Inconsistent Reporting of Preauthorization Medical Criteria for Osteochondral Allograft Transplantation Surgery.
Although osteochondral allograft (OCA) transplantation has been a standard treatment for patients with osteochondral lesions, there is a disagreement in commercial payers' medical criteria regarding the definition of medical suitability and thus authorization for OCA transplantation. The primary goal of this study was to understand where consensus between a committee of experienced cartilage restoration surgeon scientists and payer policies existed and where there was significant disagreement. U.S. private payers were identified by reviewing health insurance market research literature. Medical criteria were then obtained from publicly available payer medical polices. A literature review was conducted to identify supporting evidence for consensus statements based on private payer medical criteria. The MOCA (Metrics of Osteochondral Allograft) Committee, 30 experienced surgeons and subject-matter experts in OCA transplantation, used a Likert scale of 1 (strongly disagree) to 5 (strongly agree) to rank each statement. The extent of agreement and disagreement among participants was measured for each statement. Consensus was defined as agreement or disagreement of >75%. Fifty-seven statements regarding relevant medical criteria for OCA transplantation were included in the survey. All 30 MOCA Committee members completed the survey (100% response rate). Over half of the statements (52.6%) did not reach consensus. Of the remaining 27 statements that reached consensus, respondents agreed or strongly agreed with 16 statements, and disagreed or strongly disagreed with 11 statements. Inconsistent voting was observed for statements related to osteoarthritis, inflammation, and degenerative changes. Commercial payers are not consistent in the medical criteria used to define patient eligibility for authorization of OCA transplantation. In contrast, an expert panel of cartilage surgeons reached a consensus that OCA transplantation was clearly suitable for a variety of specific indications. This study demonstrates the need to standardize medical criteria for cartilage restoration based on the most current literature, as well as in conjunction with experienced cartilage restoration experts. Therapeutic Level V . See Instructions for Authors for a complete description of levels of evidence.


Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells.
In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.


The role of HIF in angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.
Typically associated with solid tumors, hypoxia contributes to tumor angiogenesis and lymphangiogenesis through various molecular mechanisms. Accumulating studies indicate that hypoxia-inducible factor is the key transcription factor coordinating endothelial cells to respond to hypoxia in urological cancers, mainly renal cell carcinoma, prostate cancer, and bladder cancer. Moreover, it has been suggested that tumor hypoxia in tumor microenvironment simultaneously recruits stromal cells to suppress immune activities. This review summarizes the mechanisms by which HIF regulates tumorigenesis and elaborates on the associations between HIF and angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.


BiobankUniverse: automatic matchmaking between datasets for biobank data discovery and integration.
Biobanks are indispensable for large-scale genetic/epidemiological studies, yet it remains difficult for researchers to determine which biobanks contain data matching their research questions. To overcome this, we developed a new matching algorithm that identifies pairs of related data elements between biobanks and research variables with high precision and recall. It integrates lexical comparison, Unified Medical Language System ontology tagging and semantic query expansion. The result is BiobankUniverse, a fast matchmaking service for biobanks and researchers. Biobankers upload their data elements and researchers their desired study variables, BiobankUniverse automatically shortlists matching attributes between them. Users can quickly explore matching potential and search for biobanks/data elements matching their research. They can also curate matches and define personalized data-universes. BiobankUniverse is available at http://biobankuniverse.com or can be downloaded as part of the open source MOLGENIS suite at http://github.com/molgenis/molgenis. email@example.com. Supplementary data are available at Bioinformatics online.


[Diabetes mellitus and cancer: the different expression of these diseases in Israeli Arabs and Jews].
The Arab population of Israel is a separate ethnic group from the Jewish population, embracing a different lifestyle and different nutritional habits and environmental exposures. These variations may lead to dissimilar expressions of certain diseases in the Arab Israeli as compared with the Jewish population. In recent years, the Arab population in Israel has experienced rapid and marked changes toward westernization in lifestyle, and significant increases in the incidence rate of both diabetes mellitus (DM) and cancer This is combined with an increase in known risk factors common to both illnesses. Review of recent publications and official health statistics provided the sources of information for this review. Studies show that in recent decades the incidence rate of DM in the Israeli Arab population has increased by 9.1 per 1000 persons annually and of cancer by 1.3 per 1000 person annually among males and by 1.2 per 1000 person among females. In contrast, these rates have decreased in the Jewish population. Lifestyle change in recent decades (westernization) in the Israeli Arab population has led to a marked increase in the incidence rate of DM and cancer in this group. The most influential risk factors are unhealthy diet, physical inactivity and tobacco smoking. By understanding these processes, effective intervention efforts can be initiated in order to reverse these trends.


Inhibition of sodium currents by local anesthetics in chloramine-T-treated squid axons. The role of channel activation.
In order to test the requirement of Na channel inactivation for the action of local anesthetics, we investigated the inhibitory effects of quaternary and tertiary amine anesthetics on normally inactivating and noninactivating Na currents in squid axons under voltage clamp. Either the enzymatic mixture pronase, or chloramine-T (CT), a noncleaving, oxidizing reagent, was used to abolish Na channel inactivation. We found that both the local anesthetics QX-314 and etidocaine, when perfused internally at 1 mM, elicited a "tonic" (resting) block of Na currents, a "time-dependent" block that increased during single depolarizations, and a "use-dependent" (phasic) block that accumulated as a result of repetitive depolarizations. All three effects occurred in both control and CT-treated axons. As in previous reports, little time-dependent or phasic block by QX-314 appeared in pronase-treated axons, although tonic block remained. Time-dependent block was greatest and fastest at large depolarizations (Em greater than +60 mV) for both the control and CT-treated axons. The recovery kinetics from phasic block were the same in control and CT-modified axons. The voltage dependence of the steady state phasic block in CT-treated axons differed from that in the controls; an 8-10% reduction of the maximum phasic block and a steepening and shift of the voltage dependence in the hyperpolarizing direction resulted from CT treatment. The results show that these anesthetics can bind rapidly to open Na channels in a voltage-dependent manner, with no requirement for fast inactivation. We propose that the rapid phasic blocking reactions in nerve are consequences primarily of channel activation, mediated by binding of anesthetics to open channels, and that the voltage dependence of phasic block arises directly from that of channel activation.


Elimination of stabilised hyaluronan from the knee joint in healthy men.
To investigate the elimination of stabilised hyaluronan following intra-articular injection into the knee joint. This was a single-centre, single-dose study in healthy human volunteers. Six healthy men, aged 28 to 47 (mean 38) years, were enrolled in the study. Subjects received a single intra-articular injection (3ml; 20 mg/ml) of (131)I-labelled non-animal stabilised hyaluronic acid (NASHA). Radioactivity in the knee, blood, urine and over the liver was measured with gamma counters for 3 weeks post-injection; magnetic resonance and gamma camera imaging of the knee were also performed at 24 hours post-injection. Radioactivity uptake data were tested for conformity of fit to different mathematical models. Elimination of (131)I-labelled NASHA from the knee was characterised by a fast initial phase and a slow late phase, and conformed to a three-exponential-function model with elimination half-lives of 1.5 hours, 1.5 days and 4 weeks. Radioactivity distribution within the knee joint was homogenous, and no local leakage was observed. Hepatic radioactivity uptake was low, but significantly above background levels, for the first 2 days post-injection, before declining to background levels. Visual imaging indicated an increase in intra-articular fluid volume at 24 hours post-injection. The elimination kinetics of (131)I-labelled NASHA from the human knee joint were described by three distinct phases, with half-times of 1.5 hours, 1.5 days and 4 weeks. Most likely, the last value reflects the true half-life of NASHA following intra-articular injection since the labelling method used causes minimal modification of hyaluronan.


Human epidermal Langerhans' cells in bullous pemphigoid.
Through the epidermal analysis of 13 patients with bullous pemphigoid compared to controls, using OKT6 monoclonal antibodies on the light microscopic level and electron-microscopy, we found a redistribution of the Langerhans' cells towards the basal membrane in combination with an increased total number of Langerhans' cells. This redistribution was also noted in clinically normal skin from patients with bullous pemphigoid. The findings may be consistent with the theory of antigen presentation.


Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis.
The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis. Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy. Time (days) to colonoscopy after a positive FIT result. Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors. Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients). Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.


Daily GRACE satellite data evaluate short-term hydro-meteorological fluxes from global atmospheric reanalyses.
Changes in terrestrial water storage as observed by the satellite gravity mission GRACE (Gravity Recovery and Climate Experiment) represent a new and completely independent way to constrain the net flux imbalance in atmospheric reanalyses. In this study daily GRACE gravity field changes are used for the first time to investigate high-frequency hydro-meteorological fluxes over the continents. Band-pass filtered water fluxes are derived from GRACE water storage time series by first applying a numerical differentiation filter and subsequent high-pass filtering to isolate fluxes at periods between 5 and 30 days corresponding to typical time-scales of weather system persistence at moderate latitudes. By comparison with the latest atmospheric reanalysis ERA5 of the European Centre for Medium-Range Weather Forecasts (ECWMF) we show that daily GRACE gravity field models contain realistic high-frequency water flux information. Furthermore, GRACE-derived water fluxes can clearly identify improvements realized within ERA5 over its direct predecessor ERA-Interim particularly in equatorial and temperate climate zones. The documented improvements are in good agreement with rain gauge validation, but GRACE also identifies three distinct regions (Sahel Zone, Okavango Catchment, Kimberley Plateau) with a slight degradation of net-fluxes in ERA5 with respect to ERA-Interim, thereby highlighting the potentially added value of non-standard daily GRACE gravity series for hydro-meteorological monitoring purposes.


Protein folding: search for basic physical models.
How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context of in vivo protein folding (which has been studied only for a few proteins), the roles of the fundamental physical forces in the in vitro folding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces). Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.


Allelic fusion of DNA topoisomerase II alpha and retinoic acid receptor alpha genes in adriamycin-resistant p388 murine leukemia revealed by fluorescence in situ hybridization.
Fluorescence in situ hybridization (FISH) analysis of metaphase and decondensed free chromatin fibers from Adriamycin (ADR)-sensitive and ADR-resistant murine cells demonstrated a close juxtaposition of topoisomerase II alpha (Top2a) and retinoic acid receptor alpha (Rara) genes in adjacent chromatin in the drug-resistant cells, and a close but separate genetic proximity in normal murine chromatin. This provides physical evidence that the chromosome 11 allelic rearrangement resulting in a chimeric truncated Top2a/Rara transcript in the ADR-resistant cells is due to a novel fusion of the Topo2a and Rara genes. This is the first description of a Rara gene disruption in cells selected for antineoplastic drug resistance.


The proteomic constraint and its role in molecular evolution.
Recently, the concept of a "Proteomic Constraint" was introduced to explain the frequency of genetic code deviations in mitochondrial genomes. The Proteomic Constraint was proposed to be proportional to the size of the mitochondrially encoded proteome, hence small proteomes are expected to experience smaller total numbers of errors resulting from genetic code deviations, leading to less likelihood of causing lethality. The concept is now extended to encompass several other aspects of the genetic information system. When the Proteomic Constraint is small, it is proposed that there is little selective pressure to evolve or maintain error correction mechanisms, as a result of the smaller total number of errors that accumulate. Conversely, a large Proteomic Constraint is proposed to result in a correspondingly large selective pressure to evolve or maintain error correction mechanisms. Differences in the size of the Proteomic Constraint can help to explain differences in replicational, transcriptional, and translational fidelities between genomes. A key piece of evidence is the existence of negative power law relationships between proteome size and error rates; these are demonstrated to be diagnostic of the action of the Proteomic Constraint. The Proteomic Constraint is argued to be a major factor determining mutation rates in a diverse range of DNA genomes, implying that mutation rates are clock like. A small Proteomic Constraint partly explains why RNA viruses possess high mutation rates. A reduced Proteomic Constraint in intracellular pathogenic bacteria predicts a drift upwards in mutation rates. Differences in the Proteomic Constraint also appear to be linked to differences in recombination rates between eukaryotes. In addition, a reduced Proteomic Constraint may explain features of resident genomes, such as loss of DNA repair pathways, increased substitution rates, and AT biases, in addition to the occurrence of genetic code deviations. Thus, it is argued that the Proteomic Constraint is a universal factor that influences a wide range of properties of the genetic information system.


Characterization of Dizziness After Lasmiditan Usage: Findings From the SAMURAI and SPARTAN Acute Migraine Treatment Randomized Trials.
SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies conducted in the United States, as well as the United Kingdom and Germany (SPARTAN only). Individuals with migraine were randomized to receive oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo within 4 hours of onset of a migraine attack. The aim of this analysis was to characterize dizziness reported with lasmiditan treatment. Data from SAMURAI and SPARTAN were pooled for the current post hoc analyses. Onset time and duration of dizziness were analyzed using descriptive statistics. Subgroup analyses based on presence/absence of dizziness were performed for the endpoints of interference with daily activity, patient global impression of change (PGIC), pain at 2 hours, and most bothersome symptom (MBS) at 2 hours based on adverse events occurring within 2 hours of taking study drug. Dizziness incidence was as follows: Placebo (N = 1262), 2.9% (0.1% severe); lasmiditan 50 mg (N = 654), 8.6% (0.3% severe); lasmiditan 100 mg (N = 1265), 14.9% (0.7% severe); and lasmiditan 200 mg (N = 1258), 16.8% (1.4% severe). Among participants who received lasmiditan as their first dose, risk factors for dizziness were higher lasmiditan dosage, being non-Hispanic/Latino, mild or moderate severity of migraine attack, and lower body mass index. The median time to onset of dizziness was generally 30-40 minutes, and the median duration was 1.5-2 hours. The presence of dizziness did not appear to have a negative influence on lasmiditan's effect on daily activity, PGIC, freedom from pain, or MBS. Overall, 21 participants experienced vertigo: Lasmiditan 50 mg, n = 2 (0.3%); 100 mg, n = 11 (0.9%); 200 mg, n = 7 (0.6%); and placebo, n = 1 (<0.1%). The incidence of dizziness with lasmiditan increased with dose. Dizziness was generally mild or moderate in severity and of quick onset and short duration. The presence of dizziness did not influence drug efficacy.


Discrimination between peptide 3(10)- and alpha-helices. Theoretical analysis of the impact of alpha-methyl substitution on experimental spectra.
Detailed spectral simulations based on ab initio density functional theory computations of the amide I and II infrared (IR) and vibrational circular dichroism (VCD) spectra for Ac-(Ala)(4)-NH(2), Ac-(Aib-Ala)(2)-NH(2), and Ac-(Aib)(4)-NH(2) constrained to 3(10)- and alpha-helical conformations are presented. Parameters from these ab initio calculations are transferred onto corresponding larger oligopeptides to simulate the spectra for dodecamers. The differences between conformations and for different Aib substitution patterns within a conformation are reflected in observable spectral patterns where data are available. Simulated IR spectra show small frequency shifts in the amide I maxima between 3(10)- and alpha-helices, but the same magnitude shifts occur within one conformation upon Aib substitution. Thus, from a computational basis, the frequency of the amide I maximum does not discriminate between the 3(10)- or alpha-helical conformations. Calculated VCD band shapes for 3(10)-helices showed more significant changes in amplitude, with change in the fraction of Aib, than those for alpha-helices. Generally, with increasing Aib content, the overall amide I VCD intensity becomes weaker and the amide I couplet becomes more conservative, while the amide II VCD is less affected. Although the detailed band shape is shown to be sensitive to alpha-Me substitution, the basic pattern of amide I and II relative VCD intensities still differs between alpha- and 3(10)-helices and, as a consequence, successfully discriminates between them. These predictions are all borne out in experimental spectra of Aib, mixed Aib-Ala, and Ala-based helical peptides, where available.


Polyelectrolyte thromboresistant affinity coatings for modification of devices contacting blood.
The modification of hydrophobic polyethylene/polystyrene surfaces of medical devices with bilayer/multilayer coatings (BCs/MCs) based on polyelectrolyte complexes (PEC) of modified poly(N-vinylpyrrolidone-co-maleic acid) copolymer (VPMA) with chitosan, amphiphilic chitosan, or albumin was studied. The VPMA contained l-Lysine as affinity ligand for plasminogen attached through alpha-amino group. The surface properties and chemical composition of the surfaces investigated were analyzed, using sessile-drop water contact angle measurements, attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The specific adsorption of plasminogen (precursor of fibrinolytic enzyme plasmin) from its solutions and from human blood plasma on the modified surfaces was investigated. It was established that polyelectrolyte MCs are more efficient than single-layer BCs and the affine polymer coatings without interlayer. A thrombogenicity decrease for the materials modified with BCs and MCs was shown in in vitro and ex vivo trials.


Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke.
Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging. Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information. Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts. Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.


Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis.
Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria, involves a random walk biased by the time derivative of attractant concentration, but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons (ASEL and ASER) are ablated, indicating that this pair has a dominant role. Although these neurons are left-right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference. Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON-cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON-OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion (runs) whereas ASER promotes direction changes (turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis. Evidence for ON and OFF cells in other chemosensory networks suggests that this motif may be common in animals that navigate by taste and smell.


Phosphate solubilizing bacteria from soils with varying environmental conditions: Occurrence and function.
Phosphate solubilizing bacteria (PSB) is an advantageous way to supply phosphate (P) to plants. The Mediterranean climate of Morocco, especially the low-lying areas, is semi-arid with nutrient-depleted soils in which small-scale, low-income farmers dominate without access to expensive inorganic fertilizers. However, there is not a wide range of PSBs suitable for various agroecological situations. Furthermore, our understanding of the soil and climatic variables that influence their development is limited. This study aims to examine the impacts of specific environmental factors, such as climate and soil, on the abundance, potential, and diversity of PSBs in four agricultural regions of Morocco. To assess the possible impact of these factors on the P solubilization capacity of PSBs and plant growth-promoting (PGP) traits, we analyzed the soil and climate of each sample studied. Similarly, we tested the P solubilization efficiency of the isolates. The bacteria were isolated in a National Botanical Research Institute's phosphate (NBRIP) agar medium. A total of 51 PSBs were studied in this work. The P-solubilization average of Rock P (RP) and Tricalcium P (TCP) of all strains that were isolated from each of the four regions ranged from 18.69 mg.L-1 to 40.43 mg.L-1 and from 71.71 mg.L-1 to 94.54 mg.L-1, respectively. The PGP traits of the isolated strains are positively correlated with the PSBs abundance and the sample characteristics (soil and climate). The morphological and biochemical characteristics of the strain allowed us to identify around nine different bacterial genera, including Bacillus, Pseudomonas, and Rhizobium. The findings showed that bacterial communities, density, and potency are closely correlated to various edapho-climatic conditions such as temperature, precipitation, soil nutrient status, and soil texture. These findings could be used to improve an effective plant-PSBs system and increase agricultural output by taking into account their specific ecological traits and plant growth mechanisms.


Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation.
Periprosthetic joint infections (PJIs) are a devastating complication that occurs in 2% of patients following joint replacement. These infections are costly and difficult to treat, often requiring multiple corrective surgeries and prolonged antimicrobial treatments. The Gram-positive bacterium Staphylococcus aureus is one of the most common causes of PJIs, and it is often resistant to a number of commonly used antimicrobials. This tolerance can be partially attributed to the ability of S. aureus to form biofilms. Biofilms associated with the surface of indwelling medical devices have been observed on components removed during chronic infection, however, the development and localization of biofilms during PJIs remains unclear. Prior studies have demonstrated that synovial fluid, in the joint cavity, promotes the development of bacterial aggregates with many biofilm-like properties, including antibiotic resistance. We anticipate these aggregates have an important role in biofilm formation and antibiotic tolerance during PJIs. Therefore, we sought to determine specifically how synovial fluid promotes aggregate formation and the impact of this process on surface attachment. Using flow cytometry and microscopy, we quantified the aggregation of various clinical S. aureus strains following exposure to purified synovial fluid components. We determined that fibrinogen and fibronectin promoted bacterial aggregation, while cell free DNA, serum albumin, and hyaluronic acid had minimal effect. To determine how synovial fluid mediated aggregation affects surface attachment, we utilized microscopy to measure bacterial attachment. Surprisingly, we found that synovial fluid significantly impeded bacterial surface attachment to a variety of materials. We conclude from this study that fibrinogen and fibronectin in synovial fluid have a crucial role in promoting bacterial aggregation and inhibiting surface adhesion during PJI. Collectively, we propose that synovial fluid may have conflicting protective roles for the host by preventing adhesion to surfaces, but by promoting bacterial aggregation is also contributing to the development of antibiotic tolerance.


Expression and localization of translationally controlled tumor protein in rat urinary organs.
This study describes the very first assessment of the expression and localization of translationally controlled tumor protein (TCTP) in adult rat urinary organs. TCTP expression levels in kidneys, urinary bladder, and urethra were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, and its cellular localization was examined immunohistochemically in paraffin sections of various urinary organs. TCTP was found in all urinary organs. Its expression was high in the urethra and low in the bladder. TCTP was localized in glomerular podocytes, epithelium of proximal and distal renal tubules, in the loop of Henle, and in the transitional epithelium of the bladder and urethra, mostly in basal cell layers). The subcellular localization of TCTP in these urinary organs was cytoplasmic. These findings suggest that TCTP may be involved in urine formation and excretion.


Frequency of Peri-operative Hypertension in a tertiary care hospital in Karachi, Pakistan.
This study aims to determine the frequency of perioperative hypertension and its types (pre, intra and post-operative) hypertension in patients admitted for surgical procedures. This was a cross-sectional study conducted between the years 2012-2013 at the Aga Khan University Hospital, Karachi. Patients admitted for any surgical procedure during this time were included. Perioperative hypertension has been defined as systolic blood pressure of >140 mm Hg or a diastolic blood pressure of >90 mm Hg or whose blood pressure increased by 20% during surgery. A total of 428 surgical procedures were reviewed for the study. Overall perioperative hypertension was present in 231 (54%) of the patients. In the sample, 91 (21.7%) had pre-operative hypertension, 126(29.4%) reported pre-surgery hypertension, 24(5.6%) had intra-operative hypertension and 63(14.7%) had post-operative hypertension. Mean pain score was 1.43(1.4) v 1.25(1.2) in those with postoperative hypertension v no post-operative hypertension (p value 0.009).


Feasibility of circulating tumor DNA testing in hepatocellular carcinoma.
Advancement of technologies enabling clinical assessment of circulating tumor DNA (ctDNA) are allowing for assessment of tumor specific genetic alterations in patients. This holds incredible promise for early detection of disease, serial monitoring of tumor heterogeneity, elucidation of therapeutic targets, and evaluation of treatment response and mechanisms of resistance. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is often diagnosed late, recurs commonly, and is often diagnosed based upon imaging features alone. A comprehensive evaluation of real-time evaluation of ctDNA in patients with HCC has thus far not been undertaken. From January 2015 to February 2018, 35 patients with biliary tract cancer (BTC) at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples were tested utilizing the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively; and in some, amplifications, fusions, and indels. A total of 44 samples were collected on these 35 patients, with >70% having stage 3 or 4 disease. Among all samples the median number of alterations per sample, excluding variants of undetermined significance (VUS), was 3.5, with a median allele frequency of 0.65%. A total of 122 unique genetic alterations, excluding VUS or synonymous alterations, were seen. The overall landscape of alterations is described. The top 10 genes altered in this cohort of patients, excluding VUS or synonymous alterations, were TP53 (18%), TERT (14%), CTNNB1 (13%), ARID1A (9%), MYC (5%), BRAF (4%), CCND1 (4%), CDK6 (4%), and MET (4%), and EGFR (3%). Herein, we describe feasibility of ctDNA testing and results from such testing in HCC patients undergoing ctDNA testing in a real-time clinical context. Patients with these cancers stand to benefit immensely from the use of ctDNA technologies, and concerted efforts at further investigation of such are critically needed.


In Vitro Antifungal Susceptibility of Oral Candida Isolates from Patients Suffering from Caries and Chronic Periodontitis.
Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.


Let us fight and support one another: adolescent girls and young women on contributors and solutions to HIV risk in Zambia.
In Zambia, adolescent girls and young women (AGYW) are disproportionately affected by human immunodeficiency virus (HIV), social, cultural and economic factors making them particularly vulnerable. This study was designed to understand the context in which AGYW are at risk and to identify perceived drivers of the epidemic and potential strategies to reduce HIV risk. Focus group discussions were conducted with AGYW in Zambian districts with the highest HIV prevalence from February through August 2016. The focus group guide addressed HIV risk factors and strategies for HIV prevention in AGYW. Focus group discussions were recorded, translated and transcribed, themes identified and responses coded. Results suggest that gender inequality undermined potentially protective factors against HIV among AGYW. Poverty and stigmatization were major barriers to accessing available HIV prevention services as well as primary risk factors for HIV infection. Sponsorship to support AGYW school attendance, programs for boys and girls to foster gender equality and financial assistance from the government of Zambia to support AGYW most in need were proposed as strategies to reduce HIV risk. Results highlight the utility of using community-based research to guide potential interventions for the affected population. Future research should explore the use of multilevel interventions to combat HIV among AGYW.


Pediatrician-parent communication in a continuity-of-care setting.
This study investigated pediatrician-parent communication by content, analyzing medical encounters in a setting providing continuity of care. Thirty-eight encounters between middle class families and three senior pediatricians were audio-taped, transcribed, and analyzed for content. The categories of medical communication coded from the interactions were related to each family's medical and demographic characteristics. Five patterns of results emerged: (1) There was a highly stylizied active-passive role relationship, with doctors asking twice as many questions and making twice as many commands as the parent did. (2) A strong reciprocity norm existed between pediatricians and parents for the communication of affect. (3) The higher the experience, income, and educational levels of the parents, the shorter the encounters were, the less frequently symptoms were discussed, and the more frequently medication and professional treatment were mentioned. (4) Parents discussed health more in terms of organicity of causes than did pediatricians who, more frequently, raised environmental factors. (5) The more the family had a history of past illnesses, the more frequently the doctors made affect comments during the encounters. Comparing the results to findings drawn from an emergency clinic documented the importance of sustained relationships between practitioners and patients.


Haemophilus influenzae and the lung (Haemophilus and the lung).
Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. This bacterium is divided into typeable forms (such as type b) or nontypeable forms based on the presence or absence of a tough polysaccharide capsule. Respiratory disease is predominantly caused by the nontypeable forms (NTHi). Haemophilus influenzae has evolved a number of strategies to evade the host defense including the ability to invade into local tissue. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of this bacterium from the upper airway to the bronchi of the lung. This can result in airway inflammation and colonization particularly in chronic obstructive pulmonary disease. Treatment of respiratory tract infection with Haemophilus influenzae is often only partially successful with ongoing infection and inflammation. Improvement in patient outcome will be dependent on a better understanding of the pathogenesis and host immune response to this bacterium.


Circadian photoreception in the retinally degenerate mouse (rd/rd).
We have examined the effects of light on circadian locomotor rhythms in retinally degenerate mice (C57BL/6J mice homozygous for the rd allele: rd/rd). The sensitivity of circadian photoreception in these mice was determined by varying the irradiance of a 15 min light pulse (515 nm) given at circadian time 16 and measuring the magnitude of the phase shift of the locomotor rhythm. Experiments were performed on animals 80 days of age. Despite the loss of visual photoreceptors in the rd/rd retina, animals showed circadian responses to light that were indistinguishable from mice with normal retinas (rd/+ and +/+). While no photoreceptor outersegments were identified in the retina of rd/rd animals (80-100 days of age), we did identify a small number of perikarya that were immunoreactive for cone opsins, and even fewer cells that contained rod opsin. Using HPLC, we demonstrated the presence and photoisomerization of the rhodopsin chromophore 11-cis retinaldehyde. The rd/rd retinas contained about 2% of 11-cis retinaldehyde found in +/+ retinas. We have yet to determine whether the opsin immunoreactive perikarya or some other unidentified cell type mediate circadian light detection in the rd/rd retina.


Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren's syndrome.
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.


Zeolite thin film-coated long period fiber grating sensor for measuring trace chemical.
This paper reports the development of a new zeolite thin film-coated long period fiber grating (LPFG) sensor for direct measurement of trace organic vapors. The sensor was fabricated by growing pure silica MFI-type zeolite thin film on the optical fiber grating by in situ hydrothermal crystallization. The sensor measures chemical vapor concentration by monitoring the molecular adsorption-induced shift of LPFG resonant wavelength (lambda(R)) in near infrared (IR) region. Upon loading analyte molecules, the zeolite's refractive index changes in the close vicinity of the fiber index where the LPFG has a large response to achieve high sensitivity.


Probable Posttraumatic Stress Disorder in the US Veteran Population According to DSM-5: Results From the National Health and Resilience in Veterans Study.
With the publication of DSM-5, important changes were made to the diagnostic criteria for posttraumatic stress disorder (PTSD), including the addition of 3 new symptoms. Some have argued that these changes will further increase the already high rates of comorbidity between PTSD and other psychiatric disorders. This study examined the prevalence of DSM-5 PTSD, conditional probability of PTSD given certain trauma exposures, endorsement of specific PTSD symptoms, and psychiatric comorbidities in the US veteran population. Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a Web-based survey of a cross-sectional, nationally representative, population-based sample of 1,484 US veterans, which was fielded from September through October 2013. Probable PTSD was assessed using the PTSD Checklist-5. The weighted lifetime and past-month prevalence of probable DSM-5 PTSD was 8.1% (SE = 0.7%) and 4.7% (SE = 0.6%), respectively. Conditional probability of lifetime probable PTSD ranged from 10.1% (sudden death of close family member or friend) to 28.0% (childhood sexual abuse). The DSM-5 PTSD symptoms with the lowest prevalence among veterans with probable PTSD were trauma-related amnesia and reckless and self-destructive behavior. Probable PTSD was associated with increased odds of mood and anxiety disorders (OR = 7.6-62.8, P < .001), substance use disorders (OR = 3.9-4.5, P < .001), and suicidal behaviors (OR = 6.7-15.1, P < .001). In US veterans, the prevalence of DSM-5 probable PTSD, conditional probability of probable PTSD, and odds of psychiatric comorbidity were similar to prior findings with DSM-IV-based measures; we found no evidence that changes in DSM-5 increase psychiatric comorbidity. Results underscore the high rates of exposure to both military and nonmilitary trauma and the high public health burden of DSM-5 PTSD and comorbid conditions in veterans.


Polymeric Microporous Nanofilms as Smart Platforms for in Vitro Assessment of Nanoparticle Translocation and Caco-2 Cell Culture.
The study of nanomaterial translocation across epithelial barriers is often hindered by the low permeability of transwell membranes to nanoparticles. To address this issue ultra-thin poly(L-lactic acid) nanofilms with zero tortuosity micropores were developed for use in nanoparticle passage tests. In this study we demonstrate that microporous polymeric nanofilms allow a significantly higher passage of silver nanoparticles in comparison with commercial membranes normally used in transwell inserts. A reliable procedure for collecting free-standing nanofilms which enables their manipulation and use in lab-on-chip systems is described. We also demonstrate the cytocompatibility of porous nanofilms and their ability to sustain the adhesion and proliferation of Caco-2 cells. Ultra-thin microporous membranes show promise as low-cost nanomaterial screening tools and may be used as matrices for the development of bioengineered systems for mimicking the intestinal epithelium.


Abiotic and biotic context dependency of perennial crop yield.
Perennial crops in agricultural systems can increase sustainability and the magnitude of ecosystem services, but yield may depend upon biotic context, including soil mutualists, pathogens and cropping diversity. These biotic factors themselves may interact with abiotic factors such as drought. We tested whether perennial crop yield depended on soil microbes, water availability and crop diversity by testing monocultures and mixtures of three perennial crop species: a novel perennial grain (intermediate wheatgrass-Thinopyrum intermedium-- that produces the perennial grain Kernza®), a potential perennial oilseed crop (Silphium intregrifolium), and alfalfa (Medicago sativa). Perennial crop performance depended upon both water regime and the presence of living soil, most likely the arbuscular mycorrhizal (AM) fungi in the whole soil inoculum from a long term perennial monoculture and from an undisturbed native remnant prairie. Specifically, both Silphium and alfalfa strongly benefited from AM fungi. The presence of native prairie AM fungi had a greater benefit to Silphium in dry pots and alfalfa in wet pots than AM fungi present in the perennial monoculture soil. Kernza did not benefit from AM fungi. Crop mixtures that included Kernza overyielded, but overyielding depended upon inoculation. Specifically, mixtures with Kernza overyielded most strongly in sterile soil as Kernza compensated for poor growth of Silphium and alfalfa. This study identifies the importance of soil biota and the context dependence of benefits of native microbes and the overyielding of mixtures in perennial crops.


A Population Health Measurement Framework: Evidence-Based Metrics for Assessing Community-Level Population Health in the Global Budget Context.
Population health is one of the pillars of the Triple Aim to improve US health care. The authors developed a framework for population health measurement and a proposed set of measures for further exploration to guide the population health efforts in Maryland. The authors searched peer-reviewed, expert-authored literature and current public health measures. Using a semi-structured analysis, a framework was proposed, which consisted of a conceptual model of several domains and identified population health measures addressing them. Stakeholders were convened to review the framework and identified the most feasible population health measures considering the underlying health information technology (IT) infrastructure in Maryland. The framework was organized based on health system factors, determinants of health, and population-based and clinical outcomes. Measurement specifications were developed that addressed different aspects of selected measures and assessed various national and local data sources for selected measures. Data sources were identified based on their key characteristics, challenges, opportunities, and potential applicability to the proposed measures, as well as the issue of interoperability of data sources among different organizations. The proposed framework and measures can act as a platform to quantify the determinants of health and the state overall population health goals. Key considerations for developing a population health measures framework include health IT infrastructure, data denominators, feasibility, health system environment, and policy factors. Measurement development and progression using the framework will largely depend on the users' focus areas and availability of data. The authors believe that the proposed framework and road map can serve as a model for communities elsewhere.


Benign extracerebral fluid collections in infancy: clinical presentation and long-term follow-up.
Benign extracerebral fluid collections are common in infants, but there are unanswered questions regarding presentation and long-term outcome. This study was undertaken to establish head size at birth, head size at presentation, head growth over time, history of presentation, indications for surgery, and long-term results. Cases of benign extracerebral fluid collections in infancy were retrospectively reviewed. Data pertaining to clinical presentation, progress, and long-term follow-up were evaluated. Patients were divided into two groups on the basis of the presence or absence of increased signal intensity of fluid in the extracerebral space on T1-weighted magnetic resonance images. Group 1 consisted of 39 patients who had benign extracerebral fluid collections without any subdural collections. Group 2 consisted of nine patients who had a chronic subdural hematoma or hygroma without a history of trauma and had generous subarachnoid spaces and/or a history of premature birth. Patients were observed for an average of 49 months. Group 1 included 39 patients (ages at presentation 3-12 months); the most common presentation in this group was macrocephaly (28 cases). Of those Group 1 cases in which data regarding gestational age at birth were available, 15 births were either severely or mildly premature and 14 were full term. Of those Group 1 patients with adequate data, 14 had an occipitofrontal circumference (OFC) in the 50th to 98th percentile at birth and two had OFCs greater than the 98th percentile. Measurements obtained at 24 months of age were available for 18 Group 1 patients: OFC was at approximately the 98th percentile in eight (all eight born at full term) and more than 1 cm larger than the 98th percentile in 10. Head growth in Group 1 patients continued to decrease, approaching the 98th percentile after 24 months of age. Only three of the 39 patients in Group 1 required shunt placement. Of the 33 Group 1 patients for whom long-term follow-up was available, 30 were developing normally, and three had mild developmental delays. Group 2 included nine patients (ages at presentation 3-7 months); the most common presentations were large head (three patients) and seizures (three patients). Data concerning gestational age at birth were available in eight Group 2 cases: birth was severely premature in four and gestation was full term in four. Five Group 2 patients were treated surgically-two with subduroperitoneal (SDP) shunt placement, two with subdural punctures, and one with subdural punctures and SDP shunt placement. Adequate follow-up information was available in eight of nine Group 2 cases; all eight patients were found to be developing normally. Group 1 patients usually had a normal head size at birth, they rarely required shunt placement, their head growth eventually leveled off toward the 98th percentile line, and their outcomes were generally good. Although five of nine Group 2 patients required subdural punctures and/or SDP shunt placement, that group of patients also developed well. Infants with nontraumatic subdural hematomas or hygromas, presumably associated with benign extracerebral fluid collections, can often experience significant resolutions of the hematoma or hygroma within several months without surgical treatment.


Morpho-functional characterization of human mesenchymal stem cells from umbilical cord blood for potential uses in regenerative medicine.
Mesenchymal stem cells (MSCs) represent a promising source of progenitor cells having the potential to repair and to regenerate diseased or damaged skeletal tissues. Bone marrow (BM) has been the first source reported to contain MSCs. However, BM-derived cells are not always acceptable, due to the highly invasive drawing and the decline in MSC number and differentiative capability with increasing age. Human umbilical cord blood (UCB), obtainable by donation with a noninvasive method, has been introduced as an alternative source of MSCs. Here human UCB-derived MSCs isolation and morpho-functional characterization are reported. Human UCB-derived mononuclear cells, obtained by negative immunoselection, exhibited either an osteoclast-like or a mesenchymal-like phenotype. However, we were able to obtain homogeneous populations of MSCs that displayed a fibroblast-like morphology, expressed mesenchym-related antigens and showed differentiative capacities along osteoblastic and early chondroblastic lineages. Furthermore, this study is one among a few papers investigating human UCB-derived MSC growth and differentiation on three-dimensional scaffolds focusing on their potential applications in regenerative medicine and tissue engineering. UCB-derived MSCs were proved to grow on biodegradable microfiber meshes; additionally, they were able to differentiate toward mature osteoblasts when cultured inside human plasma clots, suggesting their potential application in orthopedic surgery.


Hidden pulmonary arteries in tetralogy of Fallot and pulmonary artery pressure in patients operated with a pulmonary artery.
The absence of a pulmonary artery is a rare congenital anomaly that occurs isolated or with other congenital cardiac disorders, particularly tetralogy of Fallot (TOF); meanwhile, a hidden pulmonary artery might exist and originate from a closed ductus arteriosus (DA), which can be stented to reach the artery. This prospective study describes cardiac catheterization of nine TOF patients diagnosed with the absence of the left pulmonary artery before the operation. The patients were stratified into three groups: group one, whose closed DA was found and connected to the hidden pulmonary artery with a stent; group two, whose hidden pulmonary arteries were found via the pulmonary vein angiography; and group three, for whom we could not find the remnant of the DA, or our attempt to stent the DA to the hidden pulmonary artery was not successful. We also evaluated outcomes of six other surgically-corrected TOF patients who were operated with the absent left pulmonary artery. The first group included the patients aged 1, 24, and 30 months, whose CT angiography 6-9 months after stenting showed acceptable left pulmonary artery diameter for surgical correction, and the pulmonary vein angiography of the second group showed a hidden left pulmonary artery with a suitable diameter for surgical correction. However, we were unable to find or stent the DA of group three patients, aged 12, 38, 60, and 63 months. Earlier Angiography might have increased the chance of access to the hidden vessel. Apart from these three groups, follow-ups of six other patients previously corrected with only the right pulmonary artery revealed pulmonary artery hypertension in all patients. The concealed pulmonary artery might be found, and stenting of the closed DA to it might be performed to improve the diameter of the diminutive pulmonary artery. This procedure may allow TOF total surgical correction with two pulmonary arteries. Besides, pulmonary vein angiography can reveal the hidden pulmonary artery.


Helping with inquiries or helping with profits? The trials and tribulations of a technology of forensic reasoning.
The commercialization of forensic scientific provision in the UK over the last two decades has had a major role in shaping a changing epistemic identity for forensic scientists working within this jurisdiction. Efforts to match the presumed epistemological standards of the 'pure' sciences have been brought together with concerns about value for money in a new approach to the interpretation of evidence, an activity that lies at the heart of criminal investigative practice. A study of the Case Assessment and Interpretation method developed by members of the UK Forensic Science Service is used to show how a technical innovation in the delivery of forensic science services to the police has instantiated these two recent social processes.


Affective priming and cognitive load: Event-related potentials suggest an interplay of implicit affect misattribution and strategic inhibition.
Prior research suggests that the affective priming effect denoting prime-congruent evaluative judgments about neutral targets preceded by affective primes increases when the primes are processed less deeply. This has been taken as evidence for greater affect misattribution. However, no study so far has combined an experimental manipulation of the depth of prime processing with the benefits of ERPs. Forty-seven participants made like/dislike responses about Korean ideographs following 800-ms affective prime words while 64-channel EEG was recorded. In a randomized within-subject design, three levels of working-memory load were applied specifically during prime processing. Affective priming was significant for all loads and even tended to decrease over loads, although efficiency of the load manipulation was confirmed by reduced amplitudes of posterior attention-sensitive prime ERPs. Moreover, ERPs revealed greater explicit affective discrimination of the prime words as load increased, with strongest valence effects on central/centroparietal N400 and on the parietal/parietooccipital late positive complex under high load. This suggests that (a) participants by default tried to inhibit the processing of the prime's affect, and (b) inhibition more often failed under cognitive load, thus causing emotional breakthrough that resulted in a binding of affect to the prime and, hence, reduced affect misattribution to the target. As a correlate of affective priming in the target ERP, medial-frontal negativity, a well-established marker of (low) stimulus value, increased with increasing negative affect of the prime. Findings support implicit prime-target affect transfer as a major source of affective priming, but also point to the role of strategic top-down processes.


Traumatic brain injury.
There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad.


The association of the presence of seminal plasma and its components with sperm longevity in fractionated stallion ejaculates.
Semen jets in the stallion's ejaculate differ in both the biochemical composition of seminal plasma (SP) and in sperm concentration, forming sperm-rich fractions (HIGH) and sperm-poor fractions (LOW). This study examined (i) the association of the levels of selected components of SP [alkaline phosphatase (AP), acid phosphatase (ACP), Na(+), Cl(-), K(+), Ca, Mg and prostaglandin E(2)] with semen quality, sperm longevity and fertility; (ii) the effects of the presence of SP on sperm survival during cooled storage; (iii) the differences in the composition of SP between sperm-rich and sperm-poor ejaculatory fractions; (iv) the differences between these fractions in the effects of SP on sperm longevity. The levels of AP, ACP and Na(+) were higher in HIGH compared with LOW, whereas higher concentrations of Ca, K(+) and Mg were found in LOW than in HIGH. None of the measured components were correlated to the first cycle pregnancy rate. The presence of SP during cooled storage caused DNA degradation, but total and progressive sperm motility was not affected. Sperm-rich fractions stored with low levels of SP maintained higher level of DNA integrity compared with sperm-rich fractions in higher levels of SP, or sperm-poor fractions irrespective of the proportion of SP. The concentration of K(+) in LOW may give some indication on the maintenance of total sperm motility during cooled storage.


HTLV-I: newest addition to blood donor screening.
The Food and Drug Administration has recommended that blood donated for transfusion in the United States be screened for antibodies to human T lymphotropic virus type I. Since seropositive donors will be referred to health care providers for advice, physicians should become familiar with HTLV-I, its modes of transmission and its disease associations. According to current knowledge, seropositive persons should neither donate blood for transfusion nor share needles. Women should be advised against breast feeding. Advice about sexual activity is more difficult to formulate and must be individualized.


Optical single molecule characterisation of natural and synthetic polymers through nanopores.
Nanopore techniques are now widely used to sequence DNA, RNA and even oligopeptide molecules at the base pair level by measuring the ionic current. In order to build a more versatile characterisation system, optical methods for the detection of a single molecule translocating through a nanopore have been developed, achieving very promising results. In this work, we developed a series of tools to interpret the optical signals in terms of the physical behaviour of various types of natural and synthetic polymers, with high throughput. We show that the measurement of the characteristic time of a translocation event gives access to the apparent molecular weight of an object, and allows us to quantify the concentration ratio of two DNA samples of different molecular weights in solution. Using the same tools for smaller synthetic polymers, we were able to obtain information about their molecular weight distribution depending on the synthesis method.


Effect of Melatonin on the Expression of Apoptotic Genes in Vitrified-thawed Spermatogonia Stem Cells Type A of 6-Day-Old Mice.
Being secreted by the pineal gland, melatonin induces cell proliferation in normal cells and induced apoptosis in cancer cells. The purpose of this study was to investigate effects of melatonin on main components and the expression of apoptotic genes in vitrified-thawed testicular germ cells of 6- day-old mice. Testes of neonate Balb/c mice were vitrified- thawed under standard condition with or without the addition of 100 μM melatonin to both vitrification and thawing solutions. Subsequently, Vitrified-thawed whole testes were digested under standard condition and spermatogonial stem cells type A were separate in the suspension with CD90.1 (Thy1.1(+)) micro beads. Extraction of RNA and synthesis of cDNA was performed. Expression levels of apoptotic genes (Fas, P53, BCL-2 and BAX) were determined using Real-time PCR. Results : With all genes being expressed, level of expression for Fas was higher and for that of P-53 was lower than the remaining genes. Conclusion : Melatonin may cause apoptosis in cells being damaged under the influence of freezing thawing process. In order to examine the exact effects of melatonin on spermatogonia stem cells apoptosis, additional studies are required.


Ab initio phonon thermal transport in monolayer InSe, GaSe, GaS, and alloys.
We compare vibrational properties and phonon thermal conductivities (κ) of monolayer InSe, GaSe, and GaS systems using density functional theory and Peierls-Boltzmann transport methods. In going from InSe to GaSe to GaS, system mass decreases giving both increasing acoustic phonon velocities and decreasing scattering of these heat-carrying modes with optic phonons, ultimately giving [Formula: see text]. This behavior is demonstrated by correlating the scattering phase space limited by fundamental conservation conditions with mode scattering rates and phonon dispersions for each material. We also show that, unlike flat monolayer systems such as graphene, in InSe, GaSe and GaS thermal transport is governed by in-plane vibrations. Alloying of InSe, GaSe, and GaS systems provides an effective method for modulating their κ through intrinsic vibrational modifications and phonon scattering from mass disorder giving reductions ∼2-3.5 times. This disorder also suppresses phonon mean free paths in the alloy systems compared to those in their crystalline counterparts. This work provides fundamental insights of lattice thermal transport from basic vibrational properties for an interesting set of two-dimensional materials.


Renal epithelioid angiomyolipoma: imaging characteristics in nine cases with radiologic-pathologic correlation and review of the literature.
The purpose of this study was to describe the imaging features of renal epithelioid angiomyolipoma (EAML), a rare subtype of angiomyolipoma, with clinical and pathologic correlation. This study was a retrospective review of nine cases from a single institution in which total resection and preoperative imaging were performed and the diagnosis of EAML was made. Imaging included CT (nine cases), MRI (five cases), and ultrasound (one case), and the images were reviewed in consensus by two radiologists. Patient demographics, disease associations, presentation, and outcomes were determined by chart review. The patients were nine women and one man (mean age, 42 years). Two patients had tuberous sclerosis complex. The size of the nine EAMLs ranged from 1.4 to 22 cm (mean, 7.8 cm). Six lesions had minor components of fat identifiable at imaging. The contrast enhancement pattern was heterogeneous in eight lesions, five of which contained cysts, necrosis, and hematoma. Four presentations were acute hemorrhage, with ruptured EAML in three of the four. Five tumors extended into the renal sinus. Two tumors were locally invasive. One patient had metastatic disease at presentation with epithelioid tumor identified in a single lymph node. The follow-up periods ranged from 0 to 89 months, and there was one case of suspected but not yet proved recurrence. Renal EAML can have a range of imaging appearances and can be indistinguishable from renal cell carcinoma and angiomyolipoma with minimal fat. EAML can be considered when a mass is found that has small foci of macroscopic fat without calcification or when acute hemorrhage of a renal mass occurs.


Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. II. Relationship of the anti-lymphocytic choriomeningitis immune response to tissue injury in chronic lymphocytic choriomeningitis disease.
Tissue injury (chronic disease) associated with persistent LCM infection is apparently caused by the host immune response to the virus. Employing parabiosis or cell transfer from hyperimmune donors to isologous virus carriers, the tissue injury of chronic disease could be initiated and/or intensified. Furthermore, the transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells. The pathogenesis of the nonglomerular tissue injury of chronic LCM disease is apparently at least in part related to the interaction of circulating anti-LCM antibody with viral antigen at the tissue site. Trapping of circulating virus-antibody complexes in the glomerular filter is apparently the major cause of the glomerulonephritis.


Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors.
The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients), and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. Rolandic cortex was activated by tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electrocortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with > 2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.


Matching the Drug to the Patient: The rational use of antiarthritic drugs.
Antirheumatic drugs now available are often effective in helping control the more serious rheumatic disorders, but are not curative. All have potentially serious side effects and need to be used with caution in the presence of recognized risk factors. Treatment should be individualized for the diagnosis and severity of the underlying disease, which must be of sufficient magnitude to justify the risk of potential adverse reactions from the prescribed medication.


Polycystic ovaries - beyond menopause.
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in the reproductive age group; it is characterized by oligo-ovulation or anovulation, hyperandrogenism and the presence of polycystic ovaries. It affects 8-10% of women in the reproductive age group and its main presentations are irregular periods, hirsutism and infertility in this group. Women with PCOS have impaired glucose tolerance, dyslipidemia, and increased risk of type 2 diabetes and metabolic syndrome. The phenotype of PCOS in menopausal women is difficult to define. Studies have included previous history of oligomenorrhea, infertility and hyperandrogenism (clinical or biochemical) to describe the phenotype for postmenopausal women. Hyperandrogenism seen in PCOS women persists after the menopausal transition. Similarly, PCOS women continue to manifest the metabolic alterations such as insulin resistance after menopause, which makes them more susceptible to type 2 diabetes mellitus. The metabolic syndrome occurs more often in women with PCOS and has been shown to be associated with increased risk of cardiovascular disease. Whether PCOS itself causes an increased cardiovascular disease risk later in life is still uncertain. This dilemma needs to be solved since young women with PCOS may be required to undergo expensive investigations and screening for cardiovascular disease, whilst their true disease risk is still unknown.


Chemical sympathectomy and two-way escape and avoidance learning in the rat.
Six experiments are reported on the effects of 2,4,5-trihydroxyphenylethyl-amine (6-hydroxydopamine) on two-way escape and avoidance learning. Rats were tested on either escape or avoidance learning at 80 days of age after chemical sympathectomy at birth or 40 or 80 days of age. Neonatal and chronic sympathectomy (at 40 days), but not acute sympathectomy (at 80 days), resulted in depressed escape learning. Avoidance learning was affected by neonatal sympathectomy and partially by acute sympathectomy. The results have implications for the role of the autonomic nervous system in escape-avoidance learning.


Head Pitch Angular Velocity Discriminates (Sub-)Acute Neck Pain Patients and Controls Assessed with the DidRen Laser Test.
Understanding neck pain is an important societal issue. Kinematic data from sensors may help to gain insight into the pathophysiological mechanisms associated with neck pain through a quantitative sensorimotor assessment of one patient. The objective of this study was to evaluate the potential usefulness of artificial intelligence with several machine learning (ML) algorithms in assessing neck sensorimotor performance. Angular velocity and acceleration measured by an inertial sensor placed on the forehead during the DidRen laser test in thirty-eight acute and subacute non-specific neck pain (ANSP) patients were compared to forty-two healthy control participants (HCP). Seven supervised ML algorithms were chosen for the predictions. The most informative kinematic features were computed using Sequential Feature Selection methods. The best performing algorithm is the Linear Support Vector Machine with an accuracy of 82% and Area Under Curve of 84%. The best discriminative kinematic feature between ANSP patients and HCP is the first quartile of head pitch angular velocity. This study has shown that supervised ML algorithms could be used to classify ANSP patients and identify discriminatory kinematic features potentially useful for clinicians in the assessment and monitoring of the neck sensorimotor performance in ANSP patients.


Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones.
Three glycosilated flavonoids (diosmin, hesperidin and naringin) and respective aglycones were characterized in terms of their apparent ionisation constants and bidirectional permeability using the cellular model Caco-2 as well as the artificial membrane model PAMPA. Ionisation curves were established by capillary electrophoresis. It was confirmed that significant amounts of the aglycones are ionised at physiological pH whereas the glycosides are in the neutral form. Permeation was not detected for the glycosides in either the apical-to-basolateral or basolateral-to-apical directions confirming the need for metabolism before absorption through the intestinal membrane. The aglycones permeated in both directions with apparent permeabilities (P(app)) in the range of 1-8x10(-5) cm/s. The results from both in vitro methods correlated providing some evidence of passive transport; however, the hypothesis of active transport cannot be excluded particularly in the case of diosmetin. Metabolism of the aglycones was detected with the cell model, more extensively when loading in the apical side. Some of the metabolites were identified as glucuronide conjugates by enzymatic hydrolysis.


YD277 Suppresses Triple-Negative Breast Cancer Partially Through Activating the Endoplasmic Reticulum Stress Pathway.
Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor clinical outcomes. YD277 is a novel small molecule derived from ML264, a KLF5 inhibitor that elicits cytotoxic effects in colon cancer cell lines. Our previous studies suggest that Krüpple-like factor 5 (KLF5) is a promising therapeutic target for TNBC. In this study, we demonstrated that YD277 significantly induced G1 cell cycle arrest and apoptosis in MDA-MB-231 and MDA-MB-468 TNBC cells, independent of KLF5 inhibition. YD277 also reduced the protein expression levels of Cyclin D1, Bcl2 and Bclxl and promoted the expression of p21 and p27. Moreover, the pro-apoptotic activity of YD277 in TNBC was mediated by the transcription of IRE1α, a key molecule in the endoplasmic reticulum (ER) stress pathway. Finally, YD277 (15 mg/kg) significantly suppressed the growth of MDA-MB-231 tumor xenografts in nude mice. These findings indicate that YD277 is a promising chemotherapeutic candidate for TNBC.


Controlling inventory performance in a just-in-time environment.
This article will enable the reader to: 1) discover how to implement a cycle counting system to ensure inventory accuracy, 2) learn how to modify a cycle counting system to be successful in a point-of-use/backflush system, and 3) discuss the roles of production, materiel, engineering, and quality in a successful just-in-time cycle counting system.


A quantitative assessment of facial protection systems in elective hip arthroplasty.
We aimed to assess the risk to surgeons of blood splatter during total hip arthroplasty. Hoods from personal protection systems used in 34 consecutive total hip replacements were collected and the area of blood splatter was measured and compared to goggles and visors. Thirty one primary THA's (13 cemented, 4 hybrid, 14 uncemented) and 3 revisions (1 hybrid, 2 uncemented) were collected. Splashes were detected on all of the masks with a mean of 034% cover. Splatter was greatest for the operating surgeon, followed by the first assistant, though the difference was not statistically significant. Operating personnel were at greater risk of contamination during uncemented arthroplasty (p < 0.0001; 95% CI). On average 50.60% and 45.40% of blood cover was outside the area protected by goggles and visors respectively. There was a significant difference between the Personal Protection Systems (PPS) and goggles (p = 0.0231; 95% CI) as well as between the PPS and visors (p = 0.0293; 95% CI).


Heterogeneity of tyrosine hydroxylase expressing neurons in the main olfactory bulb of the mouse.
The structural features of dopamine (DA)-GABAergic neurons in the mouse main olfactory bulbs were examined, using both wild type and transgenic TH-GFP mice, with the combination of several methods; the immunocytochemistry, biotinylated dextran amine labeling, lucifer yellow injection in fixed slices, biocytin injection in live slice and the functional olfactory deprivation. DA-GABAergic neurons were clustered in the glomerular layer (GL) but they also scattered in other layers. DA-GABAergic juxtaglomerular neurons, were classified into 5 groups based on their structural features and named as follows: 1) Large periglomerular (LPG) cells with tuft-like glomerular dendritic branches and apparent axons extending to the distant glomeruli, which correspond to the " inhibitory juxtaglomerular association (IJGA) neurons" participating in the interglomerular association system. 2) Small periglomerular (SPG) cells including both axonic and anaxonic ones; the axonic SPG cells might correspond to the classical periglomerular cells. 3) Transglomerular cells extending dendritic processes spanning 2 or more glomeruli. 4) Incrusting cells extending their dendritic branches mainly in the periphery of the glomeruli. 5) Other various neurons not-yet classified. In the layers other than the GL various types of TH expressing neurons were scattered; some of them extended dendritic processes into the GL.


Effects of modafinil on cognitive performance and alertness during sleep deprivation.
The performance- and alertness-sustaining/restoring effects of modafinil during sleep deprivation in normal, healthy adults were reviewed. Results indicate that modafinil is efficacious for sustaining/restoring objective performance and alertness during sleep deprivation with few adverse effects. At appropriate dosages, modafinil restores performance and alertness to non-sleep deprived levels. Modafinil also impairs post-sleep deprivation recovery sleep, but from the few studies available addressing this issue, it is unclear whether these sleep impairments translate into post-sleep performance impairments. Further research is needed to determine whether modafinil restores performance on simple cognitive tasks only or whether modafinil additionally restores executive functions (e.g., abstract thought, critical reasoning, planning, decision-making, situational awareness, and effective judgment) which are critical in most modern operational settings. In addition, studies are needed to determine whether modafinil use during sleep deprivation is preferable to that of other available controlled stimulants (such as dextroamphetamine) or non-controlled stimulants (such as caffeine). Such studies would be comprised of direct, head-to-head comparisons among various stimulants across a range of dosages.


Covalent binding of a nickel macrocyclic complex to a silica support: towards an electron exchange column.
Ni(II)L(2), L(2) = 1-propyl-1,3,5,8,12-pentaazacyclotetradecane, was covalently bound to a silica support. This complex can be reversibly oxidized to the corresponding Ni(III) complex. The latter complex is relatively long lived. Therefore electron exchange columns based on this material can be prepared.


First-trimester diagnosis of fetal abnormalities. A report of three cases.
First-trimester sonography is used extensively for dating pregnancy and in conjunction with chorionic villus sampling. It is crucial to examine the fetus carefully, even at this early stage, since some fetal abnormalities are detectable in the first trimester. In three cases encephalocele, thanatophoric dwarf and cystic hygroma were diagnosed with sonography in the first trimester.


Suppression of ring artefacts when tomographing anisotropically attenuating samples.
There are many objects for which the attenuation varies significantly as they are rotated during computerized X-ray tomography, for example plate samples. This can lead to significant ring artefacts in the subsequent tomographic reconstructions. In this paper a new method is presented that can successfully suppress such ring artefacts and is applicable to both parallel and cone-beam geometries. Rapid correction is achieved via an analytical formula which involves only a matrix-vector multiplication, for which the matrix is known and depends on a regularization parameter. The efficacy of the method is demonstrated for a paleontological sample (calcified shark cartilage) and a carbon-carbon composite/Ti-SiC metal matrix composite test sample.


Estimation of water quality by UV/Vis spectrometry in the framework of treated wastewater reuse.
The aim of this study is to investigate the potential of ultraviolet/visible (UV/Vis) spectrometry as a complementary method for routine monitoring of reclaimed water production. Robustness of the models and compliance of their sensitivity with current quality limits are investigated. The following indicators are studied: total suspended solids (TSS), turbidity, chemical oxygen demand (COD) and nitrate. Partial least squares regression (PLSR) is used to find linear correlations between absorbances and indicators of interest. Artificial samples are made by simulating a sludge leak on the wastewater treatment plant and added to the original dataset, then divided into calibration and prediction datasets. The models are built on the calibration set, and then tested on the prediction set. The best models are developed with: PLSR for COD (Rpred2 = 0.80), TSS (Rpred2 = 0.86) and turbidity (Rpred2 = 0.96), and with a simple linear regression from absorbance at 208 nm (Rpred2 = 0.95) for nitrate concentration. The input of artificial data significantly enhances the robustness of the models. The sensitivity of the UV/Vis spectrometry monitoring system developed is compatible with quality requirements of reclaimed water production processes.


Biomining active cellulases from a mining bioremediation system.
Functional metagenomics has emerged as a powerful method for gene model validation and enzyme discovery from natural and human engineered ecosystems. Here we report development of a high-throughput functional metagenomic screen incorporating bioinformatic and biochemical analyses features. A fosmid library containing 6144 clones sourced from a mining bioremediation system was screened for cellulase activity using 2,4-dinitrophenyl β-cellobioside, a previously proven cellulose model substrate. Fifteen active clones were recovered and fully sequenced revealing 9 unique clones with the ability to hydrolyse 1,4-β-D-glucosidic linkages. Transposon mutagenesis identified genes belonging to glycoside hydrolase (GH) 1, 3, or 5 as necessary for mediating this activity. Reference trees for GH 1, 3, and 5 families were generated from sequences in the CAZy database for automated phylogenetic analysis of fosmid end and active clone sequences revealing known and novel cellulase encoding genes. Active cellulase genes recovered in functional screens were subcloned into inducible high copy plasmids, expressed and purified to determine enzymatic properties including thermostability, pH optima, and substrate specificity. The workflow described here provides a general paradigm for recovery and characterization of microbially derived genes and gene products based on genetic logic and contemporary screening technologies developed for model organismal systems.


Neonatal Outcomes in Very Preterm Infants With Severe Congenital Heart Defects: An International Cohort Study.
Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (CHDs) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007-2015 at 24 to 31 weeks' gestation with birth weights <1500 g. Severe CHDs were defined by International Classification of Diseases, Ninth Revision (ICD-9) and Tenth (ICD-10) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in-hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score-matched odds ratios (ORs) were calculated. Analyses were stratified by type of CHD, gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score-matched OR, 2.30; 95% CI, 1.61-3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score-matched OR (4.96; 95% CI, 2.11-11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at <27 weeks' gestational age, adjusted OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76-20.70) at 31 weeks' gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.


Implantation of exogenous enzymatic activity in isolated alveolar macrophages.
Alveolar macrophages acquired the capacity to oxidize uric acid after exposure to uricase. Presumably this resulted from intracellular incorporation of the enzyme by endocytosis. This approach may provide a general method for (i) testing regulatory biochemical mechanisms, (ii) therapeutic replacement of deficient regulatory macromolecules, and (iii) studying environmental factors that produce genetic alterations.


Changes in Activity of the Same Thalamic Neurons to Repeated Nociception in Behaving Mice.
The sensory thalamus has been reported to play a key role in central pain sensory modulation and processing, but its response to repeated nociception at thalamic level is not well known. Current study investigated thalamic response to repeated nociception by recording and comparing the activity of the same thalamic neuron during the 1st and 2nd formalin injection induced nociception, with a week interval between injections, in awake and behaving mice. Behaviorally, the 2nd injection induced greater nociceptive responses than the 1st. Thalamic activity mirrored these behavioral changes with greater firing rate during the 2nd injection. Analysis of tonic and burst firing, characteristic firing pattern of thalamic neurons, revealed that tonic firing activity was potentiated while burst firing activity was not significantly changed by the 2nd injection relative to the 1st. Likewise, burst firing property changes, which has been consistently associated with different phases of nociception, were not induced by the 2nd injection. Overall, data suggest that repeated nociception potentiated responsiveness of thalamic neurons and confirmed that tonic firing transmits nociceptive signals.


[Evolutionistic significance of biological form-function relationship based on the example of the shoulder-blade in higher primates. II. Form and function, goal and random factor: literature].
The shoulder-blades of the monkeys are mainly constructed as a shock-absorbing platform, supporting the weight of the torso, which is hung up between the 2 forelegs in a muscle sling, composed by the M. serratus ventralis. The mobility of the arms are of less importance, although this mobility is more developed in monkeys than in other quadrupedal mammals. The shoulder-blades of the hominoids are freed from the supporting function and are mainly constructed for the mobility of the arms. Therefore all the areas are well developed, where the important arm-moving muscles originate. The constructions of the catarrhine shoulder-blades are in a very close accordance with the function. Under the modern viewpoint of scientific evolutionary theory the relation between form and function is causal and is developing in the time-space continuum. It can be shown that the thinking in categories of time, space and causality is inadequate for the understanding of the evolutionary process. The hazardness which plays an important role in the neo-darwinistic modell, where mutations occur, has to bee replaced by synchronistic phenomena. Therefore the facts of live refer empirically to the existence of the "One-beeing". According to this, evolution occurs as a psycho-physical process, which is experiencable by synchronistic phenomena in archetypical moments as a reference to a reality, which is feeling its way in a finalistic manner.


Epidemiology of Ebstein anomaly: prevalence and patterns in Texas, 1999-2005.
Ebstein anomaly is a rare but serious cardiac defect, however, little is known about the etiology of this condition. The goal of this study was to expand our limited understanding of the epidemiology of Ebstein anomaly. Data for cases with Ebstein anomaly, as well as all live births, were obtained from the Texas Birth Defects Registry (TBDR) and Center for Health Statistics for the period 1999-2005. Descriptive analyses and estimates of birth prevalence and crude prevalence ratios were used to characterize this defect in Texas during the study period. There were 188 definite cases of Ebstein anomaly identified in the TBDR. The overall prevalence was 0.72 per 10,000 live births. Variables associated with an increased prevalence of non-syndromic Ebstein anomaly included: maternal age >39 years (compared to those 20-24 years), maternal residence along the Texas-Mexico border (compared to non-border residence), and conception in fall or winter (compared to summer). In addition, infants with Ebstein anomaly were at a greater risk of preterm birth and being small for gestational age. These findings help to define subgroups of women at increased risk of having offspring affected by Ebstein anomaly. Furthermore, our findings add to the limited body of literature on this rare but serious malformation.