Mobilizing the U.S. Military's TRICARE Program for Value-Based Care: A Report From the Defense Health Board.
The U.S. Military Health System spends about $50 billion annually to provide care to 9.6 million active duty service members, retirees, and their families through its TRICARE health plans. TRICARE follows the predominant payment model in the USA-fee-for-service-although the Department of Defense (DoD) and Congress encourage and mandate a move toward alternative payment models-mainly, fee-for-value. For the next TRICARE contracts which will begin in 2023, the DoD asked its health-focused federal advisory committee, the Defense Health Board (DHB), to recommend how best to assess and prioritize leading value-based healthcare initiatives identified from private, public, and employer-based health plans. The November 2020 report, 'Modernization of the TRICARE Benefit', specifies a rubric to evaluate these value-based care initiatives not only in traditional measures of effectiveness but also in terms of the Defense Health Agency's Quadruple Aim with its focus on readiness. The goal of TRICARE's move toward value-based care is to leverage its size and focus on prevention of disease and injury to maintain the readiness of the U.S. Armed Forces in addition to delivering great outcomes and value to the DoD's nearly 10 million beneficiaries. The DHB emphasizes that TRICARE's size and focus on providing quality care at lower cost will incentivize providers to participate in the shift toward value-based care despite the potential challenges in transitioning to this system. This shift also aims to motivate other large government and private payors to accelerate the adoption of value-based care through TRICARE's example.


[Incidence of drug-induced thrombocytopenia in hospitalized patients].
To find out the incidence of drug-induced thrombocytopenia and which medications are implicated, and to establish pharmaceutical activity for its prevention and resolution. A prospective study was conducted between June and December 2009 in hospitalized patients over 18 years of age with thrombocytopenia. The medications considered to be associated with thrombocytopenia were included in a database drawn up from the bibliography. In a suspected case, the doctor was recommended to discontinue, decrease the dosage or keep the drug under observation; and a follow-up of the patient's platelet count was made in order to classify the relationship between the drug and thrombocytopenia. 273 patients were included (61.5% men) with a mean age of 60 ± 15 years. Mean stay was 18 ± 17 days. TCP incidence was 2.26%. The services most involved were Haematology (56), Intensive Care Medicine (48) and Oncology (40). TCP was moderate in 69% of cases, mild in 26 % and severe in 5%. There were 8 cases of drug-induced thrombocytopenia (0.063% incidence), which were resolved in an average of 7.6 days. The medications related were enoxaparin (2), linezolid (2), tacrolimus (2), thymoglobulin (1) and heparin (1). The doctor was recommended to discontinue the drug (2), decrease the dosage (3) or keep it under observation (3), with 100% acceptance. Pharmaceutical validation must incorporate an assessment of the platelet count, as it may contribute both to early identification of thrombocytopenia, and to following up platelet counts in patients receiving therapy with thrombocytopenia related drugs.


Functional proteomics of light-harvesting complex proteins under varying light-conditions in diatoms.
Comparative proteome analysis of subcellular compartments like thylakoid membranes and their associated supercomplexes can deliver important in-vivo information on the molecular basis of physiological functions which go far beyond to that what can be learnt from transcriptional-based gene expression studies. For instance, the finding that light intensity influences mainly the relative stoichiometry of subunits could be obtained only by high resolution proteome analysis. The high sensitivity of LC-ESI-MS/MS based proteome analysis allows the determination of proteins in very small subfractions along with their non-labeled semi quantitative analysis. This provides insights in the protein-protein interactions of supercomplexes that are the operative units in intact cells. Here, we have focused on functional proteome approaches for the identification of microalgal light-harvesting complex proteins in chloroplasts and the eyespot in general and in detail for those of diatoms that are exposed to varying light conditions.


Diverse Durham collection phages demonstrate complex BREX defense responses.
Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 1025 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicrobial resistance. This effort may be hindered due to bacterial defenses such as Bacteriophage Exclusion (BREX) that have arisen from the constant evolutionary battle between bacteria and phages. For phages to be widely accepted as therapeutics in Western medicine, more must be understood about bacteria-phage interactions and the outcomes of bacterial phage defense. Here, we present the annotated genomes of 12 novel bacteriophage species isolated from water sources in Durham, UK, during undergraduate practical classes. The collection includes diverse species from across known phylogenetic groups. Comparative analyses of two novel phages from the collection suggest they may be founding members of a new genus. Using this Durham phage collection, we determined that particular BREX defense systems were likely to confer a varied degree of resistance against an invading phage. We concluded that the number of BREX target motifs encoded in the phage genome was not proportional to the degree of susceptibility. IMPORTANCE Bacteriophages have long been the source of tools for biotechnology that are in everyday use in molecular biology research laboratories worldwide. Phages make attractive new targets for the development of novel antimicrobials. While the number of phage genome depositions has increased in recent years, the expected bacteriophage diversity remains underrepresented. Here we demonstrate how undergraduates can contribute to the identification of novel phages and that a single City in England can provide ample phage diversity and the opportunity to find novel technologies. Moreover, we demonstrate that the interactions and intricacies of the interplay between bacterial phage defense systems such as Bacteriophage Exclusion (BREX) and phages are more complex than originally thought. Further work will be required in the field before the dynamic interactions between phages and bacterial defense systems are fully understood and integrated with novel phage therapies.


Haploid, diploid, and triploid--discrimination ability against polyploid mating partner in the parasitic wasp, Bracon brevicornis (Hymenoptera: Braconidae).
Because the quality of mating partners varies, females of several taxa have evolved the ability to discriminate against low-quality mates. Although males in the Hymenoptera are usually haploid, diploid males may occur in species with complementary sex determination. Diploid males are almost always sterile in most of the species studied so far. They are thus of very low quality as mating partners, especially when females mate only once in life. We hypothesize that hymenopteran females might have evolved the ability to discriminate against infertile diploid males and avoid mating with them. To test this hypothesis, we studied diploid male fitness in the parasitoid wasp Bracon brevicornis Wesmael (Hymenoptera: Braconidae) by measuring survival rate and fertility and then estimated their chances of actually mating with a female. Flow cytometry was used to determine the ploidy level of wasps. The fitness costs of mating a diploid male are indeed high in this species: only 15% were able to sire daughters, of which 97% were triploid and hardly able to produce viable offspring. In contrast to the hypothesis of unsuitable mate discrimination though, no evidence was found for increased rejection of diploid males by females. Male discrimination against an unsuitable partner did also not occur: triploid females elicited the same intensity of courtship behavior in males than did diploid ones.


5-HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo.
Pulmonary fibrosis is characterized by excessive accumulation of connective tissue, along with activated extracellular matrix (ECM)-producing cells, myofibroblasts. The pathological mechanisms are not well known, however serotonin (5-HT) and 5-HT class 2 (5-HT2) receptors have been associated with fibrosis. The aim of the present study was to investigate the role of 5-HT2B receptors in fibrosis, using small molecular 5-HT2B receptor antagonists EXT5 and EXT9, with slightly different receptor affinity. Myofibroblast differentiation [production of alpha-smooth muscle actin (α-SMA)] and ECM synthesis were quantified in vitro, and the effects of the receptor antagonists were evaluated. Pulmonary fibrosis was also modeled in mice by subcutaneous bleomycin administrations (under light isoflurane anesthesia), and the effects of receptor antagonists on tissue density, collagen-producing cells, myofibroblasts and decorin expression were investigated. In addition, cytokine expression was analyzed in serum. Lung fibroblasts displayed an increased α-SMA (P < 0.05) and total proteoglycan production (P < 0.01) when cultured with TGF-β1 together with 5-HT, which were significantly reduced with both receptor antagonists. Following treatment with EXT5 or EXT9, tissue density, expression of decorin, number of collagen-producing cells, and myofibroblasts were significantly decreased in vivo compared to bleomycin-treated mice. Receptor antagonization also significantly reduced systemic levels of TNF-α and IL-1β, indicating a role in systemic inflammation. In conclusion, 5-HT2B receptor antagonists have potential to prevent myofibroblast differentiation, in vitro and in vivo, with subsequent effect on matrix deposition. The attenuating effects of 5-HT2B receptor antagonists on fibrotic tissue remodeling suggest these receptors as novel targets for the treatment of pulmonary fibrosis.


Evidence of brain methyltransferase inhibition and early brain involvement in HIV-positive patients.
The myelopathy associated with human immunodeficiency virus (HIV) infection closely resembles that in subacute combined degeneration, a disorder of vitamin B12 metabolism. To investigate whether the disorders share a pathogenetic mechanism, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were measured in the cerebrospinal fluid (CSF) of 20 HIV-seropositive patients and 30 HIV-negative patients who were undergoing lumbar puncture for other medical reasons. The HIV-seropositive patients had significantly lower CSF concentrations of SAM (mean 77 [SD 25] vs 131 [35] nmol/l; p less than 0.001) and significantly higher concentrations of SAH (30.5 [6.8] vs 19.0 [7.1] nmol/l; p less than 0.001) than the controls. There was therefore a significant difference between the groups in the SAM/SAH (methylation) ratio (HIV 2.7 [1.0] vs control 7.6 [3.4]; p less than 0.001). There were no correlations between SAM or SAH concentrations or methylation ratio and age or sex in both groups, or serum B12 and folate concentrations, CSF folate, serum or CSF methylmalonic acid, risk factors, body mass index, specific drug treatment received, or disease stage in the HIV group. This finding suggests that HIV affects the brain from a very early stage of the infection. We suggest that, as in the pig, the CSF methylation ratio closely reflects that in the brain. In HIV-infected patients a reduced brain methylation ratio would inhibit methyltransferase enzymes, which would lead to hypomethylation in the central nervous system and ultimately to neurological lesions. In a pig model of subacute combined degeneration and in vitamin-B12-deficient human beings, the primary cause of the low methylation ratio is impaired recycling of SAH back to SAM, a process which requires vitamin-B12-dependent methionine synthase. The HIV patients in this study were vitamin B12 and folate replete, which suggests a different cause for the low methylation ratio.


Quintuple Function Integration in Two-Dimensional Cr(II) Five-Membered Heterocyclic Metal Organic Frameworks via Tuning Ligand Spin and Lattice Symmetry.
Two-dimensional (2D) semiconductors (SCs) integrated with two or more functions are the cornerstone for constructing multifunctional nanodevices but remain largely limited. Here, by tuning the spin state of organic linkers and the symmetry/topology of crystal lattices, we predict a class of unprecedented multifunctional SCs in 2D Cr(II) five-membered heterocyclic metal organic frameworks that simultaneously possess auxetic effect, room-temperature ferrimagnetism, chiral ferroelectricity (FE), electrically reversible spin polarization, and topological nodal lines/points. Taking 2D Cr(TDZ)2 (TDZ = 1.2.5-thiadiazole) as an exemplification, the auxetic effect is produced by the antitetra-chiral lattice structure. The high temperature ferrimagnetism originates from the strong d-p direct magnetic exchange interaction between Cr cations and TDZ doublet radical anions. Meanwhile, the clockwise-counterclockwise alignment of TDZ's dipoles results in unique 2D chiral FE with atomic-scale vortex-antivortex states. 2D Cr(TDZ)2 is an intrinsic bipolar magnetic SC where half-metallic conduction with switchable spin-polarization direction can be induced by applying a gate voltage. In addition, the symmetry of the little group C4 of the lattice structure endows 2D Cr(TDZ)2 with topological nodal lines and a quadratic nodal point in the Brillouin zone near the Fermi level.


Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra.
Cerebral dopamine neurotrophic factor (CDNF) has shown therapeutic potential in rodent and non-human primate models of Parkinson's disease by protecting the dopamine neurons from degeneration and even restoring their phenotype and function. Previously, neurorestorative efficacy of CDNF in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease as well as diffusion of the protein in the striatum (STR) has been demonstrated and studied. Here, experiments were performed to characterize the diffusion and transport of supra-nigral CDNF in non-lesioned rats. We injected recombinant human CDNF to the substantia nigra (SN) of naïve male Wistar rats and analyzed the brains 2, 6, and 24 h after injections. We performed immunohistochemical stainings using an antibody specific to human CDNF and radioactivity measurements after injecting iodinated CDNF. Unlike the previously reported striatonigral retrograde transport seen after striatal injection, active anterograde transport of CDNF to the STR could not be detected after nigral injection. There was, however, clear diffusion of CDNF to the brain areas surrounding the SN, and CDNF colocalized with tyrosine hydroxylase (TH)-positive neurons. Overall, our results provide insight on how CDNF injected to the SN may act in this region of the brain.


A case for using randomly labeled polymers to study long-range polymer chain dynamics by fluorescence.
The process of excimer formation was studied for a series of pyrene end-labeled polystyrenes (PS(X)-Py 2 where X is the polymer molecular weight equal to 3, 4.5, 8, 12.7, and 14.6 K) and two series of polystyrenes randomly labeled with pyrene (CoE-PS and CoA-PS) in seven different solvents. The solvent viscosities ranged from 0.41 to 1.92 mPa x s, while the solvent quality ranged from good to poor solvents for polystyrene, as determined by intrinsic viscosity measurements. Steady-state fluorescence spectra of the pyrene-labeled polymers were acquired, and the excimer to monomer ratios showed that excimer formation increased strongly with a decrease in solvent viscosity. The monomer and excimer time-resolved fluorescence decays were also acquired and fitted globally to either the Birks' scheme or the fluorescence blob model (FBM) for the end- or randomly labeled polymers, respectively. All parameters reporting on the long-range polymer chain dynamics (LRPCD) obtained from the analysis of the fluorescence data acquired with the PS(X)-Py 2, CoE-PS, and CoA-PS series yielded virtually identical trends, demonstrating that these fluorescence experiments yield results that are internally consistent with one another. Considering the substantial advantages associated with the preparation and study of randomly labeled polymers, this report presents an appealing case for the use of randomly labeled polymers in the study of LRPCD.


The Role of MicroRNAs in Development of Endometrial Cancer: A Literature Review.
Endometrial cancer (EC) ranks as the second most common gynaecological cancer worldwide. EC patients are diagnosed at an early clinical stage and generally have a good prognosis. Therefore, there is a dire need for development of a specific marker for early detection of endometrial adenocarcinoma. The development of EC is conditioned by a multistep process of oncogenic upregulation and tumor suppressor downregulation as shown by molecular genetic evidence. In this setting, microRNAs appear as significant regulators of gene expression and several variations in the expression of microRNAs have been implicated in normal endometrium, endometrial tissue, metrorrhagia, and endometrial cancer. Furthermore, microRNAs act as highly precise, sensitive, and robust molecules, making them potential markers for diagnosing specific cancers and their progression. With the rising incidence of EC, its management remains a vexing challenge and diagnostic methods for the disease are limited to invasive, expensive, and inaccurate tools. Therefore, the prospect of exploiting the utility of microRNAs as potential candidates for diagnosis and therapeutic use in EC seems promising.


Synchronized firing among retinal ganglion cells signals motion reversal.
We show that when a moving object suddenly reverses direction, there is a brief, synchronous burst of firing within a population of retinal ganglion cells. This burst can be driven by either the leading or trailing edge of the object. The latency is constant for movement at different speeds, objects of different size, and bright versus dark contrasts. The same ganglion cells that signal a motion reversal also respond to smooth motion. We show that the brain can build a pure reversal detector using only a linear filter that reads out synchrony from a group of ganglion cells. These results indicate that not only can the retina anticipate the location of a smoothly moving object, but that it can also signal violations in its own prediction. We show that the reversal response cannot be explained by models of the classical receptive field and suggest that nonlinear receptive field subunits may be responsible.


[The action of Sequostat in comparison to Sequence Ovosiston on selected metabolic parameters].
The effects of two sequential oral contraceptive preparations, Sequostat (6 days ethinylestradiol 0.05 mg, 15 days ethinylestradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequence-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg) on triglycerides, total cholesterol, HDL- and LDL-Cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase and antithrombin III were studied in two groups of 46 and 29 young women respectively. Investigations were performed prior to the hormonal intake and after treatment for 3, 6 and 12 months. In nearly all parameters studied significant but minimal changes could be demonstrated which in most cases showed a minor degree in the Sequostat-group, while Sequence-Ovosiston exerted a less effect on glucose tolerance. A significant increase of HDL-cholesterol and a reduction of LDL/HDL-cholesterol relation could be demonstrated at least in the first six months, resulting from the estrogen dominance of the contraceptives.


Spectral Inspections on Molecular Configurations of Nile Blue A Adsorbed on the Elementary Clay Sheets.
Studies on the configuration of dye molecules are of great importance in revealing origins of the electronic bands as well as understanding their transitions. In this work, we utilized dye molecules named Nile blue A, which are a type of oxazine dyes, to study the molecular configurations when they are transferred from solutions to a solid surface. The Langmuir-Blodgett (LB) technique was employed to construct such an interface where the interaction between the dye molecules and solid supports can be pursued. Hybrid films were prepared via the LB depositions, and the dye molecules were assembled on the elementary clay sheets (laponite, saponite). The configuration of Nb reflected by the molecular orientation, packing density, phase behavior, and variances of the surface tension has been derived. The ex situ spectroscopy characterizations such as UV-vis absorption, fluorescence emission, and excitation spectra were carried out on these LB films to reveal the fact that the adsorbed Nb molecules are mainly assembled in two types of configurations. Adsorbed state I was found to be achieved at high concentrations (1-10 ppm) of clay dispersions and low surface pressure (∼5 mN/m). In this state the anionic oxazine rings of Nb are adsorbed on clay sheets sharing a large lift-off area. This configuration gives allowable fluorescence (λ = 550 nm). Lower clay concentration (<1 ppm) and high surface pressure (10-30 mN/m) yield the adsorbed state II in which the oxazine chromophores were arranged in a side-by-side style, and the dye molecules stand perpendicularly to the clay sheets. This conformation exhibits no photoluminescence.


Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion.
Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.


Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil.
Self-nanoemulsifying drug delivery systems (SNEDDS) were developed with the objective to overcome problems associated with the delivery of cefpodoxime proxetil (CFP), a poorly bioavailable high dose antibiotic having pH dependant solubility. Solubility of CFP in oily phases and surfactants was determined to identify components of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify selected oily phases. Ternary phase diagrams were constructed to identify area of nanoemulsification for the selected systems. The influence of CFP and the pH of dilution medium on the phase behavior of selected system were assessed. The globule size of optimized CFP SNEDDS in various dissolution media was determined to check the effect of pH on its behavior. The optimized CFP SNEDDS needed surfactant content less than 40% and yielded nanoemulsion of mean globule size 170 nm, which was not affected by the pH of dilution medium. The optimized SNEDDS released CFP completely within 20 min irrespective of the pH of dissolution medium.


The Effects of Time Lag and Cure Rate on the Global Dynamics of HIV-1 Model.
In this research article, a new mathematical model of delayed differential equations is developed which discusses the interaction among CD4 T cells, human immunodeficiency virus (HIV), and recombinant virus with cure rate. The model has two distributed intracellular delays. These delays denote the time needed for the infection of a cell. The dynamics of the model are completely described by the basic reproduction numbers represented by R0, R1, and R2. It is shown that if R0 < 1, then the infection-free equilibrium is locally as well as globally stable. Similarly, it is proved that the recombinant absent equilibrium is locally as well as globally asymptotically stable if 1 < R0 < R1. Finally, numerical simulations are presented to illustrate our theoretical results. Our obtained results show that intracellular delay and cure rate have a positive role in the reduction of infected cells and the increasing of uninfected cells due to which the infection is reduced.


COVID-19 Vaccines: "Warp Speed" Needs Mind Melds, Not Warped Minds.
In this review, we address issues that relate to the rapid "Warp Speed" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of humans and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans and discuss the outcome and interpretation of virus challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which were not included in the initial wave of Warp Speed immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV) vaccines. We conclude by outlining the possible outcomes of the Warp Speed vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.


[Gender issues in the epidemiology of cardiovascular diseases].
In the last decade our knowledge about sex differences in the epidemiology of cardiovascular diseases has substantially increased. However; most information relates to coronary heart disease, and relatively little information is available on other forms of heart disease or cerebrovascular diseases. In the present paper, first, the age-adjusted mortality and morbidity rates of men and women across different European countries will be described as well as differences in case-fatality after myocardial infarction. Second, gender differences regarding the impact of traditional and novel risk factors on the development of coronary heart disease will be addressed, together with recent evidence from cardiac rehabilitation research. In general, we can say that significant sex differences exist at each stage of coronary heart disease, which need to be taken into account in primary prevention, acute therapy, and long-term rehabilitation. Further research is required on other forms of cardiovascular diseases, which are more prevalent among women than among men, especially in higher age groups.


Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs.
Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients.


Acoustic radiation force due to incident plane-progressive waves on coated spheres.
The acoustic radiation force exerted by a traveling plane wave on a coated sphere was theoretically investigated. After carefully re-calculating the scattering coefficients of a model presented by Mitri [Eur. Phys. J. B 43, 379-386 (2005)], a missing term is found that is related to absorption in the particle shell. By amending the theory, it is shown that nonphysical consequences predicted earlier disappear. The homogeneous sphere results in the long-wavelength limit are also correctly recovered.


Complete global myocardial ischemia in dogs.
Complete global myocardial ischemia or zero coronary arterial flow in dogs results in a series of well-defined changes which begin when the myocardium converts from aerobic to anaerobic metabolism. These processes continue until the myocardium dies. The products of anaerobic metabolism, chiefly glycolytic intermediates, inorganic phosphate, H+, and creatine, are produced intracellularly and accumulate in the tissue. Because the demand for high-energy phosphates (HEP) in the tissue exceeds the supply available from anaerobic glycolysis and HEP reserves, net ATP level declines, approaching zero after 100 min of ischemia at 37 degrees C. At this time, the changes in totally ischemic tissue in vitro are equivalent to those seen in myocytes irreversibly injured by severe ischemia in vivo. During reoxygenation after total ischemia, the resumption of effective contractile activity depends partly on the metabolic changes and degree of myocyte injury sustained during ischemia.


Join the Movement to Have Healthy Bone Project (JHBP): changing behavior among older women in Thailand.
Osteoporosis is a common silent disease in older adults presenting with fragility fractures. Lifestyle modifications may be an imperative strategy to minimize the increase of either osteoporosis or osteoporosis-related fractures. Targeted education is one way to promote osteoporosis preventive behaviors. Our aim of this study was to test the feasibility of the Join the Movement to Have Healthy Bone Project (JHBP) that was developed on osteoporosis preventive behaviors for Thai older women. By succeeding in making appropriate lifestyle changes, these women ultimately may reduce the risk of osteoporosis or fractures in later life.


Real-Time Modulation of Physical Training Intensity Based on Wavelet Recursive Fuzzy Neural Networks.
In this study, a wavelet recurrent fuzzy neural network is used to conduct in-depth research and analysis on the real-time regulation of physical training intensity. Firstly, an inter-process control technique is proposed to solve the problem of incomplete control flow graph construction caused by the inability to effectively collect all program control flow information in the process of static analysis, in preparation for the research of fuzzy testing technique. Next, a wavelet recursive fuzzy neural network-guided fuzzy testing technique is proposed to solve the problem of fuzzy tests falling into invalid variation due to the lack of directionality in the fuzzy testing process. Each neuron in the feedforward network is divided into different groups according to the order of receiving information. Each group can be regarded as a neural layer. The neurons in each layer receive the output of the neurons in the previous layer and output to the neurons in the next layer. The empirical data show that injury-preventive fitness training can effectively improve all physical qualities in the first phase of preparation and can effectively maintain the physical state and effectively contribute to their abilities during the competition period, and its injury-preventive fitness training interventions were verified by statistical analysis to have a dangerous main effect on their pre and post-test performance. Therefore, it is still not possible to determine its correlation with the coordination and improvement of the athletes' physical fitness, and the integration of the basic physical training and rehabilitation physical training systems, making this theory a new special training theory.


GeneXpert MTB/RIF assay in the diagnosis of urinary tuberculosis from urine specimens.
Conventional bacteriological methods are not generally helpful in diagnosing urinary tuberculosis (UTB). GeneXpert is endorsed for the detection of pulmonary tuberculosis, whereas the data on its utility for urine specimens is limited. In this study, we aimed to evaluate its performance on urine specimens in a country with high TB incidence. A total of 163 suspected UTB patients were consecutively enrolled in the analysis, including 37 (22.7%) culture-positive and 44 (27.0%) clinically diagnosed UTB cases. Compared with conventional culture, the sensitivity of GeneXpert (94.6%) was significantly higher than that of smear microscopy (40.5%, P < 0.001). When setting clinical diagnosis as gold standard, 51 out of 81 clinically diagnosed UTB cases were detected by GeneXpert, demonstrating a sensitivity of 63.0%, which was significantly higher than that of smear microscopy (18.5%, P < 0.001) and culture (45.7%, P = 0.027), respectively. In addition, the proportion of UTB cases in the migrant population was significantly higher than that in the resident population (P = 0.019). To conclude, our data demonstrate that GeneXpert outperforms AFB smear and culture for the detection of MTB in urine samples, which provides an alternative for the diagnosis of UTB. The migrant population and previously diagnosed TB cases are high risk factors for developing UTB cases.


Incidental finding of papillary thyroid carcinoma on CT examination of mandibular lesion: Case report.
The number of significant incidental findings identified on radiographic examinations has increased. In total, 169 patients, 87 males and 82 females, with a mean age of 67.3 years (range, 17-92 years), as well as 65 patients (38.5%), 43 (66.2%) female and 22 (33.8%) male had abnormal findings in the thyroid for one year in our institution. Thyroid nodules are the most common incidental findings on oral and maxillofacial evaluations. Computed tomography (CT) and magnetic resonance imaging (MRI) examination are frequently used to detect thyroid abnormality. The present study reported a case of papillary thyroid carcinoma (PTC) detected following CT and MRI examination of a mandibular lesion. The CT examination of the oral and maxillofacial region included the thyroid, which must be examined carefully to detect various diseases, including PTC. Collaboration between radiologists and clinicians is important to manage these incidental findings.


Conceptualizing and measuring family quality of life.
Increasing emphasis on family-centred approaches to services and supports for families of children with disabilities has surfaced the issue of accountability for family outcomes. We present a review of literature about the impacts of children with disabilities on families as a backdrop to proposing family quality of life as a concept that encompasses impacts of disability and one that can be used to assess the impact of supports and services on families. We briefly introduce the Beach Center Family Quality of Life Scale, providing information about its factor structure, reliability and convergent validity. The Beach Center Family Quality of Life Scale contains 25 items assessing family ratings of importance and satisfaction with five domains: Family interaction, Parenting, Emotional well-being, Physical/material well-being and Disability-related supports. We present a framework for utilizing a measure of family quality of life as a long-term outcome in concert with other short-term measures of service outcomes for families.


High-performance liquid chromatography as a tool for the chemical standardisation of Triphala--an Ayurvedic formulation.
Triphala is an anti-oxidant-rich herbal formulation containing fruits of Emblica officinalis, Terminalia chebula and T. belerica in equal proportions. The preparation is frequently used in Ayurvedic medicine to treat diseases such as anaemia, jaundice, constipation, asthma, fever and chronic ulcers. Anti-mutagenic effects of the polyphenolic fractions isolated from Triphala have been reported, thus indicating that the phenols present in the formulation might be responsible for its therapeutic efficacy. A simple high-performance liquid chromatography method for the separation and quantitative determination of the major antioxidant polyphenols from Triphala has been developed. The use of an RP18 column with an acidic mobile phase enabled the efficient separation of gallic acid, tannic acid, syringic acid and epicatechin along with ascorbic acid within a 20 min analysis. Validation of the method was performed in order to demonstrate its selectivity, linearity, precision, accuracy and robustness. In addition, optimisation of the complete extraction of phenolic compounds was also studied.


Formation of Highly Substituted Indenes through Acid Promoted Cyclodehydration with Nucleophile Incorporation.
Readily accessible 3-aryl-2-carboxypropenones (by Knoevenagel condensation) undergo acid promoted cyclodehydration with nucleophile incorporation to form highly substituted indenes. For stronger nucleophiles, nucleophile incorporation precedes cyclodehydration in a nucleophilic-addition-cyclodehydration (NAC) sequence. For weaker nucleophiles, cyclodehydration precedes nucleophile incorporation in a cyclodehydrative-nucleophilic-trapping (CNT) sequence, involving a reactive allyl cation intermediate. The substrate scope and preferred cyclization pathway (NAC or CNT) has been studied with respect to 3-aryl-2-carboxypropenone and the nature of the nucleophile. Also, for 1,3-diaryl-2-carboxypropenones, which can also undergo Nazarov cyclization, delineation between competing Nazarov and CNT pathways is controlled by the nature of the acid catalyst.


[125Iodo]BE 2254, a new radioligand for alpha 1-adrenoceptors.
[125Iodo]2-[beta-(14-hydroxyphenyl)-ethyl-aminomethyl]-tetralone([125Iodo]BE 2254 or IBE 2254), a new iodinated radioligand of high specific radioactivity (2175 Ci/mmol), was synthesized and used to characterize alpha 1-adrenoceptors in rat lung and cerebral cortex membranes. The binding constants of IBE 2254, using rat lung and cortex membranes, were Kd = 53 +/- 10 pM, Bmax = 53 +/- 8 fmol/mg; and Kd = 78 +/- 14 pM, Bmas = 210 +/- 26 fmol/mg, respectively (Kd = dissociation constant of IBE 2254 determined in saturation experiments). In equilibrium binding experiments with IBE 2254, at concentrations of the free ligand up to 1.2 nM, only one class of binding sites could be detected. In kinetic experiments, the association and dissociation rate constants were 2.3 X 10(9) M-1 min-1 and 0.10 min-1, respectively. In rat cerebral cortex membranes, alpha-adrenoceptor antagonists competed for IBE 2254 binding in the following order: prazosin greater than BE 2254 greater than WB 4101 greater than phentolamine greater than corynanthine greater than yohimbine greater than rauwolscine, indicating strongly that IBE 2254 binds to alpha 1-adrenoceptors. The calculated affinities of different alpha-adrenoceptor blocking agents from inhibition of IBE 2254 binding were nearly identical in rat lung and cerebral cortex. The low dissociation constant of the ligand together with its high specific radioactivity allows binding studies to be carried out with tissue samples where only small densities of alpha 1-adrenoceptors are present.


Leiomyoma in the Retzius space.
Parauterine location of leiomyomas is observed to be an extremely rare clinical condition. However, when benign or malignant primary tumours are detected in that area, they are often found in the Retzius space. There have been only six cases of leiomyomas in the Retzius space reported in the literature so far. The paper presents one such leiomyoma case located in the Retzius space. This extremely rare location of the tumour justifies its presentation. The medical records of the patient treated in the outpatient's obstetrics and gynaecology (ob-gyn) clinic, her case history, and hospital records, supplemented by information obtained from the patient's daughter, were analysed. The patient, a 50-year-old woman with type 2 diabetes, was referred to hospital for diagnosed secondary anaemia due to heavy menstruation for four months, which was associated with intramural leiomyoma in the anterior wall of the uterine body. Clinical examination found a large leiomyoma located in the anterior wall of the uterus. Laparotomy was performed: apart from and a leiomyoma in the uterine body it found a tumour, 140 × 100 mm in size, in the Retzius space. Total resection of the tumour was performed. Since the leiomyoma was located in the uterine wall, hysterectomy with bilateral excision of adnexa was also performed. The patient was discharged home in generally good condition on the sixth day following the operation. Concomitant occurrence of leiomyoma atypically located in the Retzius space and leiomyoma in the uterine body made perioperative diagnosis very difficult.


Measuring research impact in medical research institutes: a qualitative study of the attitudes and opinions of Australian medical research institutes towards research impact assessment frameworks.
The question of how to measure, assess and optimise the returns from investment in health and medical research (HMR) is a highly policy-relevant issue. Research Impact Assessment Frameworks (RIAFs) provide a conceptual measurement framework to assess the impact from HMR. The aims of this study were (1) to elicit the views of Medical Research Institutes (MRIs) regarding objectives, definitions, methods, barriers, potential scope and attitudes towards RIAFs, and (2) to investigate whether an assessment framework should represent a retrospective reflection of research impact or a prospective approach integrated into the research process. The wider objective was to inform the development of a draft RIAF for Australia's MRIs. Purposive sampling to derive a heterogeneous sample of Australian MRIs was used alongside semi-structured interviews with senior executives responsible for research translation or senior researchers affected by research impact initiatives. Thematic analysis of the interview transcriptions using the framework approach was then performed. Interviews were conducted with senior representatives from 15 MRIs. Participants understood the need for greater research translation/impact, but varied in their comprehension and implementation of RIAFs. Common concerns included the time lag to the generation of societal impacts from basic or discovery science, and whether impact reflected a narrow commercialisation agenda. Broad support emerged for the use of metrics, case study and economic methods. Support was also provided for the rationale of both standardised and customised metrics. Engendering cultural change in the approach to research translation was acknowledged as both a barrier to greater impact and a critical objective for the assessment process. Participants perceived that the existing research environment incentivised the generation of academic publications and track records, and often conflicted with the generation of wider impacts. The potential to improve the speed of translation through prospective implementation of impact assessment was supported, albeit that the mechanism required development. The study found that the issues raised regarding research impact assessment are less about methods and metrics, and more about the research activities that the measurement of research translation and impact may or may not incentivise. Consequently, if impact assessment is to contribute to optimisation of the health gains from the public, corporate and philanthropic investment entrusted to the institutes, then further inquiry into how the assessment process may re-align research behaviour must be prioritised.


Novel Self-Expanding Interwoven Nitinol Stent for Treating Femoropopliteal Artery Disease: 12-Month Results of Single-Center First-in-Man Study.
To evaluate the safety and efficacy of Innospring® stent, a novel self-expanding interwoven nitinol stent, in treating femoropopliteal atherosclerotic lesions. A prospective, single-center, single-arm, first-in-human study enrolled 15 patients (mean age 73.1 years; 13 men) to evaluate the safety and efficacy of the Innospring® stent monitored by core laboratories. The inclusion criteria were claudication or ischemic rest pain, de novo lesions or nonstented restenosis, >70% stenosis, lesion length <20 cm, and a reference vessel diameter of 4-7 mm. The primary safety endpoint was 30-day major adverse events. The primary efficacy end point was stent patency at 12 months. Follow-up evaluations were conducted at 30 days, 6 months, and 12 months. The lesion length was 6.1 ± 3.5 mm. Fourteen (93.3%) patients had lesions of the superficial femoral artery and 3 (20.0%) patients had lesions of the popliteal artery. Nine (60.0%) patients had moderate-to-severe calcified lesion. Technical and procedural success was 100%. No patients experienced major adverse events in the first 30 days. The Rutherford category showed significant and sustained improvement at 6 and 12 months. The 12-month follow-up radiographs obtained in 13 patients confirmed the absence of stent fractures in 100% of examinations. The cumulative primary stent patency rate at 6 and 12 months were 93.3% and 84.6%, respectively. Stenting of the superficial femoral and popliteal arteries using the Innospring® stent is safe and effective. This competing interwoven nitinol stent may provide superior stent integrity and fracture-resistance as well as serve areas under extreme mechanical stress. Endovascular recanalization is a widely accepted and recommended treatment for symptomatic peripheral artery diseases. The Innospring® stent is a novel self-expanding interwoven stent containing eight nitinol wires with additional radial force, fracture-resistance, and visibility under fluoroscopy. This first-in-human study using the Innospring® stent in patients with femoropopliteal occlusive disease reported that stenting of the superficial femoral and popliteal arteries using the Innospring® stent is safe and effective. This competing interwoven nitinol stent may provide an impressive stent integrity and fracture-resistance as well as serve areas under extreme mechanical stress.


Assignment of histidine resonances in the 1H NMR (500 MHz) spectrum of subtilisin BPN' using site-directed mutagenesis.
A spin-echo pulse sequence has been used to resolve the six histidine C-2H protons in the 500-MHz NMR spectrum of subtilisin BPN'. Five of these residues have been substituted by site-directed mutagenesis, and this has enabled a complete assignment of these protons to be obtained. Analysis of the pH titration curves of these signals has provided microscopic pKas for the six histidines in this enzyme. The pKas of the histidine residues in subtilisin BPN' have been compared with the values obtained for the histidines in the homologous enzyme from Bacillus licheniformis (subtilisin Carlsberg). Four of the five conserved histidines titrate with essentially identical pKa's in the two enzymes. It therefore appears that the assignments made for these residues in subtilisin BPN' can be transferred to subtilisin Carlsberg. On the basis of these assignments, the one histidine that titrates with a substantially different pKa in the two enzymes can be assigned to histidine-238. This difference in pKa has been attributed to a Trp to Lys substitution at position 241 in subtilisin Carlsberg.


The hunt for gene effects pertinent to behavioral traits and psychiatric disorders: from mouse to human.
The field of behavioral genetics was reviewed in the classic 1960 text by Fuller and Thompson. Since then, there has been remarkable progress in the genetic analysis of animal behavior. Many molecular genetic methods in common use today were not even anticipated in 1960. Animal models for many human psychiatric disorders have been discovered or created. In human behavior genetics, however, powerful new methods have failed to reveal even one bona fide, replicable gene effect pertinent to the normal range of variation in intelligence and personality. There is no explanatory or predictive value in that genetic information. For several psychiatric disorders, including autism and schizophrenia, many large genetic effects arise from de novo mutations. Genetically, the disorders are heterogeneous; different cases with the same diagnosis have different causes. The promises of the molecular genetic revolution have not been fulfilled in behavioral domains of most interest to human psychology.


Detection of synergistic effect of superoxide dismutase and jujubosides on scavenging superoxide anion radical by capillary electrophoresis.
A new capillary electrophoresis method was developed to study the synergistic effect of superoxide dismutase and jujuboside A or B on scavenging superoxide anion radical in serum matrix respectively, in which superoxide anion radical was generated from pyrogallol autoxidation. The electrophoresis conditions, and the factors affecting the productive rate of purpurogallin, such as pyrogallol autoxidation product and the activity of superoxide dismutase, were optimized. Under optimal conditions, the content of superoxide dismutase in Gibco newborn calf serum was 7.06 mg/L, RSD was 2.01% and the average recovery was 98.4%. The values of IC50 for jujuboside A and B in the serum matrix were 157.67 and 31.60 mg/L respectively, and they both had synergy on scavenging superoxide anion radical with superoxide dismutase, but there was no the dose-dependency on this synergy.


Shigella actin-based motility in the absence of vinculin.
Reports on the role of vasodilator-stimulated phosphoprotein (VASP) and proline-rich sequences in actin-based motility of Listeria and potentially of Shigella flexneri have led to the suggestion that vinculin might be an essential docking protein on the surface O2 motile Shigella. Therefore, whether vinculin had a functional role in Shigella actin-based motility was tested by examining Shigella infection of the vinculin-deficient F9 cell line variant 5.51. Shigella are able to form actin tails and surface protrusions in 5.51 cells that are indistinguishable from those they produce in F9 cells, and Shigella rates of intracellular movement and protrusion formation are similar in the two cell lines. These data disprove the model of Shigella actin-based motility in which vinculin is an essential docking protein for either the formation of actin tails or the acceleration of motile bacteria.


[The study of the in vivo-in vitro correlation of the naftopidil sustained-release tablet in dog].
We studied the correlation of sustained-release tablet of naftopidil between the in vitro release and the in vivo absorption in the dog. The release rate (X) of naftopidil sustained-release tablet in artificial gastric fluid was determined and the naftopidil concentration in plasma was determined after a single oral dose of 100 mg naftopidil (tablet or sustained-release tablet) in the dog. The absorbed fraction(F) and in vivo absorption rate (A) of the NAF sustained-release tablet in the dog at different time were calculated by W-N method and deconvolution method, respectively. Then the regression equations between F or A and X of the corresponding time point were obtained: F=2. 1533X - 27. 636(r = 0.9927) and A=2.3452X - 25.474(r= 0.9938). W-N method and deconvolution method both indicated that the correlation between the in vitro release and the in vivo absorption in the dog of the NAF sustained-release tablet was good.


The susceptibility of certain bacterial strains to imidazotriazine derivatives.
The synthesized imidazo[2,1-c]triazines were tested for their antimicrobial activity. Microbiological screening tests conducted in relation to 54 strains of Gram-positive and 52 strains of Gram-negative bacteria, 6 strains of yeast-like fungi and 3 strains of moulds showed significant activity of compound 19 against 52 Gram-negative bacterial strains. This compound was active against 16 strains of Escherichia coli, 12 strains of Pseudomonas, 10 strains of Proteus spp., 8 strains of Klebsiella pneumoniae and 6 strains of Enterobacter aerogenes in the examined concentrations (100 microg ml(-1) and 200 microg ml(-1)).


Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: a pharmacodynamic study of dual pathway inhibition vs. dual antiplatelet therapy.
Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited. This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel. Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations. ClinicalTrials.gov identifier: NCT03718429.


Audit of waist measurement methods during statutory diving medical assessments.
Measurement of waist circumference is used to assess abdominal fat and risk of heart disease, type 2 diabetes, cancer and stroke. It is performed in several clinical settings for health promotion and medical assessment purposes, including statutory medical assessments where results may influence decisions on fitness to work. Under the Diving at Work Regulations 1997, working divers must have an annual assessment of their fitness to dive performed by an approved medical examiner of divers (AMED), appointed by the Health and Safety Executive (HSE). The assessment includes measurement of height, weight and waist circumference, the latter used as an indicator of central adiposity and associated health risks. To establish the practice of AMEDs in measuring waist circumference of working divers undergoing medical assessment to determine their fitness to dive. Ninety-seven AMEDs were sent a questionnaire and asked to describe their current practice in measuring waist circumference. The response rate was 79%. The audit standard used was the consensus document published by the World Health Organization (WHO). Of the 77 responses, 76 were completed sufficiently to allow analysis. When the waist was measured, there was consistency in the diver's level of clothing, stage of breathing and posture for the procedure but variability in the site of measurement. Only 7/76 (9%) respondents carried out waist measurement fully in line with WHO guidance. The audit has identified that there is a need for guidance for AMEDs on measuring waist circumference in the statutory medical assessment of working divers.


Trust Model of Wireless Sensor Networks and Its Application in Data Fusion.
In order to ensure the reliability and credibility of the data in wireless sensor networks (WSNs), this paper proposes a trust evaluation model and data fusion mechanism based on trust. First of all, it gives the model structure. Then, the calculation rules of trust are given. In the trust evaluation model, comprehensive trust consists of three parts: behavior trust, data trust, and historical trust. Data trust can be calculated by processing the sensor data. Based on the behavior of nodes in sensing and forwarding, the behavior trust is obtained. The initial value of historical trust is set to the maximum and updated with comprehensive trust. Comprehensive trust can be obtained by weighted calculation, and then the model is used to construct the trust list and guide the process of data fusion. Using the trust model, simulation results indicate that energy consumption can be reduced by an average of 15%. The detection rate of abnormal nodes is at least 10% higher than that of the lightweight and dependable trust system (LDTS) model. Therefore, this model has good performance in ensuring the reliability and credibility of the data. Moreover, the energy consumption of transmitting was greatly reduced.


Stellate Cells in the Medial Entorhinal Cortex Are Required for Spatial Learning.
Spatial learning requires estimates of location that may be obtained by path integration or from positional cues. Grid and other spatial firing patterns of neurons in the superficial medial entorhinal cortex (MEC) suggest roles in behavioral estimation of location. However, distinguishing the contributions of path integration and cue-based signals to spatial behaviors is challenging, and the roles of identified MEC neurons are unclear. We use virtual reality to dissociate linear path integration from other strategies for behavioral estimation of location. We find that mice learn to path integrate using motor-related self-motion signals, with accuracy that decreases steeply as a function of distance. We show that inactivation of stellate cells in superficial MEC impairs spatial learning in virtual reality and in a real world object location recognition task. Our results quantify contributions of path integration to behavior and corroborate key predictions of models in which stellate cells contribute to location estimation.


Helicobacter pylori infection and the risk of colorectal cancer: a nationwide population-based cohort study.
The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings. This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study. A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC. The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection. Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.


Uncovering Factors Influencing Instructors' Decision Process when Considering Implementation of a Course-Based Research Experience.
Course-based undergraduate research experiences (CUREs) are an effective way to expose large numbers of students to authentic research, yet most laboratory courses still use traditional "cookbook" methods. While barriers to using CUREs have been captured postimplementation, little is known about the decision mindset before implementation or what features of CURE design may mitigate perceived barriers. Perception of an innovation (such as a CURE) influences the likelihood of its adoption, and diffusion of innovations theory posits that the decision to adopt is largely influenced by five perceived features of an innovation: relative advantage, compatibility, complexity, observability, and trialability. We conducted interviews with instructors considering using the Prevalence of Antibiotic Resistance in the Environment (PARE) project to assess their perceptions of CUREs and motivations for using PARE. Instructors viewed CUREs as having relative advantages over traditional methods; however, CUREs were also viewed as complex, with instructors citing multiple barriers. Instructors were motivated to use PARE because of its potential scientific impact and compatibility with their courses' structures and resources. Instructors perceived PARE to have few barriers to implementation compared with other CUREs. Designing CUREs that address common instructor barriers and drivers could increase the rate of diffusion of CUREs.


Hyperacute Incidental Late Myocardial Enhancement in Ischemic Stroke Using Chest Spectral CT: Relationship with Etiology.
Hyperacute cardiac imaging of patients with acute ischemic stroke (AIS), though desirable, is impractical. Using delayed-enhancement, low-dose, non-gated, chest spectral computed tomography scans (DESCT), we explored the prevalence and patterns of incidental myocardial late iodine enhancement (LIE) and embolic sources, and their relationship with stroke etiology. Since July 2020, DESCT was performed after cerebrovascular CT angiography (CTA) among patients with suspected AIS undergoing CT using a dual-layer spectral scanner, without additional contrast administration. Images were analyzed using monoenergetic reconstructions and iodine density maps, and the myocardial extracellular volume fraction (ECV, %) was calculated. Eighty patients with AIS were included. DESCT identified a cardiac thrombi in 6 patients (7.5%), and a complex aortic plaque in 4 (5%) cases; reclassifying 5 embolic strokes of uncertain source (28% of ESUS) to cardioembolic (CE, n = 3) and non-CE (n = 2) etiologies. LIE was identified in 38 (48%) patients, most commonly (82%) of ischemic pattern. We did not identify significant relationships between AIS etiology and the presence, pattern, and extent of LIE (p > 0.05); ECV (p = 0.56), severe aortic (p = 0.25) or valvular (p = 0.26) disease, or the extent of coronary calcification (p = 0.39). Patients with evidence of major cardiovascular DESCT findings had higher rates of all-cause death at 90 days (42% vs. 19%, p = 0.037). In this study, hyperacute cardiac imaging of AIS with DESCT identified a high prevalence of incidental cardiac disease predominantly involving LIE of ischemic etiology and mostly not related to the stroke etiology.


Properties of a self-assembled phospholipid membrane supported on lipobeads.
The overall objective of our work was to make a hydrogel-supported phospholipid bilayer that models a cytoskeleton-supported cell membrane and provides a platform for studying membrane biology. Previously, we demonstrated that a pre-Lipobead, consisting of phospholipids covalently attached to the surface of a hydrogel, could give rise to a Lipobead when incubated with liposomes because the attached phospholipids promote self-assembly of a phospholipid membrane on the pre-Lipobead. We now report the properties of that Lipobead membrane. The lateral diffusion coefficient of fluorescently labeled phosphatidylcholine analogs in the membrane was measured by fluorescence recovery after photobleaching and was found to decrease as the surface anchor density and hydrogel crosslinking density increased. Results from the quenching of phosphatidylcholine analogs suggest that the phospholipid membrane of the Lipobead was composed mostly of a semipermeable lipid bilayer. However, the diffusional barrier properties of the Lipobead membrane were demonstrated by the entrapment of 1.5-3.0 K dextran molecules in the hydrogel core after liposome fusion. This hydrogel-supported bilayer membrane preparation shows promise as a new platform for studying membrane biology and for high throughput drug screening.


Increased risk of lethal graft-versus-host disease-like syndrome after transplantation into NOD/SCID mice of human mobilized peripheral blood stem cells, as compared to bone marrow or cord blood.
We tested the ability of human cells from different hematopoietic tissues to generate graft versus host disease-like syndrome (GVHD) in sublethally irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tissue sources of human hematopoietic cells were: (1) bone marrow (BM), (2) nonmobilized peripheral blood (PB), (3) mobilized peripheral blood stem-progenitor cells (PBSC), and (4) cord blood (CB). To avoid interindividual donor variation, part of this study was done using BM, PB, and PBSC donated by a single healthy adult volunteer. A total of 179 NOD/SCID mice received graded human hematopoietic cell doses [5-500 x 10(6) mononuclear cells (MNC), containing 2-325 x 10(6) CD3(+) T cells, per mouse] from individual donors. Mice were observed for the development of GVHD and sacrificed 60 days after transplantation (earlier if ill). Mice were analyzed quantitatively by flow cytometry for human hematopoietic cell types and histologically, especially for human T lymphocytes infiltrating BM. No mouse transplanted with the tested doses of human CB or BM cells developed GVHD (experimentally defined as >10% human T lymphocytes infiltrating the mouse BM). For PB and PBSC, the frequencies of death, death with GVHD, and GVHD were directly related to the dose and source of human cells. Because PB cells contaminate harvested BM, the results from infused BM and PB were next combined for further analysis (BM/PB). The relative risks (hazard ratios estimated from the proportional hazards model) for death with GVHD, for each 10 human T cell dose increase, were 1.15 for BM/PB (p < 0.0001) and 1.47 for PBSC (p < 0.0001). In this in vivo xenogeneic model, the average T cell from human PBSC generated GVHD more potently than did the average T cell from human BM/PB, and the average CB T cell had a much lower GVHD potential. These results suggest that the potential for clinical GVHD from an HLA-disparate donor graft is likely to be quantitatively dependent both on the total number of T lymphocytes in the donor graft and the tissue source of the graft. Quantitative criteria for optimal T cell content of allogeneic donor hematopoietic grafts from different sources are discussed.


Structures of non-canonical tandem base pairs in RNA helices: review.
The structures of tandem non-canonical base pairs, a frequently recurring motif in RNA molecules, are reviewed and analysed. The tandem non-canonical base pair motifs can be roughly divided in three groups, containing seven subgroups based on their base pairing patterns and local geometries. Structural details and helical parameters that can be used to numerically distinguish between the subgroups are tabulated. Remarkably, while the individual helical twists of the tandem and adjacent base pair steps can be substantially smaller or larger than the typical A-form value of 32.7 degrees, the average value is close to A-form. This and other striking regularities resulting from compensating geometrical adjustments, important for understanding and predicting the configurations of non-canonical base pairs geometries are discussed.


Tuberculosis in swine co-infected with Mycobacterium avium subsp. hominissuis and Mycobacterium bovis in a cluster from Argentina.
SUMMARY In Argentina little is known about the epidemiology of tuberculosis (TB) infection in swine. We characterized the epidemiological dynamics of Mycobacterium avium complex (MAC) infection in a swine population of Argentina using molecular tools and spatial analysis techniques. Isolates (n = 196) obtained from TB-like lesions (n = 200) were characterized by polymerase chain reaction. The isolates were positive to either M. bovis (IS6110) (n = 160) or M. avium (IS1245) (n = 16) while the remaining 20 (10.2%) isolates were positive to both M. bovis and M. avium. The detection of both bacteria together suggests co-infection at the animal level. In addition, MAC-positive isolates (n = 36) were classified as M. avium subsp. avium (MAA) (n = 30) and M. avium subsp. hominissuis (MAH) (n = 6), which resulted in five genotypes when they were typed using mycobacterial interspersed repetitive unit, variable number of tandem repeats (MIRU-VNTR). One significant (P = 0.017) spatial clustering of genotypes was detected, in which the proportion of MAH isolates was larger than expected under the null hypothesis of even distribution of genotypes. These results show that in Argentina the proportion of TB cases in pigs caused by M. avium is larger than that reported in earlier studies. The proportion of M. bovis-MAC co-infections was also higher than in previous reports. These results provide valuable information on the epidemiology of MAC infection in swine in Argentina.


Sequence and functional characterization of feline interleukin 2.
Since the discovery of its involvement in the pathogenesis of feline immunodeficiency virus infection ("cat AIDS") and feline leukemia virus infection, the role of feline interleukin 2 (IL-2) has been a focus of particular interest. The purpose of this study was to clone feline IL-2 cDNA, as well as synthesize bioactive recombinant feline IL-2. The isolation of cDNA encoding feline IL-2 was carried out using a PCR-based strategy and screening of a feline leukocyte cDNA library. Feline IL-2 consists of 154 amino acids including a putative signal sequence and has 81%, 69%, 60% and 64% identity to human, bovine, murine and rat IL-2, respectively. Feline IL-2 cDNA was expressed in COS-7 cells. The secreted protein has CTLL-4 murine cytotoxic T cell proliferative activity characteristic of authentic IL-2. These data confirm the synthesis of bioactive recombinant feline IL-2.


Tranexamic Acid Dosing in Craniosynostosis Surgery: A Systematic Review with Meta-analysis.
This study aimed to compare operative time, blood loss, and transfusion requirement in patients receiving a high tranexamic acid (TXA) dose of greater than 10 mg/kg versus those receiving a low dose of 10 mg/kg or less. PubMed, Cochrane Central, and Embase were queried to perform a systematic review with meta-analysis. Studies reporting outcomes of TXA use in craniosynostosis surgery were included. TXA dosing, operative time, blood loss, and transfusion requirement were the primary outcomes studied. Other variables studied included age and types of craniosynostosis. In total, 398 individuals in the included articles received TXA for craniosynostosis surgery. TXA loading doses ranged from 10 mg/kg to 50 mg/kg. Overall, administration of TXA was not associated with changes in operative time, but was associated with decreased blood loss and transfusion requirement on meta-analysis. Comparison of high dose TXA (>10 mg/kg) versus low dose (10 mg/kg or less) showed no statistical differences in changes in operative time, blood loss, or transfusion requirement. Overall, TXA reduced blood loss and transfusion requirement in patients undergoing surgery for craniosynostosis. There was no difference in outcomes between high dose and low dose regimens amongst those receiving TXA. Low dose TXA appears adequate to achieve clinical efficacy with a low adverse event rate.


Characterisation of the growth behaviour of Listeria monocytogenes in Listeria synthetic media.
The foodborne pathogen Listeria monocytogenes can grow in a wide range of environmental conditions. For the study of the physiology of this organism, several chemically defined media have been developed over the past decades. Here, we examined the ability of L. monocytogenes wildtype strains EGD-e and 10403S to grow under salt and pH stress in Listeria synthetic medium (LSM). Furthermore, we determined that a wide range of carbon sources could support the growth of both wildtype strains in LSM. However, for hexose phosphate sugars such as glucose-1-phosphate, both L. monocytogenes strains need to be pre-grown under conditions, where the major virulence regulator PrfA is active. In addition, growth of both L. monocytogenes strains was observed when LSM was supplemented with the amino acid sugar N-acetylmannosamine (ManNAc). We were able to show that some of the proteins encoded in the operon lmo2795-nanE, such as the ManNAc-6-phosphate epimerase NanE, are required for growth in the presence of ManNAc. The first gene of the operon, lmo2795, encodes a transcriptional regulator of the RpiR family. Using electrophoretic mobility shift assays and quantitative real-time PCR analysis, we were able to show that Lmo2795 binds to the promoter region of the operon lmo2795-nanE and activates its expression.


Triggering receptor expressed on myeloid cells-1 (TREM-1): a new player in antiviral immunity?
The triggering receptor expressed on myeloid cells (TREM) family of protein receptors is rapidly emerging as a critical regulator of a diverse array of cellular functions, including amplification of inflammation. Although the ligand(s) for TREM have not yet been fully identified, circumstantial evidence indicates that danger- and pathogen-associated molecular patterns (DAMPs and PAMPs) can induce cytokine production via TREM-1 activation. The discovery of novel functions of TREM, such as regulation of T-cell proliferation and activation of antigen-presenting cells, suggests a larger role of TREM proteins in modulation of host immune responses to microbial pathogens, such as bacteria and fungi. However, the significance of TREM signaling in innate immunity to virus infections and the underlying mechanisms remain largely unclear. The nature and intensity of innate immune responses, specifically production of type I interferon and inflammatory cytokines is a crucial event in dictating recovery vs. adverse outcomes from virus infections. In this review, we highlight the emerging roles of TREM-1, including synergy with classical pathogen recognition receptors. Based on the literature using viral PAMPs and other infectious disease models, we further discuss how TREM-1 may influence host-virus interactions and viral pathogenesis. A deeper conceptual understanding of the mechanisms associated with pathogenic and/or protective functions of TREM-1 in antiviral immunity is essential to develop novel therapeutic strategies for the control of virus infection by modulating innate immune signaling.


Cardioversion for atrial fibrillation: the views of consultant physicians, geriatricians and cardiologists.
Atrial fibrillation (AF) increases the risk of stroke and also has adverse haemodynamic consequences. Cardioversion of AF to sinus rhythm may obviate the need for long-term anticoagulation and improve cardiovascular haemodynamics, but is probably underused. We therefore investigated the views of hospital consultants about cardioversion for AF. 336 Postal questionnaires were sent to all 186 consultant physicians, 54 cardiologists and 96 geriatricians in Scotland, followed by one reminder letter to non-responders. 71% Of questionnaires were returned. Cardiologists referred 18% of AF patients for cardioversion, while physicians referred 11% and geriatricians 5%. Cardiologists had better access to cardioversion facilities and were less likely to consider an enlarged left atrium and organic heart disease to be contra-indications to cardioversion. Anticoagulation was given for less than 3 weeks before cardioversion by 9% of cardiologists, 39% of physicians and 65% of geriatricians (P<0.001), and for less than 3 weeks after cardioversion by 17% of cardiologists, 45% of physicians and 47% of geriatricians (P = 0.7). The wide variation in practice both between and within the different specialties suggests that consensus guidelines based on the best available evidence should be developed.


Stabilizing P2-Type Ni-Mn Oxides as High-Voltage Cathodes by a Doping-Integrated Coating Strategy Based on Zinc for Sodium-Ion Batteries.
The key to development of high-voltage P2-type Na0.66Ni0.33Mn0.67O2 is the modification methods that can effectively improve its electrochemical reversibility. Herein, a doping-integrated coating strategy based on zinc element is proposed to modify P2-type Na0.66Ni0.33Mn0.67O2, which can be achieved by a facile one-step solid-state reaction. The formation mechanism of firstname.lastname@example.com (firstname.lastname@example.com) is investigated, revealing that the spinel and P3 intermediate phases appear prior to the formation of the P2 phase. Ni2+ can be preferentially incorporated into the P2 structure in competition with Zn2+ at high temperature, resulting in a uniform enrichment of ZnO on the surface. A small amount of Zn2+ doping significantly suppresses the Na+/vacancy ordering effect and improves the structural reversibility. Furthermore, the electrolyte decomposition is effectively reduced because of the presence of the ZnO coating layer, leading to the formation of a thin cathode electrolyte interphase film that is favorable to fast Na+ diffusion. In virtue of the Zn2+ doping and in situ formed ZnO coating, email@example.com exhibits excellent cycling stability with a capacity retention of 83.7% after 100 cycles at 100 mA g-1 and rate performance with a discharge capacity of 56.4 mAh g-1 at 2000 mA g-1, which significantly outperforms the uncoated Na0.66Ni0.26Zn0.07Mn0.67O2 and the Na0.66Ni0.26Zn0.07Mn0.67O2/0.06ZnO with the coating layer introduced by mechanical milling. This work provides a new strategy to design high-performance cathode materials for sodium-ion batteries.


Local anesthesia during interstitial laser coagulation of the prostate.
With the emergence of minimally invasive therapies for the management of symptoms of benign prostatic hyperplasia (BPH), as well as the reality of a changing medical economic environment, there is a need for a reliable local anesthesia protocol. The protocol described here for prostate anesthetic block is a safe, economical, and effective way to perform interstitial laser coagulation and other minor endoscopic urologic procedures in the office setting. Most patients experience little discomfort and recover quickly, with prompt return to normal activities. Urologists should be aware of and comfortable with these techniques.


Postnatal ontogeny of intestinal GCPII and the RFC in pig.
In humans and pigs, hydrolysis of dietary polyglutamyl folates is carried out by intestinal brush border folate hydrolase [glutamate carboxypeptidase II (GCPII)], whereas the transport of the monoglutamyl folate derivatives occurs via the intestinal brush border reduced folate carrier (RFC). The study objective was to measure the expression of intestinal GCPII and RFC during postnatal development of pigs and their effects on plasma and liver folate concentrations. Duodenum, jejunum, ileum, liver, and plasma samples were collected from female Yorkshire pigs at birth, 24 h, 1 wk, 3 wk, and 6 mo (n=6 at each time point). GCPII mRNA transcripts and protein (normalized using beta-actin), and enzyme activity (normalized per mg mucosal protein) were highest in all segments of small intestine at birth and were undetectable in ileum after 1 wk, whereas jejunal protein and activity predominated at 6 mo. RFC mRNA transcripts were present in all segments of small intestine at birth and declined significantly throughout development to 6 mo. Conversely, RFC protein increased twofold during the first 24 h and remained constant throughout development in all segments of small intestine. Liver RFC mRNA transcripts were detected at birth but were reduced by 6 mo. Liver folate concentration increased throughout postnatal development, whereas plasma folate levels increased during the first 24 h but decreased over time, reflecting the pattern of RFC expression in small intestine. These findings show that intestinal GCPII and intestinal and hepatic RFC all exhibit ontogenic changes in the pig that are reflected in postnatal folate status.


Extraordinary diversity in vasopressin (V1a) receptor distributions among wild prairie voles (Microtus ochrogaster): patterns of variation and covariation.
The vasopressin V1a receptor is a gene known to be central to species differences in social behavior, including differences between the monogamous prairie vole and its promiscuous congeners. To examine how individual differences compare with species differences, we characterize variability in the expression of the vasopressin V1a receptor (V1aR) in a large sample of wild prairie voles. We find a surprising degree of intraspecific variation in V1aR binding that does not seem attributable to experimental sources. Most brain regions exhibit differences between upper and lower quartiles that are comparable to differences between species in this genus. Regions that are less variable have been implicated previously in regulating monogamous behaviors, suggesting that the lack of variation at these sites could reflect natural selection on mating system. Many brain regions covary strongly. The overall pattern of covariation reflects the developmental origins of brain regions. This finding suggests that shared mechanisms of transcriptional regulation may limit the patterns of gene expression. Such biases may shape both the efficacy of selection and the pattern of individual and species differences. Overall, our data indicate that the prairie vole would be a useful model for exploring how individual differences in gene expression influence complex social behaviors.


Effect of Ichthyophthirius multifiliis parasitism on the survival, hematology and bacterial load in channel catfish previously exposed to Edwardsiella ictaluri.
The effect of Ichthyophthirius multifiliis (Ich) parasitism on survival, hematology and bacterial load in channel catfish, Ictalurus punctatus, previously exposed to Edwardsiella ictaluri was studied. Fish were exposed to E. ictaluri 1 day prior to Ich in the following treatments: (1) infected by E. ictaluri and Ich at 2,500 theronts/fish; (2) infected by E. ictaluri only; (3) infected by Ich at 2,500 theronts/fish only; and (4) non infected control. Mortality was significantly higher in fish previously exposed to E. ictaluri and then infected by Ich (71.1 %). Mortalities were 26.7 %, 28.9 % and 0 % for fish infected by E. ictaluri only, by Ich only and non-infected control, respectively. Quantitative polymerase chain reaction demonstrated the presence of E. ictaluri in the brain, gill, kidney and liver of fish infected with E. ictaluri regardless of Ich parasitism. At day 8, E. ictaluri parasitized fish had significantly more bacteria present in the brain, gill and liver, with no bacteria detected in these organs in the E. ictaluri-only treatment, suggesting that the bacteria persisted longer in parasitized fish. Decreased red blood cells count and hematocrit in fish at days 8 and 19 after co-infection suggests chronic anemia. Lymphocyte numbers significantly decreased in all infected treatments versus the non-infected controls at days 2, 8 and 19. Lymphopenia suggests that lymphocytes were actively involved in the immune response. Bacterial clearance was probably influenced by the stress of parasitism and/or the mucosal response induced by ectoparasitic Ich that resulted in the higher mortality seen in the co-infected treatment.


Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR.
To assess removal of cytomegalovirus (CMV) by leukocyte depletion (LD) filters, we developed a spiking model of latent virus using peripheral blood mononuclear cells (PBMCs) infected by coculture with CMV-infected human fibroblasts. Infected PBMCs were purified by dual magnetic column selection and then spiked into whole blood units or buffy coat pools prior to LD by filtration. CMV load and fibroblast contamination were assessed using quantitative CMV DNA real-time PCR and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of mRNA encoding the fibroblast-specific splice variant of prolyl-4-hydroxylase, respectively. After correcting for fibroblast-associated CMV, the mean CMV load was reduced in whole blood by LD from 7.42 x 10(2) to 1.13 copies per microliter (2.81(10)log reduction) and from 3.8 x 10(2) to 4.77 copies per microliter (1.9(10)log reduction) in platelets. These results suggest that LD by filtration reduces viral burden but does not completely remove CMV from blood components.


Interface profiles near three-phase contact lines in electric fields.
Long-range electrostatic fields deform the surface profile of a conductive liquid in the vicinity of the contact line. We have investigated the equilibrium profiles by balancing electrostatic and capillary forces locally at the liquid vapor interface. Numerical results show that the contact angle at the contact line approaches Young's angle. Simultaneously, the local curvature displays a weak algebraic divergence. Furthermore, we present an asymptotic analytical model, which confirms these results and elucidates the scaling behavior of the profile close to the contact line.


Identification of WNT/beta-CATENIN signaling pathway components in human cumulus cells.
Signaling via the conserved WNT/beta-CATENIN pathway controls diverse developmental processes. To explore its potential role in the ovary, we investigated the expression of WNTs, frizzled (FZD) receptors and other pathway components in human cumulus cells obtained from oocytes collected for in vitro fertilization. Proteins were detected in cultured cells using immunofluorescence microscopy. Protein-protein interactions were analyzed by means of immunoprecipitation. WNT2, FZD2, FZD3 and FZD9 were identified but WNT1, WNT4 and FZD4 were not detected. WNT2 is co-expressed with FZD2, FZD3 and FZD9. Co-immunoprecipitation using WNT2 antibody demonstrated that WNT2 interacts with both FZD3 and FZD9, but only FZD9 antibody precipitated WNT2. We also identified DVL (disheveled), AXIN, GSK-3beta (glycogen synthase kinase-3beta) and beta-CATENIN. beta-CATENIN is concentrated in the plasma membranes. DVL co-localizes with FZD9 and AXIN in the membranes, but GSK-3beta has little co-localization with AXIN and beta-CATENIN. Interestingly, beta-CATENIN is highly co-localized with FZD9 and AXIN. CDH1 (E-cadherin) was also detected in the plasma membranes and cytoplasm, co-localized with beta-CATENIN, and CDH1 antibody precipitated beta-CATENIN. The results suggest that WNT2 could act through its receptor FZD9 to regulate the beta-CATENIN pathway in cumulus cells, recruiting beta-CATENIN into plasma membranes and promoting the formation of adherens junctions involving CDH1.


Rapid, quantitative, semiautomated assay for virus-induced and immune human interferons.
An improved human interferon (IF) assay is described. This procedure is based on the ability of encephalomyocarditis virus to replicate in WISH cell microcultures with the production of discrete plaques in the presence of a liquid tissue culture medium. Performance of 50% plaque reduction endpoint assays in micro-culture required only 0.1 ml of specimen for determinations using duplicate dilutions beginning at 1:3. Semiautomated equipment facilitated simultaneous in situ dilution and distribution of multiple IF samples in cultures containing preformed WISH cell monolayers. An incubation period of 5 to 6 h was adequate for development of maximal antiviral activity by both virus- and immune-induced IF. Sensitivity of the encephalomyocarditis microplaque reduction assay was comparable to that of other commonly used techniques. The method is rapid, can be completed within 30 h from the beginning of the IF assay, and is able to accommodate as many as 40 to 50 samples at a single time. Encephalomyocarditis microplaque reduction is suitable for the quantitation of IF as an antiviral agent or a lymphokine.


On representing the prognostic value of continuous gene expression biomarkers with the restricted mean survival curve.
Researchers developing biomarkers for cancer prognosis from quantitative gene expression data are often faced with an odd methodological discrepancy: while Cox's proportional hazards model, the appropriate and popular technique, produces a continuous and relative risk score, it is hard to cast the estimate in clear clinical terms like median months of survival and percent of patients affected. To produce a familiar Kaplan-Meier plot, researchers commonly make the decision to dichotomize a continuous (often unimodal and symmetric) score. It is well known in the statistical literature that this procedure induces significant bias. We illustrate the liabilities of common techniques for categorizing a risk score and discuss alternative approaches. We promote the use of the restricted mean survival (RMS) and the corresponding RMS curve that may be thought of as an analog to the best fit line from simple linear regression. Continuous biomarker workflows should be modified to include the more rigorous statistical techniques and descriptive plots described in this article. All statistics discussed can be computed via standard functions in the Survival package of the R statistical programming language. Example R language code for the RMS curve is presented in the appendix.


Hand and ultrasonic instrumentation in the treatment of chronic periodontitis after supragingival plaque control.
This study compared the clinical effects of hand or ultrasonic scaling and root planing on the treatment of chronic periodontitis. After supragingival plaque control, twenty patients were examined by a blinded and calibrated examiner for probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP). Experimental teeth were allocated to the following subgingival treatment groups according to PPD: 1) hand instrumentation; 2) hand instrumentation with irrigation; 3) ultrasonic instrumentation; 4) ultrasonic followed by hand instrumentation. Time used in the procedures was recorded. Follow-up examinations were performed at 30 and 90 days after treatment. Each patient's individual BOP, PPD and CAL means were analyzed with repeated-measures ANOVA. Differences in the instrumentation time were analyzed with 1-way ANOVA. Significance level was established at 5%. All treatments produced significant changes in the clinical parameters. BOP reduced, in proximal surfaces, from 67.21-79.17% at baseline to 45.75-51.54% at 90 days. Significant reductions were also found for PPD and CAL in all groups, both in proximal and free surfaces. Reductions in mean PPD at 90 days ranged from 0.92 to 1.14 mm for the free surfaces and from 1.01 to 1.35 mm for proximal surfaces, whereas reductions in CAL ranged from 0.43 to 0.82 mm and from 0.60 to 0.73 mm for free and proximal surfaces, respectively. Mean instrumentation time ranged from 4.77 to 5.30 minutes. No statistically significant differences were found among the four study groups. It can be concluded that the four methods of subgingival instrumentation were equally efficacious in the improvement of the studied clinical parameters.


Therapy outcomes associated with prescription cannabidiol use at 12 months post-initiation.
This study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy. A single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type. The 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31-196) and 104 (IQR 38-179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use. Despite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.


Mathematical model for the luminol chemiluminescence reaction catalyzed by peroxidase.
A kinetic model that accurately describes intensity vs. time reaction profiles for the chemiluminescence reaction between luminol and hydrogen peroxide, as catalyzed by horseradish peroxidase, is derived and evaluated. A set of three differential equations is derived and solved to provide intensity time information for the first 200 seconds of the reaction. The model accurately predicts intensity-time profiles when literature values are used for all but one of the reaction rate constants. Furthermore, the model predicts a nonlinear curve for plots of light intensity versus the initial hydrogen peroxide concentration. Experimental data confirm that such plots are nonlinear. Finally, a linear double-reciprocal plot is predicted by the model and the experimental data verify this relationship.


Reducing the risk of benign prostatic hyperplasia progression.
The incidence of benign prostatic hyperplasia increases with age; the probability of progression rises with age at diagnosis and with baseline symptom severity. Although it is not life-threatening, the condition and its complications have a serious impact on quality of life. Acute urinary retention (AUR), though no longer thought an indication for immediate surgery, still requires treatment, often including surgery. Drug therapy with alpha-adrenergic receptor blockers or 5-alpha-reductase inhibitors, such as finasteride, reduces the risk for AUR and the need for surgery, as well as symptoms and bother. Finasteride therapy also results in long-term reduction in prostate volume.