum type III export machinery. These structures have been shown to be highly expressed and present in large numbers on Buchnera cells. No recognizable pathogenicity factors or secreted proteins have been identified in the Buchnera genome, and the relevance of this protein complex to the symbiosis is unknown. Here, we show isolation of Buchnera flagellum basal body proteins from the cellular membrane of Buchnera, confirming the enrichment of flagellum basal body proteins relative to other proteins in the Buchnera proteome. This will facilitate studies of the structure and function of the Buchnera flagellum structure, and its role in this model symbiosis.


Cytokines promote glomerular mesangial cell survival in vitro by stimulus-dependent inhibition of apoptosis.
Resolution of glomerular inflammation requires the removal of proliferating resident glomerular mesangial cells, but excessive loss of glomerular cells is a feature of postinflammatory scarring. Because apoptosis regulates mesangial cell number in glomerular inflammation, we have studied the exogenous control of apoptosis triggered in cultured mesangial cells by stimuli likely to be important in vivo. Apoptosis could be induced by serum deprivation to model decreased availability of survival factors, by etoposide as an example of DNA-damaging agents, by ligation of mesangial cell Fas, and by protein synthesis inhibition by cycloheximide. Insulin-like growth factor I (IGF-I), IGF-II, and basic fibroblast growth factor were each able to suppress apoptosis induced by serum deprivation, whereas TGF-beta 1, epidermal growth factor, and platelet-derived growth factor had no effect. IGF-I and IGF-II (but not basic fibroblast growth factor) were also able to protect cells from apoptosis induced by etoposide or cycloheximide. However, Fas-mediated apoptosis was resistant to suppression by all three cytokines. None of the cytokines tested caused a change in the levels of expression of Bcl-2, Bax, Bcl-x, or Bak proteins. The survival-promoting properties of serum-free medium conditioned by mesangial cells was abrogated by neutralizing IGF-I Ab. These experiments are the first to define cytokines that inhibit apoptosis and thereby promote survival of mesangial cells, and the data indicate a paracrine survival signaling role for IGF-I. Finally, the data show that Fas ligation can override cytokine survival signaling, emphasizing a candidate role for this molecule in the undesirable apoptotic loss of mesangial cells during the progression of glomerular scarring.


A Land Plant-Specific Transcription Factor Directly Enhances Transcription of a Pathogenic Noncoding RNA Template by DNA-Dependent RNA Polymerase II.
Some DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato (Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP PSTVd replication in the nucleoplasm generates (-)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (-)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA-9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.


Diagnosis and evaluation of mitral valve disease using transseptal Doppler ultrasound catheterization.
In 33 patients with confirmed mitral valve disease, the mitral valve flow velocity traces were recorded by means of a directional Doppler ultrasonic velocimeter using the transseptal route, and correlated with the clinical and haemodynamic data. In all cases, characteristic anomalies of the mitral flow velocity patterns were noted and could be related to the type of lesion, stenosis, regurgitation, or a combination of these. Furthermore, specific patterns of the flow velocity traces were shown to correlate satisfactorily with the degree of severity of the disease. The authors propose a pathophysiological interpretation of the anomalies of the velocity patterns, based on turbulence for stenosis and backward flow wave for regurgitation. They conclude that the transseptal directional Doppler catheterization provides a new reliable method for establishing the diagnosis and grading the severity of mitral valve disease using pattern recognition, and, moreover, offers a new approach to the understanding of mitral haemodynamic disturbances on a beat-to-beat basis.


Fate of effluent organic matter (EfOM) and natural organic matter (NOM) through riverbank filtration.
Understanding the fate of effluent organic matter (EfOM) and natural organic matter (NOM) through riverbank filtration is essential to assess the impact of wastewater effluent on the post treatment requirements of riverbank filtrates. Furthermore, their fate during drinking water treatment can significantly determine the process design. The objective of this study was to characterise bulk organic matter which consists of EfOM and NOM during riverbank filtration using a suite of innovative analytical tools. Wastewater effluent-derived surface water and surface water were used as source waters in experiments with soil columns. Results showed the preferential removal of non-humic substances (i.e. biopolymers) from wastewater effluent-derived surface water. The bulk organic matter characteristics of wastewater effluent-derived surface water and surface water were similar after 5 m soil passage in laboratory column experiment. Humic-like organic matter in surface water and wastewater effluent-derived surface water persisted through the soil passage. More than 50% of total dissolved organic carbon (DOC) removal with significant reduction of dissolved oxygen (DO) was observed in the top 50 cm of the soil columns for both surface water and wastewater effluent-derived surface water. This was due to biodegradation by soil biomass which was determined by adenosine triphosphate (ATP) concentrations and heterotrophic plate counts. High concentrations of ATP in the first few centimeters of infiltration surface reflect the highest microbial activity which correlates with the extent of DOC reduction. Good correlation of DOC removal with DO and biomass development was observed in the soil columns.


Mesenchymal Stem Cells and Nano-Bioceramics for Bone Regeneration.
Orthopedic disorders and trauma usually result in bone loss. Bone grafts are widely used to replace this tissue. Bone grafts excluding autografts unfortunately have disadvantages like evoking immune response, contamination and rejection. Autografts are of limited sources and optimum biomaterials that can replace bone have been searched for several decades. Bioceramics, which have the similar inorganic structure of natural bone, are widely used to regenerate bone or coat metallic implants. As people continuously look for a higher life quality, there are developments in technology almost everyday to meet their expectations. Nanotechnology is one of such technologies and it attracts everyone's attention in biomaterial science. Nano scale biomaterials have many advantages like larger surface area and higher biocompatibility and these properties make them more preferable than micro scale. Also, stem cells are used for bone regeneration besides nano-bioceramics due to their differentiation characteristics. This review covers current research on nano-bioceramics and mesenchymal stem cells and their role in bone regeneration.


Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation.
Cardiac amyloidosis is common in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI). We hypothesized that patients with dual aortic stenosis and cardiac amyloid pathology (AS-amyloid) would have different baseline characteristics, periprocedural and mortality outcomes. Patients aged ≥75 with severe AS referred for TAVI at two sites underwent blinded bone scintigraphy prior to intervention (Perugini Grade 0 negative, 1-3 increasingly positive). Baseline assessment included echocardiography, electrocardiogram (ECG), blood tests, 6-min walk test, and health questionnaire, with periprocedural complications and mortality follow-up. Two hundred patients were recruited (aged 85 ± 5 years, 50% male). AS-amyloid was found in 26 (13%): 8 Grade 1, 18 Grade 2. AS-amyloid patients were older (88 ± 5 vs. 85 ± 5 years, P = 0.001), with reduced quality of life (EQ-5D-5L 50 vs. 65, P = 0.04). Left ventricular wall thickness was higher (14 mm vs. 13 mm, P = 0.02), ECG voltages lower (Sokolow-Lyon 1.9 ± 0.7 vs. 2.5 ± 0.9 mV, P = 0.03) with lower voltage/mass ratio (0.017 vs. 0.025 mV/g/m2, P = 0.03). High-sensitivity troponin T and N-terminal pro-brain natriuretic peptide were higher (41 vs. 21 ng/L, P < 0.001; 3702 vs. 1254 ng/L, P = 0.001). Gender, comorbidities, 6-min walk distance, AS severity, prevalence of disproportionate hypertrophy, and post-TAVI complication rates (38% vs. 35%, P = 0.82) were the same. At a median follow-up of 19 (10-27) months, there was no mortality difference (P = 0.71). Transcatheter aortic valve implantation significantly improved outcome in the overall population (P < 0.001) and in those with AS-amyloid (P = 0.03). AS-amyloid is common and differs from lone AS. Transcatheter aortic valve implantation significantly improved outcome in AS-amyloid, while periprocedural complications and mortality were similar to lone AS, suggesting that TAVI should not be denied to patients with AS-amyloid.


Annexin A3 Regulates Early Blood Vessel Formation.
Annexins are a large family of calcium binding proteins that associate with cell membrane phospholipids and are involved in various cellular processes including endocytosis, exocytosis and membrane-cytoskeletal organization. Despite studies on numerous Annexin proteins, the function of Annexin A3 (Anxa3) is largely unknown. Our studies identify Anxa3 as a unique marker of the endothelial and myeloid cell lineages of Xenopus laevis during development. Anxa3 transcripts are also detected in endothelial cells (ECs) of zebrafish and mouse embryos, suggesting an important evolutionary function during formation of blood vessels. Indeed, Anxa3 loss-of-function experiments in frog embryos reveal its critical role during the morphogenesis of early blood vessels, as angioblasts in MO injected embryos fail to form vascular cords. Furthermore, in vitro experiments in mammalian cells identify a role for Anxa3 in EC migration. Our results are the first to reveal an in vivo function for Anxa3 during vascular development and represent a previously unexplored aspect of annexin biology.


New roles of the multidimensional adipokine: chemerin.
The discovery of several adipokines with diverse activities and their involvement in regulation of various pathophysiological functions of human body has challenged the researchers. In the family of adipokine, chemerin is a novel and unique addition. Ever since the first report on chemerin as a chemo-attractant protein, there are numerous studies showing a multitasking capacity of chemerin in the maintenance of homeostasis, for the activation of natural killer cells, macrophages and dendritic cells in both innate and adaptive immunity. Its diversity ranges from generalized inflammatory cascades to being explicitly involved in the manifestation of arthritis, psoriasis and peritonitis. Its association with certain cancerous tissue may render it as a potential tumor marker. In present review, we aim to consolidate recent data of investigations on chemerin in context to functional characteristics with a special reference to its role as a metabolic signal in inflammation and non-metabolic syndromes.


Gender differences in the dual-task effects on autobiographical memory retrieval during social problem solving.
A dual-task paradigm was used to explore the effects of cognitive load on social problem solving and autobiographical memory retrieval. The role that gender may play in mediating the relationship was also examined. Participants performed a secondary task concurrently with two primary tasks: (a) a cueing task, and (b) the Means-End Problem-Solving (MEPS) Task, during which they were required to attend to the memories retrieved during solution generation. Two dual-task conditions were employed in order that two levels of secondary task difficulty could be explored. Level of difficulty proved to be an important factor in the effects of resource reduction on the two primary tasks. Retrieval during the MEPS was effected by both the easy and difficult secondary task whereas retrieval on the cueing task was affected by the difficult task only. The results also showed that females (in contrast to males) favoured a more detailed SPS style using a specific memory database. Consequently, under central executive pressure, females' performance was significantly affected while males' performance remained largely unchanged.


[Changes of platelet endothelial cell adhesion molecule-1, tissue type plasminogen activator and plasminogen activator inhibitor-1 expression in the lung tissue of neonatal rats after intraperitoneal injection with lipopolysaccharide].
To further explore the pathogenesis of neonatal acute lung injury and neonatal pulmonary hemorrhage by establishing the animal model of neonatal acute lung injury (ALI) and by investigating the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1), tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in ALI. Totally 88 neonatal rats which were divided into 8 groups randomly including one normal saline control group and 30 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h post injection groups. The changes of lung pathology in newborn rats were observed at different time after LPS was injected intraperitoneally. The changes of PECAM-1 protein, t-PA and PAI-1 mRNA expression were measured by immunohistochemistry and RT-PCR. The expression of PECAM-1 protein and mRNA was decreased and the lowest level was reached at 8 h and 16 h post injection, respectively. The average values were 95.1 +/- 9.76 and 0.861 +/- 0.016, respectively, which were significantly lower than those in the control group (129.5 +/- 6.15, 1.192 +/- 0.035, P < 0.01). The expression of t-PA and PAI-1 mRNA was increased after LPS was injected. The highest level of t-PA mRNA expression was observed at 2 h after injection. The average value was 1.195 +/- 0.036, which was significantly higher than that in the control group (0.781 +/- 0.017, P < 0.01). The highest level of PAI-1 mRNA expression was observed at 2 h, 4 h and 8 h post injection. The average values were 1.178 +/- 0.069, 1.153 +/- 0.036 and 1.176 +/- 0.044, respectively, which was significantly higher than those of the control group (0.681 +/- 0.019, P < 0.01). The expression of PECAM-1 protein and mRNA was decreased after LPS injection, suggesting the disruption of the tissue protective mechanism; the expression of t-PA and PAI-1 mRNA was increased, indicating the presence of a hypercoagulability state. At the same time, the expression of t-PA mRNA was increased which caused the extra-cellular matrix degradation at the early phase after LPS injection. These three phenomena might be the contributory factors to pulmonary hemorrhage.


A wearable solution for accurate step detection based on the direct measurement of the inter-foot distance.
Accurate step detection is crucial for the estimation of gait spatio-temporal parameters. Although several step detection methods based on the use of inertial measurement units (IMUs) have been successfully proposed, they may not perform adequately when the foot is dragged while walking, when walking aids are used, or when walking at low speed. The aim of this study was to test an original step-detection method, the inter-foot distance step counter (IFOD), based on the direct measurement of the distance between feet. Gait data were recorded using a wearable prototype system (SWING2DS), which integrates an IMU and two time-of-flight distance sensors (DSs). The system was attached to the medial side of the right foot with one DS positioned close to the forefoot (FOREDS) and the other close to the rearfoot (REARDS). Sixteen healthy adults were asked to walk over ground for two minutes along a loop, including both rectilinear and curvilinear portions, during two experimental sessions. The accuracy of the IFOD step counter was assessed using a stereo-photogrammetric system as gold standard. The best performance was obtained for REARDS with an accuracy higher than 99.8% for the instrumented foot step and 88.8% for the non-instrumented foot step during both rectilinear and curvilinear walks. Key features of the IFOD step counter are that it is possible to detect both right and left steps by instrumenting one foot only and that it does not rely on foot impact dynamics. The IFOD step counter can be combined with existing IMU-based methods for increasing step-detection accuracy.


Combined Total Talus Replacement and Total Ankle Arthroplasty.
Avascular necrosis (AVN) of the talus remains a clinical challenge with suboptimal outcomes after treatment. In cases of extensive disease, the insufficient blood supply leads to a high rate of complications including non-union after surgical treatment. This, in conjunction with the development of premature adjacent arthritis represents a challenge for the treating surgeon. Nowadays, total ankle arthroplasty is a reasonable option for the treatment of end-stage ankle arthritis with improved short- and long-term outcomes. We present a technique for patients with end-stage ankle arthritis associated to extensive talar osteonecrosis, and patients with prior total ankle replacement and talar component collapse due to AVN. This technique provides a more anatomic treatment for patients with severely deficient bone stock due to talar necrosis with ankle arthritis or failed ankle replacement. Nonetheless, evaluation of the outcomes at long-term is needed. (Journal of Surgical Orthopaedic Advances 29(4):244-248, 2020).


Consequences of elevated temperatures on legume biomass and nitrogen cycling in a field warming and biodiversity experiment in a North American prairie.
Increases in global temperature are likely to have effects on the nitrogen cycle, including those mediated through effects on legumes, which have a role in the N cycle by fixing N2. These effects may alter plant functioning and community structure, especially in N-limited ecosystems. We manipulated temperature and plant diversity in the field to investigate the effects of elevated temperature on aboveground biomass, shoot N concentration ([N]), and reliance on N2 fixation of four prairie legumes (Amorpha canescens Pursh., Dalea purpurea Vent., Lespedeza capitata Michx. and Lupinus perennis L.) planted in plots of varying species numbers. We monitored the effect of warming on soil microclimate and net N mineralisation rates, as these variables may mediate the effect of warming on legumes. Warming decreased soil moisture and increased soil temperature, but had no effect on net N mineralisation. Warming increased the aboveground biomass of D. purpurea and L. perennis, but decreased shoot [N] for all species in one year. Though the data were not optimal for quantifying N2 fixation using stable isotopes, they suggest that warming did not affect the reliance on N2 fixation. Species diversity did not have strong effects on the response to warming. These results suggest that legume-mediated effects of temperature on N cycling will arise from changes in biomass and tissue chemistry, not N2 fixation. We observed strong interannual variation between a wet and dry year for N mineralisation, shoot [N] and reliance on N2 fixation, suggesting that these may be more responsive to precipitation changes than elevated temperature.


Old age and the demographic transition.
Summary This paper examines the impact of the demographic transition upon the potential supply of, and demand for, family support for the aged in Australia. Using census and survey information on population cohorts entering old age, comparisons are drawn concerning their surviving issue, household composition and family membership. Long-term changes in fertility are shown to have had only a small impact upon the supply of potential carers among relatives and, although the demographic transition has led to a more universal inclusion of old people in family networks, there have not been major changes through time in the proportions living in extended family households. Short-term changes, however, such as low fertility during the 1930s, have caused disordered cohort flow, with the result that current generations of the elderly are members of deprived cohorts in terms of their access to family support.


Production of seafood flavor from red hake (Urophycis chuss) by enzymatic hydrolysis.
Protein hydrolysates were prepared as a natural flavor stock from the red hake (Urophycis chuss) headed-gutted (H&G) mince and frame mince using commercial enzymes, Flavourzyme and Savorase, at the natural pH of fish (6.8) and the water/fish ratio of 2:5. The addition of 1.5% NaCl and 0.4% STPP improved the flavor quality of the hydrolysate by masking bitterness and off-flavor. A 6 h hydrolysis of H&G mince with Flavourzyme yielded a hydrolysate of the highest acceptability. Hydrolysis increased the concentration of most free amino acids except Arg and His. Leu, Lys, and Arg were predominant free amino acids in the hydrolysates, whereas Leu and Arg were major ones in the cooking juice. The concentration of Glu responsible for umami taste was increased by 6-9 times upon hydrolysis. Hydrolysates contained higher percentages of free amino acids giving both umami and sweet tastes than did cooking juice.


Muscle tension and its relation to symptoms in the premenstruum.
Muscle tension as a function of sympathetic arousal may play a causal or contributory role in symptomatology in the premenstruum. The purpose of this study was to determine whether women exhibit an increase in muscle tension in the premenstrual phase over that in the follicular phase of the menstrual cycle, and whether the incidence and severity of premenstrual symptoms were associated with premenstrual muscle tension. A sample of 22 women with variable levels of predicted premenstrual symptomatology was chosen. A report of symptoms was obtained in the premenstrual and follicular phases of the menstrual cycle. Frontalis and trapezius muscle tension levels also were obtained during these cycle phases, during relaxation, and during focus on an emotional image. A difference was found in the subjects' premenstrual and follicular phase frontalis electromyogram (EMG) levels both in the initial relaxation period and while focusing on an emotional image. A significant positive correlation was found between the premenstrual physiologic symptoms women predicted they would have and the premenstrual frontalis EMG levels measured during relaxation. The results suggest that training in muscle tension reduction may benefit premenstrual symptoms.


Metastatic insulinoma with long survival and glucagonoma syndrome.
In 1966, during cholecystectomy for cholecystolithiasis, a 56-year-old man was found to have islet-cell carcinoma metastatic to the liver; his fasting serum glucose level was normal. In 1971, he developed peptic ulcer disease and symptoms of fasting hypoglycemia; inappropriate secretion of insulin was shown. His primary pancreatic tumor was removed in 1973. During the next 9 years, his liver metastases continued to grow and his fasting serum glucose level was maintained at 35 to 116 mg/dL with diazoxide and hydrochlorothiazide therapy. In 1982, he developed clinical evidence of the glucagonoma syndrome, with glucagon levels between 4000 and 11 000 pg/mL. Since then, his fasting serum glucose level has been maintained at 58 to 119 mg/dL without medication. This patient has survived 17 years with a malignant insulinoma and without islet-cell chemotherapy. His course shows that malignant insulinomas may secrete other peptide hormones that can induce various clinical syndromes.


Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients.
How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels. Influenza disease correlates with increases in IL-6/IL-8/MIP-1α/β cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells correlates with peak antibody-secreting cells and influenza heamaglutinin-specific memory B-cell numbers, which phenotypically differs from vaccination-induced B-cell responses. Numbers of influenza-specific CD8+ or CD4+ T cells increase early in disease and retain an activated phenotype during patient recovery. We report the characterisation of immune cellular networks underlying recovery from influenza infection which are highly relevant to other infectious diseases.


Acute enhancement of Romanian deadlift performance after consumption of caffeinated chewing gum.
This study investigates the effect of the consumption of caffeinated chewing gum on the performance of Romanian deadlift on the flywheel training device. A total of 19 participants completed a randomized, cross-over, single-blind experiment with food-grade caffeinated chewing gum trial (CAF) or placebo trail (PL). Gum were chewed for 10 min and rest for 15 min prior to the Romanian deadlift test using the inertial resistance training machine. 5 sets of 6 Romanian deadlifts were performed, with a 3-min rest between sets, followed by a 7-day washout period before the next set of trials. The average power, average force, total peak power, peak concentric power, peak eccentric power, heart rate, and rating of perceived exertion (RPE) for each trials were analyzed using paired-T test. Compared to placebo, caffeinated chewing gum trial enhanced peak concentric power (P = 0.016, Cohen's d = 0.44), peak eccentric power (P = 0.005, Cohen's d = 0.55), average power (P = 0.013, Cohen's d = 0.43), and total work (P = 0.026, Cohen's d = 0.28). However, in average force (P = 0.063, Cohen's d = 0.50), RPE (P = 0.266), and heart rate (P = 0.143), were no significant differences between trials. Caffeinated chewing gum with a dose of caffeine of 200 mg for 10 min may acutely enhance Romanian deadlift performance on the flywheel machine.


Oral progesterone treatment in chronic obstructive lung disease: failure of voluntary hyperventilation to predict response.
Previous studies have shown that some patients with chronic obstructive lung disease and hypercapnia will respond to medroxyprogesterone with improvement in arterial blood gases. The exact mechanism of this effect is unclear but it is presumed to be a result of ventilatory stimulation. To determine whether the ability to correct arterial blood gas abnormalities by voluntary hyperventilation would predict a subsequent favourable response to progesterone, we studied 11 subjects with chronic obstructive lung disease and chronic hypercapnia. Five subjects had chronic obstructive lung disease of moderate severity with mean (SE) FEV1 1.8 (0.34) 1 maximum voluntary ventilation (MVV) 40.4 (7.16) 1/min-1, arterial oxygen tension (Pao2) 53.8 (2.40 mm Hg, and arterial carbon dioxide tension Paco2) 49.6 (3.91) mm Hg, and were able to normalise their blood gas tensions during voluntary hyperventilation (Pao2 85.4 (8.01) mm Hg; Paco2 32.8 (3.43) mm Hg). Six subjects had severe chronic obstructive lung disease with FEV1 0.77 (0.12) 1, MVV 19 (3.09) 1/min-1, Pao2 60.0 (2.89) mm Hg and Paco2 50.5 (1.38) mm Hg, and they could not significantly alter their blood gases with voluntary hyperventilation (Pao2 62.5 (3.19) mm Hg, Paco2 49.7 (1.84) mm Hg). The groups were similar in age, height, weight, and resting Pao2 and Paco2. Each subject received one month of oral placebo and one month of medroxyprogesterone acetate (Provera). 20 mg orally thrice daily, given in a randomised, double blind fashion. The groups responded similarly with a significantly higher Pao2 and lower Paco2 while having medroxyprogesterone acetate than while having placebo. Two patients with polycythaemia showed a reduction in haemoglobin concentration while taking progesterone. It is concluded that the response to medroxyprogesterone is not predictable from spirometric or blood gas changes after voluntary hyperventilation.


Risk of Fracture in Women with Sarcopenia, Low Bone Mass, or Both.
To determine whether women with sarcopenia and low bone mineral density (BMD) are at greater risk of clinical fractures than those with sarcopenia or low BMD alone. Women's Health Initiative (WHI) Observational and Clinical trials. Three U.S. clinical centers (Pittsburgh, PA; Birmingham, AL; Phoenix/Tucson, AZ). Women (mean age 63.3 ± 0.07) with BMD measurements (N = 10,937). Sarcopenia was defined as appendicular lean mass values corrected for height and fat mass. Low BMD was defined as a femoral neck T-score less than -1.0 based on the Third National Health and Nutrition Examination Survey reference database for white women. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We followed women for incident fractures over a median of 15.9 years. Participants were classified into mutually exclusive groups based on BMD and sarcopenia status: normal BMD and no sarcopenia (n = 3,857, 35%), sarcopenia alone (n = 774, 7%), low BMD alone (n = 4,907, 45%), and low BMD and sarcopenia (n = 1,399, 13%). Women with low BMD, with (HR = 1.72, 95% CI = 1.44-2.06) or without sarcopenia (HR = 1.58, 95% CI = 1.37-1.83), had greater risk of fracture than women with normal BMD; the difference remained statistically significant after adjustment for important covariates. Women with low BMD, with (HR = 2.78, 95% CI = 1.78-4.30 and without (HR = 2.42, 95% CI = 1.63-3.59) sarcopenia had higher risk of hip fractures. Women with sarcopenia alone had similar HRs to women with normal BMD. Compared to women with normal BMD.


Surface functionalization of thin-film composite membranes with copper nanoparticles for antimicrobial surface properties.
Biofouling is a major operational challenge in reverse osmosis (RO) desalination, motivating a search for improved biofouling control strategies. Copper, long known for its antibacterial activity and relatively low cost, is an attractive potential biocidal agent. In this paper, we present a method for loading copper nanoparticles (Cu-NPs) on the surface of a thin-film composite (TFC) polyamide RO membrane. Cu-NPs were synthesized using polyethyleneimine (PEI) as a capping agent, resulting in particles with an average radius of 34 nm and a copper content between 39 and 49 wt.%. The positive charge of the Cu-NPs imparted by the PEI allowed a simple electrostatic functionalization of the negatively charged RO membrane. We confirmed functionalization and irreversible binding of the Cu-NPs to the membrane surface with SEM and XPS after exposing the membrane to bath sonication. We also demonstrated that Cu-NP functionalization can be repeated after the Cu-NPs dissolve from the membrane surface. The Cu-NP functionalization had minimal impact on the intrinsic membrane transport parameters. Surface hydrophilicity and surface roughness were also maintained, and the membrane surface charge became positive after functionalization. The functionalized membrane exhibited significant antibacterial activity, leading to an 80-95% reduction in the number of attached live bacteria for three different model bacterial strains. Challenges associated with this functionalization method and its implementation in RO desalination are discussed.


Reflecting peer-support groups in the prevention of stress and burnout: randomized controlled trial.
This paper is a report of a study to test the effect of participating in a reflecting peer-support group on self-reported health, burnout and on perceived changes in work conditions. Stress-related conditions are one of the most common causes for long-term sick-leave. There is limited evidence for the effectiveness of person-directed interventions aimed at reducing stress levels in healthcare workers. Prior research in the relationship between support and burnout show somewhat inconsistent results. A randomized controlled trial with peer-support groups as the intervention was conducted with 660 healthcare workers scoring above the 75th percentile on the exhaustion dimension of the Oldenburg Burnout Inventory. One hundred and fifty-one (22.9%) agreed to participate. The intervention started in 2002 with 51 participants (96.1% were women), 80 of whom constituted the control group. Potential differences in outcome measures 12 months after the intervention were compared using ancova, and data collected was completed in 2004. Qualitative content analyses were used to analyse reported experiences from group participation. Statistically significant intervention effects were found for general health, perceived quantitative demands at work, participation and development opportunities at work and in support at work. Seven categories of experiences from participating were identified: talking to others in a similar situation, knowledge, sense of belonging, self-confidence, structure, relief of symptoms and behavioural change. Peer-support groups using a problem-based method could be a useful and comparatively inexpensive tool in alleviating work-related stress and burnout.


Occurrence of Chronic Stage Chikungunya in the General Population of Martinique during the First 2014 Epidemic: A Prospective Epidemiological Study.
Chronic stage chikungunya (CHIK), defined by persisting symptoms more than 3 months after initial diagnosis of acute infection, is frequent. However, its burden and impact have rarely been described prospectively in a general population during an ongoing epidemic in the Caribbean. From January 2014 to January 2015, a severe CHIK outbreak occurred in Martinique. Our objective was to describe epidemiological characteristics and outcomes of chronic stage CHIK in its local population. Participants, clinically diagnosed with probable CHIK infection, were included prospectively by general practitioners during the epidemic's peak from April to October 2014. All identified cases benefited from a follow-up phone call 3 months or more after initial diagnosis during which they were interrogated about persisting clinical signs, past and ongoing treatment, and quality of life. Five hundred and nine subjects participated in the study. Mean age at initial diagnosis was 43.2 ± 23.6 years with a female-male ratio of 1.98. Two hundred participants (39.3%) had probable chronic stage CHIK: 98.5% still experienced pain at least 3 months after acute infection, with 84.3% of reported joint pains; 21.2% were woken up by the pain; 47.2% felt depressed/anxious; and 31.3% experienced memory/concentration disorders. Resumption of daily activity and work was complicated for 55.8% and 36.2% of cases. Persistent impact on morbidity, health outcomes, psychological, and economic aspects further underline the crucial role of community-based medicine and the necessity of an evidence-based multidisciplinary approach toward chronic stage CHIK identification, management, and follow-up in this particular world region.


Comparison of laparoscopy and laparotomy in the surgical management of early-stage ovarian cancer.
The aim of this study is to investigate the safety and efficacy of laparoscopy in the treatment of early-stage ovarian cancer (EOC). We retrospectively analyzed the clinical data of patients who underwent laparoscopy (35 patients) or laparotomy (40 patients) for the comprehensive surgical staging of EOC in Zhujiang Hospital during the period of 2002 to 2010 and compared the 2 surgical approaches in operative time, intraoperative blood loss, number of dissected lymph nodes, tumor rupture rate, length of hospital stay, time of gastrointestinal function recovery, wound healing condition, complication rate, upstaging rate, rate of postoperative chemotherapy, and postoperative follow-up condition. The laparoscopy group had significantly shorter hospital stay and time of first postoperative flatus and had significantly lower rate of poor wound healing than the laparotomy group. The 2 groups did not show significant differences in operative time, intraoperative blood loss, number of dissected lymph nodes, tumor rupture rate, complication rate, upstaging rate, and rate of postoperative chemotherapy. Laparoscopy is safe and effective for the comprehensive surgical staging of EOC and has the advantages of shorter hospital stay, faster recovery of gastrointestinal function, and good wound healing.


Sensory and physical determinants of perceived achromatic transparency.
What are the physical and sensory determinants of perceived transparency? To explore this question, we simulated pairs of physically different neutral density filters on a CRT and asked observers to match their perceived transparency. Matching was accomplished by adjusting one of two physically independent filter properties, reflectivity and inner transmittance. Results show that observers can make reliable matches through a linear trade-off of these two properties. In a separate experiment, observers matched the perceived contrast of the overlaid regions. The reflectivity and inner transmittance values for contrast matches are similar to those of perceived transparency matches, suggesting that perceived image contrast is the sensory determinant of perceived transparency. In variegated displays, neither Michelson contrast nor other standard contrast metrics predicts contrast appearance. When perceived transparency is plotted in terms of filter reflectance and filter transmittance, perceived transparency corresponds closely to filter transmittance.


Genetic analysis of spirochete flagellin proteins and their involvement in motility, filament assembly, and flagellar morphology.
The filaments of spirochete periplasmic flagella (PFs) have a unique structure and protein composition. In most spirochetes, the PFs consist of a core of at least three related proteins (FlaB1, FlaB2, and FlaB3) and a sheath of FlaA protein. The functions of these filament proteins remain unknown. In this study, we used a multidisciplinary approach to examine the role of these proteins in determining the composition, shape, and stiffness of the PFs and how these proteins impact motility by using the spirochete Brachyspira (formerly Treponema, Serpulina) hyodysenteriae as a genetic model. A series of double mutants lacking combinations of these PF proteins was constructed and analyzed. The results show the following. First, the diameters of PFs are primarily determined by the sheath protein FlaA, and that FlaA can form a sheath in the absence of an intact PF core. Although the sheath is important to the PF structure and motility, it is not essential. Second, the three core proteins play unequal roles in determining PF structure and swimming speed. The functions of the core proteins FlaB1 and FlaB2 overlap such that either one of these proteins is essential for the spirochete to maintain the intact PF structure and for cell motility. Finally, linear elasticity theory indicates that flagellar stiffness directly affects the spirochete's swimming speed.


Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration.
Spread phospholipid monolayers are particularly useful as model membranes in that changes in surface pressure (Deltapi) can be monitored in response to protein adsorption to the monolayer, thus providing a unique manner of assessing protein-membrane contact. In the present study, spread monolayers below their collapse pressures have been utilized to evaluate Ca2+-specific adsorption of several vitamin K-dependent coagulation proteins to monolayers that contain negatively charged phospholipid. From combined measurements of Deltapi and Gamma (the surface excess protein concentration), values of dGamma/dpi have been evaluated for different proteins with varying lipid composition of the monolayers. Using mixed, liquid-expanded monolayers at equivalent initial surface pressures (pii) and which contain different amounts of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine, the dGamma/dpi of bovine prothrombin was shown to decrease monotonically with increasing protein affinity for the monolayer. For example, KD values of 7, 20, and 60 nM produced dGamma/dpi values of 14, 17, and 21 nmol m-1 mN-1, respectively. However, the trend in dGamma/dpi appears to originate from characteristics of the monolayer and not from those of the protein, since a much different adsorbate (i.e., a positively charged pyrene derivative) exhibited a similar trend in dGamma/dpi with monolayer composition. On the other hand, dGamma/dpi values of bovine prothrombin, human factor IX, human protein S, bovine protein C, and human protein C, determined using liquid-expanded phosphatidylserine monolayers, were essentially equivalent. Therefore, the five vitamin K-dependent proteins that were examined were equivalent in terms of the manner in which the gamma-carboxyglutamic acid (Gla) domain of each protein perturbed the surface pressure. This study shows that Ca2+-specific membrane contact sites in the Gla domain of the five proteins tested are similar despite the naturally occurring differences in the normal Gla domain sequence of these proteins.


Expression and characterization of the chitin-binding domain of chitinase A1 from Bacillus circulans WL-12.
Chitinase A1 from Bacillus circulans WL-12 comprises an N-terminal catalytic domain, two fibronectin type III-like domains, and a C-terminal chitin-binding domain (ChBD). In order to study the biochemical properties and structure of the ChBD, ChBD(ChiA1) was produced in Escherichia coli using a pET expression system and purified by chitin affinity column chromatography. Purified ChBD(ChiA1) specifically bound to various forms of insoluble chitin but not to other polysaccharides, including chitosan, cellulose, and starch. Interaction of soluble chitinous substrates with ChBD(ChiA1) was not detected by means of nuclear magnetic resonance and isothermal titration calorimetry. In addition, the presence of soluble substrates did not interfere with the binding of ChBD(ChiA1) to regenerated chitin. These observations suggest that ChBD(ChiA1) recognizes a structure which is present in insoluble or crystalline chitin but not in chito-oligosaccharides or in soluble derivatives of chitin. ChBD(ChiA1) exhibited binding activity over a wide range of pHs, and the binding activity was enhanced at pHs near its pI and by the presence of NaCl, suggesting that the binding of ChBD(ChiA1) is mediated mainly by hydrophobic interactions. Hydrolysis of beta-chitin microcrystals by intact chitinase A1 and by a deletion derivative lacking the ChBD suggested that the ChBD is not absolutely required for hydrolysis of beta-chitin microcrystals but greatly enhances the efficiency of degradation.


Variable responses to prostaglandin E(2) in human non-pregnant myometrium.
Cumulative concentration-effect curves for prostaglandin E(2), sulprostone and butaprost were constructed in matched strips of human non-pregnant myometrium from 14 different donors. All samples were obtained from the mid-lateral wall of the uterus. Prostaglandin E(2) produced four types of concentration-effect curves: monophasic inhibitory (n = 7), monophasic excitatory (n = 2), biphasic consisting of an excitatory phase followed by an inhibitory phase (n = 4), and biphasic consisting of an inhibitory phase followed by an excitatory phase (n = 1). Sulprostone produced excitation of spontaneous contractile activity in all tissues (mean pEC(50) = 9.1+/-0.2, range 8.1-10.1, n = 14). Butaprost produced relaxation of cloprostenol-stimulated contractile activity in all tissues (mean pEC(50) = 5.7 +/- 0.1, range 5.0-6.9, n = 14). The mean pEC(50) value for sulprostone was significantly higher in tissues where prostaglandin E(2) caused some excitation (pEC(50) = 9.4 +/- 0.2, n = 7) compared to those where prostaglandin E(2) caused only inhibition (pEC(50) = 8.8 +/- 0.2, n = 7). Mean pEC(50) values for butaprost were not significantly different between these groups. These data suggest that (a) variability in EP receptor-mediated responses exists within a single anatomical site; (b) both excitatory and inhibitory EP receptor-mediated pathways are always operative in human non-pregnant myometrium, regardless of the type of tissue response to prostaglandin E(2); and (c) regulation of EP receptor-mediated responses occurs predominantly in the excitatory (EP(3) or EP(1) receptor) pathway rather than the inhibitory (EP(2) receptor) pathway.


JC virusType 2: definition of subtypes based on DNA sequence analysis of ten complete genomes.
Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5.1 kb genome of nine urinary strains of JCV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian JCV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in Japan was also sequenced. Here, we report the analysis of these ten DNA sequences and their deduced protein translations. Two phylogenetically distinct subtypes of Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the coding region sequence. A 215 bp product amplified with primers in the VP1 gene contains enough sequence information to distinguish the major types and subtypes of JCV and is suitable for application in viral epidemiological studies. The investigation of these genomic variations is of special interest because JCV Type 2 strains are found at a significantly higher frequency in brain tissue of patients with PML than would be predicted from their excretion in a control population.


Adolescent Diet Quality, Cardiometabolic Risk, and Adiposity: A Prospective Cohort.
Examine the prospective association among diet with adolescent cardiometabolic risk (CMR) and anthropometrics. Secondary analysis of an observational study of adolescents aged 10-16 years. Twenty-four-hour food recalls were used to calculate Healthy Eating Index-2015 (HEI-2015) scores. Anthropometrics were assessed using magnetic resonance imaging, dual-energy x-ray absorptiometry, and height/weight measurements. CMR included mean arterial pressure, homeostatic model assessment for insulin resistance, high-density lipoprotein cholesterol, and triglycerides. Associations between HEI-2015 score at baseline with follow-up adiposity and CMR were examined using regression models. A total of 192 adolescents were included. Baseline HEI-2015 scores were inversely associated with follow-up total CMR z-score (P = 0.01), homeostatic model assessment for insulin resistance (P < 0.01), waist circumference z-score (P = 0.02), body mass index percentile (P = 0.01), fat mass (P = 0.04), lean mass (P = 0.02), and visceral adipose tissue mass (P = 0.01). Adolescents with lower adherence to dietary guidelines and greater CMR and anthropometry measurements at baseline continued this trajectory across the observation.


Computer-based analyses of the protein constituents of transport systems catalysing export of complex carbohydrates in bacteria.
Bacteria synthesize and secrete an array of complex carbohydrates including exopolysaccharides (EPSs), capsular polysaccharides (CPSs), lipopolysaccharides (LPSs), lipo-oligosaccharides (LOSs) and teichoic acids (TCAs). We have analysed the families of homologous proteins that appear to mediate excretion of complex carbohydrates into or across the bacterial cell envelope. Two principal families of cytoplasmic-membrane transport systems appear to drive polysaccharide export: polysaccharide-specific transport (PST) systems and ATP-binding cassette-2 (ABC-2) systems. We present evidence that the secretion of CPSs and EPSs, but not of LPSs, LOSs or TCAs via a PST or ABC-2 system requires the presence of a cytoplasmic-membrane-periplasmic auxiliary protein (MPA1 or MPA2, respectively) in both Gram-negative and Gram-positive bacteria as well as an outer-membrane auxiliary (OMA) protein in Gram-negative bacteria. While all OMA proteins are included within a single family, MPA1 and MPA2 family proteins are not demonstrably homologous to each other, even though they share common topological features. Moreover, MPA1 family proteins (which function with PST systems), but not MPA2 family proteins (which function with ABC-2 systems), possess cytoplasmic ATP-binding domains that may either exist as separate polypeptide chains (for those from Gram-positive bacteria) or constitute the C-terminal domain of the MPA1 polypeptide chain (for those from Gram-negative bacteria). The sizes, substrate specificities and regions of relative conservation and hydrophobicity are defined allowing functional and structural predictions as well as delineation of family-specific sequence motifs. Each family is characterized phylogenetically.


Therapeutic Potential of Heme Oxygenase-1/carbon Monoxide System Against Ischemia-Reperfusion Injury.
Ischemia-reperfusion (I/R) injury causes the dysfunctions of different major organs, leading to morbidity and mortality on the global scale. Among a battery of therapeutic targets, the heme oxygenase- 1 (HO-1)/carbon monoxide (CO) system has been evaluated for the development of new therapies against I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three biologically active end products, namely biliverdin/bilirubin, CO and ferrous ion. Interestingly, CO is one of a few bioactive gaseous molecules with the capability of regulating inflammation, cell survival and growth. In fact, several CO-releasing compounds have been developed for directly reprogramming the intracellular apoptotic, inflammatory and proliferative signaling networks. In parallel, chemical and genetic approaches have also been evaluated for up-regulating HO-1 expression as an endogenous mechanism to ameliorate I/R injury and heal wounds. In this review, we discussed the recent studies on the therapeutic potential of HO-1/CO system in the treatment of I/R injury in the heart, brain, liver, kidney, lung, intestine and retina. We focused on the activities and underlying mechanisms of various therapeutic strategies to regulate HO-1/CO system against I/R injury. A large number of studies have demonstrated that HO-1/CO system exhibits potent anti-oxidative, antiapoptotic, anti-inflammatory and cytoprotective activities against I/R injury. The regulation of HO-1/CO expression has been achieved either by genetic overexpression of HO-1 cDNA or pharmacological induction with drugs including curcumin and resveratrol. The HO-1/CO system is a potential target for treating I/R injury. Further studies should be directed to in vivo efficacy and clinical application of HO-1/CO system in the therapy of I/R injury.


Human milk lipase substrates: electronic role.
The hydrolysis of a series of 4'-nitrophenyl 4-substituted benzoates, catalyzed by human milk lipase in the absence and presence of cholate stimulation, has been measured at pH 7.3, 37.5 degrees C. There is no evidence for an acyl site electronic interaction in the rate determining step of the esterolytic reaction. Substrate inhibition, arising from restricted rotation of the aryl residues about the ester linkage in the esterolytic site, is exhibited by these substrates.


Mathematical study of pattern formation accompanied by heterocyst differentiation in multicellular cyanobacterium.
The filamentous cyanobacterium, Anabaena sp. PCC 7120, is one of the simplest models of a multicellular system showing cellular differentiation. In nitrogen-deprived culture, undifferentiated vegetative cells differentiate into heterocysts at ~10-cell intervals along the cellular filament. As undifferentiated cells divide, the number of cells between heterocysts (segment length) increases, and a new heterocyst appears in the intermediate region. To understand how the heterocyst pattern is formed and maintained, we constructed a one-dimensional cellular automaton (CA) model of the heterocyst pattern formation. The dynamics of vegetative cells is modeled by a stochastic transition process including cell division, differentiation and increase of cell age (maturation). Cell division and differentiation depend on the time elapsed after the last cell division, the "cell age". The model dynamics was mathematically analyzed by a two-step Markov approximation. In the first step, we determined steady state of cell age distribution among vegetative cell population. In the second step, we determined steady state distribution of segment length among segment population. The analytical solution was consistent with the results of numerical simulations. We then compared the analytical solution with the experimental data, and quantitatively estimated the immeasurable intercellular kinetics. We found that differentiation is initially independent of cellular maturation, but becomes dependent on maturation as the pattern formation evolves. Our mathematical model and analysis enabled us to quantify the internal cellular dynamics at various stages of the heterocyst pattern formation.