Hemodynamic differences between the awake and anesthetized conditions in normal calves.
There is insufficient information in the literature about baseline circulatory parameters in normal calves in the anesthetized versus postoperative awake conditions under which a large volume of medical research is conducted. Eleven calves (mean body weight, 78.1 ± 14.3 kg) were implanted with a flow probe and fluid-filled pressure lines to measure cardiac output (CO), aortic (AoP), central venous (CVP), pulmonary arterial (PAP), and left atrial pressures (LAP). Systemic (SVR) and pulmonary vascular resistance (PVR) were also calculated. We obtained the above hemodynamic data (n = 11) and epicardial echocardiography (n = 7) during open-chest surgery under isoflurane anesthesia. After full recovery from surgery, animals were evaluated in the awake condition on postoperative days 6-9 using transthoracic echocardiography (n = 7) and the hemodynamic monitoring lines and probes noted (n = 11). CO, AoP, and PAP levels in the anesthetized condition were significantly lower than in the awake condition. Other hemodynamic parameters (CVP, LAP, SVR, and PVR) were not significantly different. In conclusion, data from this study quantify changes in CO, AoP, and PAP in anesthetized calves that may affect the hemodynamic response to experimental therapeutics such as new cardiac assist devices, prosthetic valves, and surgical interventions. Our study also provides baseline data for the translation of the hemodynamic data obtained in acute in vivo calf studies to that of an awake subject.


Folding of bovine pancreatic trypsin inhibitor (BPTI) variants in which almost half the residues are alanine.
Recent studies indicate that a fraction of the information contained in an amino acid sequence may be sufficient for specifying a native protein structure. An earlier alanine-scanning experiment conducted on bovine pancreatic trypsin inhibitor (BPTI; 58 residues) suggested that if cumulative mutations have additive effects on protein stability, a native protein structure could be built from BPTI sequences that contained many alanine residues distributed throughout the protein. To test this hypothesis, we designed and produced six BPTI mutants containing from 21 to 29 alanine residues. We found that the melting temperature of mutants containing up to 27 alanine residues (48 % of the total number of residues) could be predicted quite well by the sum of the change in melting temperature for the single mutations. Additionally, these same mutants folded into a native-like structure, as judged by their cooperative thermal denaturation curves and heteronuclear multiple quantum correlation (HMQC) NMR spectra. A BPTI mutant containing 22 alanine residues was further shown by 2D and 3D-NMR to fold into a structure very similar to that of native BPTI, and to be a functional trypsin inhibitor. These results provide insight into the extent to which native protein structure and function can be achieved with a highly simplified amino acid sequence.


Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer.
Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. As a first step in applying functional genomic analysis to population studies, we have examined the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n = 20), smokers without lung cancer (SNC, n = 24), and never smokers (NS, n = 8). Functional enrichment analysis showed that the NRF2-mediated, antioxidant response element (ARE)-regulated genes, were significantly lower in SC, when compared with expression levels in SNC. Importantly, we found that the expression of MAFG (a binding partner of NRF2) was correlated with the expression of ARE genes, suggesting MAFG levels may limit target gene induction. Bioinformatically we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to test the impact of genetic variation, we genotyped these putative regulatory SNPs and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we identified 30 novel SNPs and two were associated with either gene expression or lung cancer status among smokers. This work demonstrates an analysis approach that integrates bioinformatics pathway and transcription factor binding site analysis with genotype, gene expression and disease status to identify SNPs that may be associated with individual differences in gene expression and/or cancer status in smokers. These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure.


S-band gain-clamped grating-based erbium-doped fiber amplifier by forward optical feedback technique.
An S-band gain-clamped erbium-doped fiber amplifier module, employing a fiber Bragg grating to serve as a reflected element for lasing a saturated tone injected into the module by forward optical feedback method, is proposed and investigated experimentally. Moreover, the performance and behavior of the gain and noise figure in the proposed gain-clamped S-band fiber amplifier have also been discussed in the effectively wavelength range of 1478 to 1520 nm.


Gold-platinum bimetallic nanoclusters with enhanced peroxidase-like activity and their integrated agarose hydrogel-based sensing platform for the colorimetric analysis of glucose levels in serum.
This work presents a novel and facile strategy for the fabrication of gold-platinum bimetallic nanoclusters (Au-PtNCs) with adjustable Au/Pt molar ratios by a one-pot synthetic route. It was unexpectedly found that the prepared Au-PtNCs with an optimal Au/Pt molar ratio (1 : 1) could exhibit greatly enhanced peroxidase-like catalytic activity and chemical stability toward harsh conditions due to the synergistic effect of the two atoms, in contrast with pure AuNCs. These prominent advantages render Au-PtNCs capable of sensitive and selective colorimetric detection of glucose by means of a NCs-glucose oxidase (GOx) cascade-catalyzed system using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate. This assay can be used not only for visual detection of glucose by the naked eye but for reliable and convenient quantification in the range from 5 to 55 μM with a detection limit of 2.4 μM. Importantly, to widen the application of point-of-care testing (POCT) of glucose to biomedical diagnosis, an integrated agarose hydrogel-based sensing platform comprising NCs, GOx and TMB was rationally designed. It was demonstrated that this sensing platform could serve as a reagentless and instrument-free platform for direct visualization of glucose with different levels in human serum, as the results were in good accordance with those obtained from a free NC-involved detection system as well as from a commercial blood glucometer.


Delay by internists in obtaining diagnostic biopsies in patients with suspected cancer.
To investigate the degree and type of delays in performing diagnostic biopsies in medical patients with suspected malignancy. Retrospective survey of clinical histories of patients referred between January 1985 and March 1989. Inner city teaching hospital internal medicine (non-oncologic) services. Patients with gastrointestinal and lung cancers, adenocarcinoma of unknown primary site, and lymphomas were referred as inpatients by internists. Two hundred fifty-five patients were eligible, and 177 were evaluable. The number, type, and results of tests done before and after biopsy were analyzed. In 67% of patients the biopsied lesion was detected by the second day of evaluation; however, there was an 8- to 10-day delay before a biopsy was done. This delay was consistent across the four malignancy groups studied. Although logistic and other unavoidable delays occurred in 40% of the cases, in 60% delays could only be attributed to continued, frequently low yield, noninvasive tests. An average of 3.3 tests were made per patient, with only 24% leading to a definitive biopsy. Because of the performance of many other tests, a substantial delay exists in proceeding to biopsy during the diagnosis of cancer by internists.


The state of medical practice.
The fifth-annual State of Medical Practice issue highlights what healthcare industry changes MGMA members will face in 2014, from assuming risk for patients populations to big data and much more. Our subject-matter experts provide high-level perspectives to help inform your strategic plans.


Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer.
The risks of betel quid chewing with or without tobacco, alcohol drinking and cigarette smoking have been well explored in the oral cavity but not in the pharynx and larynx. We conducted a case-control study to investigate the association of these three risk factors to cancers of the pharynx and larynx in Taiwan. A total cases of 148 pharyngeal cancer, 128 laryngeal cancer and 255 hospital controls, all men, were recruited. Betel quid chewing was a significant independent risk factor (adjusted odds ratio [aOR] = 7.7; 95% confidence interval [CI] = 4.1-15.0) similar to that of alcohol drinking (aOR = 6.6; 95% CI = 3.5-13.0) for pharyngeal cancer, but not for laryngeal cancer (aOR = 1.3; 95% CI = 0.7-2.5) on which cigarette smoking (aOR = 7.1) exerts a stronger significant independent risk than alcohol drinking (aOR = 3.8). For pharyngeal cancers, chewers who consumed >20 quid/day, chewed with inflorescence in the quid or swallowed the betel quid juice were at higher risks; significant dose-response effects were found in daily quantity of drinking and chewing, and cumulative quantity of drinking. Synergistic effects from the 3 risk factors existed both on the pharynx (aOR = 96.9) and the larynx (aOR = 40.3), and attributed for 93.1% and 92.9% respectively. Our study is the first evidence to show that betel quid chewing without tobacco has different impact on the pharynx (digestive tract) and the larynx (airway), and supports the concept that exposure quantity and direct mucosal contact with the betel quid juice may contribute to carcinogenesis. Our results show an important insight into the impact of betel quid chewing on other sites of the digestive tract other than the oral cavity.


Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their activities through Src and AMPK signaling pathways.
Solid tumors often contain hypoxic regions because an abnormal and inefficient tumor vasculature is unable to supply sufficient oxygen. Tissue hypoxia is generally defined as a low oxygen concentration of less than 2%. It is well known that tumor cells under severe hypoxia, where oxygen concentration is less than 0.1%, show radioresistance. It has been reported that cells under severe hypoxia show different responses from those under mild hypoxia, where oxygen concentration is 0.5-2.0%. In the present study, we investigated the effects of severe hypoxia on expression and activities of ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), both of which regulate DNA double-strand breaks (DSBs) repair and radiation sensitivity. Signaling pathways for increasing expression and activities of ATM and DNA-PKcs under severe hypoxia were also investigated. SV40-transformed human fibroblast cell lines, LM217 and LM205, and normal human dermal fibroblasts (NHDF) were used. Cells were cultured at an oxygen concentration of less than 0.05% for 12 or 24 h. Activities and/or expression of ATM, DNA-PKcs, Src, Caveolin-1, EGFR, HIF-1α, PDK1, Akt, AMPKα, and mTOR were estimated by Western blot analyses. Severe hypoxia increased expression and activities of ATM, DNA-PKcs, Src, Caveolin-1, EGFR, PDK1, Akt, and AMPKα, and decreased expression and activity of mTOR. A specific Src inhibitor, PP2 suppressed activation of ATM, DNA-PKcs, Caveolin-1, EGFR, and Akt under severe hypoxia. Treatment with siRNA for AMPKα suppressed activation of ATM and DNA-PKcs and increase of ATM expression under severe hypoxia. Our data show that severe hypoxia increases activities of ATM and DNA-PKcs through Src and AMPK signaling pathways, and that activation of AMPK under hypoxia causes increase of ATM expression. Since ATM and DNA-PKcs play important roles in DSBs repair induced by ionizing radiation, those data provide novel insights on the molecular mechanism of the cellular radioresistance under severe hypoxia.


Hsa-miR-520d induces hepatoma cells to form normal liver tissues via a stemness-mediated process.
The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conversion of 293FT cells to hiPSCs. To identify the factors underlying this process, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after 1 month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520d appears to be through the conversion of cancer cells to normal stem cells, maintaining p53 upregulation.


Structure-based redesign of GST A2-2 for enhanced catalytic efficiency with azathioprine.
Glutathione transferase (GST) A2-2 is the most efficient human enzyme in the biotransformation of the prodrug azathioprine (Aza). The activation of Aza has therapeutic potential for possible use of GSTs in targeted enzyme-prodrug treatment of diseases. Based on the assumed catalytic mechanism and computational docking of Aza to the active site of the enzyme, active-site residues were selected for construction of focused mutant libraries, which were thereafter screened for Aza activity. Mutants with elevated Aza activity were identified, DNA sequenced, and the proteins purified. The two most active mutants showed up to 70-fold higher catalytic efficiency than the parental GST A2-2. The structure of the most active triple mutant (L107G/L108D/F222H) enzyme was determined by X-ray crystallography demonstrating significant changes in the topography of the active site facilitating productive binding of Aza as a substrate.


Overexpression of platelet-type 12-lipoxygenase promotes tumor cell survival by enhancing alpha(v)beta(3) and alpha(v)beta(5) integrin expression.
Arachidonic acid metabolism leads to the generation of biologically active metabolites that regulate cell growth and proliferation, as well as survival and apoptosis. We have demonstrated previously that platelet-type 12-lipoxygenase (LOX) regulates the growth and survival of a number of cancer cells. In this study, we show that overexpression of platelet-type 12-LOX in prostate cancer PC3 cells or epithelial cancer A431 cells significantly extended their survival and delayed apoptosis when cultured under serum-free conditions. These effects were shown to be a result of enhanced surface integrin expression, resulting in a more spread morphology of the cells in culture. PC3 cells transfected with 12-LOX displayed increased alpha(v)beta(3) and alpha(v)beta(5) integrin expression, whereas other integrins were unaltered. Transfected A431 cells did not express alpha(v)beta(3); however, alpha(v)beta(5) integrin expression was increased. Treatment of both transfected cell lines with monoclonal antibody to alpha(v)beta(5) (and in the case of PC3 cells, anti-alpha(v)beta(3)) resulted in significant apoptosis. In addition, treatment with 100 nM 12(S)-hydroxy-eicosatetraenoic acid, the end product of platelet-type 12-LOX, but not other hydroxy-eicosatetraenoic acids, enhanced the survival of wild-type PC3 and A431 cells and resulted in increased expression of alpha(v)beta(5). Furthermore, Baicalein or N-benzyl-N-hydroxy-5-phenylpentamide, specific 12-LOX inhibitors, significantly decreased alpha(v)beta(5)-mediated adhesion and survival in 12-LOX-overexpressing cells. The results show that 12-LOX regulates cell survival and apoptosis by affecting the expression and localization of the vitronectin receptors, alpha(v)beta(3) and alpha(v)beta(5), in two cancer cell lines.


Motility in Echinosphaerium nucleofilum. I. An analysis of particle motions in the axopodia and a direct test of the involvement of the axoneme.
The motion of particles in the axopodia of Echinosphaerium nucleofilum is saltatory. In the present study, photokymograph records of 123 motions from six axopodia have been analyzed. Particles followed rectilinear paths of from 1 to 15 mum while in continuous motion at an average velocity of 0.66 plus or minus 0.32 mum/s. The velocity of the particles was variable in 36% of the cases measured. Some motions were punctuated by pauses either before continuing in the same direction or reversing. Frequently, several particles were moving at the same velocity, but neighboring particles showed no motion or moved in the opposite direction. Two particles occasionally contacted one another and travelled as a unit for varying lengths of time but subsequently moved independently. These motions reflect the underlying mechanism of motive force production. Furthermore, a glass microneedle can be substituted for the microtubular axoneme in the axopodia. In these artificial axopodia, bidirectional particle motions occurred which were similar to those in normal axopodia. Colchicine, at the threshold dose for axonemal dissolution, had no affect on these particel motions. It is concluded that the microtubular axoneme is not responsible for particle motions and also that individual microtubules are unlikely candidates for motive force production in this system.


Halictine social evolution: the Australian enigma.
Australian halictines belong to the primitive genus Lasioglossum or related subgenera. The underground nests have lined cells in series or clusters and sometimes at the end of laterals. Two full generations per year are produced in the communal nests. Overwintered and newly emerged females form unique "pseudosocieties" rather than matrifilial societies along Holarctic patterns. Several Chilalictus species produce a "male caste" of big-headed, flightless males, in addition to normal individuals. Oviposition of unfertilized eggs on large pollen balls causes such allometric bees.


Ocular syphilis and HIV infection.
Syphilitic ocular involvement is thought to be rare in HIV infected patients. During a 5-year study in 509 HIV-positive patients, syphilis was diagnosed in 3.9%, and the eye was involved in one-fifth of these. The high risk for sequelae emphasizes the need for prevention and for early diagnosis.


[Quality assessment of tobacco flavor by classification of principal component analysis-mahalanobis distance combined with FTIR-ATR fingerprint].
In normal condition, 150 Fourier transform infrared-attenuated total reflection spectra of three kinds of tobacco flavor were measured. Mean centering and Karl Norris second derivative filter were employed for treating the spectra data. Whereafter, class models of tobacco flavor were established with classification of principal component analysis-Mahalanobis distance. Class models have been applied to multivariate statistical process control(MSPC) for the quality assessment of tobacco flavor in site. The upper control limit(UCL) was based on this kind of average Mahalanobis distance within +3sigma. The results of monitoring are correct.


Predicting the cumulative number of cases for the COVID-19 epidemic in China from early data.
We model the COVID-19 coronavirus epidemic in China. We use early reported case data to predict the cumulative number of reported cases to a final size. The key features of our model are the timing of implementation of major public policies restricting social movement, the identification and isolation of unreported cases, and the impact of asymptomatic infectious cases.


High TNF-α levels in resting B cells negatively correlate with their response.
Aging significantly decreases the influenza vaccine-specific response as we and others have previously shown. Based on our previous data in aged mice, we hypothesize that the inflammatory status of the individual and of B cells themselves would impact B cell function. We here show that the ability to generate a vaccine-specific antibody response is negatively correlated with levels of serum TNF-α. Moreover, human unstimulated B cells from elderly make higher levels of TNF-α than those from young individuals, and these positively correlate with serum TNF-α levels. These all negatively correlate with B cell function, measured by activation-induced cytidine deaminase, the enzyme of class switch recombination and somatic hypermutation. Only memory B cells (either IgM or switched), but not naïve B cells, make appreciable levels of TNF-α and more in elderly as compared to young individuals. Finally, an anti-TNF-α antibody can increase the response in cultured B cells from the elderly, suggesting that TNF-α secreted by memory B cells affects IgM memory B cells and naïve B cells in an autocrine and/or paracrine manner. Our results show an additional mechanism for reduced B cell function in the elderly and propose B cell-derived TNF-α as another predictive biomarker of in vivo and in vitro B cell responses.


Kinetic Trans-Assembly of DNA Nanostructures.
The central dogma of molecular biology is the principal framework for understanding how nucleic acid information is propagated and used by living systems to create complex biomolecules. Here, by integrating the structural and dynamic paradigms of DNA nanotechnology, we present a rationally designed synthetic platform that functions in an analogous manner to create complex DNA nanostructures. Starting from one type of DNA nanostructure, DNA strand displacement circuits were designed to interact and pass along the information encoded in the initial structure to mediate the self-assembly of a different type of structure, the final output structure depending on the type of circuit triggered. Using this concept of a DNA structure "trans-assembling" a different DNA structure through nonlocal strand displacement circuitry, four different schemes were implemented. Specifically, 1D ladder and 2D double-crossover (DX) lattices were designed to kinetically trigger DNA circuits to activate polymerization of either ring structures or another type of DX lattice under enzyme-free, isothermal conditions. In each scheme, the desired multilayer reaction pathway was activated, among multiple possible pathways, ultimately leading to the downstream self-assembly of the correct output structure.


Impaired cerebromicrovascular perfusion. Summary of evidence in support of its causality in Alzheimer's disease.
After nearly a century of inquiry, the cause of Alzheimer's disease (AD) remains to be found. In this review, basic and clinical evidence is presented that assembles and hypothetically explains most of the key pathologic events associated with the development of AD. These pathologic events are triggered in AD by impaired cerebral perfusion originating in the microvasculature that affects the optimal delivery of glucose and oxygen and results in an energy metabolic breakdown of brain cell biosynthetic and synaptic pathways. We propose that two factors must be present before cognitive dysfunction and neurodegeneration is expressed in the AD brain: (1) advanced aging, (2) presence of a condition that lowers cerebral perfusion, such as a vascular risk factor. The first factor introduces a normal but potentially menacing process that lowers cerebral blood flow in proportion to increased aging, while the second factor adds a crucial burden that further lowers brain perfusion and places vulnerable neurons in a state of metabolic compromise leading to a death pathway. These two factors will lead to a critically attained threshold of cerebral hypoperfusion (CATCH). CATCH is a self-sustaining and progressive circulatory insufficiency that will destabilize neurons, synapses, neurotransmission, and cognitive function, creating in its wake a neurodegenerative process characterized by the formation of senile plaques, neurofibrillary tangles, amyloid angiopathy, and, in some cases, Lewy bodies. Since any of a considerable number of vessel-related conditions must be present in the aging individual for cognition to be affected, CATCH supports the heterogeneic disease profile assumed to be characteristic of the AD syndrome. A brief discussion of target therapy based on the proposed pathogenesis of AD is also reviewed.


Analyzing Complex Longitudinal Data in Educational Research: A Demonstration With Project English Language and Literacy Acquisition (ELLA) Data Using xxM.
When analyzing complex longitudinal data, especially data from different educational settings, researchers generally focus only on the mean part (i.e., the regression coefficients), ignoring the equally important random part (i.e., the random effect variances) of the model. By using Project English Language and Literacy Acquisition (ELLA) data, we demonstrated the importance of taking the complex data structure into account by carefully specifying the random part of the model, showing that not only can it affect the variance estimates, the standard errors, and the tests of significance of the regression coefficients, it also can offer different perspectives of the data, such as information related to the developmental process. We used xxM (Mehta, 2013), which can flexibly estimate different grade-level variances separately and the potential carryover effect from each grade factor to the later time measures. Implications of the findings and limitations of the study are discussed.


A test strip for diamines in tuna.
This study describes the production of a solid-phase assay (test strip/dipstick test) for putrescine and cadaverine in tuna based on the coupling of an amine oxidase to a peroxidase/dye system. The assay was linear to 75 microM in phosphate buffer, and the minimum detectable concentration was 0.5 microM (< 0.1 ppm), corresponding to 0.01 mg% in spiked extracts. Intra- and interassay precisions were < 20%. Test strips were stable at 4 degrees C for at least 12 months. Lysine, ornithine, and histidine did not react with the assay, and histamine reacted only minimally. Sixteen fish samples were tested by test strip and the standard AOAC protocol, and results were in good agreement.


Preparation and characterization of poly(D,L-lactide-co-glycolide) microspheres for controlled release of human growth hormone.
The purpose of this research was to assess the physicochemical properties of a controlled release formulation of recombinant human growth hormone (rHGH) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) composite microspheres. rHGH was loaded in poly(acryloyl hydroxyethyl) starch (acHES) microparticles, and then the protein-containing microparticles were encapsulated in the PLGA matrix by a solvent extraction/evaporation method. rHGH-loaded PLGA microspheres were also prepared using mannitol without the starch hydrogel microparticle microspheres for comparison. The detection of secondary structure changes in protein was investigated by using a Fourier Transfer Infrared (FTIR) technique. The composite microspheres were spherical in shape (44.6 +/- 2.47 microm), and the PLGA-mannitol microspheres were 39.7 +/- 2.50 microm. Drug-loading efficiency varied from 93.2% to 104%. The composite microspheres showed higher overall drug release than the PLGA/mannitol microspheres. FTIR analyses indicated good stability and structural integrity of HGH localized in the microspheres. The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs.


Identification of the six ligands to manganese(II) in transition-state-analogue complexes of creatine kinase: oxygen-17 superhyperfine coupling from selectively labeled ligands.
The complete coordination scheme for Mn(II) in transition-state-analogue complexes with creatine kinase has been determined by electron paramagnetic resonance (EPR) spectroscopy. Perturbations in the EPR spectra for Mn(II) due to superhyperfine coupling to 17O of selectively labeled ligands have been used to identify oxygen ligands in the first coordination sphere of the metal ion. The results show that in the complex of enzyme-MnADP-formate-creatine, Mn(II) is bound to oxygen ligands from both the alpha- and beta-phosphate groups of ADP, to an oxygen from the carboxylate group of formate, and to three water molecules. In the complex with thiocyanate replacing formate as the stabilizing anion, previous infrared experiments [Reed, G. H., Barlow, C. H., & Burns, R. A., Jr. (1978) J. Biol. Chem. 253, 4153-4158] indicated that the nitrogen from thiocyanate was bound to the Mn(II). The magnitudes of the 17O superphyperfine coupling constants from the O- ligands of the ADP phosphate groups and from the formate carboxylate are approximately equal and are larger than that for the water ligands. The symmetry of the zero-field-splitting tensor for Mn(II) indicates that the oxygens from the alpha- and beta-phosphate groups of ADP and the ligand donor atom from the anion occupy mutually cis positions in the octahedral coordination geometry. Water proton relaxation time measurements show that the three water molecules which are bound to Mn(II) are not in free exchange with the bulk solvent. Hence, an enclosed structure at the active site is indicated. The results suggest that for creatine kinase the activating metal ion is bound to all three phosphate groups in the transition state of the reaction.


Stability of women's facial shape throughout the menstrual cycle.
Facial characteristics can serve as a cue for judgements of multiple human traits, from maternal tendencies, overall fertility to sexual openness. In this study, we tested previously found fluctuations in facial shape throughout the menstrual cycle. With methods more robust than those formerly used (larger sample size and detailed hormonal assessments determining the timing of the ovulation), we did not find significant changes in either of the three facial measurements conducted: symmetry, averageness and sexual dimorphism (all F ≤ 0.78, all partial η2 ≤ 0.01, all p ≥ 0.542). After narrowing the sample to cycles that had a higher probability of being ovulatory (based on daily measurements of luteinizing hormone and oestradiol), the results remained non-significant (all F ≤ 1.20, all partial η2 ≤ 0.03, all p ≥ 0.315). Our results (i) suggest that the previously found increased facial attractiveness of women in the most fertile phase of the menstrual cycle is not driven by changes in facial shape, but might instead stem from other changes in facial appearance, such as a more attractive skin tone; and (ii) underline the importance of replication of studies with new methods.


Identification of Areas of Epiphyseal Cartilage Necrosis at Predilection Sites of Juvenile Osteochondritis Dissecans in Pediatric Cadavers.
The pathogenesis of human juvenile osteochondritis dissecans (JOCD) remains poorly understood, with multiple factors implicated, including ischemia, repetitive trauma, and genetic predisposition. Similarities in the predilection site and the diagnostic and clinical features of JOCD to the well-characterized veterinary counterpart, osteochondrosis dissecans, suggest that, similar to the animal disease, the pathogenesis JOCD may also be initiated in the first few years of life, when disruption of blood supply to the epiphyseal growth cartilage leads to failure of endochondral ossification. To gather data in support of the hypothesis that JOCD and osteochondrosis dissecans have a shared pathogenesis, biopsy specimens obtained from predilection sites of JOCD in juvenile human cadavers were histologically examined to determine whether they contained lesions similar to those found in animals diagnosed with subclinical osteochondrosis dissecans. In this descriptive laboratory study, 59 biopsy specimens (6 mm in diameter) were harvested from the central aspect (i.e., the notch side) of the femoral condyles of 26 human cadavers (1 month to 11 years old). Specimens were histologically evaluated for the presence of areas of cartilage necrosis and the morphology of cartilage canal blood vessels. Locally extensive areas of necrotic epiphyseal cartilage were identified in 4 specimens obtained from 3 donors (ages 2 to 4 years). Areas of cartilage necrosis accompanied by focal failure of endochondral ossification or surrounded by subchondral bone were identified in biopsy specimens from 4 donors (ages 4 to 9 years). The identification of epiphyseal cartilage necrosis identical to that described in animals with subclinical osteochondrosis, found in biopsy specimens obtained from femoral predilection sites of JOCD in pediatric cadavers, suggests a shared pathogenesis of JOCD in humans and osteochondrosis dissecans in animals. These findings imply that the pathogenesis of human JOCD likely starts 5 to 10 years prior to the development of clinical symptoms. Enhanced understanding of the temporal features of JOCD pathogenesis provides an opportunity for earlier diagnosis and treatment, likely resulting in improved outcomes for this condition in the future.


Literature Review for the Effects of Physical Activity on Musculoskeletal Outcomes in Community-dwelling Older Adults.
The purpose of this study was to review the effects of physical activity on musculoskeletal outcomes in older Koreans. Experimental studies were retrieved from the search engines (PubMed, CINAHL, PsycINFO, Cochrane, RISS, KISS, and KoreaMed). The selected studies for analysis were 27 articles of musculoskeletal outcomes (gait, muscle strength, flexibility, balance, grip strength, endurance, body fat, and weight) from 515 articles. The most common type of physical activity was a resistance exercise. There were significant improvements in gait (71.4%), muscle strength (86.7%), flexibility (63.6%), balance (72.2%), grip strength (71.4%), endurance (71.4%), body fat (57.1%), and weight (28.6%). The activity programs that apply over 150 minutes a week showed greater improvement of 69.5% than 65.0% from those did not meet the guidelines totally. Based on the review, we conclude that regular physical activity in the elderly may improve the musculoskeletal outcomes. To be more effective programs, it is necessary to meet the guidelines of 150 minutes a week or 30 minutes of moderate-intensity activities on 5 days per week for the elderly.


Testing modern human out-of-Africa dispersal models and implications for modern human origins.
The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity.


[Efficiency versus quality in the NHS, in Portugal: methodologies for evaluation].
To proceed to the evaluation of the efficiency and quality in the NHS, based in methodologies of evaluation of management, indicators of benchmarking and indicators of process and outcome. The 1980 and 1990 decades have seen the proliferation of all forms of process indicators as a way to control health services. It is not a coincidence that the increase in managed care has been accompanied by an explosion of process indicators, as it has happened in the health system of the USA. More recently the attention has turned away from measures of performance, which measure the process (what has been done) to those which measure outcomes (what was the result). Quality indicators have been developed in Europe, first to be used in hospitals, but also to be used in primary health care. Conceptually the justification for the introduction of process indicators comes from the principle that their use will reinforce a modification in the quality of the proceedings, which will give origin to better outcomes as well at population level, as resource saving. Outcome indicators compared with process indicators in health care shows that process indicators have the advantage of being more sensitive than outcome indicators to differences in the quality. Optimizing health care quality has the objective of establishing a quantitative relationship between the quality of the health services and cost-effectiveness. To identify quality indicators and benchmarking and to implement plans to measure the quality of health care. In a study made in a group of senior GP, in the UK, with the objective of determining which process indicators better reflect the quality of the services in primary health care services a Delphi method was used. Only seven indicators were chosen by 75% of the respondents: the percentage of eligible patients receiving cervical screening; the percentage of generic prescribing; the percentage of eligible patients receiving childhood immunization; the percentage of eligible patients receiving influenza vaccinations; ability to see GP within 48 hours; percentage prescribing antibacterial drugs; primary care management (diabetes and asthma). The main characteristics of health indicators are: acceptability--The acceptability of the data collected using a measure will depend upon the extent to which the findings are acceptable to both those being assessed and those undertaking the assessment; feasibility--information about the quality of services is often driven by data availability rather than by epidemiological and clinical considerations. Quality measurement cannot be achieved without accurate and consistent information systems; reliability--indicators should be used to compare organisations/practitioners with similar organisations/practitioners; sensitivity to change--quality measures must be capable of detecting changes in quality of care in order to discriminate between and within subjects; validity--there has been little methodological scrutiny of the validity of consensus methods. Outcome indicators are not good performance indicators in health care. Which causes the variation in outcomes between deliverers of primary health care services are the observed differences due to differences in users, due to age, sex, co-morbidity, severity and socio-economic situation. The Medical Outcomes Study, published in 1989, has brought, for the first time, subjective indicators, based in the evaluation of users, as an important outcome indicator. Clinical indicators are those that are more associated with the outcomes. A few studies exist of the effects of management indicators in outcomes. Several indicators, however, reflect norms related with the local of work. The use of a Composite Indicator presents advantages. In England it has been used a Composite Indicator of process indicators in 302 organizations of primary health care, in 2001-2002. This study has used a mathematical model to select the best indicators which allow the evaluation of performance. It has concluded that the use of a Composite Indicator is of easy construction, interpretation, and acceptable and that has validity. Giraldes (2007) has done an evaluation of health centres in a perspective of management and quality of deliver using a Composite Indicator of Efficiency and Quality. It includes the efficiency indicators concerned with the main activities of the health centre, preventive activities, curative activities and drugs, by main pharmaco therapeutic groups, and auxiliary means of diagnosis (analysis, X Ray, ecographies and CAT by user, weighted according to the relevance of the expenditure in total expenditure). The Composite Quality Indicator includes 12 performance and 5 outcome indicators. From the 10 best health centres in an efficiency and quality perspective 3 are from the Porto Sub-Region (Negrelos, Rebordosa and Paredes) and 2 from the Braga Sub-Region (Vila Verde and Vila Nova de Famalicão I), Leiria (Pedrogão Grande and Batalha), and Vila Real (Mesão Frio and Sabrosa), while 1 belongs to the Aveiro Sub-Region (Sever do Vouga). The more efficient health centres are from the Aveiro Sub-Region, followed by Braga, Porto, and Lisboa. Sub-Regions with very similar values. Giraldes (2007) has made an evaluation of the hospital expenditure by user in an efficiency perspective and to evaluate the quality of the health system process indicators and outcome indicators. In an efficiency perspective the concept of technical efficiency has been chosen, and a correction has been made, as well, in what concerns a case-mix index (CMI). The indicators have been calculated by user in what concerns the main hospital activities (the expenditure in inpatient care by treated patient, in day hospital by treated patient, in outpatient care by consultation, etc.) and as well the auxiliary sections of clinic support and the hotel support services. All the indicators have been corrected according to the relevance of its expenditure in total expenditure. In a quality perspective two types of indicators have been considered; process indicators and outcome indicators. Process indicators, as the percentage of surgeries in ambulatory care, the percentage of cesareans in total deliveries and the rate of autopsy. The outcome indicator number of episodes of inpatient care due to surgery infection in total days of inpatient care. Those indicators have been aggregated, by a mean. The Composite Indicator of Efficiency and Quality is the mean of the Composite Indicator of Efficiency and the Composite Indicator of Quality, having this one been converted in inverse base.


[Biochemical characterization of noduleless soybean lectins].
The comparative analysis of activity and hydrocarbon specificity of lectins from common soybean and soybean in which roots the nodules do not form has been carried out. It was shown that the root lectins possesses the less activity in comparison with the seed lectins. The both kinds of lectins most specifically link with mannitol. The supposition was made about the role of activity and hydrocarbon specificity of lectins from soybean in the establishment of symbiotic systems of nitrogen fixation.


Frequency, amplitude, and propagation velocity of spontaneous Ca++-dependent contractile waves in intact adult rat cardiac muscle and isolated myocytes.
Spontaneous contractile waves due to spontaneous calcium cycling by the sarcoplasmic reticulum occur in unstimulated bulk rat papillary muscle and single rat cardiac myocytes with intact sarcolemmal function. We used video analytic techniques to quantify the wave characteristics in both bulk muscle and myocytes; laser-light scattering techniques were also employed in muscle. In muscle bathed in physiological concentrations of calcium, the true periodicity of these waves was a fraction of 1 Hz and increased up to several hertz with increases in cell calcium. This was paralleled by an increase in the frequency of scattered laser light intensity fluctuations. In myocytes, a range of spontaneous contractile wave frequencies similar to that which occurred in the muscle was observed; it could be demonstrated that an increase in superfusate calcium concentrations (2-15 mM at 23 degrees C) increases the oscillation frequency but not amplitude. In both myocytes and muscle, low concentrations of caffeine (0.5 mM) and higher temperature increased the oscillation frequency but diminished their amplitude. However, the scattered light fluctuations did not change with temperature and decreased with caffeine. These results demonstrate that (1) the true frequency of spontaneous sarcoplasmic reticulum oscillations in the unstimulated rat muscle and single myocytes with intact sarcolemmal function is low, i.e., a fraction of a hertz; (2) with cell calcium loading, the oscillation frequency accelerates to those frequencies measured previously in the "calcium overload" state; (3) while scattered light fluctuations which sample myofilament motion are a sensitive, noninvasive method of detecting the oscillations in bulk muscle, they can be insensitive to the divergent changes in oscillation amplitude and frequency.


The Cuban Twin Registry: initial findings and perspectives.
The Cuban Twin Registry is a nation-wide, prospective, population-based twin registry comprising all zygosity types and ages. It was initiated in 2004 to study genetic and environmental contributions to complex diseases with high morbidity and mortality in the Cuban population. The database contains extensive information from 55,400 twin pairs enrolled in the period 2004-2006. Additionally, 2,600 new multiple births have been included from 2007 to date. In the past 4 years, more than 130 studies have been carried out using the registry with a classical genetic epidemiological approach in which concordance rates for monozygotic and dizygotic twins and heritability of various disease traits were estimated. This article summarizes the history, registry's methodology, recent research findings, and future directions of work.


Implantation of a composite bifurcated cryopreserved aorto-iliac-femoral homograft in a patient with Candida albicans endocarditis.
A 35 year old woman, cocaine addict, suffered Candida albicans aortic valve endocarditis complicated with embolisation of infected vegetations in the distal abdominal aorta. She underwent successful staged aortic valve replacement followed by transaortic and transfemoral thrombectomy. One month later an arteriogram disclosed partial occlusion of the left iliac artery, bilateral aneurysmal degeneration of both iliac arteries and right iliac artery-right iliac vein fistula. She was operated again, performing re-laparotomy and re-exploration. A composite bifurcated cryopreserved homograft was implanted end-to-side between the infrarenal abdominal aorta, right external iliac artery and left common femoral artery. The right iliac artery-iliac vein fistula was obliterated with suture. The patient had an uneventful recovery but a relapsing arterio-venous fistula was diagnosed by arteriography. Three months later she underwent percutaneous transluminal closure of the reopened fistula. At present, 17 months after the implantation of the homograft, the patient is symptom-free, on antifungal agents and with arteriographic and clinical evidence of a well-functioning arterial homograft.


Acute renal cortical necrosis. Variable course and changing prognosis.
Three cases of acute bilateral renal cortical necrosis, each with a different clinical course, are discussed. One patient spontaneously recovered renal function after prolonged oliguria. This case should be added to the small number of similar case reports in the literature. The second patient recovered adequate renal function temporarily, but eventually required chronic hemodialysis and renal transplantation. There was pathological evidence of progression from focal to massive cortical necrosis. The third patient never regained renal function, but is well after dialysis and transplantation. The influence of modern theories of pathogenesis of the disease, and increased availability of dialysis, are discussed in relation to the initial prognostic assessment of the patient with cortical necrosis.


Transarticular screw fixation in the middle and lower cervical spine. Technical note.
Although atlantoaxial transarticular screw fixation is technically demanding and there is a significant risk of vertebral artery (VA) injury, transarticular screw insertion in the middle and lower cervical spine is simple and can be performed safely with the aid of lateral fluoroscopic guidance. The authors describe the surgical techniques and outcome of transarticular screw fixation in the middle and lower cervical spine. Transarticular screw insertion into C2-3 or caudal cervical joints was performed from the articular pillar, directing the screw anterocaudally to penetrate the facet joint and the anterior cortex of the articular pillar, parallel to the sagittal plane. Because the VA and the nerve roots are anterior to the articular pillar at these levels, the screw can be placed safely with the assistance of lateral fluoroscopic guidance. Twenty-five patients ranging in age from 15 to 84 years underwent transarticular screw fixation, with a total of 81 screws. The transarticular screw was used as an anchor screw in combination with posterior cervical instrumentation in 19 patients and for facet screw fixation itself in six patients. Screw placement was successful and uncomplicated in all cases. The follow-up period ranged from 3 months to 5 years. No instance of screw backout or loosening was identified radiographically; fusion was achieved in all patients. Biomechanical strength is maintained by penetrating four cortical layers. When performed appropriately, this method is safe and reliable and deserves more widespread use.


Cessation of contraction induces cardiomyocyte remodeling during zebrafish cardiogenesis.
Contraction regulates heart development via a complex mechanotransduction process controlled by various mechanical forces. Here, we exploit zebrafish embryos as an in vivo animal model to discern the contribution from different mechanical forces and identify the underlying mechanotransductive signaling pathways of cardiogenesis. We treated 2 days postfertilization zebrafish embryos with Blebbistatin, a myosin II inhibitor, to stop cardiac contraction, which induces a response termed cessation of contraction-induced cardiomyocyte (CM) enlargement (CCE). Accompanying the CCE, lateral fusion of myofibrils was attenuated within CMs. The CCE can be blunted by loss of blood in tail-docked zebrafish but not in cloche mutant fish, suggesting that transmural pressure rather than shear stress is accountable for the chamber enlargement. By screening a panel of small molecule inhibitors, our data suggested essential functions of phosphoinositide 3-kinase signaling and protein synthesis in CCE, which are independent of the sarcomere integrity. In summary, we defined a unique CCE response in genetically tractable zebrafish embryos. A panel of assays was established to verify the contribution from extrinsic forces and interrogate underlying signaling pathways.


The clinical utility of human leucocyte antigen B27 in axial spondyloarthritis.
The association between HLA-B27 and AS was first established in the early 1970s. Since then, our understanding of this disease has changed, such that we now recognize AS to be the extreme of the clinical phenotype within a disease spectrum known as axial SpA (axSpA). Recent advances in therapeutic options have driven the need for earlier diagnosis and many screening strategies have been proposed to facilitate this. In parallel, our understanding of axSpA genetics, and especially the contribution of HLA-B27, has expanded. In this article we will present and discuss the evidence supporting the use of HLA-B27 in clinical practice. We will briefly summarize the evolution of the concept of axSpA, the prevalence of HLA-B27 and axSpA and the potential role of HLA-B27 in the aetiopathogenesis of axSpA and focus on the utility of HLA-B27 in everyday clinical practice.


Systemic mastocytosis and bone involvement in a cohort of 75 patients.
To investigate bone involvement in a large cohort of systemic mastocytosis (SM) patients, and evaluate the efficacy of bisphosphonate therapy. From 2000 to 2004, 75 patients with SM according to WHO criteria underwent skeletal x-rays and bone mineral density (BMD) assessment. Sequential BMD assessments were performed in nine patients treated with bisphosphonate (mean follow-up 65 months). 37 patients (49%) had bone involvement according to both x-rays and BMD evaluations: osteoporosis (23 patients, 31%, mean lumbar spine T score: -3 SD), with vertebral fracture (13 patients, 17%), axial skeleton osteosclerosis (six patients, 8%), mixed patterns (three patients), osteopenia with pre-existing fractures (four patients) and focal osteolytic lesion (one patient). Blood count abnormalities were associated with osteosclerosis (p=0.005). In nine patients with osteoporosis and bisphosphonate therapy, mean lumbar spine BMD increased from 0.83 to 0.92 g/cm(2) (+11.1%; ie, +2.05% per year) without recurrence of vertebral fracture. Half of adult patients with SM have bone involvement. Osteoporosis is the most prevalent bone manifestation in SM (31%). Bisphosphonate therapy seems efficient to improve lumbar spine BMD during SM-related osteoporosis. Spine x-ray and BMD should be performed in all SM patients to detect those who may benefit from anti-osteoporotic therapy.


CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent.
the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).


Synthesis and chemical stability of a disulfide bond in a model cyclic pentapeptide: cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH.
Many cyclic peptides are formed using a disulfide bond to increase their conformational rigidity; this provides receptor selectivity and increased potency. However, degradation of the disulfide bond in formulation can lead to a loss of structural stability and biological activity of the peptide. Therefore, the objective of this study was to study the stability of peptide 1 (cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy via solution-phase peptide synthesis and purified using semi-preparative HPLC. The accelerated stability studies of the cyclic peptide were conducted in buffer solutions at pH 1.0-11.0 with controlled ionic strengths at 70 degrees C. The pH-rate profile shows that the peptide has an optimal stability around pH 3.0 with a V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0-7.0 and pH 8.0-10.0, indicating hydrolysis on different ionized forms of the cyclic peptide. One product was observed at acidic pH due to peptide bond hydrolysis at Gly2-Phe3. The number of degradation products increases as the pH increases from neutral to basic, and most of the degradation products at neutral and basic pH are derived from the degradation at the disulfide bond.


UV-B exposure of indoor-grown Picea abies seedlings causes an epigenetic effect and selective emission of terpenes.
Terpenoids are involved in various defensive functions in plants, especially conifers. Epigenetic mechanisms, for example DNA methylation, can influence plant defence systems. The purpose of the present study was to investigate the influence of UV-B exposure on the release of terpenoids from spruce seedlings and on needle DNA methylation. Ten-week-old seedlings grown indoors were exposed to UV-B radiation during 4 h, and the volatile compounds emitted from the seedlings were analysed. Analysis of the volatiles 1, 3, and 22 d after this UV-B exposure showed that bornyl acetate, borneol, myrcene, and limonene contents increased during the first 3 days, while at day 22 the level of emission had returned to the control level. UV-B exposure decreased the level of DNA methylation in needles of young seedlings, reflected in methylation changes in CCGG sequences. Exposure of young seedlings to UV-B radiation might be a way to potentiate the general defensive capacity, improving their ability to survive in outdoor conditions. UV-B-induced defence is discussed in the light of epigenetic mechanisms.


Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: potential roles in GABAergic interneuron pathology.
Neuropathological changes of the hippocampus have been associated with psychotic disorders such as schizophrenia and bipolar disorder. Recent work has particularly implicated hippocampal GABAergic interneurons in the pathophysiology of these diseases. However, the molecular mechanisms underlying structural and cellular hippocampal pathology remain poorly understood. We used data from comprehensive difference-in-gel electrophoresis (2-D DIGE) investigations of postmortem human hippocampus of people with schizophrenia and bipolar disorder, covering the acidic (isoelectric point (pI) between pH4 and 7) and, separately, the basic (pI between pH6 and 11) sub-proteome, for Ingenuity Pathway Analysis (IPA) of implicated protein networks and pathways. Comparing disease and control cases, we identified 58 unique differentially expressed proteins in schizophrenia, and 70 differentially expressed proteins in bipolar disorder, using mass spectrometry. IPA implicated, most prominently, 14-3-3 and aryl hydrocarbon receptor signaling in schizophrenia, and gluconeogenesis/glycolysis in bipolar disorder. Both disorders were characterized by alterations of proteins involved in the oxidative stress response, mitochondrial function, and protein-endocytosis, -trafficking, -degradation, and -ubiquitination. These findings are interpreted with a focus on GABAergic interneuron pathology in the hippocampus.


Mesodiencephalic dopaminergic neuronal differentiation does not involve GLI2A-mediated SHH-signaling and is under the direct influence of canonical WNT signaling.
Sonic Hedgehog (SHH) and WNT proteins are key regulators in many developmental processes, like embryonic patterning and brain development. In the brain, SHH is expressed in a gradient starting in the floor plate (FP) progressing ventrally in the midbrain, where it is thought to be involved in the development and specification of mesodiencephalic dopaminergic (mdDA) neurons. GLI2A-mediated SHH-signaling induces the expression of Gli1, which is inhibited when cells start expressing SHH themselves. To determine whether mdDA neurons receive GLI2A-mediated SHH-signaling during differentiation, we used a BAC-transgenic mouse model expressing eGFP under the control of the Gli1 promoter. This mouse-model allowed for mapping of GLI2A-mediated SHH-signaling temporal and spatial in the mouse midbrain. Since mdDA neurons are born from E10.5, peaking at E11.0-E12.0, we examined Gli1-eGFP embryos at E11.5, E12.5, and E13.5, indicating whether Gli1 was induced before or during mdDA development and differentiation. Our data indicate that GLI2A-mediated SHH-signaling is not involved in mdDA neuronal differentiation. However, it appears to be involved in the differentiation of neurons which make up a subset of the red nucleus (RN). In order to detect whether mdDA neuronal differentiation may be under the control of canonical WNT-signaling, we used a transgenic mouse-line expressing LacZ under the influence of stable β-catenin. Here, we show that TH+ neurons of the midbrain receive canonical WNT-signaling during differentiation. Therefore, we suggest that early SHH-signaling is indirectly involved in mdDA development through early patterning of the midbrain area, whereas canonical WNT-signaling is directly involved in the differentiation of the mdDA neuronal population.


Occupational Lead Exposure and Associations with Selected Cancers: The Shanghai Men's and Women's Health Study Cohorts.
Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the stomach, lung, kidney, brain, and meninges; however, the totality of the evidence is inconsistent. We investigated the relationship between occupational lead exposure and cancer incidence at the five abovementioned sites in two prospective cohorts in Shanghai, China. Annual job/industry-specific estimates of lead fume and lead dust exposure, derived from a statistical model combining expert lead intensity ratings with inspection measurements, were applied to the lifetime work histories of participants from the Shanghai Women's Health Study (SWHS; n = 73,363) and the Shanghai Men's Health Study (SMHS; n = 61,379) to estimate cumulative exposure to lead fume and lead dust. These metrics were then combined into an overall occupational lead exposure variable. Cohort-specific relative hazard rate ratios (RRs) and 95% confidence intervals (CIs) comparing exposed and unexposed participants were estimated using Cox proportional hazards regression and combined by meta-analysis. The proportions of SWHS and SMHS participants with estimated occupational lead exposure were 8.9% and 6.9%, respectively. Lead exposure was positively associated with meningioma risk in women only (n = 38 unexposed and 9 exposed cases; RR = 2.4; 95% CI: 1.1, 5.0), particularly with above-median cumulative exposure (RR = 3.1; 95% CI: 1.3, 7.4). However, all 12 meningioma cases among men were classified as unexposed to lead. We also observed non-significant associations with lead exposure for cancers of the kidney (n = 157 unexposed and 17 ever exposed cases; RR = 1.4; 95% CI: 0.9, 2.3) and brain (n = 67 unexposed and 10 ever exposed cases; RR = 1.8; 95% CI: 0.7, 4.8) overall. Our findings, though limited by small numbers of cases, suggest that lead is associated with the risk of several cancers in women and men. Liao LM, Friesen MC, Xiang YB, Cai H, Koh DH, Ji BT, Yang G, Li HL, Locke SJ, Rothman N, Zheng W, Gao YT, Shu XO, Purdue MP. 2016. Occupational lead exposure and associations with selected cancers: the Shanghai Men's and Women's Health Study cohorts. Environ Health Perspect 124:97-103; http://dx.doi.org/10.1289/ehp.1408171.


Does medical futility matter in 'do not attempt CPR' decision-making?
The current demographical trend towards an increasingly elderly population combined with advances in end of life care calls for a deeper understanding and common terminology about the concept of futility and additional influences on the resuscitation decision-making process. Such improved understanding of medical futility and other contributing factors when making DNACPR orders would help to ensure that clinicians make appropriate and thoughtful decisions on whether to recommend resuscitation in a patient. When estimating medical futility a physician should consider the chance of survival over different time periods and balance this against the chance of adverse outcomes. This information can then be offered to the patient (or the relatives) so that the patient's views about what is acceptable for the survival chance, length and type of survival can be factored into the eventual decision. Given the lack of evidence in this area and the poor level of patient knowledge and the emotive nature of the topic, it is not surprising that clinicians find such discussions hard.


Functional responses of key marine bacteria to environmental change - toward genetic counselling for coastal waters.
Coastal ecosystems deteriorate globally due to human-induced stress factors, like nutrient loading and pollution. Bacteria are critical to marine ecosystems, e.g., by regulating nutrient cycles, synthesizing vitamins, or degrading pollutants, thereby providing essential ecosystem services ultimately affecting economic activities. Yet, until now bacteria are overlooked both as mediators and indicators of ecosystem health, mainly due to methodological limitations in assessing bacterial ecosystem functions. However, these limitations are largely overcome by the advances in molecular biology and bioinformatics methods for characterizing the genetics that underlie functional traits of key bacterial populations - "key" in providing important ecosystem services, being abundant, or by possessing high metabolic rates. It is therefore timely to analyze and define the functional responses of bacteria to human-induced effects on coastal ecosystem health. We posit that categorizing the responses of key marine bacterial populations to changes in environmental conditions through modern microbial oceanography methods will allow establishing the nascent field of genetic counselling for our coastal waters. This requires systematic field studies of linkages between functional traits of key bacterial populations and their ecosystem functions in coastal seas, complemented with systematic experimental analyses of the responses to different stressors. Research and training in environmental management along with dissemination of results and dialogue with societal actors are equally important to ensure the role of bacteria is understood as fundamentally important for coastal ecosystems. Using the responses of microorganisms as a tool to develop genetic counselling for coastal ecosystems can ultimately allow for integrating bacteria as indicators of environmental change.


Effects of lysine and methionine in a low crude protein diet on the growth performance and gene expression of immunity genes in broilers.
Globally, the poultry industry is 1 of the most advanced livestock industries. Feed contributes to the biggest proportion (65-70%) of the production cost. Most feed ingredients in Malaysia are imported, which contributes to the high food bill annually, and alternative feed formulation may help decrease the cost of poultry feed. Feed formulation are improved to efficiently meet the dietary requirements of the broilers and 1 of the ways is by reducing the level of crude protein in the diet while supplementing essential amino acids. In this study, the effects of methionine and lysine, which are the 2 most limiting amino acids in the chicken diet, were supplemented in a low crude protein diet, and its effects on the growth and expression of immunity genes such as MUC2, SLC, GAL6, and LEAP-2 were studied. A total of 300 Cobb500 broilers were tested with 10 different dietary treatments. Experimental treatment diets consist of high, standard, and low levels of methionine and lysine in the diet with reduced crude protein. The control group consists of diet with standard levels of lysine, methionine, and crude protein as recommended for Cobb500 broilers. Ribonucleic acid was extracted from the jejunum, spleen, and liver for gene expression analysis which was performed with real-time polymerase chain reaction using SYBR Green chemistry. Results of the growth performance at 6 wk showed improved feed conversion ratio when lysine was increased by 0.2% in a low crude protein diet at 1.96 ± 0.11. Gene expression of MUC2 gene in the jejunum showed a significant increase across all experimental diets with the treatment with higher lysine in low crude protein diet with the highest increase of 3.8 times as compared with the control diet. The other genes expressed in the spleen and liver were mostly downregulated. It was concluded that supplementation of high lysine with standard methionine in a low crude protein diet performed better in terms of lowest feed conversion ratio and high upregulation of MUC2 gene.


Cardiovascular risk assessment and management in mental health clients: perceptions of mental health and general practitioners in New Zealand.
People with mental illness have higher rates of morbidity and mortality, largely due to increased rates of cardiovascular disease (CVD). Metabolic syndrome is well recognised but rarely expressed as a need to assess and manage cardiovascular risk factors; furthermore there is confusion about whose role this is. This study explores health practitioners' knowledge, attitudes, barriers/solutions towards cardiovascular risk assessment and management in mental health patients. A survey of mental health practitioners (MHPs n = 421) and general practitioners (GPs n = 232) Three-quarters of respondents agreed mental illness predisposes to CVD. Fifty-five percent of MH doctors agreed they could effectively assess CVD risk compared to 67% of GPs. Only 21% of MH doctors agreed they could effectively manage CVD risk compared to 57% of GPs. Seventy-nine percent of MHPs believed that assessing CVD risk was a joint responsibility between GP and MHP, compared to 33% of GPs; 62% of GPs believed it was their sole responsibility. Forty-six percent of MHPs believed managing CVD risk was a joint responsibility compared with 29% of GPs; 58% of GPs saw this as their role. Only 13% of MHPs and fewer than 4% of GPs agreed that MH services were effectively assessing and managing CVD risk. MHPs identified lack of knowledge and skills (58%) and poor communication between primary-secondary care (53%) as the main barriers. GPs identified barriers of poor communication (64%) and patient compliance with health care management (71%). The top two solutions proposed by MHPs were provision of GP subsidies (47%) and training (43%). GPs also identified provision of a subsidy (66%) and collaborative management between GPs and MH (44%) as solutions. There is widespread recognition of increased risk of CVD in MH patients. MHPs do not believe they have the knowledge and skills to manage this risk. GPs believe this is their responsibility. Both groups recognise communication with, and access to, primary care for MH patients as key barriers.


Performance-enhancing technologies for steers grazing tall fescue pastures with varying levels of toxicity1.
The objective of this study was to evaluate a combination of best management practices strategy for steer calves grazing tall fescue pastures with a range of toxicity. The experiment was conducted over 2 grazing seasons (fall 2015 for 91 d and spring 2016 for 84 d). Steers (n = 80 within season, body weight [BW] = 197.0 ± 15.43 kg [fall] and 116.9 ± 4.88 [spring]) were stocked at 2.45 and 4.1 calves/ha in fall and spring, respectively, to 16 pastures with varying levels of toxicity based on interim ergovaline (EV) concentration within season. Pastures were assigned to either mineral (MIN, n = 8) only management (MGMT) or a cumulative MGMT (CM, n = 8). The CM treatment included an implant containing 40-mg trenbolone acetate, 8-mg estradiol, and 29-mg tylosin tartrate (Component TE-G with Tylan, Elanco Animal Health, Greenfield, IN), 150 mg/calf daily monensin (Elanco Animal Health), and 1% BW of a 50:50 corn gluten feed:soybean hull supplement (as-is basis). Data were analyzed within season using pasture as the experimental unit. For fall and spring, the EV concentration was 1,476 ± 883.2 and 1,173 ± 620.6 ppb, respectively, and ranged from 90 to 2,180 ppb. During the fall, forage allowance did not differ (P = 0.76) between CM and MIN. In the spring, however, forage allowance only differed for the month of June (P ≤ 0.05, 2.55 vs. 3.22 ± 0.177 kg DM/kg BW, for MIN and CM, respectively). In the fall, average daily gain (ADG) responded to the simple effects of EV (P = 0.01) and MGMT (P < 0.001), and ADG for MIN steers was explained by ADG = 0.41 - 0.000064 × EV, whereas ADG for CM was explained by ADG = 1.05 - 0.000064 × EV. In the spring, there was an EV × MGMT interaction (P = 0.03) for ADG. For MIN, ADG = 0.80 - 0.000278 × EV, whereas for CM, ADG = 0.94 + 0.000001835 × EV. In spring, the ADG response to CM relative to MIN increased as EV increased. The CM strategy resulted in lower blood urea nitrogen than MIN in fall and spring (P < 0.01), but prolactin and serum Cu were not affected by MGMT in either season. In conclusion, performance was improved within the fescue belt by implementing feeding strategies using implants, ionophores, and supplementation, but a detailed economic analysis is warranted. Further research is needed to evaluate CM programs under varied stocking rates and in combination with dilution of endophyte-infected fescue pastures with nontoxic grasses or legumes.


Spatial learning in the cuttlefish Sepia officinalis: preference for vertical over horizontal information.
The world is three-dimensional; hence, even surface-bound animals need to learn vertical spatial information. Separate encoding of vertical and horizontal spatial information seems to be the common strategy regardless of the locomotory style of animals. However, a difference seems to exist in the way freely moving species, such as fish, learn and integrate spatial information as opposed to surface-bound species, which prioritize the horizontal dimension and encode it with a higher resolution. Thus, the locomotory style of an animal may shape how spatial information is learned and prioritized. An alternative hypothesis relates the preference for vertical information to the ability to sense hydrostatic pressure, a prominent cue unique to this dimension. Cuttlefish are mostly benthic animals, but they can move freely in a volume. Therefore, they present an optimal model to examine these hypotheses. We tested whether cuttlefish could separately recall the vertical and horizontal components of a learned two-dimensional target, and whether they have a preference for vertical or horizontal information. Sepia officinalis cuttlefish were trained to select one of two visual cues set along a 45 deg diagonal. The animals were then tested with the two visual cues arranged in a horizontal, vertical or opposite 45 deg configuration. We found that cuttlefish use vertical and horizontal spatial cues separately, and that they prefer vertical information to horizontal information. We propose that, as in fish, the availability of hydrostatic pressure, combined with the ecological value of vertical movements, determines the importance of vertical information.


A stent is not just a stent: Stent construction and design do matter in its clinical performance.
The undisputed superiority of stents over conventional balloon angioplasty has resulted in a plethora of stents in clinical use. Recent data, however, have indicated not all stent models are the same. Nuances in stent design and construction have impacted significantly on the immediate and long-term clinical outcome. Among the stainless steel stents, those with multicellular or tubular designs have proven to be superior to coiled or hybrid stent models, and thin-strut stents perform better than thicker-strut stents. Coating stainless steel stents with gold, carbide, phosphorylcholine or heparin do not appear to confer any additional benefit, compared with bare metal stents. In contrast, randomised trials have demonstrated that drug-eluting stents coated with various anti-proliferative drugs, with or without a carrier polymer, afford unparalleled restenosis rates compared with non-drug-eluting stents. Drug-eluting stents, however, are expensive, and their long-term durability and safety remain undefined. Notwithstanding these unresolved issues, it is likely that the majority of percutaneous coronary interventions will involve the use of drug-eluting stents once a more attractive balance between their cost and clinical effects is reached.


The effect of menopause on grip and pinch strength: results from the Chicago, Illinois, site of the Study of Women's Health Across the Nation.
Women may experience a decline in physical function during menopause. Whether this decline is due to aging or to changes in hormonal status is unknown. The authors performed a longitudinal data analysis on data collected between 1996 and 2001 to determine the effects of menopausal status, age, race, and use of hormone replacement therapy (HRT) on 3-year changes in grip and pinch strength. Participants were 563 women from the Chicago, Illinois, site of the Study of Women's Health Across the Nation. According to adjusted analyses, women who became postmenopausal showed a 1.04-kg decline in grip strength (p = 0.10) and a 0.57-kg decline in pinch strength (p = 0.002) relative to women who remained premenopausal. Women who became early perimenopausal showed a 0.20-kg decline in pinch strength (p = 0.04), whereas women who transitioned to late perimenopause showed a 0.93-kg decline in grip strength (p = 0.07). Effects of menopausal status on grip and pinch strength did not vary by race. A significant HRT-by-race interaction for grip strength was found; African-American HRT users had greater grip strength during the study, whereas Caucasian HRT users did not (p = 0.05). Greater physical activity was the strongest predictor of grip and pinch strength (p < 0.0001). Results indicate that transition through menopause is associated with a decline in grip and pinch strength.


CcpN controls central carbon fluxes in Bacillus subtilis.
The transcriptional regulator CcpN of Bacillus subtilis has been recently characterized as a repressor of two gluconeogenic genes, gapB and pckA, and of a small noncoding regulatory RNA, sr1, involved in arginine catabolism. Deletion of ccpN impairs growth on glucose and strongly alters the distribution of intracellular fluxes, rerouting the main glucose catabolism from glycolysis to the pentose phosphate (PP) pathway. Using transcriptome analysis, we show that during growth on glucose, gapB and pckA are the only protein-coding genes directly repressed by CcpN. By quantifying intracellular fluxes in deletion mutants, we demonstrate that derepression of pckA under glycolytic condition causes the growth defect observed in the ccpN mutant due to extensive futile cycling through the pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate kinase. Beyond ATP dissipation via this cycle, PckA activity causes a drain on tricarboxylic acid cycle intermediates, which we show to be the main reason for the reduced growth of a ccpN mutant. The high flux through the PP pathway in the ccpN mutant is modulated by the flux through the alternative glyceraldehyde-3-phosphate dehydrogenases, GapA and GapB. Strongly increased concentrations of intermediates in upper glycolysis indicate that GapB overexpression causes a metabolic jamming of this pathway and, consequently, increases the relative flux through the PP pathway. In contrast, derepression of sr1, the third known target of CcpN, plays only a marginal role in ccpN mutant phenotypes.


Poly (ADP-ribose) polymerase 3 (PARP3), a potential repressor of telomerase activity.
Considering previous result in Non-Small Cell Lung Cancer (NSCLC), we investigated in human cancer cells the role of PARP3 in the regulation of telomerase activity. We selected A549 (lung adenocarcinoma cell line) and Saos-2 (osteosarcoma cell line), with high and low telomerase activity levels, respectively. The first one was transfected using a plasmid construction containing a PARP3 sequence, whereas the Saos-2 cells were submitted to shRNA transfection to get PARP3 depletion. PARP3 expression on both cell systems was evaluated by real-time quantitative PCR and PARP3 protein levels, by Western-blot. Telomerase activity was determined by TRAP assay. In A549 cells, after PARP3 transient transfection, data obtained indicated that twenty-four hours after transfection, up to 100-fold increased gene expression levels were found in the transfected cells with pcDNA/GW-53/PARP3 in comparison to transfected cells with the empty vector. Moreover, 48 hours post-transfection, telomerase activity decreased around 33%, and around 27%, 96 hours post-transfection. Telomerase activity average ratio was 0.67 ± 0.05, and 0.73 ± 0.06, respectively, with significant differences. In Saos-2 cells, after shRNA-mediated PARP3 silencing, a 2.3-fold increase in telomerase activity was detected in relation to the control. Our data indicated that, at least in some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity, this fact contributing to telomere maintenance and, therefore, avoiding genome instability.


Linking subsistence harvest diversity and productivity to adaptive capacity in an Alaskan food sharing network.
Although anthropogenic climate change poses existential challenges for Indigenous communities in the Arctic, these challenges are not entirely unprecedented. Over many generations, Arctic peoples have developed a wide range of behavioral strategies to navigate environmental change and uncertainty, and these strategies provide a foundation for contemporary adaptation. In this article, we focus on mixed cash-subsistence economies and the social networks that underlie them in Alaska. The patterns of food production, labor exchange, and food sharing in subsistence-oriented communities throughout Alaska are driven by the productivity of keystone households who regularly harvest and share resources within and between communities. Building on previous research suggesting the critical importance of these networks to community resilience, we use network analysis to investigate whether patterns in resource transfers between households are associated with subsistence harvest diversity-the diversity of species harvested by a household unit. We use exponential random graph models to describe the structure of a sharing network from Aniak, Alaska, and model the links between harvest productivity, harvest diversity, and household position in this network. Our results indicate that both productivity and diversity are positively associated with network connections, and that productivity alone provides an incomplete model of network structure. We suggest that subsistence harvest diversity may play a unique role in supporting adaptive capacity and resilience by maintaining the productivity of keystone households despite changing environments and sustaining social network structures that circulate resources throughout the community. Harvest diversity may also serve as a broad indicator of Indigenous ecological knowledge and a tangible representation of cultural practices, values, and worldviews that underlie subsistence in Alaska. Greater attention to harvest diversity is important for understanding how subsistence networks adapt to environmental change and uncertainty linked to social and ecological dynamics of anthropogenic climate change.


Intersegmental dynamics are controlled by sequential anticipatory, error correction, and postural mechanisms.
The purpose of this study is to examine the mechanisms underlying control of intersegmental dynamics during reaching movements. Two experiments were conducted to determine the relative contributions of anticipatory and somatosensory feedback mechanisms in controlling intersegmental dynamics and whether adaptation to novel intersegmental dynamics generalizes across a range of movement directions. The mechanisms used to control interaction torques were examined by altering the inertial load of the forearm. Movements were restricted to the shoulder and elbow and supported on a horizontal plane by a frictionless air-jet system. Subjects made rapid out-and-back movements over a target line presented on a computer screen. The screen cursor disappeared at movement onset, and hand paths were displayed after each movement. After subjects adapted to a novel inertial configuration, the position of an attached mass was changed on pseudorandom trials. During these "surprise" trials, movements were initiated with the torque patterns appropriate to the previously learned inertial condition. As a result, characteristic errors in initial movement direction were predicted by an open-looped forward simulation. After these errors occurred, feedback mediated changes in torque emerged that, surprisingly, further decreased the accuracy of movement reversals. Nevertheless at the end of movement, the hand consistently returned to the starting position. It is plausible that the final position was determined completely by feedback-mediated changes in torque. In a second experiment, adaptation to a novel inertial load during movements made in a single direction showed limited transfer across a range of directions. These findings support and extend those of previous reports, which indicated combined anticipatory and postural mechanisms to coordinate rapid reaching movements. The current results indicate a three-stage control system that sequentially links anticipatory, error correction, and postural mechanisms to control intersegmental dynamics. Our results, showing limited generalization across directions, are consistent with previous reports examining adaptation to externally applied forces and extend those findings to indicate that the nervous system uses sensory information to recalibrate internal representations of the musculoskeletal apparatus itself.


Relationship between autofluorescence and advanced glycation end products in diabetic lenses.
Autofluorescence and advanced glycation end product (AGE) levels were measured in the lenses of 9 diabetic Chinese hamsters and 6 age-matched controls. Lens autofluorescence also was measured in 37 diabetic patients and 14 age-matched controls. Lens autofluorescence values were measured noninvasively with a lens measurement system using color filters with peak transmission at 365- and 434-nm wavelengths (excitation and emission, respectively) that are characteristic of AGE fluorescence. The peak lens autofluorescence level was used as the lens autofluorescence value, and the mean lens autofluorescence values from both eyes of each subject were used for statistical analysis. The AGE levels in one lens from each hamster were measured by noncompetitive enzyme-linked immunosorbent assay with a polyclonal anti-AGE antibody. We found a 2.2 times increase of the mean lens autofluorescence value of diabetic hamsters in comparison with that of controls (P<0.01). We also found a 1.5 times increase of the mean AGE level from the lenses of diabetic hamsters in comparison with that of controls (P<0.01). Moreover, a statistically significant positive correlation between the AGE level and autofluorescence value in the same lenses was observed in all hamsters (rho=0.58, P<0.05). In human subjects, we found a 1.4 times increase of the mean lens autofluorescence value of diabetic patients in comparison with that of age-matched controls (P<0.01). Our results suggest that non invasive measurement of lens autofluorescence may be a guide to AGE levels in lenses.


Description, DNA barcode and phylogeny of a new species, Macrobrachium abrahami (Decapoda: Palaemonidae) from Kerala, India.
Macrobrachium abrahami, new species is described from Vamanapuram River, Kerala, South India. DNA bar-coding using Cytochrome B gene sequences has elucidated the taxonomic status of the new species and the ML tree reveals that M. abrahami sp. nov., is phylogenetically close to M. prabhakarani, but morphologically more similar to M. scabriculum. However, the species shares certain morphological characters with M. scabriculum, M. prabhakarani and M. lanatum, but differs remarkably from these three species in distinctive diagnostic characters: rostrum moderately long, convex, distal end directed upwards, rostral formula 12-15/2-3 with 5-6 postorbital teeth, and carapace glabrous. In larger second chelate leg, fingers stout, pubescence restricted to their base; proximal half of cutting edge with fifteen denticles. In smaller second chelate leg, cutting edge of both fingers carry six small denticles situated proximally, distal one comparatively larger. Delicate setae are seen throughout the palm. A row of dark chromatophores is present along the posterio-dorsal margin of uropodal exopods and endopods, close to the base of uropodal setae. The thickness of each band of the row is almost equal to the thickness of uropodal setae.


Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers.
In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.


Epidemiological data, outcome, and costs of burn patients in Kermanshah.
Burn injuries in both developed and developing countries cause long-term disability, mortality, and socio-economic costs that are imposed on patients, families, and societies. This study was carried out to investigate the epidemiology, outcome, and cost of hospitalization of 388 burn patients admitted to the Imam Khomeini Hospital Burn Center in Kermanshah, Iran, between 21 March 2011 and 20 March 2012. The data about demographics, cause of burns, degree of burns, outcome of burns, burned body surface (BBS), length of stay (LOS), and cost of hospitalization were collected by reviewing medical records and analysed by SPSS 16. The patients' mean age was 27 years. The male/female ratio in burn patients was 1.14/1. The mean BBS was 36.06%. The mean LOS was 9.04 days. Flame (67.0%) and hot liquids (21.9%) were the major causes of burn. Burn injuries were more common in the upper limbs (81.4%), lower limbs (70.9%), and head and neck (65.2%). 11.6% of patients had all the regions involved. The fatality rate was 18.8%. The mean cost per patient was 20,463,227 Iran Rials (IRR). The cost per one percentage of burn and one day of hospitalization was 562,632 IRR and 2,263,631 IRR, respectively. The main factors relevant to death were identified including the extent of burn, gender, age, causes, and degree of burn. In addition, LOS proved to have a higher impact on costs than burn percentage.


Ozone-induced changes in photosynthesis and photorespiration of hybrid poplar in relation to the developmental stage of the leaves.
Young poplar trees (Populus tremula Michx. x Populus alba L. clone INRA 717-1B4) were subjected to 120 ppb of ozone for 35 days in phytotronic chambers. Treated trees displayed precocious leaf senescence and visible symptoms of injury (dark brown/black upper surface stippling) exclusively observed on fully expanded leaves. In these leaves, ozone reduced parameters related to photochemistry (Chl content and maximum rate of photosynthetic electron transport) and photosynthetic CO(2) fixation [net CO(2) assimilation, Rubisco (ribulose-1,5-bisphosphate carboxylase oxygenase) activity and maximum velocity of Rubisco for carboxylation]. In fully expanded leaves, the rate of photorespiration as estimated from Chl fluorescence was markedly impaired by the ozone treatment together with the activity of photorespiratory enzymes (Rubisco and glycolate oxidase). Immunoblot analysis revealed a decrease in the content of serine hydroxymethyltransferase in treated mature leaves, while the content of the H subunit of the glycine decarboxylase complex was not modified. Leaves in the early period of expansion were exempt from visible symptoms of injury and remained unaffected as regards all measured parameters. Leaves reaching full expansion under ozone exposure showed potential responses of protection (stimulation of mitochondrial respiration and transitory stomatal closure). Our data underline the major role of leaf phenology in ozone sensitivity of photosynthetic processes and reveal a marked ozone-induced inhibition of photorespiration.


Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation.
Phagocytosis involves the receptor-mediated extension of plasmalemmal protrusions, called pseudopods, which fuse at their tip to engulf a particle. Actin polymerizes under the nascent phagosome and may propel the protrusion of pseudopods. Alternatively, membrane extension could result from the localized insertion of intracellular membranes into the plasmalemma next to the particle. Here we show focal accumulation of VAMP3-containing vesicles, likely derived from recycling endosomes, in the vicinity of the nascent phagosome. Using green fluorescent protein (GFP) as both a fluorescent indicator and an exofacial epitope tag, we show that polarized fusion of VAMP3 vesicles precedes phagosome sealing. It is therefore likely that targeted delivery of endomembranes contributes to the elongation of pseudopods. In addition to mediating pseudopod formation, receptor-triggered focal secretion of endosomes may contribute to polarized membrane extension in processes such as lamellipodial elongation or chemotaxis.


Old people not known to the general practitioner: low risk group.
The elderly patients in a large general practice aged 75 and over who lived at home (n = 877) were divided into two groups according to the general practitioner's knowledge of their risk status and were designated "risk status known" (n = 679) and "risk status not known" (n = 198). Forty-three high risk patients in the risk status known group had a functional disability score and experience of mortality that was not dissimilar to those of elderly people in institutions. The medical and social characteristics of a random sample (n = 150) of the risk status known group, after excluding the high risk patients, were compared with the risk status not known group using a Barber Wallis questionnaire. A response rate of 90% was achieved from both groups and a cumulative risk score was calculated by totalling unfavourable replies to the questions. The risk status not known group, which comprised 14% of the patients who lived at home after correcting for the number who had died and moved, had appreciably less contact with the general practitioners, had an appreciably lower cumulative risk score, were confined at home less because of ill health, were less concerned about their health, and were less in need of nursing attention. The findings of this study suggest that the elderly patients who are not known to their general practitioners are in relatively good health when compared with the patients that the general practitioner knows well.


Study on development of Vipera lebetina snake anti-venom in chicken egg yolk for passive immunization.
Chicken egg yolk antibodies against Vipera lebetina venom were evaluated for their antivenom potential. White leghorn hens were immunized with detoxified V. lebetina venom (γ-irradiated venom). The detoxified venom (200 μg) was mixed with an equal volume of complete Freund's adjuvant and was injected intramuscularly into the hens. The antibodies showed high activity (1.6 LD50/mL) in egg yolks after 12 d of venom injection. The eggs were collected after 12 days, and the egg yolks were removed and washed with purified water to remove any contamination with egg whites. The purification was performed using a method described by Maya Devi et al., followed by gel filtration (Sephadex G-50). The purity and molecular weight of antivenom antibodies (IgY) were determined using electrophoresis, and the molecular weight was found to be approximately 185 kDa. The potency of IgY was 6 LD50/mL (mice), i.e., 1 mL of IgY could neutralize 43.8 μg of standard V. lebetina venom). Our results showed that chicken egg yolk antibodies were effective in neutralizing the lethality and several pharmacological effects of V. lebetina venom and could be used for developing effective antivenom.