The repetition-break plot structure: a cognitive influence on selection in the marketplace of ideas.
Using research into learning from sequences of examples, we generate predictions about what cultural products become widely distributed in the social marketplace of ideas. We investigate what we term the Repetition-Break plot structure: the use of repetition among obviously similar items to establish a pattern, and then a final contrasting item that breaks with the pattern to generate surprise. Two corpus studies show that this structure arises in about a third of folktales and story jokes. An experiment shows that jokes with this structure are more interesting than those without the initial repetition. Thus, we document evidence for how a cognitive factor influences the cultural products that are selected in the marketplace of ideas.


Remembering the SIEV X: who cares for the bodies of the stateless, lost at sea?
The SIEV X was a tiny fishing vessel traveling from Indonesia to Australia in 2001, carrying around four hundred people seeking asylum after fleeing from the warfare and persecution predominantly in Iraq and Afghanistan. Many were women and children trying to enter Australia to join fathers and husbands already granted refugee status but not allowed to bring in family members because of new Australian laws on "Temporary Protection Visas". Of these, 353 drowned when the boat sank in international waters. The conservative Australian government denied responsibility, using the event in an election campaign to play on fears about illegal entry and border defense in the Islamophobic climate in the aftermath of 9/11. Yet many everyday Australians eventually became involved in a collaborative design process to create a memorial to those asylum seekers. This article discusses the debates around memorials for those lost at sea, and particularly for those who might be portrayed as enemies or "illegal immigrants" whose coming threatens national borders. It identifies the conditions under which the campaign to commemorate those who died on the SIEV X moved from being a minority interest to become a cause so widely supported by Australians across the country that the memorial was eventually erected in the heart of the national capital.


National epidemiologic surveys of Enterobacter aerogenes in Belgian hospitals from 1996 to 1998.
Two national surveys were conducted to describe the incidence and prevalence of Enterobacter aerogenes in 21 Belgian hospitals in 1996 and 1997 and to characterize the genotypic diversity and the antimicrobial resistance profiles of clinical strains of E. aerogenes isolated from hospitalized patients in Belgium in 1997 and 1998. Twenty-nine hospitals collected 10 isolates of E. aerogenes, which were typed by arbitrarily primed PCR (AP-PCR) using two primers and pulsed-field gel electrophoresis. MICs of 10 antimicrobial agents were determined by the agar dilution method. Beta-lactamases were detected by the double-disk diffusion test and characterized by isoelectric point. The median incidence of E. aerogenes colonization or infection increased from 3.3 per 1,000 admissions in 1996 to 4.2 per 1000 admissions in the first half of 1997 (P < 0.01). E. aerogenes strains (n = 260) clustered in 25 AP-PCR types. Two major types, BE1 and BE2, included 36 and 38% of strains and were found in 21 and 25 hospitals, respectively. The BE1 type was indistinguishable from a previously described epidemic strain in France. Half of the strains produced an extended-spectrum beta-lactamase, either TEM-24 (in 86% of the strains) or TEM-3 (in 14% of the strains). Over 75% of the isolates were resistant to ceftazidime, piperacillin-tazobactam, and ciprofloxacin. Over 90% of the strains were susceptible to cefepime, carbapenems, and aminoglycosides. In conclusion, these data suggest a nationwide dissemination of two epidemic multiresistant E. aerogenes strains in Belgian hospitals. TEM-24 beta-lactamase was frequently harbored by one of these epidemic strains, which appeared to be genotypically related to a TEM-24-producing epidemic strain from France, suggesting international dissemination.


Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30.
The genetic basis for avian to mammalian host switching in influenza A virus is largely unknown. The human A/HK/156/1997 (H5N1) virus that transmitted from poultry possesses NS1 gene mutations F103L + M106I that are virulence determinants in the mouse model of pneumonia; however their individual roles have not been determined. The emergent A/Shanghai/patient1/2013(H7N9)-like viruses also possess these mutations which may contribute to their virulence and ability to switch species. NS1 mutant viruses were constructed by reverse genetics and site directed mutagenesis on human and mouse-adapted backbones. Mouse infections assessed virulence, virus yield, tissue infection, and IFN induction. NS1 protein properties were assessed for subcellular distribution, IFN antagonism (mouse and human), CPSF30 and RIG-I domain binding, host transcription (microarray); and the natural prevalence of 103L and 106I mutants was assessed. Each of the F103L and M106I mutations contributes additively to virulence to reduce the lethal dose by >800 and >3,200 fold respectively by mediating alveolar tissue infection with >100 fold increased infectious yields. The 106I NS1 mutant lost CPSF binding but the 103L mutant maintained binding that correlated with an increased general decrease in host gene expression in human but not mouse cells. Each mutation positively modulated the inhibition of IFN induction in mouse cells and activation of the IFN-β promoter in human cells but not in combination in human cells indicating negative epistasis. Each of the F103L and M106I mutations restored a defect in cytoplasmic localization of H5N1 NS1 in mouse cells. Human H1N1 and H3N2 NS1 proteins bound to the CARD, helicase and RD RIG-I domains, whereas the H5N1 NS1 with the same consensus 103F and 106M mutations did not bind these domains, which was totally or partially restored by the M106I or F103L mutations respectively. The F103L and M106I mutations in the H5N1 NS1 protein each increased IFN antagonism and mediated interstitial pneumonia in mice that was associated with increased cytoplasmic localization and altered host factor binding. These mutations may contribute to the ability of previous HPAI H5N1 and recent LPAI H7N9 and H6N1 (NS1-103L+106M) viruses to switch hosts and cause disease in humans.


Lymphocyte Subsets in a Population of Nonfrail Elderly Individuals.
Age-related frailty is characterized by increased vulnerability to stress due to decline in homeostatic reserve, which results in increased risk of adverse health outcomes including disability, hospitalization, and death. The relationship between frailty and immunological system alterations is well established. Thus, analysis of immunological changes, such as alterations in lymphocyte subsets, during senescence may provide useful markers for frailty and associated pathologies. Since reference ranges currently used for lymphocyte subsets do not specifically differentiate the elderly group, the aim of this study was to (1) establish reference ranges in nonfrail elderly individuals and (2) assess the evolution of these parameters with age. Further, the influence of other physiological and lifestyle factors was also evaluated. The study was performed on 144 elderly individuals (aged 65-95) from Galicia (in northwestern Spain). Percentages of lymphocyte subpopulations (CD3(+) T lymphocytes, CD4(+) T-helper lymphocytes, CD8(+) T-cytotoxic lymphocytes, CD19(+) B lymphocytes, and CD56(+)16(+) natural killer cells) were analyzed in peripheral blood by flow cytometry, and reference ranges were calculated. The individual status as nonfrail or prefrail did not markedly affect the immunological parameters, but an apparent influence of age was obtained for %CD3(+), %CD4(+), and %CD19(+) cells, all of which fell with increasing age. Women showed higher levels of %CD19(+) lymphocytes. No significant influence of smoking habits, physical activity, or drinking alcohol or caffeine beverages was observed. The results obtained may serve as a basis to establish comparisons between frail and nonfrail elderly individuals, in order to determine the usefulness of lymphocyte subsets as immunological biomarkers of frailty.


Induction of apoptosis by apicidin, a histone deacetylase inhibitor, via the activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive leukemia cells.
Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide that exhibits potent antiproliferative activity against various cancer cell lines. The aim of this study was to examine the potential of apicidin to induce apoptosis in human Bcr-Abl-positive leukemia cells and to assess the mechanism of apicidin-induced apoptosis. Cells were exposed to various concentrations of apicidin for 2-72 h, after which the levels of apoptosis, histone acetylation, mitochondrial damage, caspase activation, and Bcr-Abl expression were assessed. Apicidin induced apoptosis in K562 cells in a concentration- and time-dependent manner. Similarly, apicidin notably induced the apoptosis in the primary leukemic blasts obtained from chronic myelogenous leukemia patients in blast crisis. The acetylated histone H4 levels increased in a concentration-dependent manner in the K562 cells. However, the timing of cell death caused by apicidin did not exactly correlate with the histone deacetylase inhibitory effect. The disruption of the mitochondrial membrane potential, cytochrome c release into the cytosol, and the mitochondrial Bax translocation were notably demonstrated after the apicidin treatment. Apicidin induced the proteolytic cleavage of procaspase-9, -3, -8, and poly(ADP-ribose) polymerase. Pretreatment of the K562 cells with the caspase-3 inhibitor, DEVD-CHO, completely inhibited the apicidin-induced apoptosis, suggesting that apicidin-induced apoptosis was caspase-dependent. The Fas/Fas ligand death receptor pathway was not involved in the apicidin-mediated apoptosis in K562 cells. Pretreatment of the cells with the caspase-9 inhibitor LEHD-fmk abrogated the apicidin- induced cleavage of procaspase-3, -8, and poly(ADP-ribose) polymerase. The p210 Bcr-Abl protein levels were notably decreased after the apicidin treatment, with near complete loss after 48 h. Reverse transcription-PCR assay demonstrated that the Bcr-Abl mRNA level was also remarkably decreased in a time-dependent manner. These results indicate that apicidin effectively induces the apoptosis of Bcr-Abl-positive leukemia cells through the activation of the mitochondrial pathway-dependent caspase cascades. The down-regulation of Bcr-Abl mRNA might also be one of the mechanisms implicated in the apicidin-mediated apoptosis in the K562 cells. This study provides the rationale to additionally investigate apicidin as a potential therapeutic agent for the drug-resistant Bcr-Abl-positive leukemia cells.


Decreased muscle insulin receptor kinase correlates with insulin resistance in normoglycemic Pima Indians.
Defects in insulin receptor tyrosine kinase activity are present in insulin-resistant non-insulin-dependent diabetes mellitus patients and certain nondiabetic individuals, both lean and obese. However, the relationship between insulin receptor function, insulin action, and obesity is unclear. To address this issue, we have employed a new and highly sensitive enzyme-linked immunosorbent assay to measure in vitro insulin-stimulated autophosphorylation of immunocaptured muscle insulin receptors in a group of 25 normoglycemic Pima Indians. Insulin action, determined during two-step euglycemic insulin clamps, varied widely in these subjects. Maximal in vitro insulin stimulation of insulin receptor autophosphorylation strongly correlated with both low (Mlow)- and high (Mhigh)-dose insulin-stimulated glucose disposal (r = 0.62 and 0.51, P < 0.002 and 0.011, respectively). Insulin receptor autophosphorylation was inversely related to percent body fat (r = -0.52, P < 0.009). After control for percent body fat, receptor autophosphorylation remained correlated with Mlow (partial r = 0.49, P < 0.025). These data therefore suggest that defects in insulin receptor function are major contributors to insulin resistance in both lean and obese normoglycemic Pima Indians.


Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity.
The helicates--chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands--may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) 'flexicate' system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).


Potentiation of organophosphorus-induced delayed neurotoxicity by phenylmethylsulfonyl fluoride.
It is well known that pretreatment with the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF) can protect experimental animals from organophosphorus-induced delayed neurotoxicity (OPIDN), presumably by blocking the active site of neurotoxic esterase (NTE) such that binding and "aging" of the neuropathic OP is thwarted. We report here that while PMSF (60 mg/kg, sc) given 4 h before the neuropathic organophosphate (OP) mipafox (50 mg/kg, im) completely prevented the clinical expression of OPIDN in hens, the identical PMSF treatment markedly amplified the delayed neurotoxicity (relative to hens treated with OP only) if administered 4 h after mipafox (5 or 50 mg/kg, im). Moreover, in a separate experiment using diisopropylphosphorofluoridate (DFP) as the neurotoxicant in place of mipafox, posttreatment with PMSF 4 h after DFP (0.5 mg/kg) also accentuated the severity of ataxia. These data indicate that PMSF only protects against OPIDN if given prior to exposure to the neurotoxicant; treatment with PMSF after OP exposure critically exacerbates the delayed neurotoxicity from exposure to organophosphorus compounds.


Interaction of the lipid-associating domain of glycophorin with phospholipid bilayers.
The MN-blood group bearing glycoprotein of the human red cell membrane, glycophorin, has been shown to traverse the membrane in vivo such that the NH2-terminal portion is exposed to the external, and the COOH-terminal portion exposed to the cytoplasmic, mileiu. The intervening 23 residue lipid-associating domain (LAD) of glycophorin has been shown to have a unique overall hydrophobicity. The LAD of glycophorin can be obtained intact within an aqueous insoluble tryptic peptic, T(is). Under appropriate conditions (the reaction not being spontaneous), T(is) can be associated with phospholipid bilayers. Freeze fracture studies of T(is): phospholipid vesicles suggest that T(is) forms multimeric torus-shaped intramembranous structures 80 A in diameter with n greater than 4. The plot of T(is) concentration versus multimer density suggests there is a critical multimer concentration (CMC) for T(is) in phospholipid bilayers (L/P = 200/1). Various physico-chemical techniques such as pyrene fluorescence spectroscopy, differential scanning calorimetry, and ionic permeability were used to investigate the T(is)-lipid association. Results indicate that this system is an excellent one in which to study the boundary lipid phenomenon. In addition, T(is) association with lipid bilayers is being correlated with the natural state of glycophorin in the red cell membrane.


Chapter 1: an overview of allergens.
Most allergens are proteins or glycoproteins that range in molecular weight from 5000 to 100,000 Da, although polysaccharides and low molecular weight substances also may be allergenic. Common allergens include pollens, fungal spores, house-dust mites, and animal epithelial materials but can also include drugs, biological products, and insect venoms. The allergic response is dependent on the route of exposure. If exposure is to an inhaled aeroallergen, the allergic response will be a respiratory reaction in nature. Ingested or injected exposure gives rise to gastrointestinal, cutaneous, or anaphylactic reactions. Size of pollen determines clinical manifestation of allergy. For example, particles between 20 and 60 μm in diameter can be carried in the wind and cause nasal and ocular symptoms (allergic rhinoconjunctivitis). Particles <7 μm can deposit in the airways and cause symptoms of asthma. Animals produce allergens in forms unique to each species. Cat allergen, most importantly Fel d 1, is found mainly in cat saliva, sebaceous glands in the skin, and in urine of male cats. It is buoyant and "sticky," which means it easily remains airborne and may last in a home for up to 6-9 months after the source is removed. Cat allergen adheres to clothes and can be found in public places such as schools. Dog allergen, particularly Can f 1, is present in dander, saliva, urine, and serum. There are allergens specific to dog breeds, but all breeds produce allergenic proteins (even poodles and "hairless" dogs).


[Adiponectin levels in perimenopause].
Adiponectin is an hormone produced exclusively in adipose tissue, that actively acts in carbohydrate and fat regulation processes. To determine adiponectin levels in a women's group. Transversal study in 22 amenorrheal women with climacteric symptoms, and without estrogen therapy. There were excluded those with diabetes, hypertension, dislipoproteinemia and obesity. Significant differences among values of adiponectin in perimenopausal and young women during follicular phase of menstrual cycle were analyzed by means of Student t test. Adiponectin concentration in perimenopausal women was 14.1 +/- 8.2 microg/mL (M +/- SD), without meaningful difference compared with young women. It wasn't significant variation in adiponectin levels compared with normal menstrual cycle women. Further studies are necessary to establish adiponectin effect in postmenopause and its relation with the cardiovascular diseases.


Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product.
The PML gene product is associated with a defined nuclear structure (10-20 per cell) known variously as PML-bodies, ND10, PODs or Kr bodies. Certain conditions are known to compromise the integrity of PML-bodies; these include environmental stress (e.g. heat shock), a chromosomal translocation-associated acute promyelocytic leukaemia, and infection with certain viruses [including human cytomegalovirus (HCMV), herpes simplex virus type 1 and adenovirus]. Expression of the HCMV major immediate early (IE) protein (IE1(491aa)) is by itself sufficient to cause disruption of PML-bodies, resulting in the dispersal of the PML antigen uniformly throughout the nucleus. In uninfected cells undergoing mitosis PML is excluded from chromatin. However, both IE1(491aa) and PML were observed to associate with mitotic chromosomes in cells infected with HCMV or transfected with the IE1 gene. A series of in-frame IE1 deletion mutants was used in DNA transfection experiments to identify two large sequence elements (aa 132-274 and the C-terminal aa 347-491) not required for dispersal of the PML antigen. However, a putative leucine-zipper domain (aa 105-139), a putative zinc-finger domain (aa 267-286) and exon 2 and 3 coding sequences (aa 6-85) were required. The association of the IE1 gene product with chromatin required an acidic domain near the C terminus (aa 421-486). The interaction of IE1(491aa) with chromatin was therefore not required for the disruption of PML-bodies. Exon 2 (aa 1-24) was shown to encode a nuclear localization signal.


Calcium permeability changes and neurotransmitter release in cultured brain neurons. II. Temporal analysis of neurotransmitter release.
The coupling between depolarization-induced calcium entry and neurotransmitter release was studied in rat brain neurons in culture. The endogenous dopamine content of the cells was determined by high performance liquid chromatography utilizing electrochemical detection. The amount of dopamine in unstimulated cells was found to be about 16 ng/mg of protein. Depolarization of the neurons by elevated K+ caused a Ca2+-dependent release of dopamine from the cells. Following 1 min of depolarization, the cellular dopamine content and the amount of [3H]dopamine in cells preloaded with the radioactive transmitter were reduced by 35%. The release of [3H]dopamine by the neurons was measured at 1.5-6-s intervals by a novel rapid dipping technique. Depolarization in the presence of Ca2+ (1.8 mM) enhanced the rate of neurotransmitter release by 90-fold (0.072 +/- 0.003 s-1) over the basal release in the presence of Ca2+. The evoked release consisted of a major rapidly terminating phase (t1/2 = 9.6 s) which comprised about 40% of the neurotransmitter content of the cells and a subsequent slower efflux (t1/2 = 575 s) which was observed during following prolonged depolarization. Predepolarization of the cells in the absence of extracellular Ca2+ did not affect the kinetics of the evoked release. The fast evoked release could be re-elicited in the cells after 20 min "rest" in reference low K+ buffer. The effects of varying the extracellular Ca2+ concentrations on the kinetic parameters of the evoked release were measured. The amount of neurotransmitter released during the fast kinetic phase was very sensitive to the external Ca2+ (from 0% in the absence of Ca2+ to 40% of the neurotransmitter content at Ca2+ 0.3 mM). The rate constant of the fast release did not depend on the extracellular Ca2+, whereas the rate constant of the slow release increased from 0.0004 +/- 0.0001 s-1 at 0.4 mM Ca2+ to 0.0012 +/- 0.0002 s-1 at 0.8 mM Ca2+. The fast evoked release was inhibited by verapamil in a concentration-dependent manner. By contrast, verapamil enhanced the basal and the slow release independent of the presence of Ca2+. Both fast and slow phases of the evoked release were blocked by Co2+. Addition of Co2+ within the first 6 s after the onset of depolarization inhibited the fast release but failed to do so when added later on.(ABSTRACT TRUNCATED AT 400 WORDS)


Vascular behcet and mutations in thrombogenic genes: methylene tetrahydrofolate reductase, factor V, and prothrombin.
Vasculitis, thrombophlebitis, arterial aneurysms, and occlusions occur in about 25% of patients with Behçet's disease (BD). The common inherited gene defects, factor V (FV) 1691A (Leiden), methylene tetrahydrofolate reductase (MTHFR) 677T, and prothrombin 20210A, are known risk factors for thrombosis. The aim of the study was to evaluate the contribution of these mutations to thrombosis in Israeli patients with BD. Fifty-four patients with BD (n=54; 27 men and 27 women) underwent clinical and genetic evaluation. Most patients (n=43; 79.6%) were of Arab descent (31 sporadic and 12 familial cases from 4 families), and 11 patients (20.4%) were of Jewish descent (all sporadic cases). The FV Leiden mutation was identified in five patients (9.2%), and eight patients were MTHFR 677TT homozygotes (14.8%). None had the 20210A mutant prothrombin allele. No statistical differences between carriers and noncarriers with regards to demographic and disease manifestations were calculated. Arabs were diagnosed earlier than Jewish patients (25.8±11.6 compared with 37.2±10.7, p=0.01, respectively), but Jewish patients had, respectively, more events of deep vein thrombosis (DVT) compared with Arabs (3 of 11, 27.3% and 3 of 43, 7%, p=0.09). Thrombotic events in our patients with BD were not associated with variations in thrombophilic genes.


Cardiovascular effects of drugs used to treat Alzheimer's disease.
Drugs that are used to treat Alzheimer's disease include the acetyl cholinesterase inhibitors (ACHIs) donepezil, rivastigmine and galantamine and the NMDA receptor antagonist memantine. Adverse cardiovascular events with these drugs are very uncommon. However, there is evidence that ACHI therapy is associated with a small but significant increase in the risk of syncope and bradycardia. There are also a few reports that these drugs may occasionally be associated with QT prolongation and torsades de pointes ventricular tachycardia. Adverse cardiovascular effects of ACHIs including syncope and bradycardia are less common than their adverse gastrointestinal effects, but they remain important considerations in susceptible individuals. In contrast, animal studies and some observational studies suggest that ACHIs may reduce myocardial infarction and cardiovascular mortality and have favourable effects on hemodynamics and survival in heart failure. Further research is required to confirm these potential beneficial effects. Little is known about the cardiovascular effects of memantine but there have been reports of bradycardia and reduced cardiovascular survival associated with its use.


Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis.
There are unresolved questions regarding the association between persistent leukocytosis and risk of thrombosis and disease evolution in polycythemia vera (PV), as much of the published literature on the topic does not appropriately use repeated-measures data or time-dependent modeling to answer these questions. To address this knowledge gap, we analyzed a retrospective database of 520 PV patients seen at 10 academic institutions across the United States. Taking hematologic laboratory data at ∼3-month intervals (or as available) for all patients for duration of follow-up, we used group-based trajectory modeling to identify latent clusters of patients who follow distinct trajectories with regard to their leukocyte, hematocrit, and platelet counts over time. We then tested the association between trajectory membership and hazard of 2 major outcomes: thrombosis and disease evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia. Controlling for relevant covariates, we found that persistently elevated leukocyte trajectories were not associated with the hazard of a thrombotic event (P = .4163), but were significantly associated with increased hazard of disease evolution in an ascending stepwise manner (overall P = .0002). In addition, we found that neither hematocrit nor platelet count was significantly associated with the hazard of thrombosis or disease evolution.


[Clinico-electromyographic characteristics of piriform muscle syndromes].
The report is concerned with the screening methods of lesions of the piriformis muscle in the piriformis syndrome which is more frequently connected with sacral osteochondrosis. However, this syndrome may sometimes appear in an ankylosis of the hip joint. All the diagnostical methods may be divided into 3 groups: indirect clinical method, palpation and EMG. The first method does not require special experience. A palpation of the piriformis muscle is conducted bimanually by a method proposed by the authors. EMG studies with the aid of needle electrodes permit to distinguish spasms and more crude changes in the piriform muscle.


Physics-driven learning of x-ray skin dose distribution in interventional procedures.
Radiation doses accumulated during very complicated image-guided x-ray procedures have the potential to cause stochastic, but also deterministic effects, such as skin rashes or even hair loss. To monitor and reduce radiation-related risks to patients' skin, x-ray imaging devices are equipped with online air kerma monitoring components. Traditionally, such measurements have been used to estimate skin entrance dose by (a) estimating air kerma at the interventional reference point (IRP), (b) forward projecting the dose distribution, and (c) considering a backscatter factor among other correction factors. Unfortunately, the complicated interaction between incident x-ray photons, secondary electrons, and skin tissue cannot be properly accounted for by assuming a linear relationship between forward projected air kerma and a backscatter factor. Gold standard skin dose models are therefore determined using Monte Carlo (MC) techniques. However, MC simulations are computationally complex in general and possible acceleration mainly depends on the employed hardware and variance reduction techniques. To obtain reliable and fast dose estimates, we propose to combine MC-based simulations with learning-based methods. The basic idea of our method is to approximate the radiation physics to calculate a first-order exposure estimate quickly. This initial estimate is then refined using prior knowledge derived from MC simulations. To this end, the primary photon propagation inside a voxelized patient model is estimated using a less accurate but fast photon ray casting (RC) simulation based on the Beer-Lambert law. The results of the RC simulation are then fed into a convolutional neural network (CNN), which maps the propagation of primary photons to the dose deposition inside the patient model. Additionally, the patient model itself including anatomy and material properties, such as mass density and mass energy-absorption coefficients, are fed into the CNN as well. The CNN is trained using smoothed results of MC simulations as output and RC simulations of identical imaging settings and patient models as input. In total, 163 MC and associated RC simulations are carried out for the head, thorax, abdomen, and pelvis in three different voxel phantoms. We used 10 8 or 10 9 primarily emitted photons sampled from a 125 kV peak voltage spectrum, respectively. Edge-preserving smoothing (EPS) is applied to reduce (a) general stochastic uncertainties and (b) stochastic uncertainty concerning MC simulations of less primary photons. The CNN is trained using seven imaging settings of the abdomen in a single phantom. Testing its performance on the remaining datasets, the CNN is capable of estimating skin dose with an error of below 10% for the majority of test cases. The combination of deep neural networks and MC simulation of particle physics has the potential to decrease the computational complexity of accurate skin dose estimation. The proposed approach can provide dose distributions in under one second when running on high-end hardware. On lower cost hardware, it took up to 2 min to arrive at the same result. This makes our approach applicable in high-end environments as well as in budget solutions. Furthermore, the number of primary photons only affects the training time, while the execution time is independent of the number of primary photons.


Trends and Variation in Oral Anticoagulant Choice in Patients with Atrial Fibrillation, 2010-2017.
Since 2010, several non-vitamin K antagonist oral anticoagulants (NOACs) have been brought to the U.S. market, yet little is known regarding their evolving adoption for prophylaxis of atrial fibrillation (AF)-related stroke. We examined temporal trends in choice of oral anticoagulants (OACs) among incident OAC users with AF and its association with patient demographic and clinical characteristics. We conducted a serial cross-sectional analysis of medical and pharmacy claims for commercial and Medicare Advantage enrollees in a large, private, U.S. health plan. We identified 112,187 adults with nonvalvular AF starting OACs between October 2010 and March 2017. Multivariable logistic regression was used to examine the associations of patient characteristics with prescription of NOACs versus warfarin. Multinomial logistic regression was used to test the associations of patient characteristics with choice among NOACs. The prescription of NOACs has increased dramatically since their introduction in October 2010. In the first quarter of 2017 (2017Q1), 7502 patients started OACs, of whom 78.9% used NOACs and 21.1% warfarin. For NOACs, 3.8% used dabigatran, 25.0% rivaroxaban, and 50.1% apixaban. In multivariable analyses, factors associated with choice of NOACs versus warfarin included younger age, lower stroke or bleeding risk, fewer comorbidities, higher education level or household net worth, and prescription by cardiologists (all p<0.001). There was no sex difference in likelihood of filling NOACs versus warfarin in 2010Q4-2012, but women had higher odds of starting NOACs (odds ratio = 1.19; 95% confidence interval = 1.14-1.25) in 2015-2017Q1. Among NOAC users, the odds of apixaban prescription increased with age, female sex, stroke or bleeding risk, and comorbidities (all p<0.05). NOAC prescriptions have increased substantially among incident OAC users with nonvalvular AF, predominantly driven by increased prescription of apixaban. Warfarin and apixaban were generally preferred for elderly patients, patients with higher stroke or bleeding risk, and patients with more comorbidities.


Lineage diversification and recombination in type-4 human astroviruses.
Human astroviruses (HAstVs) are important enteric pathogens and can be classified genetically and antigenically into eight types. During surveillance of HAstVs in Italy, type-4 HAstVs were detected only sporadically and found to cluster into two distinct genetic groups. Upon sequence analysis of the 3' end of the polymerase gene (ORF1b) and of the full-length ORF2, the 2008 type-4 HAstV strains were characterised as a novel ORF2 genetic lineage, designated as 4c. The 2008 type-4 HAstVs also shared the ORF1b gene with similar HAstV-4c strains detected globally, thus displaying a conserved ORF1b/ORF2 asset. By interrogation of the databases, this novel lineage 4c accounted for 60.8% of the type-4 strains identified worldwide and the vast majority of recent type-4 HAstVs. The 2002 type-4 HAstVs displayed a type-4b ORF2, whereas in the ORF1b they resembled type-1 HAstVs. This inconsistency suggests a possible recombinant origin, with the RNA switch taking place upstream the ORF1b/ORF2 junction region. Also, recombination likely played a role in the diversification of the ORF2 of the three type-4 lineages. Multi-target analysis is required for appropriate characterisation and identification of recombinant HAstVs.


Invoking Uncertainty: Parents' Accounts for Intrusions on Medical Authority in Pediatric Neurology.
In pediatric medical visits, parents may assume the role of co-caregiver with clinicians. At times, parents challenge physicians' authority to determine diagnoses and treatments for their children. The present study uses conversation analysis to examine parents' accounts for their intrusions on medical authority in a corpus of 35 video-recorded pediatric neurology visits for overnight video-electroencephalogram monitoring. I show how parents can exploit their legitimate role as carers to challenge medical authority. Through invoking uncertainty in contexts where they have somehow challenged medical authority, parents can account for their conduct in ways that elide direct conflict with physicians and thereby minimize damage to the physician-family partnership.


The impact of cultural factors upon postpartum depression: a literature review.
Postpartum depression is a serious disorder that affects many women globally. Studies have shown that cultural factors play a significant role in postpartum depression; they may trigger postpartum depression as well as contribute to the alleviation of its depressive symptomatology. The cultural aspects of the postpartum period have been described in the literature; however, the impact of cultural factors upon postpartum depression has been less investigated, and studies that looked at this association have yielded oppositional conclusions. In addition, the literature is inconclusive as to whether there are significant differences among various cultures in the prevalence of postpartum depression. The purpose of this literature review is to identify and critically review published and unpublished studies regarding the effect of cultural factors on the alleviation or deterioration of postpartum depression. Results show that cultures have different rituals and beliefs that may affect the severity of postpartum depression.


Comparison of minimally invasive percutaneous fixation and open reduction internal fixation for patella fractures: a meta-analysis.
Open reduction internal fixation (ORIF) has long been the conventional procedure for managing displaced patella fracture. This surgical approach has certain drawbacks, which might affect clinical outcomes and patient prognosis. Minimally invasive percutaneous fixation (MIPF) was proposed to overcome these disadvantages. Few in-depth investigations have been performed to determine the superiority of MIPF over ORIF. The aim of this study was to compare the efficacies of MIPF and ORIF for patella fractures. The PubMed, Cochrane Library, Embase, and Scopus databases were searched for relevant studies from November 26 to December 17, 2020. Non-English publications and pediatric orthopedic articles were excluded. Statistical analysis was performed using Review Manager, version 5.4, with mean differences (MDs), standardized mean differences (SMDs), odds ratios (ORs), and respective 95% confidence intervals (CIs) calculated using a random effects model. The primary outcomes were the pain score, knee range of motion, and joint functionality. The secondary outcomes were the surgical time, complications, and implant removal rate. Six articles with a total of 304 patients were included in the meta-analysis. Pooled analysis revealed that patients with MIPF had a significantly reduced pain score (MD = - 1.30, 95% CI = - 1.77 to -0.82; p < 0.00001) and increased knee extension angles (MD = 0.72, 95% CI = 0.18 to 1.25; p = 0.009) at 3-month follow-up. Furthermore, knee flexion angles (MD = 8.96, 95% CI = 5.81 to 12.1; p < 0.00001) and joint functionality (SMD = 0.54, 95% CI = 0.21 to 0.86; p = 0.001) had statistically improved at 2 years. However, no difference was observed between MIPF and ORIF with regard to the surgical time. The risk of complications (OR = 0.10, 95% CI = 0.05 to 0.18; p < 0.00001) and implant removal rate (OR = 0.20, 95% CI = 0.07 to 0.57; p = 0.003) were significantly lower with MIPF than with ORIF. MIPF is more favorable than ORIF in terms of the pain score, knee range of motion, joint functionality, complications, and implant removal rate. Thus, it can be adopted as an alternative to ORIF.


Diminishing role of contrast enema in simple meconium ileus.
Contrast enema is the initial study of choice for simple meconium ileus to confirm diagnosis and to relieve obstruction. Despite favorable historically published results, our clinical impression suggests decreased effectiveness of the contrast enema resulting in more surgical interventions in contemporary practice. A retrospective multiinstitutional review for a 12-year period was conducted for neonates diagnosed with meconium ileus by contrast enema. The neonates were divided into 2 groups-historic group (HG = before 2002) and contemporary group (CG = after 2002). T test was used for comparison of continuous variables and chi(2) for categorical data. Thirty-seven total patients were identified (21 females and 16 males). Obstruction was relieved in 8 neonates (22% overall success rate). Average enema attempt per patient was decreased in the CG group compared to HG (1.4 vs 1.9). The success rate in the CG group was 5.5% (1/18) compared to 39% (7/18) in HG. In this review, success of contrast enema for relief of meconium ileus has significantly decreased over time. These findings may be because of reluctance to repeat enemas, change in radiologist experience, or use of contrast agent. As a result, higher rates of operative intervention are now observed. In stable patients, surgeons should recommend repeat enemas before exploration.


[Medical malpractice in surgery I: Suspected malpractice and patterns of risks].
Medical malpractice is assumed for surgical procedures much more often than for conservative treatment. In a nut shell there can be identified three general problem areas--treatment of patient in inappropriate facilities, inadequate information of patient and lack of documentation. Several examples are given. For the assessment of assumed medical malpractice the expert opinion and consented guidelines are crucial; they both benchmark "good medical practice". Thus these two tools have to be handled and developed carefully.


[The effect of electrostimulation of the premotor cortex and hippocampus on delayed choice in monkeys].
The influence of electrical stimulation of the prefrontal cortex and the hippocampus on solving the problem of delayed spatial choice was studied on four rhesus macaques. Stimulation was carried out by rectangular pulses of different amplitude in the first and last two seconds of delay (lasting from five to six seconds). A statistically significant increase of errors was found during the stimulation: 1) of the structures of the left hemisphere (the effect was averaged in relation to the moment of stimulations); 2) during the first two seconds of delay (the effect was averaged as related to the structures of stimuli); 3) of the hippocampus at the beginning of the delay, and of the prefrontal cortex, at its end. The data obtained point to the dynamic nature of the functional significance of the studied brain structures in the organization of a mnestic process.


Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.
Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.


Hierarchical reconstruction using geometry and sinogram restoration.
The authors describe and demonstrate a hierarchical reconstruction algorithm for use in noisy and limited-angle or sparse-angle tomography. The algorithm estimates an object's mass, center of mass, and convex hull from the available projections, and uses this information, along with fundamental mathematical constraints, to estimate a full set of smoothed projections. The mass and center of mass estimates are made using a least squares estimator derived from the principles of consistency of the Radon transform. The convex hull estimate is produced by first estimating the positions of support lines of the object from each available projection and then estimating the overall convex hull using prior shape information. Estimating the position of two support lines from a single projection is accomplished using a generalized likelihood ratio technique for estimating jumps in linear systems. Results for simulated objects in a variety of measurement situations are shown, and several possible extensions to this work are discussed.


Synergistic effects of nelfinavir and bortezomib on proteotoxic death of NSCLC and multiple myeloma cells.
Exploiting protein homeostasis is a new therapeutic approach in cancer. Nelfinavir (NFV) is an HIV protease inhibitor that induces endoplasmic reticulum (ER) stress in cancer cells. Under conditions of ER stress, misfolded proteins are transported from the ER back to the cytosol for subsequent degradation by the ubiquitin-proteasome system. Bortezomib (BZ) is a proteasome inhibitor and interferes with degradation of misfolded proteins. Here, we show that NFV and BZ enhance proteotoxicity in non-small cell lung cancer (NSCLC) and multiple myeloma (MM) cells. The combination synergistically inhibited cell proliferation and induced cell death. Activating transcription factor (ATF)3 and CCAAT-enhancer binding protein homologous protein (CHOP), markers of ER stress, were rapidly increased, and their siRNA-mediated knockdown inhibited cell death. Knockdown of double-stranded RNA activated protein kinase-like ER kinase, a signal transducer in ER stress, significantly decreased apoptosis. Pretreatment with the protein synthesis inhibitor, cycloheximide, decreased levels of ubiquitinated proteins, ATF3, CHOP, and the overall total cell death, suggesting that inhibition of protein synthesis increases cell survival by relieving proteotoxic stress. The NFV/BZ combination inhibited the growth of NSCLC xenografts, which correlated with the induction of markers of ER stress and apoptosis. Collectively, these data show that NFV and BZ enhance proteotoxicity in NSCLC and MM cells, and suggest that this combination could tip the precarious balance of protein homeostasis in cancer cells for therapeutic gain.


Coronarin K and L: Two Novel Labdane Diterpenes From Roscoea purpurea: An Ayurvedic Crude Drug.
The main objective of cancer treatment with chemotherapy is to kill the cancerous cells without affecting the healthy normal cells. In the present study, bioactivity-guided purification of the n-chloroform soluble fraction from the methanol extract of Roscoea purpurea resulted in the identification of two new labdane diterpenes: coronarin K (1) and coronarin L (2), along with eight known compounds, coronarin A (3), bisdemethoxycurcumin (4), kaempferol 3-O-methyl ether (5), kaempferol (6), fenozan acid (7), 3-(3-methoxy,4-hydroxyphenyl)-2-propenoic acid ferulic acid (8), caffeic acid (9), and gallic acid (10). The structural identification of new compounds (1 and 2) were determined by detailed analysis of 1D (1H and 13C) and 2D NMR (COSY, HSQC, and HMBC) spectroscopic data. The relative configurations of 1 and 2 were determined with the help of NOESY correlations and comparison of optical rotations with known labdane diterpenes, with established stereochemistry, while structure of known compounds was established by direct comparison of their NMR data with those reported in the literature. This is the first report of isolation of this labdane diterpenes and phenolic classes of secondary metabolites in R. purpurea. In the preliminary screening, the methanol extract and its fractions were tested for the cytotoxic activity against a panel of four cancer cell lines (A549, HCT-116, Bxpc-3, and MCF-7); extract and its chloroform fraction were found to be active against the lung cancer cell line, A-549, with IC50 value <25 μg/ml. Owing to the notable cytotoxic activity of the chloroform fraction, the compounds (1-5) were screened for their cytotoxicity against all the cell lines by MTT assay. Coronarin K, 1 showed significant cytotoxic potential against lung cancer cell lines (A-549), with IC50 value of 13.49 μM, while other compounds did not show activity below 22 μM.


The Gammaherpesvirus m2 protein manipulates the Fyn/Vav pathway through a multidocking mechanism of assembly.
To establish latent infections in B-cells, gammaherpesviruses express proteins in the infected B-cells of the host that spuriously activate signalling pathways located downstream of the B-cell receptor. One such protein is M2, a murine gammaherpesvirus 68-encoded molecule that activates the Vav1/Rac1 pathway via the formation of trimolecular complexes with Scr family members. Previous reports have shown that the formation of this heteromolecular complex involves interactions between a proline rich region of M2 and the Vav1 and Fyn SH3 domains. Here, we show that the optimal association of these proteins requires a second structural motif encompassing two tyrosine residues (Tyr120 and 129). These residues are inducibly phosphorylated by Fyn in non-hematopoietic cells and constitutively phosphorylated in B-cells. We also demonstrate that the phosphorylation of Tyr120 creates specific docking sites for the SH2 domains of both Vav1 and Fyn, a condition sine qua non for the optimal association of these two signalling proteins in vivo. Interestingly, signaling experiments indicate that the expression of M2 in B-cells promotes the tyrosine phosphorylation of Vav1 and additional signaling proteins, a biological process that requires the integrity of both the M2 phosphotyrosine and proline rich region motifs. By infecting mice with viruses mutated in the m2 locus, we show that the integrity of each of these two M2 docking motifs is essential for the early steps of murine gammaherpesvirus-68 latency. Taken together, these results indicate that the M2 phosphotyrosine motif and the previously described M2 proline rich region work in a concerted manner to manipulate the signaling machinery of the host B-cell.


Circulating Cholesterol Levels May Link to the Factors Influencing Parkinson's Risk.
A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link. Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1) were chosen as confounding variables because they may influence both cholesterol levels and PD risk. First, the marginal structure model was applied, where the associations of total- and LDL-cholesterol levels with genetic polymorphisms, statin usage, and smoking history were estimated using linear regression. Then, potential causal influences of total- and LDL-cholesterol on PD occurrence were investigated using a generalized propensity score approach in the second step. Both statins (p < 0.001) and LRP1 (p < 0.03) influenced total- and LDL-cholesterol levels. There also was a trend for APOE to affect total- and LDL-cholesterol (p = 0.08 for both), and for LRPAR1 to affect LDL-cholesterol (p = 0.05). Conversely, LDLR did not influence plasma cholesterol levels (p > 0.19). Based on propensity score methods, lower total- and LDL-cholesterol were significantly linked to PD (p < 0.001 and p = 0.04, respectively). The current study suggests that circulating total- and LDL-cholesterol levels potentially may be linked to the factor(s) influencing PD risk. Further studies to validate these results would impact our understanding of the role of cholesterol as a risk factor in PD, and its relationship to recent public health controversies.


Simple and effective label-free capillary electrophoretic analysis of sugars by complexation using quinoline boronic acids.
An effective separation and detection procedure for sugars by capillary electrophoresis (CE) using a complexation between quinolineboronic acid (QBA) and multiple hydroxyl structure of sugar alcohol is reported. We investigated the variation of fluorescence spectra of a variety of QBAs with sorbitol at a wide range of pH conditions and then found that 5-isoQBA strongly enhanced the fluorescence intensity by the complexation at basic pH conditions. The other sugar alcohols having multiple hydroxyls also revealed the enhancement of the fluorescence intensity with 5-isoQBA, whereas the alternation of the intensity was not found in the sugars such as glucose. After optimization of the 5-isoQBA concentration and pH of the buffered solution in CE analysis, 6 sugar alcohols were successfully separated in the order based on the formation constants with 5-isoQBA, which were calculated from the variation of the fluorescence intensity with each sugar alcohol and 5-isoQBA. Furthermore, the limits of detection for sorbitol and xylitol by the CE method were estimated at 15 and 27 μM, respectively.


Low melatonin secretion associates with albedo in circumpolar environments.
To clarify how seasonal changes of environmental luminosity affect melatonin secretion in human beings, nocturnal urine samples were collected every 2 months throughout the year from 20 outdoor workers living in an area, for which exact data on solar irradiance and temperature were available (67-68 degrees N). Melatonin secretion rates, determined by melatonin-specific radioimmunoassays, were found to be twice as high in December as in April, i.e. 0.88 +/- 0.16 nmol/12 hr (mean +/- S.E.) versus 0.43 +/- 0.09 nmol/12 hr, P < 0.05. Regression analyses showed that melatonin values correlated best inversely with solar irradiance reflected off the ground (albedo). A 10-fold increase in albedo for 1-4 weeks prior to the date of urine sampling was associated with a ca. 50% reduction in melatonin secretion. Association with global irradiance was weaker and did not correlate with temperature. Thus, light reaching the eyes via snow or other reflecting surfaces appears to be most effective. These results assist us in understanding some of the mechanisms involved in certain biological phenomena that exhibit seasonal variations as, for instance, reproduction and self-destructive behavior.


[Management of ipsilateral femoral shaft and neck fracture].
From Oct. 1987 to Oct. 1993, 704 patients with femoral shaft fracture were managed at our hospital. Among these, 12 patients were with combined femoral shaft and neck fracture (2%). The age ranged from 17 years to 58 years (average 38.2 years). Eleven patients were victims of traffic accidents and another 1 fell from a height. Most of them had associated injuries, including fractures elsewhere, head injury, chest and abdominal trauma. Five of them were treated with open reduction and internal fixation with Huckstep intramedullary nail, 2 with Kuntscher nail and Knowles' pin, 2 with plate and compression hip screw, 2 with plate and Knowles' pin and one patient was managed with Kuntscher nail and traction. Ten patients were followed up for more than 3 years, and the other 2 lost follow-up at 5 months and 12 months. The fractures were all united with 2 malunions. Complications included 3 deep infections and one avascular necrosis.


Three-level rating of turns while walking.
Research concerning the assessment of turns during walking in healthy older adults is scarce. This study compared three independent assessments of entry and exit points of turns during walking; participant, clinical rater, and a computer algorithm. Nineteen non-demented and nondisabled older adults (mean age 75.40 ± 5.52 years) participated in the current study. Results revealed that overall the three assessment methods were consistent (68-100% agreement). However, participants determined their turn exit point before the algorithm, (-304.53 ± 326.67 ms), t(18) = -4.06, p = .001, 95% CI [-461.98, -147.08], and clinical rater, (-225.79 ± 303.79 ms), t(18) = -3.24, p = .005, 95% CI [-372.21, -79.37]. The differences in turn determination between the algorithm and rater were significant at turn entry points (131.24 ± 127.25 ms), t(18) = 4.50, p < .001, 95% CI [69.91, 192.58] but not at turn exit points (-78.74 ± 259.66 ms), t(18) = -1.32, p < .20, 95% CI [-203.89, -46.41]. Greater time discrepancies in assessing turn exit points between the participants and both the algorithm and clinical rater were associated with worse visuospatial performance. Despite the relatively small difference among the three assessments of turns, they were consistent and can be utilized interchangeably. Further studies are necessary to determine whether differences in the ability to accurately determine turns entry and exit points are related to fall risk in normal and disease populations.


miR-27b-3p Suppressed Osteogenic Differentiation of Maxillary Sinus Membrane Stem Cells by Targeting Sp7.
To explore the critical role and function of miRNAs in the regulation of development and physiology of maxillary sinus membrane stem cell (MSMSC) osteogenesis. Microarray analysis was performed to screen the miRNAs expression profiles during the process of MSMSC osteogenic differentiation. Quantitative real-time polymerase chain reaction was applied to verify the miRNAs expression profiles. Gain- and loss-of-function experiments were used to demonstrate that miR-27b-3p inhibited MSMSC osteoblastic differentiation. Bioinformatic analysis was performed to predict the potential target of miR-27b-3p and then demonstrated by luciferase reporter assay and western blot. The negative regulation between miR-27b-3p and Sp7 was further confirmed using mimic and inhibitor of miR-27b-3p in vitro. Xenograft mice model was generated to confirm the relationship between miR-27b-3p and Sp7 using recombinant adenoviruses in vivo. MiR-27b-3p was downregulated during osteogenic differentiation of MSMSCs. The expression of Sp7, alkaline phosphatase, and osteocalcin decreased when transfected with miR-27b-3p-mimic in MSMSCs after osteogenic differentiation. MiR-27b-3p directly targeted Sp7 and inhibited the MSMSC osteogenesis in vivo. MiR-27b-3p suppressed the osteogenic differentiation of MSMSCs by directly inhibiting Sp7.


Regulation of prostaglandin endoperoxide H synthase 1 and 2 by estradiol and progesterone in nonpregnant ovine myometrium and endometrium in vivo.
PG endoperoxide H synthase-2 (PGHS-2) messenger RNA (mRNA) and protein levels are increased dramatically in ovine myometrium and endometrium during both glucocorticoid-induced premature labor and spontaneous term labor. In this study, we examined estradiol and progesterone regulation in vivo of PGHS-1 and PGHS-2 expression at both mRNA and protein levels using a nonpregnant ovariectomized sheep model. We determined the differential distribution of PGHS-2 and PGHS-1 in ovine myometrium and endometrium with immunocytochemistry. Twenty ovariectomized ewes were treated with saline (n = 5) or estradiol infused i.v. for 2 days (50 microg/day; n = 5) or an intravaginal progesterone sponge for 10 days (containing 0.3 g progesterone; n = 5) or an intravaginal progesterone sponge for 10 days with estradiol (50 microg/day) administered on days 9 and 10 with the progesterone sponge still in place (EP; n = 5). PGHS-1 and -2 mRNA and protein were measured by Northern and Western blot analyses, respectively. PGHS-2 mRNA and protein abundance increased significantly in myometrium after estradiol treatment (P < 0.01). In contrast, progesterone was a more potent stimulator than estradiol of PGHS-2 protein abundance in endometrium (P < 0.01). PGHS-1 concentration did not change after estradiol and/or progesterone administration (P > 0.05). PGHS-2 was immunolocalized in myometrial cells and endometrial glandular epithelial cells, whereas immunoreactive PGHS-1 was located in the myometrial cells, endothelial and smooth muscle cells of blood vessels, as well as epithelial cells of glands and stromal cells in endometrium. Estradiol-dependent activation of PGHS-2 gene expression resulted in increased PGHS-2 levels in sheep myometrium in vivo. Progesterone did not have any effect on PGHS-2 gene expression in the myometrium. In contrast, progesterone was a more potent stimulator of endometrial PGHS-2 abundance than estradiol. Estradiol and progesterone did not regulate PGHS-1 expression in either endometrium or myometrium. The distribution and differential regulation of PGHS-1 and -2 in myometrium and endometrium are consistent with the differential functions of both enzymes.


Diagnosis and management of ampullary adenoma: The expanding role of endoscopy.
Ampullary adenoma is a pre-cancerous lesion arising from the duodenal papilla that is often asymptomatic. It is important to distinguish whether the adenoma is sporadic or arises in the setting of familial adenomatous polyposis as this has important implications with respect to management and surveillance. Multiple modalities are available for staging of these lesions to help guide the most appropriate therapy. Those that are used most commonly include computed tomography, endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography. In recent years, endoscopy has become the primary modality for therapeutic management of the majority of ampullary adenomas. Surgery remains the standard curative procedure for confirmed or suspected adenocarcinoma. This review will provide the framework for the diagnosis and management of ampullary adenomas from the perspective of the practicing gastroenterologist.


Effects of the exposure of fish to triazine herbicides.
Triazines are an important group of herbicides, which have been used extensively or selectively both in agricultural and non-agricultural areas worldwide for more than fifty years to control broadleaf and some grassy weeds. As a consequence of their massive application, they have become and remain significant environmental pollutants, especially in aquatic ecosystems. Fish are an integral part of the aquatic environment and are, therefore, suitable models for the study of the behavioral, biological, and biochemical effects of triazine exposure. We have summarized and evaluated the effects of triazine herbicides on fish in order to provide an overview of current information on triazines. The overall effects of triazine herbicide exposure on the physiology of fish were evaluated by considering a variety of parameters in a number of reports. Haematological and biochemical profiles of blood provide important information about the internal environment of the organism and the general physiology and health status of triazine exposed fish. According to studies using biotransformation and bioaccumulation indices to estimate the effects of triazines on fish, changes in fish metabolism reflect the pollution of the environment by these herbicides. The responses of antioxidant defence systems in fish to triazine exposure could be an adaptive mechanism to protect the fish from triazine-induced oxidative stress. Acute exposure to triazines affects reproduction or reproductive development in fish; however, some triazines did not affect fish behavior during long-term exposure to low concentrations. Nevertheless, an impact on the overall behavioral response of fish cannot be excluded.


The influence of aggregation on triplet formation in light-harvesting chlorophyll a/b pigment-protein complex II of green plants.
The influence of aggregation on triplet formation in the light-harvesting pigment-protein complex of photosystem II of green plants (LHCII) has been studied with time-resolved laser flash photolysis. The aggregation state of LHCII has been varied by changing the detergent concentration. The triplet yield increases upon disaggregation and follows the same dependence on the detergent concentration as the fluorescence yield. The rate constant of intersystem crossing is not altered by disaggregation, and variations of the triplet yield appear to be due to aggregation-dependent quenching of singlet excited states. The efficiency of triplet transfer in LHCII aggregates from chlorophyll (Chl) to carotenoid (Car) is 92 +/- 7% at room temperature and 82 +/- 6% at 5 K, and does not change upon disaggregation. The Chl's that do not transfer their triplets to Car's seem to be bound to LHCII and are capable of transfering/accepting their singlet excitations to/from other Chl's. Two spectral contributions of Car triplets are observed: at 525 and 506 nm. Disaggregation of macroaggregates to small aggregates reduces by 10% the relative contribution of Car triplets absorbing at 525 nm. This effect most likely originates from a decreased efficiency of intertrimer Chl-to-Car triplet transfer. At the critical micelle concentration, at which small aggregates are disassembled into trimers, the interactions between Chl and Car are changed. At room temperature, this effect is much more pronounced than at 5 K.


Loose stools during auranofin treatment: clinical study and some pathogenetic possibilities.
Loose stools, one of the most frequent adverse reactions ascribed to the orally absorbed gold compound auranofin (AF), was studied during a longterm trial. At some time during the study 44% of 25 patients reported the occurrence of loose stools. No infection or signs of malabsorption were found; nor were loose stools caused by the presence of osmotically active substances in the gut lumen. Arguments for a direct effect of AF on the ion and water absorption in the intestine are given. Although no morphological studies on biopsy material are available, the known side effects of the drug do not seem to warrant its discontinuation in suitable patients.


Syntheses and crystal structures of two new bismuth hydroxyl borates containing [Bi2O2]2+ layers: Bi2O2[B3O5(OH)] and Bi2O2[BO2(OH)].
Two new bismuth hydroxyl borates, Bi(2)O(2)[B(3)O(5)(OH)] (I) and Bi(2)O(2)[BO(2)(OH)] (II), have been synthesized under hydrothermal conditions. Their structures were determined by single-crystal and powder X-ray diffraction data, respectively. Compound I crystallizes in the orthorhombic space group Pbca with the lattice constants of a = 6.0268(3) Å, b = 11.3635(6) Å, and c = 19.348(1) Å. Compound II crystallizes in the monoclinic space group Cm with the lattice constants of a = 5.4676(6) Å, b = 14.6643(5) Å, c = 3.9058(1) Å, and β = 135.587(6)°. The borate fundamental building block (FBB) in I is a three-ring unit [B(3)O(6)(OH)](4-), which connects one by one via sharing corners, forming an infinite zigzag chain along the a direction. The borate chains are further linked by hydrogen bonds, showing as a borate layer within the ab plane. The FBB in II is an isolated [BO(2)(OH)](2-) triangle, which links to two neighboring FBBs by strong hydrogen bonds, resulting in a borate chain along the a direction. Both compounds contain [Bi(2)O(2)](2+) layers, and the [Bi(2)O(2)](2+) layers combine with the corresponding borate layers alternatively, forming the whole structures. These two new bismuth borates are the first ones containing [Bi(2)O(2)](2+) layers in borates. The appearance of Bi(2)O(2)[BO(2)(OH)] (II) completes the series of compounds Bi(2)O(2)[BO(2)(OH)], Bi(2)O(2)CO(3), and Bi(2)O(2)[NO(3)(OH)] and the formation of Bi(2)O(2)[B(3)O(5)(OH)] provides another example in demonstrating the polymerization tendency of borate groups.


Combination of Root Surface Modification with BMP-2 and Collagen Hydrogel Scaffold Implantation for Periodontal Healing in Beagle Dogs.
Objective : Biomodification of the root surface plays a major role in periodontal wound healing. Root surface modification with bone morphogenetic protein (BMP) stimulates bone and cementum-like tissue formation; however, severe ankylosis is simultaneously observed. Bio-safe collagen hydrogel scaffolds may therefore be useful for supplying periodontal ligament cells and preventing ankylosis. We examined the effects of BMP modification in conjunction with collagen hydrogel scaffold implantation on periodontal wound healing in dogs. The collagen hydrogel scaffold was composed of type I collagen sponge and collagen hydrogel. One-wall infrabony defects (5 mm in depth, 3 mm in width) were surgically created in six beagle dogs. In the BMP/Col group, BMP-2 was applied to the root surface (loading dose; 1 µg/µl), and the defects were filled with collagen hydrogel scaffold. In the BMP or Col group, BMP-2 coating or scaffold implantation was performed. Histometric parameters were evaluated at 4 weeks after surgery. Single use of BMP stimulated formation of alveolar bone and ankylosis. In contrast, the BMP/Col group frequently enhanced reconstruction of periodontal attachment including cementum-like tissue, periodontal ligament and alveolar bone. The amount of new periodontal ligament in the BMP/Col group was significantly greater when compared to all other groups. In addition, ankylosis was rarely observed in the BMP/Col group. The combination method using root surface modification with BMP and collagen hydrogel scaffold implantation facilitated the reestablishment of periodontal attachment. BMP-related ankylosis was suppressed by implantation of collagen hydrogel.


The effects of fluoxetine on attachment and righting behaviours in marine (Gibbula unbilicalis) and freshwater (Lymnea stagnalis) gastropods.
Recent studies have highlighted that antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) entering aquatic systems through wastewater discharges might impact organisms at environmentally relevant concentrations. In this study, two snail species (Gibbula unbilicalis and Lymnea stagnalis) representing the marine and freshwater environments were exposed to a large range of fluoxetine concentrations (1 ng L-1-1 mg L-1) and two distinct behaviours (foot detachment and righting time) were recorded. Fluoxetine significantly caused foot detachment only at the higher of the concentrations (1 mg L-1) in both species during the course of this short term 1.5 h and 4 h exposures. In this study, lowest observed effect concentrations (LOECs) for foot detachment fell repeatedly within the range for other gastropod snails exposed to fluoxetine. Fluoxetine effected righting times in a concentration dependant manner but only significantly within G. unbilicalis in the highest concentration. Reviewing existing data on the effects of antidepressants on a range of endpoints in gastropod molluscs reveals wide variability of results. The importance of publishing 'negative' and/or non-dramatic results to aid risk assessment are discussed along with the variability between antidepressants, model species, experimental designs and endpoints.


Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease.
Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.


Hepatic metabolism and disposition of baicalein via the coupling of conjugation enzymes and transporters-in vitro and in vivo evidences.
Baicalein (Ba) was found to be subject to serious first-pass metabolism after oral administration. We previously revealed the important role of intestine in the low oral bioavailability of Ba. The present study aims to evaluate the hepatic metabolism and disposition of Ba. Ba was given to Sprague-Dawley rats through bolus or infusion via intravenous or intra-portal route of administrations. Both plasma and bile samples at different time intervals were obtained. Concentrations of Ba and potential metabolites in the collected samples were analyzed with HPLC/UV and identified by LC/MS/MS, respectively. Plasma concentration versus time profiles of Ba obtained from intravenous and intra-portal administrations were compared to estimate the extent of hepatic metabolism. In addition, transport studies of baicalein-7-glucuronide (BG), one of the major metabolites of Ba, were carried out using transfected cell systems overexpressing various human organic anion-transporting polypeptide (OATP) isoforms to estimate the specific transporters involved in the hepatic disposition of Ba metabolites. The results showed that liver, in addition to intestine, also conferred extensive metabolism to Ba. Several mono- and di-conjugates of Ba, which were mainly glucuronides, sulfates, and methylates, were found in bile. The transport study demonstrated that besides MRPs and BCRP, human OATP2B1 and OATP1B3 in liver might also mediate the secretion of BG to bile. In summary, liver plays an important role in the metabolism of Ba and transport of its conjugated metabolites.


Substrate curvature sensing through Myosin IIa upregulates early osteogenesis.
Topographical cues mimicking the extracellular matrix (ECM) have demonstrated control over a diverse range of cellular behaviours including: initial adhesion, migration, cell growth, differentiation and death. How cells sense, and in turn translate, the topographical cues remains to be answered, but likely involves interactions through interfacial forces that influence cytoskeletal structure and integrin clustering, leading to the downstream activity of intracellular signalling cascades. Electrospun fibers have shown significant success as a biomimetic topography for bone tissue engineering applications, but mechanisms by which osteoprogenitor cells translate the fiber geometry into intracellular signalling activity is only recently being examined. We hypothesized that increased cellular differentiation observed on fibrous topography is due to acto-myosin contractility and cellular stiffness via the small GTPase RhoA. In order to evaluate this hypothesis, MC3T3-E1 osteoprogenitor cells were grown on poly(methyl methacrylate) (PMMA) fibers of 1.153 ± 0.310 μm diameter. The elastic modulus of the cell surface was measured by atomic force microscopy (AFM) with a colloidal probe. Overall cellular stiffness was found to increase more than three-fold in osteoprogenitors adhered to a fiber, as opposed to those grown on a flat substrate. Pharmacological inhibition of RhoA signalling activity decreased cellular stiffness and cytoskeletal integrity of osteoprogenitors growing on fibrous substrates. Finally, we demonstrated not only RhoA activity through its effector Rho-associated coiled coil kinase II (ROCKII), but also Myosin IIa promotes early osteogenic differentiation, as shown by alkaline phosphatase (ALP) staining. Previous studies have demonstrated the importance of ROCKII on early differentiation. Our results shed light on mechanisms underlying geometry sensing by highlighting the role of Myosin IIa in addition to ROCKII and could ultimately contribute to scaffold design strategies.


Human colorectal cancer cells induce vascular smooth muscle cell apoptosis in an exocrine manner.
Tumor vessels often lack the smooth muscle layer, and the instability is conducive to tumor invasion and metastasis. The effect of tumor microenvironment on vascular smooth muscle cells needs to be explored. In the present study, we examined the density of the tumor vessels in human colorectal cancer tissues, and used the tumor conditioned medium of human colorectal cancer HT29 cells to mimic the tumor microenvironment. We showed that the vessel density in colorectal cancer tissues increased, which displayed a decreased expression of smooth muscle α-actin, a specific marker of vascular smooth muscle cells and an attenuated or a discontinuous layer of vascular smooth muscle cells compared with the matched normal tissues. We also showed that the tumor conditioned medium decreased the cell viability, and induced the apoptosis in vascular smooth muscle cells in a concentration-dependent manner. The expression of pro-Caspase-3 was down-regulated, accompanied by increasing of cleaved-Caspase-3 in the cells treated with the tumor conditioned medium, suggesting that Caspase-3 was activated. Moreover, the expression of Bax was increased, and the ratio of Bcl-2/Bax was decreased under the same conditions. Furthermore, the treatment with the tumor conditioned medium resulted in loss of mitochondrial membrane potential in vascular smooth muscle cells. These findings suggest that HT29 cells induce apoptosis of vascular smooth muscle cells in an exocrine manner, associated with activating caspase-3 via mitochondrial apoptotic pathway. This may be one of the mechanisms underlying tumor vascular structural abnormalities.


Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?
Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 15-20%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients.


Exploring the structure of fucosylated chondroitin sulfate through bottom-up nuclear magnetic resonance and electrospray ionization-high-resolution mass spectrometry approaches.
Fucosylated chondroitin sulfate (FCS) from sea cucumbers is composed of a chondroitin sulfate (CS) central core and branches of sulfated fucose. The structure of this complex glycosaminoglycan is usually investigated via nuclear magnetic resonance (NMR) analyses of the intact molecule, ergo through a top-down approach, which often yield spectra with intricate sets of signals. Here we employed a bottom-up approach to analyze the FCSs from the sea cucumbers Isostichopus badionotus and Ludwigothurea grisea from their basic constituents, viz. CS cores and sulfated fucose branches, obtained via systematic fragmentation through mild acid hydrolysis. Oligosaccharides derived from the central CS core were analyzed via NMR spectroscopy and the disaccharides produced using chondroitin sulfate lyase via SAX-HPLC. The CS cores from the two species were similar, showing only slight differences in the proportions of 4- or 6-monosulfated and 4,6-disulfated β-d-GalNAc. Sulfated fucose units released from the FCSs were analyzed via NMR and ESI-HRMS spectroscopies. The fucose units from each species presented extensive qualitative differences, but quantitative assessments of these units were hindered, mostly because of their extensive desulfation during the hydrolysis. The bottom-up analysis performed here has proved useful to explore the structure of FCS through a sum-of-the-parts approach in a qualitative manner. We further demonstrate that under specific acidification conditions particular fucose branches can be removed preferentially from FCS. Preparation of derivatives enriched with particular fucose branches could be useful for studies on "structure vs. biological function" of FCS.


Simultaneous measurement of mass and rotation of trapped absorbing particles in air.
We trap absorbing micro-particles in air by photophoretic forces generated using a single loosely focused Gaussian trapping beam. We measure a component of the radial Brownian motion of a trapped particle cluster and determine the power spectral density, mean squared displacement, and normalized position and velocity autocorrelation functions to characterize the photophoretic body force in a quantitative fashion for the first time. The trapped particles also undergo spontaneous rotation due to the action of this force. This is evident from the spectral density that displays clear peaks at the rotation and the particles' inertial resonance frequencies. We fit the spectral density to the well-known analytical function derived from the Langevin equation, measure the resonance and rotation frequencies, and determine the values for particle mass that we verify at different trapping laser powers with reasonable accuracy.


Taking stock of cost-effectiveness analysis of healthcare in China.
Cost-effectiveness analysis (CEA) is playing an increasingly important role in informing healthcare decision-making in China. This study aims to review the published literature on CEA in mainland China and describe its characteristics and evolution. We provide recommendations on the future direction of CEA as a methodology and as a tool to support healthcare decision-making in China. English-language cost-per-quality-adjusted life-year (QALY) and cost-per-disability-adjusted life-year (DALY) publications relating to mainland China were reviewed using the Tufts Medical Center Cost-Effectiveness Analysis Registry and Global Health Cost-Effectiveness Analysis Registry through 2017. Study features were summarised using descriptive statistics. Changes in study methodology over time were analysed by trend test, and study characteristics influencing the incremental cost-effectiveness ratio (ICER) of cost-per-QALY studies were investigated using logistic regression. 170 studies were identified reporting CEA for mainland China (cost/QALY=125, cost/DALY=45) since 1998. The number and quality of studies has increased over the past two decades, with significantly more cost-per-QALY studies compared with cost-per-DALY studies (p<0.0001) and more studies with authors affiliated with Chinese institutions (p=0.0002). The average quality score was 5.04 out of 7 for cost-per-QALY and 4.70 for cost-per-DALY studies based on Registry reviewers' subjective assessment of overall quality (methods, assumptions and reporting practices). The median ICER reported for interventions for oncology patients was higher (US$26 694 per QALY) than the median ICER reported for all interventions (US$11 503 per QALY). Oncology interventions were associated with the likelihood of reporting higher ICERs than the median ICER (p=0.003). The number of English-language published CEA studies relating to China has grown rapidly over the past 20 years. In terms of quality, the China studies compare favourably with international studies, although they remain a small proportion of studies globally.


Wax on, wax off: a rare case of catatonia.
Catatonia was first described by a German psychiatrist, Karl Kahlbaum, in 1874. It is a behavioral syndrome marked by an inability to move normally, which can occur in the context of many underlying general medical and psychiatric disorders. A wide variety of neurologic, metabolic, drug-induced, and psychiatric causes of catatonia have been reported. We present a unique case of late onset catatonia in a 56-year-old man with no prior medical or psychiatric history initially presenting with stroke-like symptoms. The patient was awake and alert, with spontaneous eye opening, but completely nonverbal and not following any commands. Specifically, the patient demonstrated stupor, catalepsy, mutism, and negativism. After extensive emergency department testing, including negative computed tomography head, negative magnetic resonance imaging brain, negative electroencephalogram, and normal laboratory results, the patient was diagnosed with new-onset bipolar disorder with depressive features presenting as catatonia. Recognizing catatonia is important because it may be caused or exacerbated by treatment of the underlying disorder. Failure to institute treatment early in the course of catatonia is associated with a poor prognosis.


Review of wheat improvement for waterlogging tolerance in Australia and India: the importance of anaerobiosis and element toxicities associated with different soils.
The lack of knowledge about key traits in field environments is a major constraint to germplasm improvement and crop management because waterlogging-prone environments are highly diverse and complex, and the mechanisms of tolerance to waterlogging include a large range of traits. A model is proposed that waterlogging tolerance is a product of tolerance to anaerobiosis and high microelement concentrations. This is further evaluated with the aim of prioritizing traits required for waterlogging tolerance of wheat in the field. Waterlogging tolerance mechanisms of wheat are evaluated in a range of diverse environments through a review of past research in Australia and India; this includes selected soils and plant data, including plant growth under waterlogged and drained conditions in different environments. Measurements focus on changes in redox potential and concentrations of diverse elements in soils and plants during waterlogging. (a) Waterlogging tolerance of wheat in one location often does not relate to another, and (b) element toxicities are often a major constraint in waterlogged environments. Important element toxicities in different soils during waterlogging include Mn, Fe, Na, Al and B. This is the first time that Al and B toxicities have been indicated for wheat in waterlogged soils in India. These results support and extend the well-known interactions of salinity/Na and waterlogging/hypoxia tolerance. Diverse element toxicities (or deficiencies) that are exacerbated during waterlogging are proposed as a major reason why waterlogging tolerance at one site is often not replicated at another. Recommendations for germplasm improvement for waterlogging tolerance include use of inductively coupled plasma analyses of soils and plants.


Do Differences in Social Environments Explain Gender Differences in Recreational Walking across Neighbourhoods?
Within a city, gender differences in walking for recreation (WfR) vary significantly across neighbourhoods, although the reasons remain unknown. This cross-sectional study investigated the contribution of the social environment (SE) to explaining such variation, using 2009 data from the How Areas in Brisbane Influence healTh and AcTivity (HABITAT) study, including 7866 residents aged 42-67 years within 200 neighbourhoods in Brisbane, Australia (72.6% response rate). The analytical sample comprised 200 neighbourhoods and 6643 participants (mean 33 per neighbourhood, range 8-99, 95% CI 30.6-35.8). Self-reported weekly minutes of WfR were categorised into 0 and 1-840 mins. The SE was conceptualised through neighbourhood-level perceptions of social cohesion, incivilities and safety from crime. Analyses included multilevel binomial logistic regression with gender as main predictor, adjusting for age, socioeconomic position, residential self-selection and neighbourhood disadvantage. On average, women walked more for recreation than men prior to adjustment for covariates. Gender differences in WfR varied significantly across neighbourhoods, and the magnitude of the variation for women was twice that of men. The SE did not explain neighbourhood differences in the gender-WfR relationship, nor the between-neighbourhood variation in WfR for men or women. Neighbourhood-level factors seem to influence the WfR of men and women differently, with women being more sensitive to their environment, although Brisbane's SE did not seem such a factor.


Harnessing CRISPR/Cas9 for Enhanced Disease Resistance in Hot Peppers: A Comparative Study on CaMLO2-Gene-Editing Efficiency across Six Cultivars.
The Capsicum annuum Mildew Locus O (CaMLO2) gene is vital for plant defense responses against fungal pathogens like powdery mildew, a significant threat to greenhouse pepper crops. Recent advancements in genome editing, particularly using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, have unlocked unprecedented opportunities for modifying disease-resistant genes and improving crop characteristics. However, the application of CRISPR technology in pepper cultivars has been limited, and the regeneration process remains challenging. This study addresses these limitations by investigating the feasibility of using the validated CaMLO2 genetic scissors system in six commercial hot pepper cultivars. We assessed the gene-editing efficiency of the previously reported high-efficiency Cas9/CaMLO2single-guide RNA (sgRNA)1-ribonucleoprotein (RNP) and the low-efficiency Cas9/CaMLO2sgRNA2-RNP systems by extending their application from the bell pepper 'Dempsey' and the hot pepper 'CM334' to six commercial hot pepper cultivars. Across the six cultivars, CaMLO2sgRNA1 demonstrated an editing efficiency ranging from 6.3 to 17.7%, whereas CaMLO2sgRNA2 exhibited no editing efficiency, highlighting the superior efficacy of sgRNA1. These findings indicate the potential of utilizing the verified Cas9/CaMLO2sgRNA1-RNP system to achieve efficient gene editing at the CaMLO2 locus in different Capsicum annuum cultivars regardless of their cultivar genotypes. This study provides an efficacious genome-editing tool for developing improved pepper cultivars with CaMLO2-mediated enhanced disease resistance.


Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography.
Twenty-four hour ambulatory electrocardiographic examination was preformed in 98 healthy active subjects, ages 60 to 85 years, who were participants in a longitudinal study on aging. Normal health was confirmed by noninvasive testing, including maximal treadmill exercise (98/98) and thallium scintigraphy (38/98). Our studies indicated that a healthy population of elderly subjects shows a substantial prevalence of supraventricular ectopic beats and ventricular ectopic beats, both isolated and complex. High degree AV block, profound sinus bradycardia, abnormal sinus pauses and sinus arrest are rare in normal elderly subjects.


Clinical usefulness of home oximetry compared with polysomnography for assessment of sleep apnea.
The practical purpose of diagnostic assessment in most cases of obstructive sleep apnea is to predict which patients have symptoms that will improve on treatment. We measured the accuracy with which clinicians make this prediction using polysomnography compared with oximeter-based home monitoring. Patients referred to a sleep center with suspicion of symptomatic obstructive sleep apnea were randomized to have polysomnography or home monitoring. Patients with comorbidity or physiologic consequences of sleep apnea were excluded. Sleep specialists estimated the likelihood of success of treatment as greater than 50% (predicted success) or less than 50% (predicted failure) on the basis of clinical data and test results. All patients were treated for 4 weeks with autoadjusting continuous positive airway pressure. Success was defined as an increase greater than 1.0 in Sleep Apnea Quality of Life Index. Correct prediction rates were compared. Two hundred eighty-eight patients were enrolled. Initial patient characteristics, compliance, and improvement in quality of life at 4 weeks were not different in the two groups. The correct prediction rate was 0.61 with polysomnography and 0.64 with home monitoring (not significant). We conclude that the ability of physicians to predict the outcome of continuous positive airway treatment in individual patients is not significantly better with polysomnography than with home oximeter-based monitoring.


The disparate histories of binocular vision and binaural hearing.
Vision and hearing are dependent on disparities of spatial patterns received by two eyes and on time and intensity differences to two ears. However, the experiences of a single world have masked attention to these disparities. While eyes and ears are paired, there has not been parity in the attention directed to their functioning. Phenomena involving binocular vision were commented upon since antiquity whereas those about binaural hearing are much more recent. This history is compared with respect to the experimental manipulations of dichoptic and dichotic stimuli and the instruments used to stimulate the paired organs. Binocular color mixing led to studies of binaural hearing and direction and distance in visual localization were analyzed before those for auditory localization. Experimental investigations began in the nineteenth century with the invention of instruments like the stereoscope and pseudoscope, soon to be followed by their binaural equivalents, the stethophone and pseudophone.


A monoclonal antibody to avidin dissociates quaternary structure and curtails biotin binding to avidin and streptavidin.
An anti-avidin mAb, viz., H12G4, is shown to release bound biotin in a dose-dependent manner from holoavidin and holostreptavidin and inhibit the binding of ligand to the two apoproteins. The release of biotin by this mAb is accompanied by quenching of ligand-induced enhanced fluorescence of the FITC-avidin conjugate. In terms of mechanism of release of bound biotin, we demonstrate that on binding to the Fab fragment of the mAb, the native tetrameric holoavidin undergoes dissociation progressively with time to monomers with no bound biotin associated with the latter. Based on the immunoreactivity associated with defined overlapping fragments of avidin obtained by chemical cleavage, the epitope recognized by mAb H12G4 has been localized to residues 58-96 of the primary sequence. By pepscan method of epitope mapping, this mAb is shown to identify a minimal core sequence of 87RNGK90 in avidin and a corresponding sequence of 84RNAH87 in streptavidin.


Time-domain room acoustic simulations with extended-reacting porous absorbers using the discontinuous Galerkin method.
This paper presents an equivalent fluid model (EFM) formulation in a three-dimensional time-domain discontinuous Galerkin finite element method framework for room acoustic simulations. Using the EFM allows for the modeling of the extended-reaction (ER) behavior of porous sound absorbers. The EFM is formulated in the numerical framework by using the method of auxiliary differential equations to account for the frequency dependent dissipation of the porous material. The formulation is validated analytically and an excellent agreement with the theory is found. Experimental validation for a single reflection case is also conducted, and it is shown that using the EFM improves the simulation accuracy when modeling a porous material backed by an air cavity as compared to using the local-reaction (LR) approximation. Last, a comparative study of different rooms with different porous absorbers is presented, using different boundary modeling techniques, namely, a LR approximation, a field-incidence (FI) approximation, or modeling the full ER behavior with the EFM. It is shown that using a LR or FI approximation leads to large and perceptually noticeable errors in simulated room acoustic parameters. The average T20 reverberation time error is 4.3 times the just-noticeable-difference (JND) threshold when using LR and 2.9 JND when using FI.


Oscillation of Branching Ratios Between the D(2s)+D(1s) and the D(2p)+D(1s) Channels in Direct Photodissociation of D_{2}.
The direct photodissociation of D_{2} at excitation energies above 14.76 eV occurs via two channels, D(2s)+D(1s) and D(2p)+D(1s). The branching ratios between the two have been measured from the dissociation threshold to 3200 cm^{-1} above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.