Utilization of the burn unit for nonburn patients: the "wound intensive care unit".
Burn units and experienced burn nurses are valuable, expensive resources that are underutilized when the burn census is low. Burn facilities can be used to treat other conditions or injuries to provide optimum wound management or to provide overflow intensive care unit beds. We studied via a questionnaire survey the admission profiles of 120 burn units in the United States to determine frequency of utilization for nonburn injuries. One hundred sixteen burn units routinely treat nonburn injuries. Seventy-seven burn units also accept overflow patients from other critical care units. A significant amount of nonburn wound care is being provided by burn units in the United States, with potential benefit to both the patient and the burn unit. The implications of the use of burn facilities as "wound intensive care units" are discussed.


A taxonomic, genetic and ecological data resource for the vascular plants of Britain and Ireland.
The vascular flora of Britain and Ireland is among the most extensively studied in the world, but the current knowledge base is fragmentary, with taxonomic, ecological and genetic information scattered across different resources. Here we present the first comprehensive data repository of native and alien species optimized for fast and easy online access for ecological, evolutionary and conservation analyses. The inventory is based on the most recent reference flora of Britain and Ireland, with taxon names linked to unique Kew taxon identifiers and DNA barcode data. Our data resource for 3,227 species and 26 traits includes existing and unpublished genome sizes, chromosome numbers and life strategy and life-form assessments, along with existing data on functional traits, species distribution metrics, hybrid propensity, associated biomes, realized niche description, native status and geographic origin of alien species. This resource will facilitate both fundamental and applied research and enhance our understanding of the flora's composition and temporal changes to inform conservation efforts in the face of ongoing climate change and biodiversity loss.


Almost pure I(alpha) cellulose in the cell wall of Glaucocystis.
Crystalline features of cellulose microfibrils in the cell walls of Glaucocystis (Glaucophyta) were studied by combined spectroscopy and diffraction techniques, and the results were compared with those of Oocystis (Chlorophyta). Although these algae are grouped into two different classes, by the composition of their chloroplasts for instance, their cell walls are quite similar in size and morphology. The most striking features of their cellulose crystallites are that they have the highest cellulose I(alpha) contents reported to date. In particular, the I(alpha) fraction of cellulose from Glaucocystis was found to be as high as 90% from (13)C NMR analysis. The mode of preferential orientation of cellulose crystallites in their cell walls is also interesting; equatorial 0.53-nm lattice planes were oriented parallel to the cell surface in the case of Glaucocystis, while the 0.62-nm planes were parallel to the Oocystis cell surface. Such a structural variation provides another link to the evolution of cellulose structure, biosynthesis, and its biocrystallization mechanism.


Growth inhibition and apoptosis of gastric cancer cell lines by Anemarrhena asphodeloides Bunge.
In this study, we aimed to determine the growth inhibition and the induction of apoptotic cell death brought about by the herb Anemarrhena asphodeloides Bunge in gastric cancer cell lines, and to clarify the mechanism of this apoptosis. Water-soluble ingredients of A. asphodeloides, and the gastric cancer cell lines, MKN45 and KATO-III, were used in vitro. Growth inhibition, induction of cell death, morphological features, the presence of DNA ladders, increases in caspase-3-like activity, the effects of a caspase-3 inhibitor on apoptotic cell death, and the release of cytochrome c by A. asphodeloides were analyzed. A. asphodeloides inhibited the growth and decreased the viability of the gastric cancer cell lines. The viability of normal skin fibroblasts in the presence of low concentrations of A. asphodeloides was higher than that of gastric cancer cells. Apoptotic bodies and DNA ladders were observed to be induced in MKN45 and KATO-III by A. asphodeloides. The caspase 3 inhibitor, Ac-DEVD-CHO, inhibited the apoptotic cell death of gastric cancer cells induced by A. asphodeloides. The caspase 3-like activity in MKN45 and KATO-III cells increased after the addition of A. asphodeloides. Cytochrome c was released from mitochondria into the cytosol 8 h after the addition of A. asphodeloides, and reached a peak at 16 h. The peak of cytochrome c release was earlier than that of caspase 3-like activity. We concluded that A. asphodeloides inhibited the growth of the gastric cancer cell lines MKN45 and KATO-III and induced apoptosis. The apoptosis of MKN45 and KATO-III cells induced by A. asphodeloides was associated with the release of cytochrome c from the mitochondria, followed by an increase in caspase 3-like activity.


Changeable camouflage: how well can flounder resemble the colour and spatial scale of substrates in their natural habitats?
Flounder change colour and pattern for camouflage. We used a spectrometer to measure reflectance spectra and a digital camera to capture body patterns of two flounder species camouflaged on four natural backgrounds of different spatial scale (sand, small gravel, large gravel and rocks). We quantified the degree of spectral match between flounder and background relative to the situation of perfect camouflage in which flounder and background were assumed to have identical spectral distribution. Computations were carried out for three biologically relevant observers: monochromatic squid, dichromatic crab and trichromatic guitarfish. Our computations present a new approach to analysing datasets with multiple spectra that have large variance. Furthermore, to investigate the spatial match between flounder and background, images of flounder patterns were analysed using a custom program originally developed to study cuttlefish camouflage. Our results show that all flounder and background spectra fall within the same colour gamut and that, in terms of different observer visual systems, flounder matched most substrates in luminance and colour contrast. Flounder matched the spatial scales of all substrates except for rocks. We discuss findings in terms of flounder biology; furthermore, we discuss our methodology in light of hyperspectral technologies that combine high-resolution spectral and spatial imaging.


Facilitation of adrenergic transmission in the canine heart by intracoronary infusion of angiotensin II: effect of prostaglandin synthesis inhibition.
We studied the effect of intracoronary angiotensin II (AII) infusion on the coronary sinus output of norepinephrine (NE) elicited by left cardiac sympathetic nerve stimulation in pentobarbital-anesthetized dogs pretreated with a prostaglandin synthesis inhibitor (indomethacin) or its vehicle. The NE output from the heart was determined from the NE levels in coronary sinus blood before and during cardiac sympathetic nerve stimulation. In both indomethacin- and vehicle-pretreated animals, infusion of AII (30 ng kg-1 min-1) into the left coronary artery augmented the coronary sinus output of NE elicited by sympathetic nerve stimulation, but had no effect on the basal output of NE from the heart. In both groups of animals, the AII-induced increase in NE output was associated with an increase in the effect of cardiac sympathetic nerve stimulation on left ventricular contractility (LVdP/dt max). All did not alter the removal of exogenous NE by the heart and moreover the AII-induced increase in the output of NE elicited by cardiac sympathetic nerve stimulation was also observed during blockade of neuronal and extraneuronal uptake with cocaine and normetanephrine, respectively. Therefore, the All-induced increase in the coronary sinus output of NE and LVdPl dt max elicited by cardiac sympathetic nerve stimulation is most likely due to enhanced NE release from adrenergic nerve terminals in the heart. The ability of All to increase the coronary sinus output of NE and the positive inotropic response elicited by cardiac sympathetic nerve stimulation was enhanced in animals pretreated with the cyclooxygenase inhibitor, indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)


Preliminary evaluation of molecular imprinting of 5-fluorouracil within hydrogels for use as drug delivery systems.
Molecular imprinting is a new and rapidly evolving technique used to create synthetic receptors and it possesses great potential in a number of applications in the life sciences. Keeping in mind the therapeutic importance of 5-fluorouracil (5-FU) and the technological significance of molecular imprinting polymers, the present study is an attempt to synthesize 2-hydroxyethylmetacrylate- and acrylic acid-based 5-FU imprinted hydrogels. For the synthesis of these hydrogels, N,N'-methylenebisacrylamide was used as a crosslinker, ammonium persulfate as an initiator and N,N,N',N'-tetramethylethylenediamine as an accelerator. Both molecular imprinted polymers (MIPs) and non-imprinted polymers were synthesized at the optimum crosslinker concentration obtained from swelling studies and used to study their recognition affinity, their swelling and the in vitro release dynamics of the drug. It was observed from this study that the recognition affinity of MIPs is increased when these are synthesized in a high concentration template solution.


Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk.
A recent genome wide association study of chronic lymphocytic leukaemia (CLL) provided evidence that common variation at 2q13 (rs17483466), 2q37.1 (rs13397985), 6p25.3 (rs872071), 11q24.1 (rs735665), 15q23 (rs7176508) and 19q13.32 (rs11083846) affects CLL risk. To verify and further explore the relationship between these variants and CLL risk we genotyped case-control datasets from Spain and Sweden (824 cases, 850 controls). Combined data provided statistically significant support for an association between genotypes at rs13397985, rs872071, rs735665, rs7176508 and rs11083846 and CLL risk. CLL risk increased with increasing numbers of risk alleles (P(trend) = 1.40 x 10(-15)), consistent with a polygenic model of disease susceptibility. These data validate the relationship between common variation and risk of CLL.


Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip.
Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells - a phenomenon known as 'thromboinflammation'. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.


Conjugated foldamers with unusually high space-charge-limited current hole mobilities.
Charge carrier mobility and its optimization play a critical role in the development of cutting-edge organic electronic and optoelectronic devices. Even though space-charge-limited current (SCLC) hole mobilities as high as 1.4 cm(2) V(-1) s(-1) have been reported for microscopically sized highly ordered liquid-crystalline conjugated small molecules, the SCLC hole mobility of device-sized thin films of conjugated polymers is still much lower, ranging from 10(-6) to 10(-3) cm(2) V(-1) s(-1). Herein, we report the synthesis, characterizations, and thin-film SCLC mobility of three discotic conjugated polymers, INDT-TT, INDT-BT, and INDT-NDT. Optical studies indicate that polymer INDT-NDT adopts a folded conformation in solutions of good or poor solvents, whereas polymer INDT-TT stays as random monomeric chains in good solvents and interchain aggregates in poor solvents. INDT-BT polymer chains, however, stay as foldamers in dilute solutions of good solvents but interchain aggregates in concentrated solutions or poor solvents. Circular dichroism spectroscopy provides clear evidence for the helical folding of INDT-NDT in solutions. Thin films spin-coated from 1,2-dichlorobenzene solutions of the polymers show SCLC hole mobility of 2.20 × 10(-6), 8.79 × 10(-5), and 2.77 × 10(-2) cm(2) V(-1) s(-1) for INDT-TT, INDT-BT, and INDT-NDT, respectively. HRTEM and powder XRD measurements show that INDT-NDT pristine thin films contain nanocrystalline domains, whereas the INDT-TT and INDT-BT films are amorphous. Thin films of INDT-NDT:PC71BM blends show increased crystallinity and further improved SCLC hole mobility up to 1.29 × 10(-1) cm(2) V(-1) s(-1), one of the highest SCLC mobility values ever recorded on solution-processed organic semiconducting thin films. The persistent folding conformation of INDT-NDT is believed to be responsible for the high crystallinity of its thin films and its high SCLC mobilities.


Combined retrograde flexible ureteroscopic lithotripsy with holmium YAG laser for renal calculi associated with ipsilateral ureteral stones.
The purpose of this study was to evaluate the effectiveness of combined ureteroscopic holmium YAG lithotripsy for renal calculi associated with ipsilateral ureteral stones. Between August 2002 and March 2007, retrograde flexible ureteroscopic stone treatment was attempted in 351 cases. Indication for treatment was concurrent symptomatic ureteral stones in 63 patients (group I). Additional operative time and perioperative complication rates were compared to a group of 39 patients submitted to ureteroscopic treatment for ureteral calculi exclusively (group II). Mean ureteral stone size was 8.0 +/- 2.6 mm and 8.1 +/- 3.4 mm for groups I and II, respectively. Mean operative time for group I was 67.9 +/- 29.5 minutes and for group 2 was 49.3 +/- 13.2 minutes (p < 0.001). Flexible ureteroscopic therapy for renal calculi increased 18 minutes in the mean operative time. The overall complication rate was 3.1% and 2.5% for groups I and II, respectively (p = 0.87). Mean renal stone size was 10.7 +/- 6.4 mm, overall stone free rate in group I was 81%. However, considering only patients with renal stones smaller than 15 mm, the stone free rate was 88%. Successful treatment occurred in 81% of patients presenting lower pole stones, but only 76% of patients with multiple renal stones became stone free. As expected, stone free rate showed a significant negative correlation with renal stone size (p = 0.03; r = -0.36). Logistic regression model indicated an independent association of renal stones smaller than 15 mm and stone free rate (OR = 13.5; p = 0.01). Combined ureteroscopic treatment for ureteral and ipsilateral renal calculi is a safe and attractive option for patients presenting for symptomatic ureteral stone and ipsilateral renal calculi smaller than 15 mm.


Effect of glutamine and maltodextrin acute supplementation on anaerobic power.
The aim of this study was to investigate whether supplementation of carbohydrate together with peptide glutamine would prevent anaerobic power decrease during repeated competitions. Twenty eight physical education male students voluntarily participated in the study. Subjects were randomly divided on a maximal power (Max power) output value basis into four groups: 1) G group (oral ingestion of glutamine at the dose of 0.25 g/kg body mass in 250 ml of water), 2) M group (a single carbohydrate at a concentration of 50g of maltodextrin in 250 ml of water), 3) GM group (carbohydrate at a concentration of 50g of maltodextrin + glutamine at the dose of 0.25 g/kg body mass in 250 ml of water) and, 4) P group (just 250 ml of water and 30 gram sweetener). Each subject performed three times Running-based Anaerobic Sprint Test (RAST) with intervals of 1 hour. Max power, Minimal power (Min power) and fatigue were calculated for each participant. There was a significant decrease in Max and Min power in P group in time series (P<0.05). Furthermore, regarding the Max and Min power, there was significant difference between P and GM group in third bout indicating stronger influence of combination of maltodextrin and glutamine in comparison with pure consumption of glutamine and maltodextrin (P< 0.05). It seems acute supplementation of glutamine and maltodextrin combination, 2 hours before exercise is more efficient in prevention of anaerobic power decrease than consumption of a pure carbohydrate or glutamine in repeated bouts of RAST protocol. Thus, supplementation with both carbohydrate and peptide glutamine improved the physical performance of athletes during repeated competitions. Obviously, it is necessary to do further studies.


Expression dynamics of the aplysia abyssovirus.
Two recent studies documented the genome of a novel, extremely large (35.9 kb), nidovirus in RNA sequence databases from the marine neural model Aplysia californica. The goal of the present study was to document the distribution and transcriptional dynamics of this virus, Aplysia abyssovirus 1 (AAbV), in maricultured and wild animals. We confirmed previous findings that AAbV RNA is widespread and reaches extraordinary levels in apparently healthy animals. Transmission electron microscopy identified viral replication factories in ciliated gill epithelial cells but not in neurons where viral RNA is most highly expressed. Viral transcripts do not exhibit evidence of discontinuous RNA synthesis as in coronaviruses but are consistent with production of a single leaderless subgenomic RNA, as in the Gill-associated virus of Penaeus monodon. Splicing patterns in chronically infected adults suggested high levels of defective genomes, possibly explaining the lack of obvious disease signs in high viral load animals.


A review of bush dog Speothos venaticus (Lund, 1842) (Carnivora, Canidae) occurrences in Paraná state, subtropical Brazil.
We report six new occurrence records of the bush dog Speothos venaticus, a widely distributed South American carnivore that is threatened with extinction. These records are accompanied by notes on the places where the records were made, such as vegetation type, date and information about the protection of areas. The records, obtained over the last 17 years in Paraná state, southern Brazil, offer an improved understanding of the species geographic range and the threats it faces and can enable better assessments of the conservation status of the species in southern Brazil.


Design of highly stable functional GroEL minichaperones.
GroEL minichaperones have potential in the biotechnology industry for the refolding of recombinant proteins. With the aim of enhancing and widening their use, we have created two highly stable functional variants of minichaperone GroEL(193-345). A sequence alignment of 130 members of the chaperonin 60 (Cpn60) family was used to design 37 single mutations. Two small-to-large mutations, A223T, A223V and one similar-size mutation, M233L, all located in the hydrophobic core were found to stabilize the protein by more than 1 kcal mol(-1) each. Six stabilizing mutations were combined, yielding two multiple mutants that were 6.99 and 6.15 kcal mol(-1) more stable than wild-type protein. Even though some of the substituted residue pairs are close to each other in the protein structure, the energetic effects of mutation are approximately additive. In particular, the stabilizing substitution A223T is unexpected and would have been missed by purely structural analysis. In the light of previously reported successes employing similar methods with several other proteins, our results show that a homology based approach is a simple and efficient method of increasing the stability of a protein.


2,6-Dichloro-aniline-4-(2,6-dichloro-anilino)-pent-3-en-2-one (1/2).
The asymmetric unit of the title compound, C6H5Cl2N·2C11H11Cl2NO, is composed of one mol-ecule of an enamino-ketone [i.e. -(2,6-dichloro-phenyl-amino)-pent-3-en-2-one] and half a mol-ecule of 2,6-dichloro-aniline, the whole mol-ecule of the latter component being generated by twofold rotational symmetry. In this latter mol-ecule, there are two intra-molecular N-H⋯Cl contacts. In the enamino-ketone mol-ecule, there is an N-H⋯O hydrogen bond of moderate strength, and the dihedral angle between the benzene ring and penta-none fragment [C-C(-N)=C-C(=O)-C; planar within 0.005 (1) Å] is 81.85 (7)°. In the crystal, two mol-ecules of the enamino-ketone are bridged by a mol-ecule of 2,6-dichloro-aniline via N-H⋯O hydrogen bonds of moderate strength. There are also π-π inter-actions present, involving the benzene rings of inversion-related enamino-ketone mol-ecules [centroid-centroid distance = 3.724 (4) Å].


Synthetic applications of hypophosphite derivatives in reduction.
The development of new tools for the reduction of organic functions to reach high chemo- and stereo-selectivity is an important research domain. Although, aluminum and boron hydrides are commonly used, they suffer from environmentally and safety issues. In particular, at industrial scale, the search for more specific and efficient reagents with a lower ecological impact remains one of the main objectives of organic chemists. This review captures highlights from literature concerning phosphonic and phosphinic acid derivatives as reducing agents and evaluates their potential as alternatives, in particular to boron and aluminum hydrides.


Endocrine regulation of the form and function of axonal arbors during insect metamorphosis.
By discrete manipulation of the endocrine cues that control insect metamorphosis, it has been possible to examine the mechanisms governing the growth of neural processes during development. During the transition from larva to pupa in the hawkmoth, Manduca sexta, identified sensory neurons reorganize their central projections to evoke a new behavior--the gintrap reflex. Topical application of a juvenile hormone analog to the peripheral cell bodies of these sensory neurons during a critical period of development caused them to retain their larval commitment rather than undergo pupal development with the rest of the animal. The sensory neurons retained the larval arborization pattern within the pupal CNS and were unable to evoke the gin-trap reflex. Thus, the hormonal environment of the cell body is critical for controlling growth and synapse formation by distant axonal processes.


Pretreatment with crocin along with treadmill exercise ameliorates motor and memory deficits in hemiparkinsonian rats by anti-inflammatory and antioxidant mechanisms.
The motor symptoms of Parkinson's disease (PD) are preceded by non-motorized symptoms including memory deficits. Treatment with dopamine replacement medications, such as L-DOPA only control motor symptoms and does not meet the clinical challenges of the disease, such as dyskinesia, non-motor symptoms, and neuroprotection. The purpose of the current study was to examine the neuroprotective potential of crocin and physical exercise in an animal model of PD. Male Wistar rats ran on a horizontal treadmill and/or pretreated with crocin at a dose of 100 mg/kg. Then, 16 μg of the neurotoxin 6-hydroxydopamine (6-OHDA) was microinjected into left medial forebrain bundle. Crocin treatment and/or exercise continued for 6 more weeks. Spatial and aversive memories, rotational behaviour, inflammatory and oxidative stress parameters were assessed at the end of week 6 post surgery. The results showed that pretreatment with crocin alone and in combination with exercise decreased the total number of rotaions as compared with 6-OHDA-lesioned group. Furthermore, treatment of parkinsonian rats with crocin along with exercise training improved aversive and spatial memories. Biochemical analysis showed that crocin and exercise (alone and in combination) reduced tumor necrosis factor- (TNF) α levels in the striatum. Moreover, treatment with crocin at a dose of 100 mg/kg decreased the lipid peroxidation levels in the hippocampus, while exercise training increased the total thiol concentration. In conclusion, our findings indicated that pretreatment with crocin along with treadmill exercise ameliorated motor and memory deficits induced by 6-OHDA, which is considered to be due to their antioxidant and anti-inflammatory activities. The results suggest that combined therapy with crocin and exercise may be protective for motor and memory deficits in PD patients.


Seasonal and daily variation of Aspergillus Mich. Ex Fr. spores in the atmosphere of Córdoba (Spain).
The atmosphere contains a complex of spores whose concentration and variation have been the subject of much study, mainly because of the relevance of fungi to allergic and aerobiological pollution problems. This paper reports on the cataloguing of the Aspergillus species present in the atmosphere of Córdoba, their seasonal and daily variation and their potential relationship with meterological parameters. The sampling was carried out in the city of Córdoba by using a volumetric trap on a culture medium; three samplings were done daily at various times throughout the year (May 1986-April 1987). An unreplicated variance analysis was applied to two variation sources in order to check for statistically significant differences between the number of colony forming units (CFU) detected at each sampling time. Meterological data and concentrations were also contrasted through statistical correlation tests. A total of 94,200 colonies were counted; 32.3% of all were from 24 species of the Aspergillus genus, of which A. fumigatus Fresen, was found to be the most abundant. Aspergillus niger Van Tiegh, A. oryzae (Ahlburg) Cohn, A. terreus Thom and A. ochraceus Wilhelm also occurred at a high frequency. All these species were detected throughout the year and in virtually all of the samplings, but particularly in autumn, which was the most favourable period for the occurrence of their spores, which in turn seemed to be conditioned by the time at which samplings were carried out, at least for the six most frequent species--A. candidus expected as it only occurred occasionally. Finally, the occurrence of spores of this genus seems to be positively and negatively correlated with meterological factors such as the wind speed and the temperature, respectively.


Mathematical model of TGF-βsignalling: feedback coupling is consistent with signal switching.
Transforming growth factor β (TGF-β) signalling regulates the development of embryos and tissue homeostasis in adults. In conjunction with other oncogenic changes, long-term perturbation of TGF-β signalling is associated with cancer metastasis. Although TGF-β signalling can be complex, many of the signalling components are well defined, so it is possible to develop mathematical models of TGF-β signalling using reduction and scaling methods. The parameterization of our TGF-β signalling model is consistent with experimental data. We developed our mathematical model for the TGF-β signalling pathway, i.e. the RF- model of TGF-β signalling, using the "rapid equilibrium assumption" to reduce the network of TGF-β signalling reactions based on the time scales of the individual reactions. By adding time-delayed positive feedback to the inherent time-delayed negative feedback for TGF-β signalling. We were able to simulate the sigmoidal, switch-like behaviour observed for the concentration dependence of long-term (> 3 hours) TGF-β stimulation. Computer simulations revealed the vital role of the coupling of the positive and negative feedback loops on the regulation of the TGF-β signalling system. The incorporation of time-delays for the negative feedback loop improved the accuracy, stability and robustness of the model. This model reproduces both the short-term and long-term switching responses for the intracellular signalling pathways at different TGF-β concentrations. We have tested the model against experimental data from MEF (mouse embryonic fibroblasts) WT, SV40-immortalized MEFs and Gp130 F/F MEFs. The predictions from the RF- model are consistent with the experimental data. Signalling feedback loops are required to model TGF-β signal transduction and its effects on normal and cancer cells. We focus on the effects of time-delayed feedback loops and their coupling to ligand stimulation in this system. The model was simplified and reduced to its key components using standard methods and the rapid equilibrium assumption. We detected differences in short-term and long-term signal switching. The results from the RF- model compare well with experimental data and predict the dynamics of TGF-β signalling in cancer cells with different mutations.


Validating Clinical Distal Radioulnar Joint Examination With Radiographic Parameters.
The purpose of this study was to quantify the in vivo displacement of bilateral distal radioulnar joints (DRUJs) in resisted pronosupination. We hypothesize that this will demonstrate no appreciable difference between the left and right DRUJ, thus validating the concept of using the uninjured wrist as a control for physical examination as well as dynamic imaging studies. Thirty-two participants without a history of wrist pathology underwent a dynamic computed tomography (CT) protocol evaluating bilateral forearm rotation in neutral forearm rotation, 60° pronation, and 60° supination, including maximal isometric muscle loading. The DRUJ alignment, specifically the absolute degree and direction of subluxation of the ulna relative to the sigmoid notch, was then assessed using a modification of the radioulnar line method. There was no significant difference in the mean displacement when comparing the right and left sides in neutral, pronation, or supination. The mean displacement was also compared between male and female patients, and there was no statistically significant difference in absolute displacement in neutral (male 0.99 mm vs female 1.38 mm) or supination (male -0.57 mm vs female -0.23 mm). However, the difference in pronation was statistically significant (male 2.69 mm vs female 3.26 mm). Of the 192 sequences, the measurements of displacement of the authors were within 1 mm 86% of the time (166 of 192). Dynamic CT of bilateral DRUJs in resisted pronation, supination, and neutral demonstrated symmetry between the right and left DRUJ, supporting the concept of using the contralateral side as a control to identify instability in an injured wrist.


Results of an open label feasibility study of sodium valproate in people with McArdle disease.
McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile.


Strong magnetization measured in the cool cores of galaxy clusters.
Tangential discontinuities, seen as x-ray edges known as cold fronts (CFs), are ubiquitous in cool-core galaxy clusters. We analyze all 17 deprojected CF thermal profiles found in the literature, including three new CFs we tentatively identify (in clusters A2204 and 2A0335). We discover small but significant thermal pressure drops below all nonmerger CFs, and argue that they arise from strong magnetic fields below and parallel to the discontinuity, carrying 10%-20% of the pressure. Such magnetization can stabilize the CFs, and explain the CF-radio minihalo connection.


Presumptive electric cataracts in a Great Horned owl (Bubo virginianus).
This case report describes suspected electrocution in a juvenile female Great Horned owl (Bubo virginianus) with subsequent bilateral cataract formation. The bird flew into a high-voltage power line and was immediately rescued. Burn wounds of the head and ataxia with apparent blindness were noted. Initial ophthalmic examination 5 days after the incident revealed bilaterally symmetrical anterior subcapsular vacuolar cataracts with absence of intraocular inflammation and a predominantly clear view to the normal appearing fundus. The bird appeared to be nonvisual. No ophthalmic medications were prescribed at initial examination. Subsequent recheck examination at 8 weeks revealed moderate resolution of the cataracts and improved vision. To the authors' knowledge, this is the first published report of suspected electric cataracts in an avian species.


Effectiveness of alcohol treatment interventions integrated into routine tuberculosis care in Tomsk, Russia.
To test the feasibility and effectiveness of brief counseling intervention (BCI) and naltrexone integrated into tuberculosis (TB) care in Tomsk, Russia. Using a factorial randomized controlled trial design, patients were randomized into: naltrexone (NTX), brief behavioral compliance enhancement therapy (BBCET), treatment as usual (TAU) and BCI. In the Tomsk Oblast, hospitalized TB patients diagnosed with alcohol use disorders (AUDs) by the DSM-IV were referred at the start of TB treatment. Of the 196 participants, the mean age was 41 years and 82% were male. Severe TB (84.7% had cavitary disease) and smoking (92.9%) were common. The majority had a diagnosis of an AUD (63.0%); 27.6% reported nearly daily drinking and consumed a median of 16 standard drinks per day. Primary outcomes were 'favorable' TB outcome (cured, completed treatment) and change in mean number of abstinent days in the last month of study compared with baseline. Change in mean number of heavy drinking days, defined as four drinks per day and five drinks per day for women and men, respectively, and TB adherence, measured as percentage of doses taken as prescribed under direct observation, were secondary outcomes. Analysis based on 'intention-to-treat' was performed for multivariable analysis. Primary TB and alcohol end-points between naltrexone and no-naltrexone or BCI and no-BCI groups did not differ significantly. TB treatment adherence and change in number of heavy drinking days also did not differ significantly among treatment arms. Among individuals with a prior quitting attempt (n = 111), naltrexone use was associated with an increased likelihood of favorable TB outcomes (92.3% versus 75.9%, P = 0.02). In Tomsk Oblast, Russia, tuberculosis patients with severe alcohol use disorders who were not seeking alcohol treatment did not respond to naltrexone or behavioral counselling integrated into tuberculosis care; however, those patients with past attempts to quit drinking had improved tuberculosis outcomes.


Effects of Manure and Tillage on Edge-of-Field Phosphorus Loss in Seasonally Frozen Landscapes.
Environmental conditions and management practices affect nutrient losses in surface runoff, but their relative impacts on phosphorus (P) loss during frozen and nonfrozen ground periods have not been well quantified. More specifically, the relative importance of manure application, tillage, and soil-test P (STP) has not been assessed at the field scale. In this study, we compiled a dataset composed of 125 site-years of data from 26 fields that were continually monitored for edge-of-field P loss during snowmelt and storm events. Regression tree analyses were performed to rank the level of influence each environmental and management factor had on nutrient loads. Dissolved P (DP) was the majority of the total P (TP) during frozen conditions, but a small portion of TP during nonfrozen conditions. Manure application had a greater influence on the flow-weighted mean concentrations (FWMCs) of TP and DP during frozen conditions than during nonfrozen conditions. No-till resulted in greater TP and DP FWMCs during frozen conditions than conventional tillage, whereas the opposite effect for TP FWMC was seen during nonfrozen conditions. However, regression tree analysis revealed that STP (0- to 5-cm depth) was the most important factor in predicting DP and TP FWMCs during frozen conditions and DP FWMC during nonfrozen conditions. Extremely high STP values were associated with late-frozen manure applications and grazed pastures. Reducing surface P loss in seasonally frozen landscapes will require prioritizing management strategies that avoid manure application through early- and late-frozen conditions and lead to a drawdown of STP, particularly in the top 5 cm.


Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome.
It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear. The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS. In the present study, a PCOS rat model was induced by letrozole, and successful establishment of the model was confirmed by examining ovarian histology and determining serum testosterone levels, by hematoxylin and eosin staining and ELISA, respectively. Subsequently, the expression of two key elements of insulin signaling, insulin receptor substrate (IRS)‑2 and phosphatidylinositol 3‑kinase (PI3K), was determined by immunohistochemistry and western blot analysis. The results demonstrated that IRS‑2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment. These results indicate that IRS‑2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS. To further confirm the effects of DMBG on insulin signaling expression during this process, the expression of an additional two downstream proteins, phosphoinositide‑dependent kinase‑1 (PDK‑1) and the mammalian target of rapamycin (mTOR), was also investigated in the present study, and the results demonstrated that the expression of PDK‑1 and mTOR was significantly reduced in PCOS ovaries and increased following DMBG treatment, further indicating that altered insulin signaling may have an important role in the development and treatment of PCOS. In conclusion, the results of the present study indicate that the reduced expression of proteins involved in insulin signaling may contribute to the development of the clinical features of PCOS, and DMBG reverses reduced expression of insulin signaling components, by a mechanism that is yet to be determined, to attenuate certain symptoms of PCOS, such as obesity. To the best of our knowledge, the present study is the first to provide data regarding the detailed changes of insulin signaling during the development and treatment of PCOS, and may provide an important reference for clinical PCOS treatment.


Symptomatic Thoracic Nerve Root Herniation into an Extradural Arachnoid Cyst: Case Report and Review of the Literature.
Spinal extradural arachnoid cysts (SEACs) are relatively rare and usually asymptomatic. They preferentially are situated in the thoracic extradural space and almost always dorsal. SEACs may present with back pain and/or cord compression symptoms. Needle aspiration, needle fenestration, or open surgical resection/fenestration have been reported as treatment modalities. We present a 35-year-old woman who complained of radiating pain from the right lower thoracic region of her back toward the right inguinal region, which was aggravated upon defecation and straining. Magnetic resonance imaging (MRI) revealed an extradural cyst located laterally at T11-T12 level on the right, with a nerve root herniation. During a T11-T12 hemilaminectomy, on resection of the cyst wall, a nerve root was noted to be herniating into the cyst cavity through a dural defect. The nerve root was released and repositioned intradurally, followed by direct suture of the dural tear. Histologic findings of the cyst wall confirmed an arachnoid cyst. Postoperative course was uneventful without complications. Postoperative MRI confirmed a complete resection of the cyst. Five years after surgery, the patient is asymptomatic with complete recovery. Thoracic SEACs can present with radiating pain due to a transdural herniation of a thoracic nerve root into the cyst, potentially due to a mechanism of intermittent pressure gradients between the intradural and extradural spaces. MRI can prove beneficial in visualizing the nerve prolapsing into the cyst. Open resection of the cyst wall, reduction of the nerve root herniation, and subsequent direct closure of the dural tear led to complete recovery.


Speech perception in the child brain: cortical timing and its relevance to literacy acquisition.
Speech processing skills go through intensive development during mid-childhood, providing basis also for literacy acquisition. The sequence of auditory cortical processing of speech has been characterized in adults, but very little is known about the neural representation of speech sound perception in the developing brain. We used whole-head magnetoencephalography (MEG) to record neural responses to speech and nonspeech sounds in first-graders (7-8-year-old) and compared the activation sequence to that in adults. In children, the general location of neural activity in the superior temporal cortex was similar to that in adults, but in the time domain the sequence of activation was strikingly different. Cortical differentiation between sound types emerged in a prolonged response pattern at about 250 ms after sound onset, in both hemispheres, clearly later than the corresponding effect at about 100 ms in adults that was detected specifically in the left hemisphere. Better reading skills were linked with shorter-lasting neural activation, speaking for interdependence of the maturing neural processes of auditory perception and developing linguistic skills. This study uniquely utilized the potential of MEG in comparing both spatial and temporal characteristics of neural activation between adults and children. Besides depicting the group-typical features in cortical auditory processing, the results revealed marked interindividual variability in children.


The psychosocial burden of childhood overweight and obesity: evidence for persisting difficulties in boys and girls.
There is evidence that overweight and obese children tend to remain overweight or obese into adolescence and adulthood. However, little is known about the long-term psychosocial outcomes of childhood overweight and obesity. This study aimed to investigate the course of psychosocial difficulties over a 2-year period for children who were overweight or obese at baseline, and a sample of children who were a healthy weight at baseline. Participants were 212 children aged 8 to 13 years at baseline, who were participating in the Childhood Growth and Development (GAD) Study. Questionnaire and interview measures were used to assess children's self-esteem, depressive symptoms, body image, eating disorder symptoms, experiences with bullying, family satisfaction and quality of life. Linear mixed models were used to consider longitudinal changes in psychosocial variables. Overweight and obese children reported greater psychosocial distress than healthy weight children, and these differences were more pronounced for girls than boys. Weight and psychosocial impairment showed stability from baseline to 2-year follow-up. The results of this study suggest that psychosocial difficulties show considerable stability in childhood, for overweight/obese and healthy weight children. What is Known: • Childhood obesity tracks into adolescence and adulthood. • Physical health problems associated with childhood obesity also persist to adulthood. What is New: • Overweight and obese children are at risk of ongoing psychosocial distress from childhood into early adolescence.


Diagnostic yield of rapid on-site evaluation transbronchial needle aspiration versus conventional transbronchial needle aspiration: a single center experience.
Trans-bronchial needle aspiration allows lymph node sampling in several thoracic conditions; the ability of Rapid On-Site Evaluation (ROSE) to predict the final diagnosis in this setting has not been well characterized. We performed a retrospective study to establish the utility of ROSE in the diagnosis of thoracic diseases with mediastinal lymph node involvement. We retrospectively reviewed 297 patients with hilar-mediastinal lymph node enlargement detected at CT scan from January 2013 to April 2016. 201 patients underwent conventional TBNA; in 96 patients, TBNA procedure was performed by on-site presence of a team of pathologists and research morphologists. Lung neoplasms, sarcoidosis, infections and lymphoma were the most common diseases diagnosed with TBNA samples. TBNA simultaneously performed in combination with ROSE produced an increase in percentage of appropriate samples compared to single cTBNA (adequate samples cTBNA vs ROSE-TBNA: 73% vs 81%; p<0.05). Our observations indicate an increase in adequacy of fine needle aspirations and increased diagnostic yield in the ROSE group. In conclusions, ROSE may serve to reduce procedure time and enhance sample triaging therefore limiting the need for further invasive diagnostic testing.


Speckle contrast optical tomography: A new method for deep tissue three-dimensional tomography of blood flow.
A novel tomographic method based on the laser speckle contrast, speckle contrast optical tomography (SCOT) is introduced that allows us to reconstruct three dimensional distribution of blood flow in deep tissues. This method is analogous to the diffuse optical tomography (DOT) but for deep tissue blood flow. We develop a reconstruction algorithm based on first Born approximation to generate three dimensional distribution of flow using the experimental data obtained from tissue simulating phantoms.


A binaural model implementing an internal noise to predict the effect of hearing impairment on speech intelligibility in non-stationary noises.
A binaural model predicting speech intelligibility in envelope-modulated noise for normal-hearing (NH) and hearing-impaired listeners is proposed. The study shows the importance of considering an internal noise with two components relying on the individual audiogram and the level of the external stimuli. The model was optimized and verified using speech reception thresholds previously measured in three experiments involving NH and hearing-impaired listeners and sharing common methods. The anechoic target, in front of the listener, was presented simultaneously through headphones with two anechoic noise-vocoded speech maskers (VSs) either co-located with the target or spatially separated using an infinite broadband interaural level difference without crosstalk between ears. In experiment 1, two stationary noise maskers were also tested. In experiment 2, the VSs were presented at different sensation levels to vary audibility. In experiment 3, the effects of realistic interaural time and level differences were also tested. The model was applied to two datasets involving NH listeners to verify its backward compatibility. It was optimized to predict the data, leading to a correlation and mean absolute error between data and predictions above 0.93 and below 1.1 dB, respectively. The different internal noise approaches proposed in the literature to describe hearing impairment are discussed.


Comparison of central laboratory HbA1c measurements obtained from a capillary collection versus a standard venous whole blood collection in the GRADE and EDIC studies.
We compared HbA1c values obtained from capillary blood collection kits versus venous whole blood collections in study participants with type 1 or type 2 diabetes. A total of 122 subjects, 64 with type 2 diabetes participating in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study and 58 with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, participated in the validation study. Capillary tubes were filled by fingerstick by the participants on the same day as the collection of venous whole blood samples in EDTA-containing test tubes and were mailed to the central laboratory. HbA1c in all samples was measured with the same high-performance liquid chromatography. GRADE participants also completed a questionnaire on the ease of performing capillary collections. Participants from 22 clinical centers (GRADE n = 5, EDIC n = 17) were between 35 and 86 years of age, with 52% male and diverse race/ethnicities. Venous HbA1c results ranged between 5.4-11.9% (35.5-106.6 mmol/mol) with corresponding capillary results ranging between 4.2-11.9% (22.4-106.6 mmol/mol). The venous and capillary results were highly correlated (R2 = 0.993) and 96.7% differed by ≤0.2% (2.2 mmol/mol). Of participants surveyed, 69% indicated that the instructions and collection were easy to follow and 97% felt the collection method would be easy to do at home. The capillary blood HbA1c results compared well with the conventional venous whole blood results. The capillary kits can be employed in other studies to reduce interruption of critical data collection and potentially to augment clinical care when in-person visits are not possible.


Wavelet processing of systolic murmurs to assist with clinical diagnosis of heart disease.
Despite advances in imaging technologies for the heart, screening of patients for cardiac pathology continues to include the use of traditional stethoscope auscultation. Detection of heart murmurs by the primary care physician often results in the ordering of additional expensive testing or referral to cardiology subspecialists, although many of the patients are eventually found to have no pathologic condition. In contrast, auscultation by an experienced cardiologist is highly sensitive and specific for detecting heart disease. Although attempts have been made to automate screening by auscultation, no device is currently available to fulfill this function. Multiple indicators of pathology are nonetheless available from heart sounds and can be elicited using certain signal processing techniques such as wavelet analysis. Results presented here show that a signal of pathology, the systolic murmur, can reliably be detected and classified as pathologic using a portable electrocardiogram and heart sound measurement unit combined with a wavelet-based algorithm. Wavelet decomposition holds promise for extending these results to detection and evaluation of other audible pathologic indicators.


The evaluation of patients with human immunodeficiency virus-related disorders and brain mass lesions.
In patients at risk for acquired immunodeficiency syndrome who present with a mass lesion, a dilemma arises as to whether to treat empirically for toxoplasmosis or perform a brain biopsy. We present data that further define the indications for performing brain biopsy vs empiric treatment. We reviewed charts on 59 patients with acquired immunodeficiency syndrome--related disorders and cerebral mass lesions. Thirty-two patients met diagnostic criteria for toxoplasmosis. Bayesian analysis demonstrated that the prior probability of toxoplasmosis was increased by the presence of contrast enhancement on computed tomographic scans (0.68) and toxoplasmosis titers greater than 1:64 (0.81). Features associated with decreasing probabilities of toxoplasmosis included the absence of contrast enhancement on computed tomographic scans (0.29) and toxoplasmosis titers less than or equal to 1:64 (0.14). Ten percent of patients had complications of brain biopsy. Treatment with pyrimethamine and sulfadiazine produced complications in 29% and serious complications in 8% of treated patients. These data favor empiric therapy for patients with typical features of toxoplasmosis and brain biopsy for defined subsets of patients with atypical features.


In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.
According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.


Flexible organic bistable devices based on graphene embedded in an insulating poly(methyl methacrylate) polymer layer.
The electrical properties of flexible nonvolatile organic bistable devices (OBDs) fabricated with graphene sandwiched between two insulating poly(methyl methacrylate) (PMMA) polymer layers were investigated. Current-voltage (I-V) measurements on the Al/PMMA/graphene/PMMA/indium-tin-oxide/poly(ethylene terephthalate) devices at 300 K showed a current bistability due to the existence of the graphene, indicative of charge storage in the graphene. The maximum ON/OFF ratio of the current bistability for the fabricated OBDs was as large as 1 x 10(7), and the endurance number of ON/OFF switchings was 1.5 x 10(5) cycles, and an ON/OFF ratio of 4.4 x 10(6) was maintained for retention times larger than 1 x 10(5) s. No interference effect was observed for the scaled-down OBDs containing a graphene layer. The memory characteristics of the OBDs maintained similar device efficiencies after bending and were stable during repetitive bendings of the OBDs. The mechanisms for these characteristics of the fabricated OBDs are described on the basis of the I-V results.


Position-based anchor optimization for point supervised dense nuclei detection.
Nuclei detection is one of the most fundamental and challenging problems in histopathological image analysis, which can localize nuclei to provide effective computer-aided cancer diagnosis, treatment decision, and prognosis. The fully-supervised nuclei detector requires a large number of nuclei annotations on high-resolution digital images, which is time-consuming and needs human annotators with professional knowledge. In recent years, weakly-supervised learning has attracted significant attention in reducing the labeling burden. However, detecting dense nuclei of complex crowded distribution and diverse appearances remains a challenge. To solve this problem, we propose a novel point-supervised dense nuclei detection framework that introduces position-based anchor optimization to complete morphology-based pseudo-label supervision. Specifically, we first generate cellular-level pseudo labels (CPL) for the detection head via a morphology-based mechanism, which can help to build a baseline point-supervised detection network. Then, considering the crowded distribution of the dense nuclei, we propose a mechanism called Position-based Anchor-quality Estimation (PAE), which utilizes the positional deviation between an anchor and its corresponding point label to suppress low-quality detections far from each nucleus. Finally, to better handle the diverse appearances of nuclei, an Adaptive Anchor Selector (AAS) operation is proposed to automatically select positive and negative anchors according to morphological and positional statistical characteristics of nuclei. We conduct comprehensive experiments on two widely used benchmarks, MO and Lizard, using ResNet50 and PVTv2 as backbones. The results demonstrate that the proposed approach has superior capacity compared with other state-of-the-art methods. In particularly, in dense nuclei scenarios, our method can achieve 95.1% performance of the fully-supervised approach. The code is available at https://github.com/NucleiDet/DenseNucleiDet.


Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia.
We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL.


AMNIOTIC MEMBRANE TRANSPLANTATION AT THE DEPARTMENT OF OPHTHALMOLOGY OF THE UNIVERSITY HOSPITAL BRNO.
The aim of the work is a discussion of amniotic membrane transplantation at the Eye Clinic of the University Hospital Brno and a retrospective evaluation of a group of patients for the period 2014-2019 who were treated for various indications. Retrospective evaluation of the number and effectiveness of individual types of amniotic membrane in a group of patients after amniotic membrane transplantation (AMT) for various indications. A total of 134 patients were included in the study group, of which 68 were men and 66 were women. The median age was 70 years. The total number of amniotic membrane transplants performed during the selected six years was 139, with half the distribution using frozen (69 eyes) and lyophilized amniotic membrane (70 eyes). The AMT technique was chosen based on the initial finding and diagnosis. The type of amniotic membrane used (lyophilized vs. frozen) depended on the urgency of the procedure. The number of amniotic membrane transplantations was evaluated in a group of 134 patients (139 eyes) and their effectiveness in individual diagnoses was demonstrated. During the follow-up period, more transplantations of amniotic membranes were performed during hospitalization than in the outpatient department, both types of membranes (frozen and lyophilized). Amniotic membrane transplantation during hospitalization was performed in 89 eyes, in the outpatient mode in 50 eyes. Indications for amniotic membrane transplantation included microperforation and corneal perforation (30 eyes), non-healing corneal defects (21 eyes), descemetocele (19 eyes), neurotrophic defects (16 eyes), ablation of pterygium (12 eyes) and corneal lysis (11 eyes). eyes). Other conditions (conjunctival lesions, fornix reconstruction, burns, peripheral ulcerative keratitis, ocular cicatricial pemphigoid and keratectomy) were represented in smaller numbers. Despite the very diverse group of indications and the advanced age of the patients, a very good efficacy of the performed amniotic membrane transplantations was found. Some patients died during the follow-up period, so the limitation of work is short and unequal follow-up period. The success of the procedure depends not only on the correct timing, indication and technique of transplantation, but also on patient compliance and well-functioning cooperation of regional ophthalmologists.


First record of Aedes albopictus in Gabon.
Aedes albopictus were collected in the French military camp of Libreville, Estuaire Province, Gabon, from January to March 2007 by human landing catches during an entomological evaluation of malaria transmission. Inspection of potential larval habitats within and outside the camp showed that Ae. albopictus was found only in artificial containers (discarded tires and small water containers). Associated species of mosquito larvae were Ae. aegypti (L.) and Culex quinquefasciatus. At the same time, Ae. albopictus adults and larvae were also collected from discarded tires in Tcheungue near Port Gentil, Ogoue Maritime Province. Ae. albopictus seems to be established in this part of Gabon's littoral. Further studies are necessary to investigate the extension of Ae. albopictus establishment throughout the country.


Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study.
Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.


Researching the disabled identity: contextualising the identity transformations which accompany the onset of impairment.
This paper outlines a recent study which, in an attempt to illuminate the processes surrounding the formation of what is increasingly being referred to as 'the disabled identity', set out to explore the effects of the onset and ongoing experience of impairment in relation to disabled people's self-perceptions. A grounded theory approach was adopted and the data derived from the stories of 92 people from four countries, through telephone dialogues and autobiographical material which sought to answer, or, in the case of unsolicited material, could be said to have answered, the question: How has [the illness or disabling condition] affected the ways in which you see yourself and how others treat you? The major areas of identity which were found to be affected by disability were those which related to independence, work and appearance/sexuality, all of which were heavily influenced by the negative attitudes of others and each of which were related to qualities which could be argued to represent the pivotal characteristics separating the 'affiliated and the marginalised' in contemporary Western society.


Visualization of synaptic inhibition with an optogenetic sensor developed by cell-free protein engineering automation.
We describe an engineered fluorescent optogenetic sensor, SuperClomeleon, that robustly detects inhibitory synaptic activity in single, cultured mouse neurons by reporting intracellular chloride changes produced by exogenous GABA or inhibitory synaptic activity. Using a cell-free protein engineering automation methodology that bypasses gene cloning, we iteratively constructed, produced, and assayed hundreds of mutations in binding-site residues to identify improvements in Clomeleon, a first-generation, suboptimal sensor. Structural analysis revealed that these improvements involve halide contacts and distant side chain rearrangements. The development of optogenetic sensors that respond to neural activity enables cellular tracking of neural activity using optical, rather than electrophysiological, signals. Construction of such sensors using in vitro protein engineering establishes a powerful approach for developing new probes for brain imaging.


Process Analytical Technology in Freeze-Drying: Detection of the Secondary Solute + Water Crystallization with Heat Flux Sensors.
In situ and non-invasive detection of solute crystallization during freeze-drying would facilitate cycle optimization and scale-up from the laboratory to commercial manufacturing scale. The objective of the study is to evaluate heat flux sensor (HFS) as a tool for monitoring solute crystallization and other first-order phase transitions (e.g., onset of freezing). HFS is a thin-film differential thermopile, which acts as a transducer to generate an electrical signal proportional to the total heat applied to its surface. In this study, HFS is used to detect both primary (ice formation) and secondary (also known as eutectic) solute + water crystallization during cooling and heating of solutions in a freeze-dryer. Binary water-solute mixtures with typical excipients concentrations (e.g., 0.9% of NaCl and 5% mannitol) and fill volumes (1 to 3 ml/vial) are studied. Secondary crystallization is detected by the HFS during cooling in all experiments with NaCl solutions, whereas timing of mannitol crystallization depends on the cooling conditions. In particular, mannitol crystallization takes place during cooling, if the cooling rate is lower than the critical value. On the other hand, if the cooling rate exceeds the critical cooling rate, mannitol crystallization during cooling is prevented, and crystallization occurs during subsequent warming or annealing. It is also observed that, while controlled ice nucleation allows initiation of the primary freezing event in different vials simultaneously, there is a noticeable vial-to-vial difference in the timing of secondary crystallization. The HFS could be a valuable process monitoring tool for non-invasive detection of various crystallization events during freeze-drying manufacturing.


Detection of Lyman-beta and Helium Resonance Radiation in the Night Sky.
A rocket-borne photometer has detected far ultraviolet night glow radiations that are identified as Lyman-beta (HI 1026 angstroms), and the helium lines at 304 or 584 angstroms, or at both. At an altitude of 227 kilometers the measured intensity for Lyman-beta was about 10 rayleighs. The discrimination characteristics of the broad-band helium radiation filter give helium line intensities, at 227 kilometers, of 4.8 and 12 rayleighs, respectively, pending identification of the wavelength of the radiation as 304 or 584 angstroms. These ultraviolet radiations appear sufficient to maintain the night E and F(1) regions of the ionosphere.


Using an ontological modeling to evaluate the consistency of clinical practice guidelines: application to the comparison of three guidelines on the management of adult hypertension.
Every year, numerous clinical practice guidelines (CPGs) are published on a same topic. They may be conflicting, thus infringing clinicians' confidence in adhering to them. In order to build a clinical decision support system to assist GPs in the management of hypertension, we have considered three recent CPGs written in French. We developed a methodological framework to evaluate how consistent the three CPGs were. After a manual extraction of recommendation rules, all patient profiles covered by the CPGs have been identified. Then, ontological modeling and reasoning were used to build a subsumption graph of all profiles. This graph allows the retrieval of recommendations that could be conflicting. Results show that if rules are different in the three CPGs according to a document-based approach, many profiles are related through subsumption, and no critical inconsistencies were discovered when implementing an ontological modeling.


The major product ion of S-adenosyl-L-methionine arises from a neighbouring group reaction.
Previous studies have shown that low-energy collision-induced dissociation (CID) of the important sulfonium ion metabolite S-adenosyl-L-methionine (AdoMet, m/z 399) yields five main product ions: an ion at m/z 250 arising from methionine loss; ions at m/z 102 and 298, which arise via cleavage of the gamma C-S bond of methionine; and ions at m/z 136 and 264, which arise via loss of protonated and neutral adenine, respectively. These metabolomics studies have, however, either totally ignored the mechanisms that govern the formation of the major product ion at m/z 250 (Gellekink H, van Oppenraaij-Emmerzaal D, van Rooij A, Struys EA, den Heijer M, Blom HJ. Clin. Chem. 2005; 51: 1487), or have proposed an oxonium ion structure that must arise via a rearrangement involving a 1,2 hydride shift (Cataldi TRI, Bianco G, Abate S, Mattia D. Rapid Commun. Mass Spectrom. 2009; 23: 3465). Here DFT calculations on a model system are used to examine potential mechanisms for the formation of the major product ion of AdoMet. These calculations suggest that a neighbouring group mechanism is preferred over a 1,2 hydride shift mechanism.


[Scientific research. Publications and behavioural ethics].
Publish or perish is the dilemma of many investigators, even more so when they are young because getting a job is often related to the quality of the research carried out and the number of papers published. However, ther are many variables which can sometimes be negative, influence the politics and process of publications. For example, peer reviewers could be interested in the same research or negative data may be present in the study. This editorial examines these variables as well as the fact that, in the post genomic era, the possibility of producing negative results is more frequent than in the past. Editors should consider this aspect when planning future publications.


Health disparities among Black deaf and hard of hearing Americans as compared to Black hearing Americans: A descriptive cross-sectional study.
There is a dearth of literature on health outcomes for Black people who identify as deaf or hard of hearing (DHH). Black DHH individuals generally experience at least 2 types of oppression, racism and audism, both of which contribute to health disparities within the Black and Deaf communities.To understand the prevalence of health outcomes in a Black DHH adult sample and compare this to a Black hearing sample.A descriptive cross-sectional study with primary Health Information National Trends Survey (HINTS)- American Sign Language survey data from Black DHH adults and secondary National Cancer Institute-HINTS English survey data from Black hearing adults.Black DHH adults and Black hearing adults (18 years or older).Using NCI's health information national trends survey in American Sign Language and English, self-reported data was gathered for all medical conditions as diagnosed by healthcare providers.The study showed that Black DHH adults had a higher likelihood for diabetes, hypertension, lung disease, cancer, and comorbidity compared to their hearing Black counterparts.Black DHH adults are at disparity for certain medical conditions compared to the general Black adult population. Future directions are needed to ensure that anti-racist policies include consideration of people with sensory disabilities. Inclusion of cultural and language needs of Black DHH patients in cultural humility training for healthcare providers is recommended to address health disparity in this population.


Trends in multimorbidity, complex multimorbidity and multiple functional limitations in the ageing population of England, 2002-2015.
This study aimed to estimate the prevalence of three measures of multimorbidity among people aged 50 years or older in England. Beside the basic measure of two or more diseases within a person, we added a measure of three or more affected body systems (complex multimorbidity) and a measure of 10 or more functional limitations. We found that the three health outcomes became more prevalent between 2002 and 2015. They were more common among females than males and were becoming more common among younger age groups. While in 2002, the prevalence of basic multimorbidity overcame 50% from the 70-74 age group upwards, in 2015 it crossed the same threshold in the 65-69 age group. The distribution of multimorbidity and multiple functional limitations were stratified by the amount of household wealth. Multiple functional limitations reflected the largest differences between the most and the least affluent groups (5.9-fold in 2014/2015), followed by the measure of complex multimorbidity (2.8-fold in 2014/2015) and basic multimorbidity (1.9-fold) in 2014/2015.While age acted as a levelling factor for the wealth differences in basic multimorbidity, it had no such effect on the two other outcomes. Our study observed social polarization among multimorbid ageing population in England where complex multimorbidity and multiple functional limitations increase faster and reflect stronger inequality than basic multimorbidity.


Towards a molecular and atomic anatomy of calmodulin and calmodulin-binding proteins.
The molecular mechanisms by which calcium regulates cellular processes such as metabolic and mechanochemical events probably involve interactions with a variety of molecules. A large body of evidence suggests that the targets of calcium's regulatory effects inside the cell are calcium-binding proteins. Our work attempts to correlate calcium-binding protein structure with activities. In this chapter we have presented some of our recent studies on these functional domains in calmodulin and calmodulin-binding proteins. Selected chemical modifications of known amino acid sequence positions have demonstrated the presence of multiple functional domains on calmodulin, have allowed the dissociation of calmodulin functions, and have provided the necessary tools for further investigations of the molecular basis of calmodulin action. One of these modifications, iodination of tyrosine-99, has allowed us to develop procedures to reproducibly detect calmodulin-binding proteins by a binding technique. This method is technically simple. It allows us to detect and study calmodulin-binding proteins (e.g., myosin heavy chain and membrane gap junction proteins) that would be difficult to study with immobilized calmodulin. We have developed a library of antibodies to calmodulin and related proteins such as troponin C and S100 beta. Some of these antisera appear to be site-specific gamma globulins. We have demonstrated that reactivity can be contained in an amino acid sequence as short as seven residues. We have demonstrated the feasibility of using an immunochemical mapping approach to study calmodulin and calmodulin-binding proteins. Comparative sequence analyses combined with functional analyses have allowed correlation of function and structure and have suggested logical candidates for functional domains on calmodulin and calmodulin-binding proteins. Although not discussed in detail in this chapter, these calmodulin-binding proteins appear to contain amino acid sequence homologies. This suggests, analogous to the approach used for calmodulin and related proteins, a logical starting point for domain analyses of calmodulin-binding proteins. Interestingly, structural homologies among calmodulin-binding proteins are reminiscent of the different phosphorylation sites found in many of the physiological substrates for protein kinases. Since a number of calmodulin-binding proteins are themselves substrates for protein kinases, these results suggest another possible point of interrelationships between calcium and cyclic nucleotide regulation.


Analysis of tumor-immune dynamics in a delayed dendritic cell therapy model.
We formulate a tumor-immune interaction model with a constant delay to capture the behavior following application of a dendritic cell therapy. The model is validated using experimental data from melanoma-induced mice. Through theoretical and numerical analyses, the model is shown to produce rich dynamics, such as a Hopf bifurcation and bistability. We provide thresholds for tumor existence and, in a special case, tumor elimination. Our work indicates a sensitivity in model outcomes to the immune response time. We provide a stability analysis for the high tumor equilibrium. For small delays in response, the tumor and immune system coexist at a low level. Large delays give rise to fatally high tumor levels. Our computational and theoretical work reveals that there exists an intermediate region of delay that generates complex oscillatory, even chaotic, behavior. The model then reflects uncertainty in treatment outcomes for varying initial tumor burdens, as well as tumor dormancy followed by uncontrolled growth to a lethal size, a phenomenon seen in vivo. Theoretical and computational analyses suggest efficacious treatments to use in conjunction with the dendritic cell vaccine. Additional analysis of a highly aggressive tumor additionally confirms the importance of representation with a time delay, as periodic solutions are strictly able to be generated when a delay is present.


Households as foci for dengue transmission in highly urban Vietnam.
Dengue control programs commonly employ reactive insecticide spraying around houses of reported cases, with the assumption that most dengue virus (DENV) transmission occurs in the home. Focal household transmission has been demonstrated in rural settings, but it is unclear whether this holds true in dense and mobile urban populations. We conducted a prospective study of dengue clustering around households in highly urban Ho Chi Minh City, Vietnam. We enrolled 71 index cases with suspected dengue (subsequently classified as 52 dengue cases and 19 non-dengue controls); each initiated the enrollment of a cluster of 25-35 household members and neighbors who were followed up over 14 days. Incident DENV infections in cluster participants were identified by RT-PCR, NS1-ELISA, and/or DENV-IgM/-IgG seroconversion, and recent infections by DENV-IgM positivity at baseline. There was no excess risk of DENV infection within dengue case clusters during the two-week follow-up, compared to control clusters, but the prevalence of recent DENV infection at baseline was two-fold higher in case clusters than controls (OR 2.3, 95%CI 1.0-5.1, p = 0.05). Prevalence of DENV infection in Aedes aegypti was similar in case and control houses, and low overall (1%). Our findings are broadly consistent with household clustering of dengue risk, but indicate that any clustering is at a short temporal scale rather than sustained chains of localized transmission. This suggests that reactive perifocal insecticide spraying may have a limited impact in this setting.


Plasma bioavailability and changes in PBMC gene expression after treatment of ovariectomized rats with a commercial soy supplement.
The health effects of soy supplementation in (post)menopausal women are still a controversial issue. The aim of the present study was to establish the effect of the soy isoflavones (SIF) present in a commercially available supplement on ovariectomized rats and to investigate whether these rats would provide an adequate model to predict effects of SIF in (post)menopausal women. Two dose levels (i.e. 2 and 20 mg/kg b.w.) were used to characterize plasma bioavailability, urinary and fecal concentrations of SIF and changes in gene expression in peripheral blood mononuclear cells (PBMC). Animals were dosed at 0 and 48 h and sacrificed 4 h after the last dose. A clear dose dependent increase of SIF concentrations in plasma, urine and feces was observed, together with a strong correlation in changes in gene expression between the two dose groups. All estrogen responsive genes and related biological pathways (BPs) that were affected by the SIF treatment were regulated in both dose groups in the same direction and indicate beneficial effects. However, in general no correlation was found between the changes in gene expression in rat PBMC with those in PBMC of (post)menopausal women exposed to a comparable dose of the same supplement. The outcome of this short-term study in rats indicates that the rat might not be a suitable model to predict effects of SIF in humans. Although the relative exposure period in this rat study is comparable with that of the human study, longer repetitive administration of rats to SIF may be required to draw a final conclusion on the suitability of the rat a model to predict effects of SIF in humans.


Transcutaneous electrical nerve stimulation and extensor splint in linear scleroderma knee contracture.
A girl with knee flexion contracture secondary to linear scleroderma with hemiatrophy was treated with hot packs, gentle stretching and a serial posterior splint. The knee range of motion gained 35 degree over a period of 16 weeks. Nine months, later knee contracture had regressed. As an alternative method of treatment, continuous stretch was applied by using a front extension splint together with transcutaneous electrical nerve stimulation. The knee range of motion gained 55 degrees over a period of 6 weeks.


Defining maltreatment chronicity: are there differences in child outcomes?
For nearly 25 years researchers have suggested that better taxonomic systems conceptualizing and reliably differentiating among different dimensions of maltreatment are required. This study examines the utility of three different characterizations of one dimension of maltreatment, chronicity, to predict child behavioral and emotional functioning in a sample of maltreated children. A secondary objective of the study is to examine additional parameters of maltreatment inherent in our definitions of chronicity: age at first report to CPS, extent and continuity of maltreatment. The study consists of children reported for maltreatment (N=519) from the larger LONGSCAN study cohort. Lifetime maltreatment data were collected from CPS records and coded into two chronicity constructs: "developmental" and "calendar" definitions. Variables for age at first report, frequency, extent and continuity of maltreatment reports also were constructed. Hierarchical regression analyses were utilized to determine the extent to which the various chronicity constructs contributed to the prediction of child outcomes. The most salient definition of chronicity, in terms of its effects on child behavioral and emotional functioning, varied by outcome. The developmental definition was found to have the most balanced sensitivity across outcomes. Among other significant findings, extent and continuity of maltreatment contributed respectively to the prediction of behavior and emotional trauma symptoms. Early age at first report was a predictor of poor daily living skills. Chronicity is a complex construct. Findings indicate there are multiple parameters that make up the chronicity construct itself that may be important for understanding child outcomes.


In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status.
Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome. Baseline and post-irradiation changes in CSC proportions were investigated by flow cytometry in a HPV-negative (UM-SCC-1) and a HPV-positive (UM-SCC-47) HNSCC cell line, using fluorescent staining with CD44/ALDH markers. CSC proportions in both irradiated and unirradiated cultures were compared for the two cell lines at various times post-irradiation. To assess repopulation of CSCs, untreated cultures were depleted of CD44+/ALDH+ cells and re-cultured for 3 weeks before flow cytometry analysis. CSC proportions in untreated cell lines were 0.57% (UM-SCC-1) and 2.87% (UM-SCC-47). Untreated cell lines depleted of CD44+/ALDH+ repopulated this phenotype to a mean of 0.15% (UM-SCC-1) and 6.76% (UM-SCC-47). All UM-SCC-47 generations showed elevated CSC proportions after irradiation, with the most significant increase at 2 days post-irradiation. The highest elevation in UM-SCC-1 CSCs was observed at 1 day post-irradiation in the 2nd generation and at 3 days after irradiation in the 3rd generation. When measured after 10 days, only the 3rd generation of UM-SCC-1 showed elevated CSCs. CSC proportions in both cell lines were elevated after exposure and varied with time post irradiation. UM-SCC-47 displayed significant plasticity in repopulating the CSC phenotype in depleted cultures, which was not seen in UM-SCC-1.


[Epidemiological survey of pneumococcus serotypes in pediatric patients with acute suppurative otitis media].
To determine the distribution of Streptococcus pneumoniae serotypes isolated from patients under 6 years of age with acute suppurative otitis media, to calculate the serotype coverage of 7-valent pneumococcal conjugate vaccine, and to clarify trends in PCG-resistant Streptococcus pneumoniae, we conducted a one-year prospective study from April 2005 to March 2006 at 10 medical institutions in Hokkaido, Miyagi, Chiba, Tokyo, Kanagawa, and Mie, Japan. Specimens collected by tympanotomy or myringotomy numbered 856, and 691 strains were isolated from 599 specimens. Of these, 219 isolates (31.7%) were identified as Streptococcus pneumoniae and 201 met study requirements. The most common serotype was 19F (52 isolates, 25.9%), followed by 6B (30 isolates, 14.9%) and 23F (24 isolates, 11.9%). Seven-valent vaccine serotype coverage was 62.7%. The percentage of PSSP was 40.3%, PISP 42.8%, and PRSP 16.9%, resistant strains (PISP and PRSP) combined accounted for 59.7%. Seven-valent vaccine serotype coverage for PISP was 80.2% and PRSP 82.4%. PBP gene mutation was observed in 175 isolates (87.1%), including 70 of gPISP (34.8%) and 105 of gPRSP (52.2%). Gene mutation induced by macrolides was found in 176 isolates (87.6%).


Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation.
Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with partial and complete hydatidiform moles. We present an unusual case in which a patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound findings were consistent with a partial hydatidiform mole. Within 24 hours of the onset of symptoms, the patient developed severe hemolysis, elevated liver enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9) cells/L. Termination of pregnancy was performed with rapid resolution of signs, symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at karyotype analysis. This case demonstrates the acuteness in which life-threatening maternal conditions can arise with this uncommon complication of pregnancy, and the importance of correct identification of the characteristic ultrasonographic findings associated with a partial hydatidiform mole.


The bone tissue compatibility of a new Ti35Nb2Ta3Zr alloy with a low Young's modulus.
Titanium (Ti) alloys of the β-type are highly attractive metallic materials for biomedical applications due to their low elastic modulus, high corrosion resistance and notable biocompatibility. A new β-type Ti35Nb2Ta3Zr alloy with a low Young's modulus of approximately 48 GPa was previously fabricated. In the present study, the biocompatibility of this alloy was evaluated. In an in vitro assay, the Ti35Nb2Ta3Zr alloy did not markedly affect the adhesion of MG63 osteoblast cells, but it increased their proliferation, alkaline phosphatase (ALP) activity, calcium deposition and mRNA expression of osteogenic genes (i.e., ALP, osteocalcin, osteopontin). In an in vivo study, no marked histological differences were observed between the new bone formed on the surface of Ti35Nb2Ta3Zr and that formed on the surface of control Ti6Al4V rods placed in the medullary canal of rabbit femurs. Additionally, no significant differences were observed in the failure load of Ti35Nb2Ta3Zr and Ti6Al4V in pull-out tests. In conclusion, the Ti35Nb2Ta3Zr alloy with a lower elastic modulus closer to that of human bone has significant bone tissue compatibility equal to that of Ti6Al4V, which has been widely used in orthopedic applications.


Ruminative and mindful self-focused attention in borderline personality disorder.
The current study investigated the short-term effects of mindful and ruminative forms of self-focused attention on a behavioral measure of distress tolerance in individuals with borderline personality disorder (BPD) who had completed an angry mood induction. Participants included 40 individuals who met criteria for BPD and were currently involved in mental health treatment. Each completed an individual 1-hr session. Following an angry mood induction, each participant was randomly assigned to engage in ruminative or mindful self-focus for several minutes. All participants then completed the computerized Paced Auditory Serial Addition Test (PASAT-C), a behavioral measure of willingness to tolerate distress in the service of goal-directed behavior. The mindfulness group persisted significantly longer than the rumination group on the distress tolerance task and reported significantly lower levels of anger following the self-focus period. Results are consistent with previous studies in suggesting that distinct forms of self-focused attention have distinct outcomes and that, for people with BPD, mindful self-observation is an adaptive alternative to rumination when feeling angry.


Nuptial gifts and the evolution of male body size.
In many insect systems, males donate nuptial gifts to insure an effective copulation or as a form of paternal investment. However, if gift magnitude is both body size-limited and positively related to fitness, then the opportunity exists for the gift to promote the evolution of large male size. In the striped ground cricket, Allonemobius socius, males transfer a body size-limited, somatic nuptial gift that is comprised primarily of hemolymph. To address the implications of this gift on male size evolution, we quantified the intensity and direction of natural (fecundity) and sexual (mating success) selection over multiple generations. We found that male size was under strong positive sexual selection throughout the breeding season. This pattern of selection was similar in successive generations spanning multiple years. Male size was also under strong natural selection, with the largest males siring the most offspring. However, multivariate selection gradients indicated that gift size, and not male size, was the best predictor of female fecundity. In other words, direct fecundity selection for larger gifts placed indirect positive selection on male body size, supporting the hypothesis that nuptial gifts can influence the evolution of male body size in this system. Although female size was also under strong selection due to a size related fecundity advantage, it did not exceed selection on male size. The implications of these results with regard to the maintenance of the female-biased size dimorphic system are discussed.


Hot topic: 16S rRNA gene sequencing reveals the microbiome of the virgin and pregnant bovine uterus.
We tested the hypothesis that the uterus of virgin heifers and pregnant cows possessed a resident microbiome by 16S rRNA gene sequencing of the virgin and pregnant bovine uterus. The endometrium of 10 virgin heifers in estrus and the amniotic fluid, placentome, intercotyledonary placenta, cervical lumen, and external cervix surface (control) of 5 pregnant cows were sampled using aseptic techniques. The DNA was extracted, the V4 hypervariable region of the 16S rRNA gene was amplified, and amplicons were sequenced using Illumina MiSeq technology (Illumina Inc., San Diego, CA). Operational taxonomic units (OTU) were generated from the sequences using Qiime v1.8 software, and taxonomy was assigned using the Greengenes database. The effect of tissue on the microbial composition within the pregnant uterus was tested using univariate (mixed model) and multivariate (permutational multivariate ANOVA) procedures. Amplicons of 16S rRNA gene were generated in all samples, supporting the contention that the uterus of virgin heifers and pregnant cows contained a microbiome. On average, 53, 199, 380, 382, 525, and 13,589 reads annotated as 16, 35, 43, 63, 48, and 176 OTU in the placentome, virgin endometrium, amniotic fluid, cervical lumen, intercotyledonary placenta, and external surface of the cervix, respectively, were generated. The 3 most abundant phyla in the uterus of the virgin heifers and pregnant cows were Firmicutes, Bacteroidetes, and Proteobacteria, and they accounted for approximately 40, 35, and 10% of the sequences, respectively. Phyla abundance was similar between the tissues of the pregnant uterus. Principal component analysis, one-way PERMANOVA analysis of the Bray-Curtis similarity index, and mixed model analysis of the Shannon diversity index and Chao1 index demonstrated that the microbiome of the control tissue (external surface of the cervix) was significantly different from that of the amniotic fluid, intercotyledonary placenta, and placentome tissues. Interestingly, many bacterial species associated with postpartum uterine disease (i.e., Trueperella spp., Acinetobacter spp., Fusobacteria spp., Proteus spp., Prevotella spp., and Peptostreptococcus spp.) were also present in the uterus of virgin heifers and of pregnant cows. The presence of 16S rRNA gene sequence reads in the samples from the current study suggests that the uterine microbiome is established by the time a female reaches reproductive maturity, and that pregnancies are established and maintained in the presence of a uterine microbiome.